Published by Paul Thompson |
Fact-checked against peer-reviewed sources | Updated March 2026
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2025 EVIDENCE-BASED GUIDE

# Top 10 Compounds for Metabolic Health & Longevity

Ranked by net benefit: efficacy + safety + accessibility. The most effective supplements and compounds for metabolic optimization backed by science.

VIEW TOP 10
10
Top Compounds
50+
RCTs Reviewed
$5-80
Monthly Cost
OTC
Available Options

## The Top 10 Metabolic Longevity Compounds

Ranked by overall benefit considering efficacy, safety profile, cost, and accessibility. Updated for 2025.

1
PRESCRIPTION

### Tirzepatide (Mounjaro/Zepbound)

The #1 choice for metabolic reset. 15-21% body weight reduction, improved insulin sensitivity, reduced liver fat, cardioprotective effects. Now preferred over semaglutide by most longevity MDs.

Typical Dose: 5-15 mg/week (subcutaneous) | Evidence: FDA-approved; 50+ RCTs
2
OTC SUPPLEMENT

### Taurine

Best value longevity compound. Nature 2023 study showed lifespan extension. Reduces inflammation, improves mitochondrial function, helps NAFLD, supports glucose control. Safe and foundational - stack with creatine.

Typical Dose: 1.5-3 g/day (oral) | Evidence: Strong animal + emerging human RCTs
3
OTC SUPPLEMENT

### Creatine Monohydrate

Increases muscle and brain ATP, reduces sarcopenia, improves glucose disposal, provides neuroprotection, reduces fatigue. Works even in sedentary/older adults - not just for athletes. 1000+ human studies with decades of safety data.

Typical Dose: 3-5 g/day (oral) | Evidence: 1000+ human studies
4
PRESCRIPTION

### Metformin (Extended Release)

Gold standard for metabolic longevity. Activates AMPK, reduces mTOR overactivation, lowers insulin/IGF-1, reduces cancer risk, potential lifespan extension (TAME trial ongoing). Best with B12 monitoring.

Typical Dose: 500-1000 mg/day (ER) | Evidence: 60+ years clinical use
5
NAD+ PRECURSOR

### NMN or NR (Niagen)

Boosts NAD+, activates sirtuins (SIRT1/3), enhances mitochondrial biogenesis, improves vascular health. NR (Niagen) preferred for regulatory confidence. NMN catching up with more research.

Typical Dose: NR: 250-300 mg/day | NMN: 250-500 mg/day | Evidence: Strong mechanistic + growing RCTs
6
PEPTIDE

### MOTS-c

Leading mitochondrial peptide. Exercise-mimetic that improves insulin sensitivity, increases muscle glucose uptake, reduces age-related metabolic decline. Best taken post-workout or AM.

Typical Dose: 5-10 mg, 2-3x/week (SC/nasal) | Evidence: Phase I trials complete 2024
7
OTC SUPPLEMENT

### Omega-3 (EPA/DHA)

Reduces triglycerides, decreases inflammation (resolvins), improves membrane fluidity, cardioprotective, supports brain aging. Use re-esterified triglyceride (rTG) form for best absorption.

Typical Dose: 1-2g EPA+DHA/day (minimum 1g EPA) | Evidence: Robust CV & cognitive meta-analyses
8
OTC SUPPLEMENT

### Magnesium (Glycinate/Malate/L-Threonate)

Cofactor for 300+ enzymes including ATP and DNA repair. Reduces insulin resistance, supports sleep and stress resilience. Glycinate for relaxation, L-Threonate for brain. Avoid oxide form.

Typical Dose: 200-400 mg elemental Mg/day | Evidence: Widespread deficiency; RCTs show benefit
9
NATURAL COMPOUND

### Berberine

AMPK activator like metformin. Reduces fasting glucose, lowers LDL, increases GLP-1, antimicrobial gut benefits. Great metformin alternative or adjunct. Note: may interact with meds (CYP3A4).

Typical Dose: 500 mg 2-3x/day (with food) | Evidence: Meta-analyses: non-inferior to metformin
10
VITAMIN

### Vitamin D3 + K2 (MK-7)

Immune modulation, reduces inflammation, supports calcium metabolism. K2 directs calcium to bones, not arteries. Test 25(OH)D first - aim for 40-60 ng/mL.

Typical Dose: D3: 1000-5000 IU/day + K2: 100-200 mcg MK-7 | Evidence: Strong mortality association + RCTs

### Important Notice

This information is for educational purposes only and is not intended as medical advice. Always consult with a qualified healthcare provider before starting any new supplement regimen. Some compounds listed (tirzepatide, metformin) require a prescription. Individual results may vary.

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