The Longevity Stack: 5 Supplements With the Best Evidence

The supplement industry is loud. Every week, a new molecule promises to extend your lifespan or reverse your biological age. Most of it is marketing. A smaller list of compounds has accumulated genuine evidence — multiple human trials, reproducible mechanisms, and clinical reasoning that holds up to scrutiny.

Here are the five with the strongest case, ranked by depth of evidence.

1. Omega-3 (EPA + DHA)

The single most-studied supplement on this list. High-quality omega-3 supplementation lowers triglycerides, reduces systemic inflammation markers, and is associated with longer telomeres in observational studies. Aim for 2–3 g of combined EPA + DHA per day from a third-party tested fish or algae oil.

2. Vitamin D3 + K2

Vitamin D deficiency is one of the most common — and most fixable — drivers of poor metabolic, immune, and cardiovascular outcomes. Pairing D3 with K2 (MK-7) ensures the calcium D mobilizes ends up in bone rather than arterial walls. Target a serum 25(OH)D of 40–60 ng/mL; for most people that's 2,000–4,000 IU/day of D3.

3. NAD+ precursors (NMN or NR)

Covered in depth in our NAD+ guide. The short version: NAD+ powers cellular energy and DNA repair, and levels fall with age. Both NMN and NR raise blood NAD+ in human trials. 250–600 mg per day, morning, with food.

4. Creatine monohydrate

Yes, the gym supplement. Creatine has the deepest safety record of anything on this list and a growing body of research on cognitive function, sarcopenia prevention, and recovery in aging adults. 5 g per day, taken any time. Cheap, proven, no loading phase needed.

5. Berberine (or metformin, if prescribed)

Insulin resistance accelerates almost every age-related condition. Berberine improves blood sugar, blood lipids, and metabolic flexibility in the same magnitude range as metformin in head-to-head trials. 500 mg, 2–3 times daily with meals.

How to combine them

A practical morning stack looks like:

• With breakfast: NMN or NR (250–600 mg) + D3/K2 + omega-3
• Mid-morning or lunch: Berberine 500 mg with food
• Anytime: Creatine 5 g (in water, coffee, or a shake)
• With dinner: Second berberine dose, second omega-3 dose if splitting

Start with one or two additions, give each 4–6 weeks, and watch how you feel. Then layer the next.

What didn't make the list

Resveratrol (poor bioavailability, contradictory trials), MCT oil (useful tool, weak longevity evidence), and most adaptogenic blends (under-dosed proprietary mixes) all got cut. They might be useful for specific people — they don't belong on a 'best evidence' shortlist.