Safety first
Supplements can interact with medications and with each other. If you’re on prescriptions (especially anticoagulants, blood pressure meds, diabetes meds, SSRIs), start with the Interactions Database.
| Intervention | Outcome | Human Evidence | Effect Size | Quality of Evidence | Reference |
|---|---|---|---|---|---|
| Creatine | Muscle Strength & Mass | Consistent increase in lean mass and strength in combined training meta-analyses. | Moderate | High | [1][2] |
| Creatine | Cognitive Function | Improvement in short-term memory and reasoning, particularly in aged or stressed individuals. | Small-to-Moderate | Moderate | [3][4] |
| Omega-3 (EPA/DHA) | Cardiovascular Events | Reduced risk of myocardial infarction (heart attack) and cardiac death; less effect on stroke. | Small | Moderate | [5][6] |
| Omega-3 (EPA/DHA) | Cognitive Decline | No significant benefit for preventing cognitive decline in general older populations; potential benefit in mild impairment. | Null/Small | Moderate | [7] |
| Vitamin D3 + K2 | Bone Mineral Density | Combined supplementation increases lumbar spine BMD more than single nutrients alone. | Small | Moderate | [8][9] |
| NAC | Psychiatric Symptoms | Adjunctive benefit for negative symptoms in schizophrenia and depressive symptoms in mood disorders. | Small-to-Moderate | Moderate | [10][11] |
| NAC | COPD Exacerbations | Reduces frequency of acute exacerbations in chronic bronchitis/COPD; no consistent effect on lung function (FEV1). | Moderate | High | [12] |
| Curcumin | Osteoarthritis Pain | Reductions in pain and stiffness comparable to NSAIDs (e.g., ibuprofen) with fewer side effects. | Moderate-to-Large | High | [13][14] |
| Ashwagandha | Stress & Anxiety | Significant reduction in perceived stress (PSS) and cortisol levels in stressed adults. | Moderate-to-Large | High | [15][16] |
| Ashwagandha | Testosterone (Men) | Increases in total testosterone and sperm quality in men (both healthy and infertile). | Moderate | Moderate | [16:1][17] |
| Spermidine | Cognitive Memory | Mixed results: Early trial showed memory improvement; larger 12-month trial found no benefit over placebo. | Inconsistent | Low | [18][19] |
| NMN | Muscle Insulin Sensitivity | Increased by 25% in prediabetic women; effect comparable to some medications. | Large | High | [20] |
Use one variable at a time and a written decision rule: N‑of‑1 Experiments
Lanhers C, et al. Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis. Sports Med. 2017;47(1):163-173. ↩︎
Chilibeck PD, et al. Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open Access J Sports Med. 2017;8:213-226. ↩︎
Avgerinos KI, et al. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol. 2018;108:166-173. ↩︎
Prokopidis K, et al. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(4):416-427. ↩︎
Bernasconi AA, et al. Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials. Mayo Clin Proc. 2021;96(2):304-313. ↩︎
Khan SU, et al. Effect of Omega-3 Fatty Acids on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. EClinicalMedicine. 2021;38:100997. ↩︎
Sydenham E, et al. Omega-3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev. 2012;(6):CD005379. ↩︎
Kuang X, et al. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food Funct. 2020;11(4):3280-3297. ↩︎
Ushiroyama T, et al. Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas. 2002;41(3):211-221. ↩︎
Fernandes BS, et al. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry. 2016;77(4):e457-466. ↩︎
Yolland CO, et al. N-acetylcysteine in the treatment of psychiatric disorders: a review of systematic reviews. Aust N Z J Psychiatry. 2020;54(5):457-470. ↩︎
Cazzola M, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015;24(137):451-461. ↩︎
Daily JW, et al. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Med Food. 2016;19(8):717-729. ↩︎
Paultre K, et al. Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: a systematic review. BMJ Open Sport Exerc Med. 2021;7(1):e000935. ↩︎
Salve J, et al. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus. 2019;11(12):e6466. ↩︎
Lopresti AL, et al. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 2019;98(37):e17186. ↩︎ ↩︎
Durg S, et al. Withania somnifera (Ashwagandha) in male infertility: An evidence-based systematic review and meta-analysis. Phytomedicine. 2018;50:247-256. ↩︎
Wirth M, et al. The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial. Cortex. 2018;109:181-188. ↩︎
Wirth M, et al. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(5):e2213875. ↩︎
Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. ↩︎