Biomarkers: What the Evidence Says About Supplements for Longevity

The supplement industry generates over $150 billion per year. Most of that money is spent on products with little to no evidence. A small number of supplements are genuinely worth considering. Here's how to tell the difference.

Supplements occupy an awkward space in evidence-based medicine. They're not drugs — so they're not held to the same standards of randomised controlled trial evidence before going to market. They're not food — so the "just eat better" dismissal doesn't fully apply either. The result is a marketplace where legitimate science sits alongside marketing dressed as science, and most consumers can't tell which is which.

We take this seriously. The following is an honest, evidence-graded assessment.

Why Most Supplements Fail the Evidence Test

The core problem is publication bias: positive results from supplement studies are far more likely to be published than negative results. The supplement industry funds a significant proportion of research, creating incentives for favourable findings. Many studies are small, short, and conducted in populations with deficiencies — making results hard to generalise.

This doesn't mean supplements are all useless. It means the evidence bar should be high before you spend money and trust your health to a product.

Our standard: would a longevity-focused physician with no commercial interest in supplements recommend this compound, for this purpose, to a patient with this marker profile?

Tier 1 — Strong Evidence, Widely Recommended

Vitamin D3 (with K2) — for deficiency

If your Vitamin D is below 75–100 nmol/L, supplementation is one of the most evidence-supported interventions in preventive medicine. The case for adding K2 (specifically MK-7 form) is based on mechanistic reasoning — Vitamin D increases calcium absorption, K2 helps route it appropriately — rather than large clinical trials, but the safety profile is excellent. Typical dose: 1,000–2,000 IU D3 + 100–200 mcg K2 MK-7.

Omega-3 (EPA + DHA)

A large 2018 trial (VITAL, 25,000 adults) found significant reduction in heart attack risk with 1g/day of omega-3. High-dose EPA specifically (2–4g/day) consistently reduces triglycerides by 20–40%. For cardiovascular risk and inflammation management, the evidence is solid. Typical dose: 1–2g combined EPA+DHA from fish oil or algae-based for non-fish-eaters.

Magnesium

Deficiency is common — processed foods and depleted soils mean many people consume less than the recommended 300–400mg/day. Magnesium plays roles in over 300 enzymatic reactions, including glucose metabolism, sleep regulation, and muscle function. Evidence supports supplementation for improving insulin sensitivity, sleep quality, and reducing migraine frequency. Typical dose: 200–400mg of magnesium glycinate or malate (better absorbed than oxide).

Tier 2 — Moderate Evidence, Condition-Specific

Berberine

An alkaloid derived from plants including barberry, berberine activates AMPK — the same cellular energy regulator targeted by metformin. Clinical trials show meaningful reductions in fasting glucose, HbA1c, and LDL in people with metabolic dysfunction. Often described as "nature's metformin," which is both an endorsement and a caveat — the effect is real but more modest. Consider if: fasting glucose, HbA1c, or LDL are above longevity targets and dietary changes have been insufficient.

Creatine monohydrate

Creatine is primarily known as a sports supplement. Its longevity case rests on muscle preservation: as we age, creatine stores in muscle decline, contributing to sarcopenia. Supplementation in older adults (50+) consistently improves strength outcomes in combination with resistance training. Evidence also suggests cognitive benefits — creatine is a phosphate donor for the brain. The evidence base is unusually robust for a supplement. Typical dose: 3–5g/day.

Collagen peptides

The evidence for joint and connective tissue support is modest but real — several randomised trials show reduced joint pain and improved skin elasticity. The mechanism (providing glycine and hydroxyproline as building blocks) is plausible. This is not a high-evidence compound, but the safety profile is excellent and the potential benefit is meaningful for anyone with joint concerns. Typical dose: 10–15g/day, ideally with Vitamin C which supports collagen synthesis.

Tier 3 — Promising but Contested

NMN and NR (NAD precursors)

Both nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) raise NAD+ levels in humans — this is established. NAD+ declines with age and plays roles in mitochondrial function and DNA repair. Animal studies showing lifespan extension are compelling. Human trials showing meaningful longevity or healthspan outcomes are limited and short-term. The compounds are almost certainly doing something. Whether that something translates to extended human lifespan is genuinely unknown. The safety profile appears good; the cost is high.

Resveratrol

The theoretical case (SIRT1 activation, mitochondrial support) is interesting. The clinical evidence is disappointing — most human trials have failed to replicate the benefits seen in cell and animal studies. Absorption is poor with standard oral supplementation. Most longevity researchers have cooled on resveratrol. May have more promise in new delivery formats.

Spermidine

A polyamine that triggers autophagy — the cellular "cleaning" process that declines with age. Observational studies in humans are promising (higher dietary spermidine is associated with longer life). Randomised trial evidence is limited. Mechanistically credible; practically unproven. Present in wheat germ, mushrooms, and aged cheese — dietary sources are worth prioritising before supplementation.

Before You Start

Three rules worth following:

• Test, then supplement: Don't guess at deficiencies. Vitamin D, ferritin, and magnesium are all measurable. Know where you start.
• Food first: Most nutrients are better absorbed from food than from pills. Omega-3s from two portions of fatty fish per week are equivalent to supplementation for most people. Magnesium from leafy greens, nuts, and seeds is better than most supplements.
• Check for interactions: Omega-3 at high doses can interact with blood thinners. Berberine may interact with diabetes medications. Always disclose supplements to your doctor if you're on any prescription medication.

We are not doctors. Nothing here is medical advice. Discuss any supplement regimen with a healthcare professional, particularly if you have chronic conditions or take medications.

The 100 Great Years perspective

The supplement industry thrives on the difficulty of the question: what actually works? 100 Great Years takes a different approach — evidence threshold first, compound not brand, and always lifestyle before supplementation. A small number of supplements genuinely support the longevity engine: correcting deficiencies that affect energy, metabolism, and cardiovascular health; reducing inflammation that accelerates the diseases of ageing; preserving muscle mass that determines independence in later life. The rest is noise. Knowing the difference is part of what 100 Great Years is here to help with.

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This article is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.