Evidence Trace, complete trial record
In plain terms
In plain terms: Resveratrol (Trans-Resveratrol) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Resveratrol (Trans-Resveratrol)
C
Limited: small, mixed or unreplicated trials
The endpoint this grade is based on: Surrogate biomarker endpoint, Metabolic markers in obese men, where one 30-day crossover of 150 mg/day was positive and the independent attempts to repeat it with clamp-measured insulin sensitivity were null (C, mixed). Pooled trials find no effect on C-reactive protein, lipids, glucose or blood pressure. In older men, 250 mg/day blunted the gains in fitness, blood pressure and lipids from exercise training (D Route 2, harm found). Sirtuin activation is a mechanism, not a use; two trials found no change in SIRT1 or its targets.
The evidence as the record states it
Timmers et al. (Cell Metabolism, 2011; PMID 22055504): 11 healthy obese men, 150 mg/day of a trans-resveratrol formulation for 30 days, randomized double-blind crossover; sleeping and resting metabolic rate lower, muscle SIRT1 and PGC-1 alpha protein higher, intrahepatic lipid, glucose, triglycerides and inflammation markers lower, systolic pressure and HOMA index improved; a co-author was employed by the company that made the formulation tested. Poulsen et al. (Diabetes, 2013; PMID 23193181): 24 obese men, high-dose resveratrol for 4 weeks, investigator-initiated parallel-group trial; clamp-measured insulin sensitivity, the primary outcome, glucose turnover, blood pressure, energy expenditure, ectopic fat and inflammatory markers all unchanged. Yoshino et al. (Cell Metabolism, 2012; PMID 23102619): 29 non-obese postmenopausal women, 75 mg/day for 12 weeks; no change in insulin sensitivity, body composition, lipids or inflammatory markers, and no change in SIRT1, AMPK, NAMPT or PGC-1 alpha. de Ligt et al. (Mol Metab, 2018; PMID 29706321): the same group and the same 150 mg formulation as Timmers, 13 first-degree relatives of people with type 2 diabetes, 30 days; muscle mitochondrial function ex vivo improved, insulin sensitivity by clamp and every other metabolic measure unchanged. Sahebkar et al. (Int J Cardiol, 2015; PMID 25885871): meta-analysis of 10 randomized trials; no effect on C-reactive protein, total or LDL cholesterol, triglycerides or glucose. Gliemann et al. (J Physiol, 2013; PMID 23878368): 27 inactive men aged about 65 randomized to 250 mg/day trans-resveratrol or placebo during 8 weeks of high-intensity training; the placebo group gained 45 percent more maximal oxygen uptake and lowered mean arterial pressure while the resveratrol group did not, and resveratrol abolished the training effects on LDL, cholesterol ratio and triglycerides; SIRT1 protein unchanged. Grade C: one positive small trial with the independent attempts to repeat it null; the exercise finding is graded on its own row as harm.
PMID 22055504 PMID 23193181 PMID 23102619 PMID 23878368 PMID 25885871 PMID 29706321
Evidence by specific use
Metabolic markers in obese men
Grade C
Mixed. Timmers et al. (2011; PMID 22055504) found calorie-restriction-like metabolic changes in 11 obese men over 30 days. Independent attempts to reproduce it with clamp-measured insulin sensitivity were null: Poulsen et al. (2013; PMID 23193181) in 24 obese men, Yoshino et al. (2012; PMID 23102619) in non-obese women with no change in SIRT1 or AMPK, and the same Maastricht group with the same formulation (de Ligt et al., 2018; PMID 29706321). Pooled trials find no effect on CRP, lipids, glucose or blood pressure (Sahebkar et al., 2015; PMID 25885871). One positive small trial against null replications is mixed, C; the positive trial's maker link is stated beside the letter.
PMID 22055504 PMID 23193181 PMID 23102619 PMID 29706321 PMID 25885871
Exercise training adaptations in older men (resveratrol added to training)
Grade D
Gliemann et al. (J Physiol, 2013; PMID 23878368): resveratrol blunted the cardiovascular and fitness gains from exercise training in older men, with measured oxygen uptake the key endpoint. Tested and worse than placebo on the stated endpoints: D on Route 2 with the harm badge. One trial, so the certainty is limited.
PMID 23878368
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What this grade covers and what it does not
Grade C, the record's best use: metabolic markers in obese men, mixed evidence, one positive 30-day trial (Timmers et al., 2011; PMID 22055504) against null independent replications on clamp-measured insulin sensitivity (Poulsen et al., 2013; PMID 23193181; Yoshino et al., 2012; PMID 23102619; de Ligt et al., 2018; PMID 29706321), with pooled risk factors unchanged (Sahebkar et al., 2015; PMID 25885871). Listed beneath it, on its own row: tested and harm found, D on Route 2, in the one randomized trial of resveratrol alongside exercise training, where 250 mg/day blunted the gains in maximal oxygen uptake, blood pressure and blood lipids in older men (Gliemann et al., J Physiol, 2013; PMID 23878368). WHAT THIS GRADE DOES NOT COVER: type 2 diabetes, where short-term HbA1c effects have been pooled separately and would need their own row; resveratrol combined with NMN or NR, which no trial has tested; and sirtuin activation as a claim, since two trials found no change in SIRT1.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.
How to track whether this is working
For the graded use, the trials measured insulin sensitivity by clamp, blood pressure, lipids and inflammatory markers over 4 to 12 weeks. Anyone combining it with exercise training is in the population where the one trial found the training gains blunted.