Sirtuin Activators and Weight Loss

1. Background and RationaleSirtuins (SIRT1‐SIRT7) are a family of NAD⁺‐dependent enzymes involved in metabolicregulation, mitochondrial biogenesis, oxidative stress response, and inflammationcontrol. Evidence from model organisms demonstrates that sirtuin overexpression canextend lifespan. In mammals, caloric restriction enhances sirtuin synthesis, leadingto improved mitochondrial function, reduced oxidative stress, and attenuatedinflammation. Collectively, these mechanisms underpin the potential role of sirtuinsin promoting metabolic health and preventing non‐communicable diseases.Numerous non‐nutritive bioactive compounds naturally present in foods activatesirtuin pathways. The most extensively studied is resveratrol, found in grapes andred wine, which has been shown to stimulate SIRT1 and downstream metabolic pathways.Additional sirtuin activators include epigallocatechin gallate (EGCG) from greentea, curcuminoids from turmeric, and quercetin, present in apples, grapes, andonions. Despite their presence in commonly consumed foods, typical dietary intake islow, suggesting that targeted supplementation may be necessary to achieve meaningfulphysiological effects‐particularly in populations at metabolic risk.Overweight and obesity remain major public health challenges worldwide. Excessadiposity is strongly associated with chronic, low‐grade inflammation and increasedrisk of cardiometabolic diseases. While caloric restriction remains a cornerstone ofweight reduction, adjunct interventions may enhance metabolic adaptations to energydeficit. SIRT1, for example, has been shown to increase energy expenditure and shiftsubstrate utilization toward enhanced fatty‐acid oxidation. Thus, supplementationwith sirtuin activators may support weight loss and metabolic improvements whencombined with a hypocaloric diet. 2. Study ObjectiveThe primary objective of this study is to evaluate the effects of supplementationwith sirtuin activators (resveratrol, curcuminoids, EGCG, quercetin) combined with ashort‐term low‐energy diet on: ‐ body weight and body composition, ‐ physical performance, ‐ blood pressure, ‐ biochemical and inflammatory markers in adults with overweight and obesity. 3. Study DesignThis research will employ a randomized, placebo‐controlled, parallel‐group design.Participants will be randomly allocated to: ‐ SIRT group: receiving daily supplementation with sirtuin activators in the form of SIRTWAY powdered shakes, ‐ PLA group: receiving visually identical placebo shakes without active compounds.Both groups will follow a structured 24‐day low‐energy dietary intervention. Studyactivities will take place between January 2026 and January 2027 at the Departmentof Human Nutrition and Dietetics, Poznań University of Life Sciences.Assessments will be conducted twice: baseline (Day 0) and post‐intervention (Day25). 4. Participants The study will enroll approximately 45 adults with overweight orobesity. All participants will provide written informed consent. 5. Supplementation ProtocolParticipants in the SIRT group will receive shakes containing microencapsulatedsirtuin activators. The daily dose of active sirtuin activators will beapproximately 1280 mg. Placebo shakes will be identical in appearance, taste, andpackaging.All components used in the supplements have established safety profiles, includingFDA GRAS status where applicable. Adverse effects documented in the literature occuronly at doses significantly higher than those used in the present protocol. 6. Dietary InterventionThe low‐energy diet will consist of three sequential phases: ‐ Phase 1 (Days 1‐3): 1000 kcal/day, 3 shakes + 1 solid meal ‐ Phase 2 (Days 4‐10): 1450 kcal/day, 2 shakes + 2 solid meals ‐ Phase 3 (Days 11‐24): 1600 kcal/day, 2 shakes + 2 solid mealsRecipes for home‐prepared meals (DASH‐based) will be provided in a dedicated e‐book. 7. Study Procedures 7.1. Anthropometry and Body Composition Body weight and heightmeasured using a medical‐grade RADWAG WPT 60/150 OW scale with stadiometer. Waistand hip circumferences measured with a standardized flexible anthropometrictape.Body composition assessed by air‐displacement plethysmography (Bod Pod,Cosmed). All procedures follow validated protocols, with participants measured in afasted state and wearing swimwear and a swim cap.7.2. Blood PressureResting blood pressure will be taken using the Omron SpotArm i‐Q142 device,following 2024 ESH guidelines. Three measurements will be taken; the average of thefinal two will be recorded.7.3. Blood Sampling and BiochemistryVenous blood (5 mL) will be drawn twice (Day 0 and Day 25) by licensed medicalstaff. Serum will be processed, aliquoted, and stored at ‐80°C.7.4. Physical Performance TestingConducted twice (Day 0 and Day 25) by experienced staff. Tests include:Handgrip strength: measured using a Kern MAP 130K1 dynamometer, three trials perhand, averaged.Short Physical Performance Battery (SPPB): assessing lower‐limb strength(chair‐stand test), static balance, and gait speed over 4 meters.Tests are low‐risk; precautionary measures will be taken to minimize falls ordiscomfort.7.5. Dietary AssessmentParticipants will complete 3‐day dietary records before intervention. Intake will beanalyzed using Dieta 6 software. 8. Safety ConsiderationsAll supplements used have established safety thresholds well above the doses administeredin the study. Risks related to blood sampling and physical tests are minimal and standardprocedures will be followed to prevent adverse events.