{"publication_id":"bb33d8d3-a744-4227-8cd9-8cae11058326","traces":[{"claim_id":"claim_1","claim":"This synthesis tests the thesis that evidence for Intermittent fasting is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Evidence-honesty note: 14/19 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes evidence on Intermittent fasting across 19 included source papers and 1344 high-confidence extracted claims. The evidence profile contains 5 direct clinical sources, 14 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. No single positive outcome class dominates the retained corpus; null signals cluster in the cardiometabolic and contextual adjacent evidence outcome classes, and negative signals cluster in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"This synthesis tests the thesis that evidence for Intermittent fasting is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"Evidence-honesty note: 14/19 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"This paper synthesizes evidence on Intermittent fasting across 19 included source papers and 1344 high-confidence extracted claims.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"The evidence profile contains 5 direct clinical sources, 14 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":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"No single positive outcome class dominates the retained corpus; null signals cluster in the cardiometabolic and contextual adjacent evidence outcome classes, and negative signals cluster in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"The conclusion is that Intermittent fasting remains a bounded evidence case: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified broad clinical claim.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-intermittent_fasting-v06-DAILY-2026-07-03T04-07-41Z`.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","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":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","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":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, safety and comorbidity); 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":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","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":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"| Cardiometabolic | Kender 2023: Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients | direction=null | directness=indirect | B2 | outcome=Cardiometabolic; direction=null | finding=representative statistic P = 0.04; source-level statistic reported |","citation_support":[{"source_id":"source_6","study":"Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients","doi":"10.3389/fendo.2023.1143799","url":"https://doi.org/10.3389/fendo.2023.1143799","support_kind":"cited_as_match","cited_as":"Kender 2023","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"BACKGROUND AND AIM: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D). STUDY DESIGN AND METHODS: Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention. RESULTS: Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention."}],"candidate_sources":[]},{"claim_id":"claim_15","claim":"| Cardiometabolic | Koh 2025: The Effectiveness of Time-Restricted Eating as an Intermittent Fasting Approach on Shift Workers’ Glucose Metabolism: A Systematic Review and Meta-Analysis | direction=unclear | directness=review | B2 | outcome=Cardiometabolic; direction=unclear | finding=representative non-significant statistic P = 0.77; not treated as positive or negative directional support unless source direction is coded |","citation_support":[{"source_id":"source_11","study":"The Effectiveness of Time-Restricted Eating as an Intermittent Fasting Approach on Shift Workers’ Glucose Metabolism: A Systematic Review and Meta-Analysis","doi":"10.3390/nu17101689","url":"https://doi.org/10.3390/nu17101689","support_kind":"cited_as_match","cited_as":"Koh 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"Background/Objectives : Shift workers face higher risks of impaired glucose metabolism due to irregular eating habits and circadian misalignment. Time-restricted eating (TRE) could improve glucose metabolism by aligning food intake with the circadian clock, but its effectiveness remains unclear. Methods : Ten electronic databases (PubMed, EMBASE, Cochrane Library, CINAHL, PsycINFO, Scopus, Web of Science, ProQuest Dissertations and Theses, Science.gov, and ClinicalTrials.gov) were searched from journal inception to September 2024. Only randomized controlled trials (RCTs) involving shift workers were included. Meta-analyses with sensitivity analyses were conducted using a random-effects model to pool glucose metabolism and sleep outcomes, with heterogeneity and quality assessments performed. Results : Six RCTs were included. TRE demonstrated positive but non-significant effects on glucose metabolism outcomes: fasting blood glucose (weighted mean difference [WMD]: -0.02 mmol/L, 95% confidence interval [CI]: -0.13 to 0.10, I 2 = 0%), fasting blood insulin (WMD: -5.77 pmol/L, 95% CI: -85.62 to 74.08, I 2 = 92%), HOMA-IR (WMD: -0.50, 95% CI: -2.76 to 1."}],"candidate_sources":[]},{"claim_id":"claim_16","claim":"| Cardiometabolic | Martinez-Montoro 2025: Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial | direction=null | directness=direct | A1 | outcome=Cardiometabolic; direction=null | finding=218 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_2","study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","support_kind":"cited_as_match","cited_as":"Martinez-Montoro 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3."}],"candidate_sources":[]},{"claim_id":"claim_17","claim":"| Cardiometabolic | Pascual 2023: A meta‐analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time‐restricted eating for weight loss | direction=null | directness=indirect | B2 | outcome=Cardiometabolic; direction=null | finding=representative non-significant statistic P = 0.37; not treated as positive or negative directional support unless source direction is coded |","citation_support":[{"source_id":"source_15","study":"A meta‐analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time‐restricted eating for weight loss","doi":"10.1002/oby.23568","url":"https://doi.org/10.1002/oby.23568","support_kind":"cited_as_match","cited_as":"Pascual 2023","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"OBJECTIVE: The objective of this meta-analysis was to compare the effectiveness of different intermittent fasting (IF) regimens on weight loss, in the general population, and compare these to traditional caloric energy restriction (CER). METHODS: Three databases were searched from 2011 to June 2021 for randomized controlled trials (RCTs) that assessed weight loss and IF, including alternate day fasting (ADF), the 5:2 diet, and time-restricted eating (TRE). A random effect network analysis was used to compare the effectiveness between the three regimens. Meta-regression analysis was presented as weighted mean differences of body weight loss. RESULTS: The exploratory random effects network analysis of 24 RCTs (n = 1768) ranked ADF as the most effective, followed by CER and TRE. The meta-analysis showed that IF regimens resulted in similar weight loss to CER (mean difference 0.26 kg, 95% CI: -0.31 to 0.84; p = 0.37). Compliance was generally high (>80%) in trials shorter than 3 months. CONCLUSIONS: The present meta-analysis concludes that IF is comparable to CER and a promising alternative for weight loss."}],"candidate_sources":[]},{"claim_id":"claim_18","claim":"| Cardiometabolic | Talebi 2023: The effects of intermittent fasting diet alone or in combination with probiotic supplementation in comparison with calorie-restricted diet on metabolic and hormonal profile in patients with polycystic ovary syndrome: study protocol for a randomized clinical trial | direction=null | directness=direct | A1 | outcome=Cardiometabolic; direction=null | finding=16 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_16","study":"The effects of intermittent fasting diet alone or in combination with probiotic supplementation in comparison with calorie-restricted diet on metabolic and hormonal profile in patients with polycystic ovary syndrome: study protocol for a randomized clinical trial","doi":"10.1186/s13063-023-07691-5","url":"https://doi.org/10.1186/s13063-023-07691-5","support_kind":"cited_as_match","cited_as":"Talebi 2023","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females characterized by ovulatory dysfunction, hyperandrogenism, and other metabolic disorders. Both intermittent fasting and specific probiotics have been suggested to help improve patients with PCOS through changes in gut microbial composition, circadian clock, and metabolic regulation. Therefore, the present study aims to investigate the effects of intermittent fasting alone or in combination with probiotic supplementation compared to the calorie-restricted (CR) diet on anthropometric measures, metabolic status, inflammation, and oxidative stress in women with PCOS. METHODS: We will carry out a randomized clinical trial for 8 weeks. Participants will be randomly assigned (1:1:1) to one of the three groups: (1) a 14:10 early time-restricted feeding (TRF) diet with probiotic supplementation (n = 30); (2) a 14:10 early TRF diet with placebo supplementation (n = 30); (3) a CR diet (energy-restricted 25% of required calories) with placebo supplementation as a control group (n = 30). The primary outcomes will be changes in body weight and insulin resistance."}],"candidate_sources":[]},{"claim_id":"claim_19","claim":"| Contextual Adjacent Evidence | Huang 2021: An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study | direction=null | directness=direct | A1 | outcome=Contextual Adjacent Evidence; direction=null | finding=16 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_17","study":"An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study","doi":"10.3390/nu13051523","url":"https://doi.org/10.3390/nu13051523","support_kind":"cited_as_match","cited_as":"Huang 2021","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"There has been increasing interest in time-restricted eating to attain intermittent fasting's metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve ( AUC 0-4 ) that were non-inferior to those who continued with the water fast ( p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC 0-4 in the FMD group was non-inferior to that in the water fast group ( p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expected."}],"candidate_sources":[]},{"claim_id":"claim_20","claim":"| Contextual Adjacent Evidence | Soliman 2022: Intermittent fasting and time-restricted eating role in dietary interventions and precision nutrition | direction=null | directness=indirect | B2 | outcome=Contextual Adjacent Evidence; direction=null | finding=1 extracted claim(s); source-level direction is the coded finding |","citation_support":[{"source_id":"source_18","study":"Intermittent fasting and time-restricted eating role in dietary interventions and precision nutrition","doi":"10.3389/fpubh.2022.1017254","url":"https://doi.org/10.3389/fpubh.2022.1017254","support_kind":"cited_as_match","cited_as":"Soliman 2022","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"Intermittent fasting (IF), time-restricted eating (TRE) and fasting-mimicking diets (FMD) are gaining popularity as weight loss programs. As such, the timing and frequency of meals have been recognized as essential contributors to improving cardiometabolic health and a role as adjuvant therapy in cancer. Randomized controlled trials suggested that the weight loss associated with IF is due to a reduced energy intake due to time restriction. Although the supervised TRE clinical trials documented the dietary caloric intake, many free-living studies focused on the timing of meals without a complete characterization of the dietary intake, caloric density, or macronutrient composition. It is possible that both caloric-restriction diets and time-restriction protocols could work synergistically or additively to improve metabolic health outcomes. Like personalized medicine, achieving precision nutrition mandates the provision of the right nutrients to the right patient at the right time. To accomplish this goal, future studies need to evaluate the benefits of IF and TRE."}],"candidate_sources":[]},{"claim_id":"claim_21","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":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"| Intermittent fasting / Contextual Adjacent Evidence | n=2; claims=17 | no extracted directional signal in 2/2 sources | 1 direct; 1 indirect | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"Direction reconciliation: receipt-level null or unclear coding is conservative claim-level coding. Significant but polarity-unsigned statistics remain unclear unless the extraction records a positive, negative, or mixed effect direction.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"Contextual Adjacent Evidence remains a separate Results slice for Intermittent fasting (n=2; claims=17; no extracted directional signal in 2/2 sources; 1 direct; 1 indirect; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. Source-level findings are:","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"Huang 2021 (An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized; 16 extracted claim(s); receipt-level direction is the coded finding; outcome=Contextual Adjacent Evidence; direction=null; directness=direct; tier=A1).","citation_support":[{"source_id":"source_17","study":"An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study","doi":"10.3390/nu13051523","url":"https://doi.org/10.3390/nu13051523","support_kind":"cited_as_match","cited_as":"Huang 2021","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"There has been increasing interest in time-restricted eating to attain intermittent fasting's metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve ( AUC 0-4 ) that were non-inferior to those who continued with the water fast ( p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC 0-4 in the FMD group was non-inferior to that in the water fast group ( p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expected."}],"candidate_sources":[]},{"claim_id":"claim_27","claim":"Soliman 2022 (Intermittent fasting and time-restricted eating role in dietary interventions and precision nutrition; 1 extracted claim(s); receipt-level direction is the coded finding; outcome=Contextual Adjacent Evidence; direction=null; directness=indirect; tier=B2).","citation_support":[{"source_id":"source_18","study":"Intermittent fasting and time-restricted eating role in dietary interventions and precision nutrition","doi":"10.3389/fpubh.2022.1017254","url":"https://doi.org/10.3389/fpubh.2022.1017254","support_kind":"cited_as_match","cited_as":"Soliman 2022","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"Intermittent fasting (IF), time-restricted eating (TRE) and fasting-mimicking diets (FMD) are gaining popularity as weight loss programs. As such, the timing and frequency of meals have been recognized as essential contributors to improving cardiometabolic health and a role as adjuvant therapy in cancer. Randomized controlled trials suggested that the weight loss associated with IF is due to a reduced energy intake due to time restriction. Although the supervised TRE clinical trials documented the dietary caloric intake, many free-living studies focused on the timing of meals without a complete characterization of the dietary intake, caloric density, or macronutrient composition. It is possible that both caloric-restriction diets and time-restriction protocols could work synergistically or additively to improve metabolic health outcomes. Like personalized medicine, achieving precision nutrition mandates the provision of the right nutrients to the right patient at the right time. To accomplish this goal, future studies need to evaluate the benefits of IF and TRE."}],"candidate_sources":[]},{"claim_id":"claim_28","claim":"For Intermittent fasting, the final interpretation is deliberately tiered: the retained direct, adjacent, and context evidence profile defines a bounded evidence rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general efficacy endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent/context evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support Intermittent fasting as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone longevity intervention with proven hard clinical-outcome effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"This synthesis maps 19 included sources on Intermittent Fasting across 3 outcome classes and 72 cross-study disagreements. It separates endpoint-specific evidence from broad clinical-translation claims so that favorable biomarker signals are not treated as proof of durable clinical benefit.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"Across 19 curated reference papers, the evidence base for intermittent fasting shows a context-dependent profile. Negative signals appear in: cardiometabolic. Null findings dominate: cardiometabolic, contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The broad aging-related case for intermittent fasting as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.","citation_support":[],"candidate_sources":[{"study":"Intermittent Fasting and Healthy Aging in Older Adults: A Systematic Review of Cardiometabolic, Mental Health and Cognitive Outcomes with a Network Meta-Analysis of Anthropometric Measures","year":2026,"doi":"10.3390/nu18091450","url":"https://doi.org/10.3390/nu18091450","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":"Couto-Alfonso 2026","excerpt":"Background/Objective : Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods : Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre-post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effect of a ketogenic diet, time-restricted eating, or alternate-day fasting on weight loss in adults with obesity: a randomized clinical trial","year":2025,"doi":"10.1186/s12916-025-04182-z","url":"https://doi.org/10.1186/s12916-025-04182-z","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":"Martinez-Montoro 2025","excerpt":"BACKGROUND: Studies evaluating the effects of novel, alternative dietary approaches for weight loss compared with the Mediterranean diet (MedDiet) are lacking. We aimed to evaluate the effects of diets with varying ketogenic potential, i.e., a very-low carbohydrate diet (ketogenic diet, KD), time-restricted eating (TRE), and modified alternate-day fasting (mADF) on weight loss in obesity, compared with a MedDiet. METHODS: Three-month, parallel-arm, randomized clinical trial including 160 adults with obesity. Participants were randomized to 1 of 5 groups: control (MedDiet), KD, early TRE (eTRE), late TRE (lTRE), or mADF. All diets were calorie-restricted. The primary outcome was differences in weight loss from baseline to 3 months between a calorie-restricted MedDiet and each of the four remaining calorie-restricted dietary interventions. Secondary outcomes included change in body mass index, body composition, and cardiometabolic risk factors. RESULTS: The mean age was 45.7 years (SD 10.7), and 70.6% were women. One hundred forty participants completed the study. Significant differences in weight loss from baseline to 3 months were found between KD and the control group [- 3.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome","year":2020,"doi":"10.1038/s41598-020-73767-w","url":"https://doi.org/10.1038/s41598-020-73767-w","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":"Mindikoglu 2020","excerpt":"Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Metabolic and Orexin-A Responses to Ketogenic Diet and Intermittent Fasting: A 12-Month Randomized Trial in Adults with Obesity","year":2026,"doi":"10.3390/nu18020238","url":"https://doi.org/10.3390/nu18020238","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":"Monda 2026","excerpt":"BACKGROUND/OBJECTIVES: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects-particularly those involving Orexin-A, a peptide implicated in energy regulation-remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. METHODS: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m 2 ) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. RESULTS: All participants completed the intervention.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Age-Specific Analysis of the Effects of Intermittent Fasting on Body Composition and Cardiometabolic Markers in Healthy Adults and Individuals with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","year":2026,"doi":"10.3390/nu18111799","url":"https://doi.org/10.3390/nu18111799","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":"Xing 2026","excerpt":"Background : Intermittent fasting (IF) is a popular dietary strategy for improving weight and cardiometabolic health. However, its effectiveness and potential risks across different adult age trajectories remain unclear. This systematic review and meta-analysis evaluated the age-specific effects of IF on body composition and cardiometabolic markers. Methods : Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) up to September 2025. Participants were stratified into three cohorts: <30 years, 30-44 years, and ≥45 years. Random-effects meta-analyses and leave-one-out sensitivity analyses were conducted on body composition, lipid profiles, glycemic markers, and blood pressure. Additionally, a conservative methodological sensitivity analysis (imputed correlation r = 0.5) and subgroup analyses by fasting modality (TRF vs. intermittent energy restriction) were performed. Risk of bias was assessed using the RoB 2 tool. Results : Analysis of 28 RCTs (N = 1833) demonstrated that IF significantly reduced body weight and BMI across all age groups.","source_id":"source_5","support_kind":"candidate_source_row"}]}]}