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In the news: Resveratrol: Adjuvant Role in Wet AMD? Fine Tuning Melatonin Dose & Timing

Resveratrol Associated with Fewer IV Injections in Wet AMD Patients

Resveratrol is a polyphenol found primarily in grapes, berries and peanuts. A possible role for resveratrol as an adjuvant to anti-vascular endothelial growth factor (VEGF) treatment in wet AMD has recently been suggested based on experimental and preliminary clinical findings.

Resveratrol has anti-inflammatory, antioxidant and anti-angiogenic properties. Within retinal cells, it’s been shown to suppress VEGF-A and -C secretion due to inflammatory cytokines, transforming growth factor-B and hypoxia, and to prolong the effect of the anti-VEGF treatment bevacizumab (Avastin).

Researchers from the Dept of Ophthalmology, University of Athens in Greece previously reported that in patients with wet AMD treated with Aflibercept (Eyela), the addition of oral resveratrol led to improvements in contrast sensitivity and overall quality of life over a 12-month period(1).

In a new study(2), the same research team studied 50 treatment-naive participants assigned to receive injections of 2.0 mg Aflibercept alone or to receive the injections plus 60 mg of resveratrol daily. All participants were treated according to a “Pro re nata” protocol: 3 monthly intravitreal injections followed by injections according to need.

Over the 24-month study period, there was no difference between groups in best corrected visual acuity or central foveal thickness. The resveratrol-supplemented group had significantly fewer injections vs. the injection-only group (9.32 + 1.37 vs. 7.4 + 1.8, p<0.001).

Notably, the resveratrol group also had a lower rate of macular fibrosis progression (p=0.04). Fibrosis, or the formation of scar tissue in the macula, can lead to permanent damage and vision loss.

The authors note that the number of injections between groups did not differ in their first study, but in the current study a difference was first noted at 18 months and became more prominent at 24 months.

It should be noted that the study supplement also contained omega-3 fatty acids and several vitamins and minerals, though the authors attribute the findings largely to the anti-fibrotic actions of resveratrol.

The study had limitations including the small sample size and the relatively high frequency of established fibrosis in participants at the study’s start. These preliminary findings call for larger studies of longer duration to determine whether resveratrol is a useful complement to standard wet AMD treatments.

Best Dose & Time to Take Melatonin for Sleep

Poor sleep quality can lead to impaired daily functioning and increase the likelihood of developing chronic health problems. Trouble falling asleep (sleep latency) or staying asleep is reported by about 1/3 of US adults. Some people with sleep problems turn to melatonin, although the optimal dose and timing to use melatonin for sleep promotion has been ambiguous.

To help clarify this issue, researchers conducted a meta-analysis of 26 randomized controlled trials that included nearly 1,700 participants.

Melatonin modestly reduced sleep latency by an average of 9 minutes vs. placebo. Doses of 4 mg had the largest effect. Effects were greatest when given 2-3 hours before bedtime with the largest effect at 3 hours.

Compared to placebo, melatonin increased sleep duration by an average of 20 minutes. Doses of 3 mg had the greatest effect given 3-3.5 hours pre bedtime.

In short, the benefits seem of melatonin seem to be greatest with a dose of 3-4 mg taken 2-3 hours prior to bedtime. Three hours may be best for slow-release formulations to reach peak blood concentrations.

References

1. Datseris I, et al. One-year outcomes of reproterol supplement with aflibercept vs. aflibercept monotherapy in wet age-related macular degeneration. Int J Ophthalmol. 16:1496-1502, 2023.
2. Datseris I, et al. Resveratrol Supplementation in wet AMD: Association with fewer intravitreal injections and reduced macular fibrosis. Clin Ophthalmol. 19:217-225, 2025.
3. Cruz-Sanabria F, et al. Optimizing the time and dose of melatonin as a sleep-promoting Drug: A systematic review of randomized controlled trials and dose-response meta-analysis. J Pineal Res. 76(5): e12985, 2024.