Supplements: the few that work and the many that don't

The global dietary supplement market is worth over $150 billion. The evidence supporting most of those products could fit on a napkin. Here's an honest, evidence-based look at which supplements are actually worth taking — and which ones are expensive placebo.

The ones that work (with evidence)

Vitamin D — if you're deficient

Vitamin D deficiency affects 40–60% of adults in Central and Northern Europe and roughly 42% of US adults. If your 25-OH vitamin D is below 30 ng/mL, supplementation is straightforward: 2,000–4,000 IU daily, recheck in 3 months. The evidence for bone health and immune function in deficient individuals is strong. The key word is deficient — supplementation in people with adequate levels has not been shown to prevent cancer, cardiovascular disease, or depression in large trials (VITAL, n=25,871).

Omega-3 (EPA/DHA) — specific contexts

The evidence for omega-3 supplementation is more nuanced than the supplement industry suggests. The REDUCE-IT trial showed that high-dose EPA (icosapent ethyl, 4g/day) reduced cardiovascular events by 25% in patients with elevated triglycerides already on statins. But the STRENGTH trial, using a combination EPA/DHA product, found no benefit. The difference likely lies in the dose, the formulation, and the patient population. General-population supplementation with over-the-counter fish oil capsules (typically 1g with low EPA content) has not shown cardiovascular benefit in most trials.

Magnesium — common deficiency

Magnesium deficiency affects 10–30% of the population, driven by processed food diets, PPI use, and diuretics. Symptoms include muscle cramps, fatigue, and arrhythmias. Supplementation with magnesium glycinate (400–600mg daily) in deficient individuals is well-supported. As with vitamin D, the key is documenting deficiency first — our DETECT panel includes serum magnesium for exactly this reason.

B12 — if below 400 pg/mL

B12 deficiency is common in older adults (reduced absorption), vegetarians/vegans, and PPI users. The OPTIMA trial showed that B12 levels below 400 pg/mL are associated with accelerated brain atrophy. Supplementation is cheap and effective — 1,000μg oral daily, or intramuscular injection if levels are very low (<200).

The ones that don't work (despite the marketing)

Multivitamins

Multiple large randomized trials — including the Physicians' Health Study II (n=14,641) and the COSMOS trial — have found no meaningful benefit of daily multivitamin supplementation for cardiovascular disease, cancer, or cognitive decline in well-nourished adults. A multivitamin is not harmful in most cases, but it's not doing what people think it's doing.

NAD+ and NMN

Nicotinamide mononucleotide (NMN) and NAD+ precursors are among the hottest supplements in the longevity space. The animal data is genuinely interesting — NAD+ levels decline with age, and restoring them in mice improves various markers of aging. The human data, however, is extremely limited. No large randomized trial has shown clinical benefit. The supplements are expensive ($50–200/month), and the optimal dose, formulation, and long-term safety in humans are unknown.

Collagen supplements

The evidence for oral collagen supplements improving skin, joints, or bones is weak. The theoretical problem is basic biochemistry: collagen is a protein, your digestive system breaks it down into amino acids, and those amino acids don't preferentially reassemble into collagen in your skin. Small studies showing modest improvements have significant methodological limitations.

Testosterone boosters

"Natural testosterone boosters" — typically containing ashwagandha, tribulus, fenugreek, or D-aspartic acid — do not meaningfully raise testosterone levels in men with normal hormonal function. The studies cited by manufacturers are typically small, short, and use surrogate endpoints that don't translate to clinical outcomes.

The evidence hierarchy for supplements

• Strong evidence (supplement if deficient): Vitamin D, B12, iron (if ferritin is low), magnesium, folate (pregnancy)
• Moderate evidence (specific clinical contexts): High-dose EPA (elevated TG on statins), calcium + D (postmenopausal osteoporosis), creatine (exercise performance)
• Weak or no evidence: Multivitamins, NAD+/NMN, collagen, testosterone boosters, most "longevity stacks"
• Evidence of harm: High-dose vitamin E (increased mortality), high-dose beta-carotene (increased lung cancer in smokers), excessive vitamin A

The pattern is clear: supplements work when they correct a documented deficiency. They rarely work as general health enhancers in well-nourished people. And in a few cases, they cause genuine harm. The only way to know which category you're in is to measure first — which is exactly what the DETECT panel does.