In plain terms: Pterostilbene has been tested in human trials aimed at the relevant outcome and did not show benefit at the doses and durations studied. The animal research may be encouraging, but it has not yet translated to humans in these trials.
Pterostilbene
The evidence as the record states it
Riche et al. (Evid Based Complement Alternat Med, 2014; PMID 25057276): randomized, double-blind, placebo-controlled, 80 adults with total cholesterol of 200 mg/dL or more or LDL of 100 mg/dL or more, four arms, 6 to 8 weeks; the stated endpoints were lipids, blood pressure and weight. LDL cholesterol rose by 17.1 mg/dL on pterostilbene alone (P=0.001) and did not rise when grape extract was added; systolic and diastolic blood pressure fell at the higher dose (7.8 and 7.3 mmHg). The authors' conclusion is that pterostilbene increases LDL and reduces blood pressure. Whether lipids were the pre-specified primary endpoint is not stated in the abstract and the registration (NCT01267227) was not read in this pass. Funding: the full text states the trial was supported by a grant through the company that makes the pterostilbene tested, which also supplied the pterostilbene and the placebo, and that the company had no role in the collection or interpretation of the data. Grade D, Route 2: in a population enrolled for raised cholesterol, the lipid result went the wrong way. Companion and later trials: Riche et al. (J Toxicol, 2013; PMID 23431291), the safety report from the same 80-person trial, no hepatic, renal or glucose signals up to 250 mg/day, the same trial and not a replication. Otsuka et al. (J Nutr Sci Vitaminol, 2025; PMID 40024751): 12-week placebo-controlled pilot of 10 or 100 mg/day in 30 healthy men; blood microRNA expression and safety only, no clinical efficacy outcome. Senguttuvan et al. (Antioxidants, 2025; PMID 40227411): randomized phase II of pterostilbene with megestrol against megestrol alone before hysterectomy for endometrial cancer, 44 patients; Ki-67 primary null, lipid metabolism unchanged, a different population and a combination. Trials of nicotinamide riboside combined with pterostilbene are a different product and do not grade pterostilbene alone.
Trials showing no benefit
Low to moderate. Single small placebo-controlled trial; LDL moved in the harm direction in people enrolled for raised cholesterol; primary-endpoint status not stated in the abstract.
Evidence by specific use
Why Grade D Route 2 and not Grade C
Grade D Route 2 applies when a compound has been tested in humans and benefit was not shown. Pterostilbene has been tested in 1 human trial on endpoints relevant to the claim being evaluated, and the primary endpoint was not met.
A randomized, placebo-controlled trial pre-specifying a meaningful clinical or functional endpoint and demonstrating statistically significant benefit would move this to Grade C or higher, depending on effect size, population size, and whether it is independently replicated.
What this grade covers and what it does not
What would move this grade
A randomized, placebo-controlled trial pre-specifying a clinical aging endpoint and demonstrating statistically significant benefit on that primary endpoint would be sufficient to move this to Grade C or higher, depending on effect size and population.