{"publication_id":"2371a466-c045-460d-a766-e242574bcc65","traces":[{"claim_id":"claim_1","claim":"Alpha memo: Effects of resveratrol on changes in trimethylamine N oxide and circulating cardiovascular factors following exercise Hypothesis level alpha signal; not clinical advice. Core signal Two 2024 randomized trials in older adults define the same dose/regime but land on different ledger sides. 10.1002/ptr.8171 is a systematic review of randomized clinical trials in older adults reporting that resveratrol combined with exercise improved exercise adaptation, muscle function, and physical performance/mobility. 10.1016/j.exger.2024.112479 is the embedded dose ranging trial that explicitly set out to test resveratrol + exercise training on trimethylamine N oxide in older adults with high CVD risk and observed that TMAO concentration increased over time regardless of treatment arm (p = 0.04), with each dose producing distinct metabolite signatures.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"Two 2024 randomized trials in older adults define the same dose/regime but land on different ledger sides. 10.1002/ptr.8171 is a systematic review of randomized clinical trials in older adults reporting that resveratrol combined with exercise improved exercise adaptation, muscle function, and physical performance/mobility. 10.1016/j.exger.2024.112479 is the embedded dose-ranging trial that explicitly set out to test resveratrol + exercise training on trimethylamine-N-oxide in older adults with high CVD risk and observed that TMAO concentration increased over time regardless of treatment arm (p = 0.04), with each dose producing distinct metabolite signatures.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"10.1016/j.exger.2024.112479 — role=evidence; design=randomized_trial; population=human older adults with high CVD risk; outcome=dose/risk (TMAO and metabolite signatures); direction=negative/positive; support=direct/high.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"10.1002/ptr.8171 — role=positive_signal; design=randomized_trial systematic review; population=human older adults; outcome=chronic/dose/long (muscle function, mobility, neuroprotection, cognition); direction=positive; support=direct/high.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"10.1249/MSS.0000000000000620 — role=mechanism; design=randomized_trial review; population=human; outcome=performance/risk/stress (ROS as adaptive signal); direction=negative/positive; support=direct/high.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"10.1113/jphysiol.2013.266999 — role=boundary; design=randomized_trial commentary; population=human; outcome=damage/long/risk (vascular function); direction=negative; support=direct/high.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"Receipts describe trial and review-level safety reporting only; no clinical advice is inferred. The TMAO increase and the attenuated-exercise boundary are observed findings in the cited studies, not generalizable safety claims.","citation_support":[],"candidate_sources":[{"study":"Effects of resveratrol on changes in trimethylamine-N-oxide and circulating cardiovascular factors following exercise training among older adults.","year":2024,"doi":"10.1016/j.exger.2024.112479","url":"https://doi.org/10.1016/j.exger.2024.112479","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":"primary","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Effects and safety of resveratrol supplementation in older adults: A comprehensive systematic review.","year":2024,"doi":"10.1002/ptr.8171","url":"https://doi.org/10.1002/ptr.8171","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":"primary","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.","year":2015,"doi":"10.1249/MSS.0000000000000620","url":"https://doi.org/10.1249/MSS.0000000000000620","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":"primary","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Attenuated effects of exercise with an antioxidant supplement: too much of a good thing?","year":2013,"doi":"10.1113/jphysiol.2013.266999","url":"https://doi.org/10.1113/jphysiol.2013.266999","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":"primary","source_id":"source_4","support_kind":"candidate_source_row"}]}]}