💊 Evidence-Based Supplements Database

A curated, open-source database of dietary supplements graded by scientific evidence. Every entry includes evidence grades, dosing protocols, interactions, and primary research citations.

The supplement industry is worth over $177 billion globally — and most of it runs on marketing, not science [1]. This repository exists to cut through the noise. Every supplement listed here has been evaluated against peer-reviewed clinical trials, meta-analyses, and systematic reviews from PubMed, Cochrane, and NIH databases.

For a comprehensive breakdown of which supplements actually work and how to build an evidence-based stack, see the Health Secrets supplements guide.

Evidence Grading System

Grade	Meaning	Criteria
A	Strong Evidence	Multiple RCTs, meta-analyses, or systematic reviews supporting efficacy
B	Moderate Evidence	At least 1-2 well-designed RCTs with positive results
C	Preliminary Evidence	Animal studies, in vitro data, or small human trials only
D	Insufficient/Negative	No significant evidence of efficacy, or evidence of no effect

Vitamins & Minerals

Vitamin D3

Evidence Grade: A
Primary Uses: Immune function, bone health, mood regulation
Effective Dose: 1,000–4,000 IU/day (dose to serum level of 40–60 ng/mL)
Key Research: BMJ meta-analysis (25 RCTs, n=11,321) — 12% reduction in respiratory infections; 70% reduction in severely deficient individuals [2]
Interactions: May increase calcium absorption (monitor with thiazide diuretics); enhanced by K2 co-supplementation
Safety: Upper limit 4,000 IU/day (IOM); toxicity rare below 10,000 IU/day
NIH Fact Sheet: ods.od.nih.gov/factsheets/VitaminD

Magnesium (Glycinate/Threonate)

Evidence Grade: A
Primary Uses: Sleep quality, muscle relaxation, stress reduction, migraine prevention
Effective Dose: 200–400 mg elemental magnesium/day
Key Research: 2017 systematic review — magnesium supplementation improved subjective measures of insomnia (ISI score, sleep efficiency, sleep onset latency) [3]
Interactions: May reduce absorption of antibiotics (tetracyclines, quinolones); space 2 hours apart
Safety: Glycinate and threonate forms best tolerated; oxide form may cause GI distress
Forms: Glycinate (sleep/relaxation), Threonate (cognitive), Citrate (general), Taurate (cardiovascular)

Zinc

Evidence Grade: A
Primary Uses: Immune function, wound healing, testosterone support
Effective Dose: 15–30 mg/day (elemental zinc)
Key Research: Cochrane review — zinc lozenges within 24h of cold onset reduced duration by ~33% [4]
Interactions: Competes with copper absorption (supplement copper at 1–2 mg if taking >30 mg zinc long-term); reduces iron absorption
Safety: Upper limit 40 mg/day; chronic excess causes copper deficiency
Best Forms: Picolinate, bisglycinate, acetate (for lozenges)

Iron

Evidence Grade: A (for deficiency)
Primary Uses: Anemia, energy, cognitive function
Effective Dose: 18–65 mg/day depending on deficiency severity
Key Research: Well-established for iron-deficiency anemia; every-other-day dosing may improve absorption [5]
Interactions: Reduced by calcium, tea, coffee; enhanced by vitamin C
Safety: Do NOT supplement without confirmed deficiency via blood test; excess iron is harmful

B-Complex

Evidence Grade: B
Primary Uses: Energy metabolism, nervous system, methylation
Effective Dose: Varies by B vitamin; look for methylated forms (methylfolate, methylcobalamin)
Key Research: 2022 systematic review found B-vitamin supplementation may reduce stress and improve mood in healthy adults [6]
Interactions: B6 >100 mg/day long-term may cause peripheral neuropathy
Safety: Water-soluble; excess generally excreted

Further reading: Health Secrets supplements guide — full vitamin & mineral deep-dive with dosing calculators.

Herbal & Botanical Supplements

Ashwagandha (Withania somnifera)

Evidence Grade: B+
Primary Uses: Stress/cortisol reduction, anxiety, sleep, athletic performance
Effective Dose: 300–600 mg/day of root extract (standardized to 5%+ withanolides)
Key Research: 2022 systematic review of 12 RCTs — significant reductions in stress and anxiety (Hamilton Anxiety Scale) vs. placebo [7]
Interactions: May potentiate sedatives, thyroid medications, immunosuppressants
Safety: Generally well-tolerated; rare liver injury reports at high doses; avoid in pregnancy
Best Forms: KSM-66 or Sensoril (standardized extracts with most clinical data)

Milk Thistle (Silybum marianum)

Evidence Grade: B
Primary Uses: Liver protection, detoxification support, antioxidant
Effective Dose: 200–400 mg/day silymarin (standardized to 70–80% silymarin)
Key Research: Meta-analysis showed reduced liver enzyme levels (ALT, AST) in NAFLD patients [8]
Interactions: May affect CYP3A4 and CYP2C9 metabolism; check with medications metabolized by these enzymes
Safety: Very well tolerated; mild GI side effects in some

Curcumin (Turmeric Extract)

Evidence Grade: B+
Primary Uses: Inflammation, joint pain, antioxidant
Effective Dose: 500–1,000 mg/day (with piperine or liposomal form for absorption)
Key Research: 2016 systematic review — efficacy comparable to ibuprofen for osteoarthritis pain [9]
Interactions: May thin blood (caution with anticoagulants); enhances effect of some diabetes medications
Safety: Generally safe; high doses may cause GI upset
Bioavailability: Standard curcumin has ~1% bioavailability; use enhanced forms (Meriva, Longvida, BCM-95)

Rhodiola Rosea

Evidence Grade: B
Primary Uses: Fatigue, stress resilience, cognitive performance
Effective Dose: 200–600 mg/day (standardized to 3% rosavins, 1% salidroside)
Key Research: 2012 systematic review found improvements in physical and cognitive fatigue symptoms [10]
Interactions: May interact with SSRIs, MAOIs, stimulants
Safety: Generally well-tolerated; may cause dizziness or dry mouth

Berberine

Evidence Grade: B+
Primary Uses: Blood sugar regulation, lipid management, gut health
Effective Dose: 500 mg 2–3x daily with meals
Key Research: Meta-analysis of 27 RCTs — comparable to metformin for blood glucose reduction in type 2 diabetes [11]
Interactions: Significant drug interactions — inhibits CYP2D6, CYP3A4; may interact with diabetes meds, statins, blood thinners
Safety: GI side effects common; do NOT combine with metformin without medical supervision

Amino Acids & Compounds

L-Theanine

Evidence Grade: B+
Primary Uses: Calm focus, anxiety reduction, sleep quality
Effective Dose: 100–400 mg/day
Key Research: 2019 RCT — 200 mg/day for 4 weeks significantly reduced stress-related symptoms and improved cognitive function [12]
Interactions: May enhance effects of caffeine (synergistic for focus); may potentiate sedatives
Safety: Very safe; no significant adverse effects reported in clinical trials

Creatine Monohydrate

Evidence Grade: A
Primary Uses: Muscle performance, cognitive function, neuroprotection
Effective Dose: 3–5 g/day (loading phase optional)
Key Research: Most-studied sports supplement in history; 2017 ISSN position stand confirms efficacy for strength and power [13]
Interactions: Minimal; may increase water retention
Safety: Extremely well-studied; safe for long-term use; kidney concerns debunked in healthy individuals

Omega-3 (EPA/DHA)

Evidence Grade: A
Primary Uses: Cardiovascular health, inflammation, brain function, mood
Effective Dose: 1–3 g/day combined EPA+DHA (higher EPA for mood; higher DHA for cognition)
Key Research: AHA recommends for cardiovascular risk reduction; meta-analysis shows antidepressant effects for EPA-dominant formulas [14]
Interactions: May enhance anticoagulant effects; monitor with blood thinners
Safety: Generally safe; fishy taste/burps with low-quality products; choose IFOS-certified

CoQ10 (Ubiquinol)

Evidence Grade: B+
Primary Uses: Mitochondrial function, statin side effects, cardiovascular health, energy
Effective Dose: 100–300 mg/day (ubiquinol form preferred over ubiquinone for absorption)
Key Research: Meta-analysis — CoQ10 supplementation improved symptoms of heart failure and reduced major adverse cardiovascular events [15]
Interactions: May reduce efficacy of warfarin; statins deplete CoQ10 (supplementation recommended with statin use)
Safety: Very well-tolerated; rare mild GI effects

Further reading: For evidence-based supplement stacks organized by health goal, see the Health Secrets supplements guide.

Probiotics & Gut Health

Lactobacillus rhamnosus GG

Evidence Grade: A
Primary Uses: Gut health, immune function, antibiotic-associated diarrhea prevention
Effective Dose: 10–20 billion CFU/day
Key Research: Most-studied probiotic strain; Cochrane review confirms efficacy for preventing antibiotic-associated diarrhea [16]
Cross-reference: See Awesome Gut Health for full gut health resources

Bifidobacterium lactis BB-12

Evidence Grade: B+
Primary Uses: Immune support, digestive regularity, respiratory infection reduction
Effective Dose: 1–10 billion CFU/day
Key Research: RCTs show reduced incidence of respiratory infections in elderly populations [17]

Saccharomyces boulardii

Evidence Grade: A
Primary Uses: Diarrhea prevention/treatment, gut barrier function
Effective Dose: 250–500 mg (5–10 billion CFU) daily
Key Research: Meta-analysis of 27 RCTs — effective for preventing traveler’s diarrhea and antibiotic-associated diarrhea [18]

Supplement Interaction Checker

Combination	Status	Notes
Zinc + Iron	⚠️ Take separately	Compete for absorption; space 2+ hours apart
Vitamin D + K2	✅ Synergistic	K2 directs calcium to bones, away from arteries
Calcium + Magnesium	⚠️ Take separately	Compete for absorption at high doses
Curcumin + Piperine	✅ Synergistic	Piperine increases curcumin bioavailability by 2,000%
Berberine + Metformin	❌ Avoid	Risk of hypoglycemia; consult physician
L-Theanine + Caffeine	✅ Synergistic	Calm focus without jitters
Omega-3 + Blood Thinners	⚠️ Monitor	May enhance anticoagulant effects
Ashwagandha + Thyroid Meds	⚠️ Monitor	May increase thyroid hormone levels
Iron + Vitamin C	✅ Synergistic	Vitamin C enhances non-heme iron absorption
St. John’s Wort + SSRIs	❌ Avoid	Risk of serotonin syndrome

Dosing Protocols by Goal

🛡️ Immune Support Stack

Vitamin D3: 2,000–4,000 IU/day (with K2)
Zinc: 15–25 mg/day
Vitamin C: 500 mg 2x/day
L. rhamnosus GG: 10 billion CFU/day
Omega-3: 1 g EPA+DHA/day

🧠 Cognitive Performance Stack

Omega-3 (DHA-dominant): 1–2 g/day
Creatine: 5 g/day
L-Theanine: 200 mg + caffeine 100 mg (morning)
Magnesium Threonate: 144 mg elemental Mg (evening)
B-Complex (methylated): 1 capsule/day

💪 Longevity & Recovery Stack

CoQ10 (ubiquinol): 200 mg/day
Omega-3: 2 g EPA+DHA/day
Curcumin (enhanced form): 500 mg/day
Creatine: 3–5 g/day
Vitamin D3: 2,000–4,000 IU/day
Magnesium Glycinate: 300 mg (evening)

😴 Sleep & Stress Stack

Magnesium Glycinate: 300–400 mg (before bed)
Ashwagandha (KSM-66): 300 mg (evening)
L-Theanine: 200–400 mg (before bed)
Vitamin D3: 2,000 IU/day (morning — may disrupt sleep if taken at night)

Cross-reference: See Detox Protocols for liver support and detox supplement protocols.

📋 Free Tools

Build your personalized stack with free interactive Notion templates:

💊 Evidence-Based Supplement Stack Builder — Goal-based stacks with dosing tables, interaction checkers, and quality checklists you can customize for your needs

→ Browse all free health tools on Notion

Contributing

Contributions are welcome! To contribute:

Fork this repository
Add or update supplement entries using the template format above
Include at minimum: evidence grade, effective dose range, 1+ primary research citation with DOI or PubMed URL
Submit a pull request with a brief explanation of changes

Contribution Standards

All claims must be backed by peer-reviewed research (Tier 1 or 2 sources preferred)
Include the full citation in the References section
Evidence grades must follow the grading system defined above
Disclose any conflicts of interest

Disclaimer

This repository is for educational purposes only. The information provided does not constitute medical advice. Consult a qualified healthcare professional before starting any supplement protocol. Individual responses to supplements vary. Dosages listed are general ranges from clinical research and may not be appropriate for everyone.

References

Grand View Research. “Dietary Supplements Market Size Report, 2030.” 2023. https://www.grandviewresearch.com/industry-analysis/dietary-supplements-market
Martineau, A.R. et al. “Vitamin D supplementation to prevent acute respiratory tract infections.” BMJ, 2017. https://doi.org/10.1136/bmj.i6583
Abbasi, B. et al. “The effect of magnesium supplementation on primary insomnia in elderly.” Journal of Research in Medical Sciences, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703169/
Singh, M. & Das, R.R. “Zinc for the common cold.” Cochrane Database of Systematic Reviews, 2013. https://doi.org/10.1002/14651858.CD001364.pub4
Stoffel, N.U. et al. “Iron absorption from oral iron supplements given on consecutive versus alternate days.” The American Journal of Clinical Nutrition, 2017. https://doi.org/10.3945/ajcn.117.161414
Young, L.M. et al. “A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress.” Nutrients, 2019. https://doi.org/10.3390/nu11092232
Lopresti, A.L. et al. “An investigation into the stress-relieving and pharmacological actions of an ashwagandha extract.” Medicine, 2019. https://doi.org/10.1097/MD.0000000000017186
Zhong, S. et al. “The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease.” Clinical and Molecular Hepatology, 2017. https://doi.org/10.3350/cmh.2017.0066
Daily, J.W. et al. “Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis.” Journal of Medicinal Food, 2016. https://doi.org/10.1089/jmf.2016.3705
Hung, S.K. et al. “The effectiveness and efficacy of Rhodiola rosea L.: a systematic review.” Phytomedicine, 2011. https://doi.org/10.1016/j.phymed.2010.08.014
Liang, Y. et al. “Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis.” Endocrine Journal, 2019. https://doi.org/10.1507/endocrj.EJ18-0109
Hidese, S. et al. “Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions.” Nutrients, 2019. https://doi.org/10.3390/nu11102362
Kreider, R.B. et al. “International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation.” JISSN, 2017. https://doi.org/10.1186/s12970-017-0173-z
Liao, Y. et al. “Efficacy of omega-3 PUFAs in depression: A meta-analysis.” Translational Psychiatry, 2019. https://doi.org/10.1038/s41398-019-0515-5
Mortensen, S.A. et al. “The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure.” JACC: Heart Failure, 2014. https://doi.org/10.1016/j.jchf.2014.06.008
Goldenberg, J.Z. et al. “Probiotics for the prevention of Clostridium difficile-associated diarrhea.” Cochrane Database of Systematic Reviews, 2017. https://doi.org/10.1002/14651858.CD006095.pub4
Lehtoranta, L. et al. “Probiotics in respiratory virus infections.” European Journal of Clinical Microbiology, 2014. https://doi.org/10.1007/s10096-014-2086-y
McFarland, L.V. “Systematic review and meta-analysis of Saccharomyces boulardii.” World Journal of Gastroenterology, 2010. https://doi.org/10.3748/wjg.v16.i18.2202
NIH Office of Dietary Supplements. “Dietary Supplement Fact Sheets.” https://ods.od.nih.gov/factsheets/list-all/
Examine.com. “Evidence-based analysis on supplements and nutrition.” https://examine.com/