From vitamin D to creatine, we summarize what randomized trials and meta-analyses actually show — including the unflattering parts. Each entry lists effective dose ranges, common interactions, and population-specific caveats.
Effect sizes for most supplements depend heavily on baseline status and dose. A deficient population responds; a replete one usually doesn't.
Bioavailability differs sharply between salt forms (e.g., magnesium citrate vs. oxide). Trial outcomes don't transfer across forms.
St. John's Wort, vitamin K, and high-dose calcium each meaningfully affect prescription drug levels. Always disclose to your prescriber.
Independent third-party testing (USP, NSF, ConsumerLab) is the simplest signal. Label claims alone are not regulated for accuracy.
25,871 adults randomized to 2,000 IU/day vitamin D₃ vs placebo for a median 5.3 years; no reduction in invasive cancer or major cardiovascular events overall. Largest definitive trial dampening enthusiasm for routine supplementation in replete adults.
Manson et al., NEJM, 2019 · Source ↗
Comprehensive physiology review covering serum vs intracellular status, bioavailability of common forms (citrate, glycinate, oxide, chloride), and effect sizes for sleep, cramps, and blood pressure. Foundational reference for clinical magnesium use.
de Baaij et al., Physiol Rev, 2015 · Source ↗
Comprehensive position paper concluding creatine monohydrate (3–5 g/day, no loading required) is the most effective ergogenic supplement for high-intensity exercise and lean mass, with an excellent long-term safety record. Emerging evidence in cognition and recovery from concussion.
Kreider et al., JISSN, 2017 · Source ↗
Pooled RCT data show standardized ashwagandha extract (KSM-66, 300–600 mg/day) modestly reduces self-reported anxiety and morning cortisol vs placebo. Effect sizes are real but small; caution in hyperthyroidism.
Akhgarjand et al., Phytother Res, 2022 · Source ↗
8,179 statin-treated patients with elevated triglycerides; 4 g/day prescription EPA reduced major ischemic events by 25% over 4.9 years. STRENGTH (mixed EPA/DHA) was negative — formulation matters.
Bhatt et al., NEJM, 2019 · Source ↗
Reviews mechanism of C677T/A1298C variants and rationale for 5-MTHF (methylated folate) over folic acid in homozygous carriers, particularly during preconception. Effect on hard outcomes outside neural tube defect prevention remains modest.
Liew & Gupta, Eur J Med Genet, 2015 · Source ↗