Best Sirtuin Supplements 2025

The best sirtuin supplements combine direct SIRT1 activators like high-purity trans-resveratrol (500mg+ daily) with NAD+ boosters like NMN (250-500mg). Premium resveratrol supplements with enhanced bioavailability (liposomal or with piperine) rank highest. For synergistic effects, many longevity enthusiasts stack resveratrol with NMN to provide both the activator and the essential NAD+ cofactor.

Sirtuins are naturally activated by caloric restriction (eating 20-30% fewer calories), intermittent fasting, exercise, and having adequate NAD+ levels. Dietary compounds like resveratrol (found in red grapes and wine), pterostilbene (blueberries), and quercetin (onions, apples) also activate sirtuins, though supplementation provides concentrations far higher than food sources can deliver.

Research shows sirtuin activators like resveratrol and NAD+ boosters can increase SIRT1 activity and improve various health markers in both animal and human studies. Evidence is strongest for metabolic benefits, cardiovascular health, and inflammation reduction. The combination of resveratrol (direct activation) and NMN (NAD+ cofactor support) shows the most promising results for comprehensive sirtuin activation. However, more long-term human trials are needed to fully confirm longevity benefits.

Pterostilbene is a methylated derivative of resveratrol with significantly better bioavailability—up to 80% absorption compared to just 20% for standard resveratrol. Both compounds activate SIRT1, but pterostilbene has a longer half-life in the body and superior cellular uptake. However, resveratrol has decades more research backing. Premium supplements often combine both compounds to leverage resveratrol's extensive research with pterostilbene's superior absorption.

Yes, resveratrol and NMN are highly synergistic for optimal sirtuin activation. NMN boosts NAD+ levels (the essential cofactor that sirtuins require to function), while resveratrol directly activates SIRT1. This combination provides both the gas pedal (resveratrol activation) and the fuel (NAD+ cofactor). Many longevity researchers follow this dual approach. Take resveratrol with dietary fat for better absorption, and NMN in the morning (sublingual or with meals depending on formulation).

The seven sirtuins (SIRT1-7) regulate different aspects of cellular aging: SIRT1 (metabolic regulation, DNA repair, inflammation control—most studied for longevity), SIRT2 (cell cycle, tubulin deacetylation, fat metabolism), SIRT3 (mitochondrial function, energy production, antioxidant defense), SIRT4 (insulin secretion, mitochondrial metabolism), SIRT5 (mitochondrial metabolism, detoxification), SIRT6 (DNA repair, telomere maintenance, glucose metabolism), and SIRT7 (ribosomal RNA transcription, protein synthesis, heart health). SIRT1 and SIRT3 have the most extensive longevity research.