{"publication_id":"2f99ba23-7327-40ed-9dbd-509dfb346ff4","traces":[{"claim_id":"claim_1","claim":"This paper synthesizes evidence on zinc supplementation effects across 32 accepted source papers and 1454 high-confidence extracted claims. The evidence profile contains 4 direct clinical sources, 28 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base. Positive study-level signals are summarized in the immune and inflammation, longevity outcome classes, null signals in the contextual adjacent evidence, deficiency prevalence, immune and inflammation outcome classes, and negative signals in the immune and inflammation, contextual adjacent evidence outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that zinc supplementation effects remains a bounded evidence hypothesis: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any over-broad aging-related claim. For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"This paper synthesizes evidence on zinc supplementation effects across 32 accepted source papers and 1454 high-confidence extracted claims.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"The evidence profile contains 4 direct clinical sources, 28 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"Positive study-level signals are summarized in the immune and inflammation, longevity outcome classes, null signals in the contextual adjacent evidence, deficiency prevalence, immune and inflammation outcome classes, and negative signals in the immune and inflammation, contextual adjacent evidence outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"The conclusion is that zinc supplementation effects remains a bounded evidence hypothesis: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any over-broad aging-related claim.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"This synthesis evaluates evidence on zinc supplementation effects across 32 included source papers and 1454 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"The corpus contains 4 direct clinical sources, 28 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"The background evidence for zinc supplementation effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Barffour 2020, Baissary 2025, Wessells 2019 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.","citation_support":[{"source_id":"source_1","study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","support_kind":"cited_as_match","cited_as":"Barffour 2020","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL)."}],"candidate_sources":[]},{"claim_id":"claim_17","claim":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"Across the retained sources, positive signals cluster around the immune and inflammation, longevity outcome classes; null signals around the contextual adjacent evidence, deficiency prevalence, immune and inflammation outcome classes; and negative or adverse signals around the immune and inflammation, contextual adjacent evidence outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, immune and inflammation, longevity, mortality and survival); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_27","claim":"| Zinc Supplementation Effects / Contextual Adjacent Evidence | n=9; claims=404 | significant source statistic in 8/9 sources; receipt-level direction coded unclear | 1 direct; 4 indirect; 4 review | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"Aging and geroscience context: 1 sources; significant source statistic in 1/1 sources; receipt-level direction coded null.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"Contextual Adjacent Evidence: n=9; claims=404; mixed signal in 6/9 sources | directness: 1 direct; 4 indirect; 4 review; main limitation: directionally heterogeneous.","citation_support":[],"candidate_sources":[{"study":"Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial","year":2020,"doi":"10.7189/jogh.10.010424","url":"https://doi.org/10.7189/jogh.10.010424","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"direct","cited_as":"Barffour 2020","excerpt":"BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial","year":2024,"doi":"10.1016/j.tjnut.2024.04.018","url":"https://doi.org/10.1016/j.tjnut.2024.04.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Kemp 2024","excerpt":"BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis","year":2020,"doi":"10.3390/nu12020491","url":"https://doi.org/10.3390/nu12020491","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Oh 2020","excerpt":"Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease","year":2020,"doi":"10.1186/s12944-020-01298-4","url":"https://doi.org/10.1186/s12944-020-01298-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Hamedifard 2020","excerpt":"BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (β - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (β - 1.37 μIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (β 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (β - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (β 5.13 μmol/L, 95% CI, 1.85, 8.41; P = 0.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effect of Zinc Supplementation vs Placebo on Mortality Risk and HIV Disease Progression Among HIV-Positive Adults With Heavy Alcohol Use","year":2020,"doi":"10.1001/jamanetworkopen.2020.4330","url":"https://doi.org/10.1001/jamanetworkopen.2020.4330","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Freiberg 2020","excerpt":"IMPORTANCE: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation. OBJECTIVE: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS. DESIGN, SETTING, AND PARTICIPANTS: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020. INTERVENTION: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"Two systematic reviews anchor the cardiometabolic evidence base for zinc supplementation, each pooling randomized controlled trials across heterogeneous populations. Jayawardena 2022 synthesized studies in prediabetes mellitus, while Khazdouz 2020 aggregated randomized controlled trials evaluating cardiometabolic risk factors more broadly. Both reviews summarize zinc delivered as an oral supplement, alone or in combination with other micronutrients, against comparators that varied across the included primary trials. The principal endpoints assessed were fasting and post-load glucose, glycated hemoglobin, and related metabolic indices. The two reviews together provide the principal human-evidence substrate for the cardiometabolic class within this corpus.","citation_support":[{"source_id":"source_17","study":"Zinc supplementation in prediabetes mellitus.","doi":"10.23736/s2724-6507.21.03234-x","url":"https://doi.org/10.23736/s2724-6507.21.03234-x","support_kind":"cited_as_match","cited_as":"Jayawardena 2022","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"INTRODUCTION: Certain pharmacological and lifestyle interventions have been shown to reduce progression of prediabetes. We aimed to perform a systematic review and meta-analyses of studies assessing the outcomes of zinc supplementation in individuals with prediabetes. EVIDENCE ACQUISITION: A comprehensive search was conducted in PubMed, SciVerse Scopus and Web of Science databases. Controlled clinical trials in prediabetics individuals, on zinc supplementation with or without other nutrients, assessing at least one accepted glycemic parameter as an outcome were deemed eligible. EVIDENCE SYNTHESIS: Three papers were included in the systematic review and meta-analysis, with a total of 265 participants. Duration of zinc supplementation ranged from 6-12 months. The zinc dose ranged from 20-30 mg/day. In the pooled analysis, zinc supplementation significantly reduced FBG both when given alone (-10.86 mg/dL; 95% CI, -14.74 to -6.98; P<0.001) and with other micronutrients (-11.77 mg/dL; P<0.001). Similarly, 2hr-OGTT blood glucose was reduced by 21.08 mg/dL (95% CI, -40.05 to -2.11; P=0.03) in the pooled analysis of studies using zinc alone and in combination with other micronutrients."},{"source_id":"source_18","study":"Effects of Zinc Supplementation on Cardiometabolic Risk Factors: a Systematic Review and Meta-analysis of Randomized Controlled Trials.","doi":"10.1007/s12011-019-01870-9","url":"https://doi.org/10.1007/s12011-019-01870-9","support_kind":"cited_as_match","cited_as":"Khazdouz 2020","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on cardiometabolic risk factors are unequivocal. This systematic review and meta-analysis of randomized controlled trials was conducted to evaluate the effects of zinc supplementation on cardiometabolic risk factors. A systematic search was conducted through international databases (PubMed/Medline, Institute of Scientific Information, and Scopus) until December 2018 to include all randomized controlled trials (RCT), quasi-RCT, and controlled clinical trials which assessed the effect of zinc supplementation on cardiometabolic risk factors including lipid profile, glycemic indices, blood pressure, and anthropometric indices. Random- or fixed-effects meta-analysis method was used to estimate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies were included in the meta-analysis, which included a total of 1141 participants in the intervention group. Meta-analysis showed that zinc supplementation significantly decreased plasma levels of triglyceride (SMD - 0.66, 95% CI - 1.27, - 0."}],"candidate_sources":[]}]}