In plain terms: 2-HOBA (2-Hydroxybenzylamine) 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.
2-HOBA (2-Hydroxybenzylamine)
The evidence as the record states it
Yoneda et al. (Circ Arrhythm Electrophysiol, 2025; PMID 40709466): randomized, double-blind, placebo-controlled pilot trial, 93 adults randomized and 82 analyzed, 750 mg three times daily from 3 days before to 28 days after atrial fibrillation ablation; recurrence in the first 28 days was 60.5 percent on 2-HOBA against 35.9 percent on placebo (adjusted odds ratio 3.65, 95% CI 1.31 to 10.16); isolevuglandin levels did not differ; no difference over 12 months after the drug was stopped; enrollment stopped early for futility. Funded by the American Heart Association; an author is employed by the company that licenses 2-HOBA and holds 2-HOBA patents; the paper states that company had no role in design or analysis. Pitchford et al. (BMC Pharmacol Toxicol, 2020; PMID 31907026): randomized, double-blind, placebo-controlled safety and pharmacokinetics trial in healthy volunteers, 500 or 750 mg every eight hours for two weeks; safe and well tolerated; no efficacy outcome; authors employed by the company that licenses 2-HOBA. Rathmacher et al. (Inflammation, 2023; PMID 36935449): 15 days of 2-HOBA in two healthy cohorts, changes in 15 plasma immune proteins on a targeted panel; not a randomized comparison and no clinical outcome; authors employed by the company that licenses 2-HOBA. D Route 2 with the harm badge: the basis is Yoneda 2025, the only randomized trial on a clinical outcome.
Trials showing no benefit
Low to moderate. One single-center pilot trial stopped early for futility; the harm was pre-specified and survived post hoc adjustment, and did not persist after the drug was stopped.
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. 2-HOBA (2-Hydroxybenzylamine) 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.