Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL)

Nguyen C, Coudeyre E, Boutron I, et al. · PLoS Medicine

Null on the primary endpoint: knee pain (0-100 NRS) fell -15.7 with resveratrol and -15.2 with placebo at 3 months, an absolute difference of -0.6 (95% CI -8.0 to 6.9, p=0.88), a CI that excludes any clinically important benefit. At 6 months the difference was 0.4 (95% CI -8.4 to 9.1); WOMAC function and patient global assessment did not differ at either point, and OARSI-OMERACT responder rates were about 50% in both arms at both timepoints. Serious adverse events occurred in 3 participants on resveratrol and 2 on placebo, none judged related.

Population

Adults with painful knee osteoarthritis (pain >=40/100), 3 tertiary care centers, France (Phase 3)

Intervention

Oral trans-resveratrol in a soluble caplet formulation designed to overcome poor absorption (40 mg twice daily for 1 week, then 20 mg twice daily) for 6 months, as add-on to usual care

Comparator

Matched placebo

Limitations

Stopped at 142 of a planned 164 participants (COVID accrual and lack of further funding) and self-described as underpowered against an optimistic planned effect size of 0.55; co-interventions were not controlled. Tested one low-dose regimen of a patented soluble formulation whose 40 mg dose gave a 10-fold higher plasma peak than dry-powder resveratrol in the group's crossover PK study, relevant to but not identical with the hundreds-of-milligram powder doses sold as supplements. Publicly funded (French Ministry of Health, PHRC National 2015, project 15-15-0234), a statement the article carries only in its metadata; the resveratrol and placebo were supplied by the Yvery laboratory, holder of the formulation patent.