In plain terms: Trehalose 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.
Trehalose
The evidence as the record states it
DeBosch et al. (Science Signaling, 2016; PMID 26905426): trehalose autophagy mechanism in ANIMALS. Kaplon et al. (Aging, 2016; PMID 27208415): randomized double-blind trial, 32 healthy adults aged 50 to 77, 100 g/day oral trehalose against isocaloric maltose for 12 weeks; resistance artery endothelial function did not change significantly in the full sample, with a rise only in participants whose weight changed by less than 2.3 kg; no effect on conduit artery function, arterial stiffness, oxidative stress or inflammation; NIH-funded. Jamialahmadi et al. (Biomed Pharmacother, 2022; PMID 35045351): 15 patients with a history of myocardial infarction and C-reactive protein above 2 mg/L, 15 g intravenous trehalose once weekly or placebo for 12 weeks; no change in arterial wall inflammation on PET or carotid intima-media thickness. HEALEY ALS Platform Trial, group-authored (Lancet Neurology, 2025; PMID 40409314): intravenous trehalose 0.75 g/kg weekly in ALS, no difference in disease progression; serious adverse events 16 against 7 percent and discontinuations 12 against 2 percent versus the regimen placebo. Yap et al. (Parkinsonism Relat Disord, 2024; PMID 38843619): 100 g/day oral trehalose in spinocerebellar ataxia type 3, no effect on ataxia at an unplanned interim analysis, trial stopped for slow recruitment. Yoshizane et al. (Nutr J, 2020; PMID 32646428): 3.3 g/day for 12 weeks in 50 healthy Japanese adults, no between-group difference in body composition or blood chemistry; all authors employed by the trehalose manufacturer that sponsored it. D Route 2: the basis is Kaplon 2016, the oral trial in healthy older adults, null on its full-sample analysis.
Trials showing no benefit
Low. One small trial; the full-sample analysis was not significant and the positive result is confined to a post hoc weight-stable subgroup.
Low. Very small trial of an intravenous form; supporting context, not the basis.
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. Trehalose has been tested in 2 human trials 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.