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Supplements & Compounds (Biohacking)
Supplement and compound interventions that can be tested with clear parameters and tracking.
PAGE CONTENTS
Supplements & Compounds
Good “First” Supplements (Evidence + Safety Generally Favorable)
Commonly Discussed (Evidence Varies by Outcome/Population)
Evidence Summary (Human Outcomes)
Stacking Strategy (Meta)
Experiment Guidance
References

Supplements & Compounds

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.

Good “First” Supplements (Evidence + Safety Generally Favorable)

Commonly Discussed (Evidence Varies by Outcome/Population)

Evidence Summary (Human Outcomes)

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]

Stacking Strategy (Meta)

Experiment Guidance

Use one variable at a time and a written decision rule: N‑of‑1 Experiments

References

  1. Lanhers C, et al. Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis. Sports Med. 2017;47(1):163-173. ↩︎

  2. 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. ↩︎

  3. 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. ↩︎

  4. 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. ↩︎

  5. 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. ↩︎

  6. Khan SU, et al. Effect of Omega-3 Fatty Acids on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. EClinicalMedicine. 2021;38:100997. ↩︎

  7. Sydenham E, et al. Omega-3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev. 2012;(6):CD005379. ↩︎

  8. 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. ↩︎

  9. 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. ↩︎

  10. 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. ↩︎

  11. 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. ↩︎

  12. 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. ↩︎

  13. 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. ↩︎

  14. 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. ↩︎

  15. 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. ↩︎

  16. 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. ↩︎ ↩︎

  17. Durg S, et al. Withania somnifera (Ashwagandha) in male infertility: An evidence-based systematic review and meta-analysis. Phytomedicine. 2018;50:247-256. ↩︎

  18. 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. ↩︎

  19. 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. ↩︎

  20. Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. ↩︎

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