What is a recommended longevity stack of supplements and medications based on current knowledge?

Recommended Longevity Stack Based on Current Evidence 2025

Based on the most recent and highest quality evidence, the optimal longevity stack should focus on regular exercise, calorie management, and targeted supplementation with alpha-ketoglutarate, allicin, and potentially rapamycin or metformin under medical supervision, rather than broad supplementation with unproven compounds. 1

Core Interventions with Strong Evidence

Physical Activity

• Aerobic exercise and high-intensity interval training have consistently demonstrated reduction in frailty markers and improved longevity in both animal models and humans 1
• Implement 150+ minutes of moderate activity weekly or 75+ minutes of vigorous activity
• Include both cardiovascular exercise and resistance training

Dietary Approaches

1. Calorie restriction/management

   • Shown to reduce frailty indices and increase healthy lifespan in multiple species including primates 1
   • Consider intermittent fasting for males (less evidence for benefit in females) 1
   • Focus on modest restriction rather than severe calorie cutting

2. Diet composition

   • Emphasize foods rich in:
     • Monounsaturated and polyunsaturated fats (Mediterranean-style diet) 1
     • Fiber-rich carbohydrates from vegetables, fruits, legumes, and whole grains 1
     • Fatty fish containing EPA and DHA at least twice weekly 1
   • Minimize added sugars and sugar-sweetened beverages 1
   • Avoid dietary restrictions unless medically necessary 1

Evidence-Based Supplements

Tier 1 (Strongest Evidence)

1. Alpha-ketoglutarate

   • Extends lifespan and reduces frailty indices across the life course in both sexes 1
   • Dosage: Based on animal studies showing benefit

2. Allicin (garlic-derived compound)

   • Attenuates inflammation and reduces frailty indices in aging models 1
   • Consider garlic supplements standardized for allicin content

Tier 2 (Moderate Evidence)

1. Vitamin D

   • Currently being investigated in mega-trials for reducing all-cause mortality 2
   • Recommended only for those with documented deficiency
   • Monitor levels to maintain optimal range

2. Resveratrol

   • Antioxidant properties that may reduce frailty 1
   • Evidence primarily from animal studies

Not Recommended Based on Current Evidence

1. Omega-3 fatty acid supplements

   • Not recommended for general longevity purposes 3
   • Instead, obtain from food sources (fatty fish twice weekly) 1
   • Exception: High-dose (3-4g/day) may be considered for severe hypertriglyceridemia 3

2. Vitamin E, B vitamins, selenium, copper supplements

   • Not recommended for prevention or correction of cognitive decline 1
   • No clear evidence of benefit for longevity in those without deficiencies 1

Prescription Medications with Longevity Potential

Under Medical Supervision Only

1. Rapamycin (mTOR inhibitor)

   • Extends health span and reduces frailty indices in multiple animal models 1, 4, 2
   • Currently in clinical trials for longevity effects in humans 2
   • Significant side effects require medical supervision

2. Metformin

   • Shows promise for cardiovascular and cancer mortality reduction 4, 2
   • Being investigated in clinical trials for anti-aging effects 2
   • Should only be used under physician guidance

3. Enalapril (ACE inhibitor)

   • Reduces frailty indices in aging mice 1
   • Reduces biological age and increases life expectancy in animal models 1
   • Prescription medication requiring medical supervision

Implementation Strategy

1. Start with fundamentals:

   • Implement exercise regimen and dietary modifications first
   • These have the strongest evidence base for longevity

2. Add targeted supplements:

   • Begin with alpha-ketoglutarate and allicin
   • Consider vitamin D if deficient

3. Consult healthcare provider:

   • Discuss prescription options like metformin or rapamycin
   • Regular monitoring for efficacy and side effects

Important Caveats

• Sex differences exist: Some interventions (like intermittent fasting) show benefits primarily in males 1
• Polypharmacy risks: Multiple medications can increase frailty; de-prescribing may be beneficial 1
• Individual variation: Response to interventions varies based on genetic factors and baseline health status
• Supplement quality matters: Choose pharmaceutical-grade supplements with third-party testing
• Regular monitoring: Track biomarkers and adjust interventions based on response

The field of longevity medicine is rapidly evolving, with new clinical trials constantly emerging. This stack represents the current evidence as of 2025, but should be reassessed as new data becomes available.