Innovative Health

References

The published research behind our recommendations, grouped by health goal and by supplement.

Innovative Health is educational, not medical advice. Where strong evidence exists, we cite it plainly and link to the study so you can read it yourself. Where the evidence is only modest or mixed, we say so in a note rather than overstating it. If the research does not support a claim, we do not make it.

Every study below is linked to its source. Always talk with your own healthcare provider before starting any supplement — see our Medical Disclaimer.

By health goal

Energy & Focus

  1. Ishaque S, Shamseer L, Bukutu C, Vohra S. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complement Altern Med. 2012;12:70. View study →Note: Early trials are promising but had methodological limitations, so the evidence isn't yet definitive.
  2. Tsai IC, Hsu CW, Chang CH, et al. Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2022;13:883251. View study →

Better Sleep

  1. Schuster J, Cycelskij I, Lopresti A, et al. Magnesium Bisglycinate Supplementation in Healthy Adults Reporting Poor Sleep: A Randomized, Placebo-Controlled Trial. Nat Sci Sleep. 2025;17:2027-2040. View study →
  2. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773. View study →
  3. Cruz-Sanabria F, Bruno S, Crippa A, et al. Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis. J Pineal Res. 2024;76(5):e12985. View study →

Immune Support

  1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. View study →
  2. Hemilä H, Petrus EJ, Fitzgerald JT, Prasad A. Zinc acetate lozenges for treating the common cold: an individual patient data meta-analysis. Br J Clin Pharmacol. 2016;82(5):1393-1398. View study →
  3. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013;(1):CD000980. View study →Note: Regular vitamin C doesn't appear to prevent colds in the general population, but it modestly shortens how long they last.

Joint & Mobility

  1. Feng J, Li Z, Tian L, et al. Efficacy and safety of curcuminoids alone in alleviating pain and dysfunction for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. BMC Complement Med Ther. 2022;22(1):276. View study →
  2. Simental-Mendía M, Ortega-Mata D, Acosta-Olivo CA, et al. Effect of collagen supplementation on knee osteoarthritis: an updated systematic review and meta-analysis of randomised controlled trials. Clin Exp Rheumatol. 2025;43(1):126-134. View study →
  3. Yu G, Xiang W, Zhang T, et al. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20(1):225. View study →

Stress & Mood

  1. Akhgarjand C, Asoudeh F, Bagheri A, et al. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2022;36(11):4115-4124. View study →
  2. Hidese S, Ogawa S, Ota M, et al. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019;11(10):2362. View study →
  3. Williams JL, Everett JM, D'Cunha NM, et al. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review. Plant Foods Hum Nutr. 2020;75(1):12-23. View study →

Digestive & Gut

  1. Chen M, Yuan L, Xie CR, et al. Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis. Int J Surg. 2023;109(11):3631-3647. View study →
  2. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014;48(6):505-512. View study →
  3. Black CJ, Yuan Y, Selinger CP, et al. Efficacy of soluble fibre, antispasmodic drugs, and gut-brain neuromodulators in irritable bowel syndrome: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(2):117-131. View study →

Heart Health

  1. Wang T, Zhang X, Zhou N, et al. Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2023;12(11):e029512. View study →
  2. Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016;68(2):324-333. View study →
  3. Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020;(3):CD003177. View study →Note: Omega-3s reliably lower triglycerides, but this large review found little or no effect on preventing heart attacks or strokes — the clearest benefit is for blood fats, not cardiovascular events.

Brain & Memory

  1. Shahinfar H, Yazdian Z, Avini NA, et al. A systematic review and dose-response meta-analysis of omega-3 supplementation on cognitive function. Sci Rep. 2025;15(1):30610. View study →Note: The evidence is mixed — benefits appear mainly at higher doses and in early or mild cognitive decline, with little effect in advanced disease.
  2. Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, et al. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535. View study →
  3. Mori K, Inatomi S, Ouchi K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009;23(3):367-372. View study →Note: This is a small, early trial; larger studies are needed before drawing firm conclusions.

Weight Management

  1. Phung OJ, Baker WL, Matthews LJ, et al. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. Am J Clin Nutr. 2010;91(1):73-81. View study →Note: The effect is modest — small reductions in weight and BMI, most evident when combined with caffeine.
  2. Gibb RD, Sloan KJ, McRorie JW Jr. Psyllium is a natural nonfermented gel-forming fiber that is effective for weight loss: A comprehensive review and meta-analysis. J Am Assoc Nurse Pract. 2023;35(8):468-476. View study →
  3. Sood N, Baker WL, Coleman CI. Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis. Am J Clin Nutr. 2008;88(4):1167-1175. View study →Note: Effects on weight are modest and not seen in every trial; fiber like this works best alongside a reduced-calorie diet.

Bone Strength

  1. Weaver CM, Alexander DD, Boushey CJ, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 2016;27(1):367-376. View study →Note: Supports calcium and vitamin D taken together; more recent trials of vitamin D alone in general populations show little benefit, so the effect is clearest for the combination in older or at-risk adults.
  2. Ma ML, Ma ZJ, He YL, et al. Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Front Public Health. 2022;10:979649. View study →
  3. Groenendijk I, van Delft M, Versloot P, et al. Impact of magnesium on bone health in older adults: A systematic review and meta-analysis. Bone. 2022;154:116233. View study →Note: Higher magnesium intake is linked to better bone density; its effect on preventing fractures is less certain.

Skin, Hair & Nails

  1. de Miranda RB, Weimer P, Rossi RC. Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta-analysis. Int J Dermatol. 2021;60(12):1449-1461. View study →
  2. Pu SY, Huang YL, Pu CM, et al. Effects of Oral Collagen for Skin Anti-Aging: A Systematic Review and Meta-Analysis. Nutrients. 2023;15(9):2080. View study →
  3. Nukaly HY, Halawani IR, Irtaza HM, et al. Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials. Front Med (Lausanne). 2026;13:1618306. View study →

Women's Health

  1. Low MS, Speedy J, Styles CE, et al. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev. 2016;(4):CD009747. View study →
  2. McCabe D, Lisy K, Lockwood C, Colbeck M. The impact of essential fatty acid, B vitamins, vitamin C, magnesium and zinc supplementation on stress levels in women: a systematic review. JBI Database System Rev Implement Rep. 2017;15(2):402-453. View study →
  3. Robinson J, Ferreira A, Iacovou M, Kellow NJ. Effect of nutritional interventions on the psychological symptoms of premenstrual syndrome in women of reproductive age: a systematic review of randomized controlled trials. Nutr Rev. 2025;83(2):280-306. View study →Note: Findings are mixed across nutrients; the most consistent signals were for calcium and vitamin B6.

Prenatal & Pregnancy

  1. Viswanathan M, Urrutia RP, Hudson KN, et al. Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2023;330(5):460-466. View study →
  2. Middleton P, Gomersall JC, Gould JF, et al. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;(11):CD003402. View study →
  3. Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;(7):CD004736. View study →

Blood Sugar

  1. Xie W, Su F, Wang G, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045. View study →
  2. Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther. 2014;39(3):292-306. View study →Note: Results are mixed; the most consistent benefit is a modest improvement in blood sugar among people who already have diabetes.
  3. Akbari M, Ostadmohammadi V, Lankarani KB, et al. The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Metabolism. 2018;87:56-69. View study →

Muscle & Recovery

  1. Wang Z, Qiu B, Li R, et al. Effects of Creatine Supplementation and Resistance Training on Muscle Strength Gains in Adults <50 Years of Age: A Systematic Review and Meta-Analysis. Nutrients. 2024;16(21):3665. View study →
  2. Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52(6):376-384. View study →
  3. Chilibeck PD, Kaviani M, Candow DG, Zello GA. 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. View study →

Eye Health

  1. Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-2015. View study →
  2. Ma L, Dou HL, Wu YQ, et al. Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis. Br J Nutr. 2012;107(3):350-359. View study →
  3. Giannaccare G, Pellegrini M, Sebastiani S, et al. Efficacy of Omega-3 Fatty Acid Supplementation for Treatment of Dry Eye Disease: A Meta-Analysis of Randomized Clinical Trials. Cornea. 2019;38(5):565-573. View study →Note: Evidence is mixed — this analysis found a benefit, but a large 2018 trial (DREAM) found omega-3 no better than placebo for dry eye.

Liver & Detox

  1. de Avelar CR, Pereira EM, de Farias Costa PR, et al. Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis. World J Gastroenterol. 2017;23(27):5004-5017. View study →Note: Studied mainly in people with existing liver disease, where milk thistle (silymarin) modestly improved liver enzyme levels.

Metabolism

  1. Hursel R, Viechtbauer W, Dulloo AG, et al. The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis. Obes Rev. 2011;12(7):e573-e581. View study →Note: The increase in calorie burn is small; catechins and caffeine work together, and the effect is a modest addition to diet and activity.
  2. Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther. 2014;39(3):292-306. View study →Note: Results are mixed; the most consistent benefit is a modest improvement in blood sugar among people who already have diabetes.
  3. Xie W, Su F, Wang G, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:1015045. View study →

Respiratory & Lungs

  1. Cazzola M, Calzetta L, Page C, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015;24(137):451-461. View study →Note: Studied in people with chronic bronchitis or COPD, where N-acetylcysteine reduced the rate of flare-ups.
  2. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. View study →

Inflammation Support

  1. Kavyani Z, Musazadeh V, Fathi S, et al. Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: An umbrella meta-analysis. Int Immunopharmacol. 2022;111:109104. View study →
  2. Sahebkar A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res. 2014;28(5):633-642. View study →
  3. Yu G, Xiang W, Zhang T, et al. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20(1):225. View study →

By supplement

5-HTP

  1. Javelle F, Lampit A, Bloch W, et al. Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis. Nutr Rev. 2020;78(1):77-88. View study →Note: Found signals of benefit in depression, but the studies were weak and few had placebo groups — it isn't a substitute for treatment.

Acetyl-L-Carnitine

  1. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol. 2003;18(2):61-71. View study →Note: Pooled trials found a modest benefit in mild cognitive impairment and mild Alzheimer's disease; it didn't study healthy people.

Alpha-GPC

  1. De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. 2003;25(1):178-193. View study →Note: In 261 people with mild-to-moderate Alzheimer's disease, alpha-GPC improved cognitive scores over six months versus placebo.
  2. Lee G, Choi S, Chang J, et al. Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years. JAMA Netw Open. 2021;4(11):e2136008. View study →Note: In a Korean cohort of 12 million adults, alpha-GPC users had a higher risk of stroke over 10 years. The study was observational and can't prove cause.

Andrographis

  1. Hu XY, Wu RH, Logue M, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLoS One. 2017;12(8):e0181780. View study →Note: Across 33 trials, andrographis improved cough and sore throat and shortened symptoms, but product quality was rarely reported.
  2. Worakunphanich W, Thavorncharoensap M, Youngkong S, Thadanipon K, Thakkinstian A. Safety of Andrographis paniculata: A systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2021;30(6):727-739. View study →Note: Serious side effects were very rare, but mild stomach and skin reactions were common.

Apple Cider Vinegar

  1. Shishehbor F, Mansoori A, Shirani F. Vinegar consumption can attenuate postprandial glucose and insulin responses; a systematic review and meta-analysis of clinical trials. Diabetes Res Clin Pract. 2017;127:1-9. View study →Note: Pooled small trials showing vinegar with a meal lowered the post-meal rise in blood sugar and insulin.

Artichoke

  1. Wider B, Pittler MH, Thompson-Coon J, Ernst E. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev. 2009;(4):CD003335. View study →Note: Found some evidence that artichoke leaf extract can lower cholesterol, but cautioned that the trials were few and modest.

Astaxanthin

  1. Zhou X, Cao Q, Orfila C, Zhao J, Zhang L. Systematic Review and Meta-Analysis on the Effects of Astaxanthin on Human Skin Ageing. Nutrients. 2021;13(9):2917. View study →Note: Across 9 small trials, oral astaxanthin modestly improved skin moisture and elasticity, but not wrinkle depth.

B-Complex

  1. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy — A Review. Nutrients. 2016;8(2):68. View study →Note: A narrative review arguing that low or borderline B-vitamin status is common in developed countries, and that people without an optimal diet may benefit from a full B-complex.

Beetroot

  1. Bahadoran Z, Mirmiran P, Kabir A, et al. The Nitrate-Independent Blood Pressure-Lowering Effect of Beetroot Juice: A Systematic Review and Meta-Analysis. Adv Nutr. 2017;8(6):830-838. View study →

Beta-Alanine

  1. Saunders B, Elliott-Sale K, Artioli GG, et al. Beta-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis. Br J Sports Med. 2017;51(8):658-669. View study →

Beta-Glucan

  1. Ho HV, Sievenpiper JL, Zurbau A, et al. The effect of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials. Br J Nutr. 2016;116(8):1369-1382. View study →Note: Oat beta-glucan lowered LDL cholesterol, non-HDL cholesterol, and apoB across randomized trials.

Betaine (TMG)

  1. Zawieja EE, Zawieja B, Chmurzynska A. Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis. J Diet Suppl. 2021;18(1):105-117. View study →Note: Betaine reliably lowers homocysteine but was found to moderately raise total and LDL cholesterol — a reason for caution at higher doses.

Bilberry

  1. Canter PH, Ernst E. Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision — a systematic review of placebo-controlled trials. Surv Ophthalmol. 2004;49(1):38-50. View study →Note: The more rigorous placebo-controlled trials found no benefit for night vision; positive results came from weaker studies.
  2. Ozawa Y, Kawashima M, Inoue S, et al. Bilberry extract supplementation for preventing eye fatigue in video display terminal workers. J Nutr Health Aging. 2015;19(5):548-554. View study →Note: In office workers, 8 weeks of bilberry extract eased some measures of screen-related eye fatigue.

Biotin

  1. Patel DP, Swink SM, Castelo-Soccio L. A Review of the Use of Biotin for Hair Loss. Skin Appendage Disord. 2017;3(3):166-169. View study →Note: Every reported benefit came from people with an underlying cause of poor hair or nail growth; the authors found insufficient evidence for supplementing healthy people.

Black Cohosh

  1. Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev. 2012;(9):CD007244. View study →Note: Across 16 trials (2,027 women), black cohosh was no better than placebo for hot flashes; evidence was insufficient to support its use.
  2. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145(12):869-879. View study →Note: In a year-long trial, black cohosh and other herbal approaches were no better than placebo for hot flashes and night sweats.

Boron

  1. Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015;14(4):35-48. View study →Note: A narrative review of mostly small and early studies, not a systematic analysis of trials.

Bromelain

  1. de Souza GM, Fernandes IA, Dos Santos CRR, Falci SGM. Is bromelain effective in controlling the inflammatory parameters of pain, edema, and trismus after lower third molar surgery? A systematic review and meta-analysis. Phytother Res. 2019;33(3):473-481. View study →Note: Pooled a few trials and found bromelain reduced pain, swelling, and jaw stiffness after wisdom-tooth surgery; the authors called for higher-quality studies.

Chlorella

  1. Fallah AA, Sarmast E, Habibian Dehkordi S, et al. Effect of Chlorella supplementation on cardiovascular risk factors: A meta-analysis of randomized controlled trials. Clin Nutr. 2018;37(6 Pt A):1892-1901. View study →Note: Found chlorella modestly lowered cholesterol, blood pressure, and fasting glucose; it did not assess detox claims.

Choline

  1. Caudill MA, Strupp BJ, Muscalu L, et al. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. FASEB J. 2018;32(4):2172-2180. View study →

Chondroitin

  1. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795-808. View study →Note: This large NIH trial (GAIT) found glucosamine and chondroitin, alone or combined, were not significantly better than placebo overall for knee osteoarthritis pain.

Cinnamon

  1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11(5):452-459. View study →Note: Cinnamon was associated with modest improvements in fasting glucose and lipids, but effects on longer-term control (HbA1c) were not established and study quality varied.

Citicoline (CDP-Choline)

  1. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev. 2005;(2):CD000269. View study →Note: Found some evidence of short- to medium-term benefit for memory and behavior in older adults with chronic brain disorders; the studies were varied and often short.
  2. Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Nutr. 2021;151(8):2153-2160. View study →Note: In healthy older adults with age-related memory complaints, 500 mg/day for 12 weeks improved episodic and overall memory versus placebo.

CLA

  1. Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E. The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr. 2012;51(2):127-134. View study →Note: Found a small drop in body fat (about 1.3 kg) with long-term CLA, which the authors judged not clinically convincing.

Colostrum & Immunoglobulins

  1. Jones AW, March DS, Curtis F, Bridle C. Bovine colostrum supplementation and upper respiratory symptoms during exercise training: a systematic review and meta-analysis of randomised controlled trials. BMC Sports Sci Med Rehabil. 2016;8:21. View study →Note: Across 5 small trials (152 active people), colostrum cut upper-respiratory symptom days by about 44% during training; study reporting was poor.
  2. Wilson D, Evans M, Weaver E, Shaw AL, Klein GL. Evaluation of serum-derived bovine immunoglobulin protein isolate in subjects with diarrhea-predominant irritable bowel syndrome. Clin Med Insights Gastroenterol. 2013;6:49-60. View study →Note: A small pilot study found symptom improvements in people with diarrhea-predominant IBS taking SBI; it wasn't designed to prove benefit.

Copper

  1. Duncan A, Morrison I, Bryson S. Iatrogenic copper deficiency: Risks and cautions with zinc prescribing. Br J Clin Pharmacol. 2023;89(9):2825-2829. View study →Note: Found zinc-induced copper deficiency is easily missed (half the confirmed cases had gone undiagnosed) and called for safer zinc-dosing guidance.

Cranberry

  1. Xia JY, Yang C, Xu DF, et al. Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis. PLoS One. 2021;16(9):e0256992. View study →

D-Mannose

  1. Hayward G, Mort S, Hay AD, et al. d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial. JAMA Intern Med. 2024;184(6):619-628. View study →Note: In 598 women with recurrent UTIs, daily D-mannose for six months didn't reduce medically attended UTIs compared with placebo.
  2. Kranjčec B, Papeš D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014;32(1):79-84. View study →Note: An open-label trial found fewer recurrences with D-mannose than with no treatment; it wasn't placebo-controlled.

Dandelion

  1. Schütz K, Carle R, Schieber A. Taraxacum — a review on its phytochemical and pharmacological profile. J Ethnopharmacol. 2006;107(3):313-323. View study →Note: Summarizes mostly laboratory and animal research; human clinical trials are scarce.

DGL Licorice

  1. Bardhan KD, Cumberland DC, Dixon RA, Holdsworth CD. Clinical trial of deglycyrrhizinised liquorice in gastric ulcer. Gut. 1978;19(9):779-782. View study →Note: In 96 people with gastric ulcer, DGL healed ulcers no better than placebo after four weeks.
  2. Sigurjónsdóttir HA, Franzson L, Manhem K, et al. Liquorice-induced rise in blood pressure: a linear dose-response relationship. J Hum Hypertens. 2001;15(8):549-552. View study →Note: Even 50 g of whole licorice a day for two weeks raised blood pressure — the reason DGL removes glycyrrhizin.

DHEA

  1. Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006;355(16):1647-1659. View study →Note: Two years of DHEA in older adults raised hormone levels but didn't improve body composition, physical performance, insulin sensitivity, or quality of life.
  2. Scheffers CS, Armstrong S, Cantineau AE, Farquhar C, Jordan V. Dehydroepiandrosterone for women in the peri- or postmenopausal phase. Cochrane Database Syst Rev. 2015;(1):CD011066. View study →Note: In peri- and postmenopausal women, DHEA didn't improve quality of life, and androgenic side effects (mainly acne) were more common than with placebo.

Digestive Enzymes

  1. Montalto M, Nucera G, Santoro L, et al. Effect of exogenous beta-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study. Eur J Clin Nutr. 2005;59(4):489-493. View study →Note: In a small placebo-controlled crossover trial, lactase taken with lactose sharply reduced breath hydrogen and symptoms in people with lactose intolerance.
  2. Ianiro G, Pecere S, Giorgio V, Gasbarrini A, Cammarota G. Digestive Enzyme Supplementation in Gastrointestinal Diseases. Curr Drug Metab. 2016;17(2):187-193. View study →Note: Reviews enzyme therapy in digestive disease: pancreatic enzymes and lactase are established for specific deficiencies, while broader uses are still being explored.

DIM

  1. Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016;74(7):432-443. View study →Note: Reviews mostly laboratory and early human research on DIM in breast cancer prevention; human evidence is limited.

Echinacea

  1. Karsch-Völk M, Barrett B, Kiefer D, et al. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014;(2):CD000530. View study →Note: Found echinacea products haven't been shown to help treat colds, though some may have a weak preventive effect; products vary widely.

Elderberry

  1. Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019;42:361-365. View study →Note: Pooled small trials totaling 180 people and found fewer upper-respiratory symptoms; larger independent trials are still needed.

Electrolytes

  1. Hahn S, Kim S, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children. Cochrane Database Syst Rev. 2002;(1):CD002847. View study →Note: Reduced-osmolarity oral rehydration solution meant fewer unplanned IV fluid treatments than the older WHO formula in children with acute diarrhea.
  2. Sawka MN, Burke LM, Eichner ER, et al. American College of Sports Medicine position stand. Exercise and fluid replacement. Med Sci Sports Exerc. 2007;39(2):377-390. View study →Note: Sports medicine guidance: drinks with electrolytes and carbohydrate can beat water alone in some situations, and fluid intake should match sweat losses rather than exceed them.

Evening Primrose Oil

  1. Bamford JT, Ray S, Musekiwa A, et al. Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013;(4):CD004416. View study →Note: Oral evening primrose oil was no better than placebo for eczema symptoms.
  2. Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome?. Control Clin Trials. 1996;17(1):60-68. View study →Note: The two best-controlled trials found no benefit for PMS; the authors concluded evening primrose oil is of little value.

Fenugreek

  1. Neelakantan N, Narayanan M, de Souza RJ, van Dam RM. Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycemia: a meta-analysis of clinical trials. Nutr J. 2014;13:7. View study →Note: Fenugreek lowered fasting glucose and HbA1c, mainly at medium-to-high doses in people with diabetes; most trials were low quality.
  2. Mansoori A, Hosseini S, Zilaee M, Hormoznejad R, Fathi M. Effect of fenugreek extract supplement on testosterone levels in male: A meta-analysis of clinical trials. Phytother Res. 2020;34(7):1550-1555. View study →Note: Pooled just four trials and found fenugreek extract raised total testosterone in men.

Flaxseed

  1. Sahebkar A, Katsiki N, Ward N, Reiner Ž. Flaxseed Supplementation Reduces Plasma Lipoprotein(a) Levels: A Meta-Analysis. Altern Ther Health Med. 2021;27(3):50-53. View study →Note: Found flaxseed lowered lipoprotein(a), a cardiovascular lipid marker; flaxseed's broader effects on LDL and blood pressure are supported by separate trials.

GABA

  1. Hepsomali P, Groeger JA, Nishihira J, Scholey A. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Front Neurosci. 2020;14:923. View study →Note: Found limited evidence for stress relief and very limited evidence for sleep benefits from oral GABA.

Garlic

  1. Ried K. Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review. J Nutr. 2016;146(2):389S-396S. View study →

Ginger

  1. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J. 2014;13:20. View study →

Ginkgo Biloba

  1. DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. 2008;300(19):2253-2262. View study →Note: This large trial (GEM) found ginkgo did not reduce the incidence of dementia or Alzheimer's disease in older adults.

Glutathione

  1. Richie JP Jr, Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54(2):251-263. View study →Note: Six months of oral glutathione raised glutathione stores in blood and cells; levels returned to baseline a month after stopping.
  2. Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med. 2011;17(9):827-833. View study →Note: Four weeks of oral glutathione didn't change glutathione levels or oxidative stress markers in healthy adults.

Glycine

  1. Bannai M, Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 2012;118(2):145-148. View study →Note: A review by researchers at Ajinomoto, a glycine manufacturer, summarizing their small studies of glycine before bed.

Grape Seed Extract

  1. Foshati S, Nouripour F, Sadeghi E, Amani R. The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials. Pharmacol Res. 2022;175:105905. View study →

Gymnema

  1. Devangan S, Varghese B, Johny E, Gurram S, Adela R. The effect of Gymnema sylvestre supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis. Phytother Res. 2021;35(12):6802-6812. View study →Note: Pooled small trials in type 2 diabetes found better blood sugar and lipids, but results varied enormously between studies.
  2. Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci. 2010;340(6):514-517. View study →Note: Case report of liver injury in a patient taking gymnema for diabetes.

HMB

  1. Wu H, Xia Y, Jiang J, et al. Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr. 2015;61(2):168-175. View study →Note: In older adults, HMB helped preserve muscle mass; fat mass didn't change.
  2. Rowlands DS, Thomson JS. Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: a meta-analysis. J Strength Cond Res. 2009;23(3):836-846. View study →Note: HMB gave small strength gains in untrained men but trivial effects in trained lifters.

Holy Basil (Tulsi)

  1. Jamshidi N, Cohen MM. The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature. Evid Based Complement Alternat Med. 2017;2017:9217567. View study →Note: Reviewed 24 human studies that reported favorable effects, including for stress; the authors noted the right dose, form, and best-suited users still need clarifying.

Hyaluronic Acid

  1. Kawada C, Yoshida T, Yoshida H, et al. Ingested hyaluronan moisturizes dry skin. Nutr J. 2014;13:70. View study →Note: A review by researchers at Kewpie Corporation, which makes a hyaluronan supplement, drawing largely on small Japanese trials.

Inositol

  1. Unfer V, Facchinetti F, Orrù B, et al. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6(8):647-658. View study →

Iodine

  1. Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015;3(4):286-295. View study →Note: Covers how both too little and too much iodine can disrupt thyroid function.

Krill Oil

  1. Ulven SM, Holven KB. Comparison of bioavailability of krill oil versus fish oil and health effect. Vasc Health Risk Manag. 2015;11:511-524. View study →Note: Found limited, hard-to-compare evidence: two human studies suggested krill oil's omega-3s may be absorbed somewhat better, but effects on lipids and inflammation were limited for both oils.

L-Arginine

  1. Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-965. View study →Note: Found oral L-arginine lowered blood pressure by about 5/3 mmHg across small trials (387 people in total).

L-Carnitine

  1. Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K, Olyaeemanesh A. The effect of (L-)carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2016;17(10):970-976. View study →Note: Carnitine produced a small extra weight loss versus control, and the effect shrank over time.
  2. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576-585. View study →Note: Found gut bacteria turn carnitine into TMAO, which promoted atherosclerosis in mice; its relevance to supplement users is debated.

L-Citrulline

  1. Trexler ET, Persky AM, Ryan ED, et al. Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis. Sports Med. 2019;49(5):707-718. View study →Note: Found a small but significant improvement in high-intensity strength and power performance.

L-Glutamine

  1. Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr. 2008;138(10):2045S-2049S. View study →Note: Concluded glutamine supplements do little for performance, recovery, or immune function in healthy athletes.

L-Lysine

  1. Chi CC, Wang SH, Delamere FM, et al. Interventions for prevention of herpes simplex labialis (cold sores on the lips). Cochrane Database Syst Rev. 2015;(8):CD010095. View study →Note: A Cochrane review of 32 cold-sore prevention trials; it found no evidence that lysine prevents recurrences.
  2. Mailoo VJ, Rampes S. Lysine for Herpes Simplex Prophylaxis: A Review of the Evidence. Integr Med (Encinitas). 2017;16(3):42-46. View study →Note: Found doses under 1 g/day appear ineffective, while doses above 3 g/day may help some people; better trials are needed.

L-Tyrosine

  1. Jongkees BJ, Hommel B, Kühn S, Colzato LS. Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands — A review. J Psychiatr Res. 2015;70:50-57. View study →Note: Concluded tyrosine may help maintain cognitive performance under short-term stress or high demand, but is unlikely to help under normal, rested conditions.

Lactoferrin

  1. Abu Hashim H, Foda O, Ghayaty E. Lactoferrin or ferrous salts for iron deficiency anemia in pregnancy: A meta-analysis of randomized trials. Eur J Obstet Gynecol Reprod Biol. 2017;219:45-52. View study →Note: In pregnant women with iron-deficiency anemia, lactoferrin improved blood counts as well as ferrous sulfate, with fewer stomach side effects.
  2. Ali AS, Hasan SS, Kow CS, Merchant HA. Lactoferrin reduces the risk of respiratory tract infections: A meta-analysis of randomized controlled trials. Clin Nutr ESPEN. 2021;45:26-32. View study →Note: Pooled trials suggested lactoferrin lowered the odds of respiratory infections; some studies had a high risk of bias.

Lemon Balm

  1. Ghazizadeh J, Sadigh-Eteghad S, Marx W, et al. The effects of lemon balm (Melissa officinalis L.) on depression and anxiety in clinical trials: A systematic review and meta-analysis. Phytother Res. 2021;35(12):6690-6705. View study →Note: Found lemon balm may improve anxiety and depressive symptoms, but the trials were few and varied, and the authors urged caution.
  2. Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004;66(4):607-613. View study →Note: In a small lab study, single doses of lemon balm improved calmness during a stressful task.

Lycopene

  1. Rowles JL 3rd, Ranard KM, Smith JW, An R, Erdman JW Jr. Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017;20(4):361-377. View study →Note: Higher dietary and blood lycopene were linked to modestly lower prostate cancer risk in observational studies.
  2. Cheng HM, Koutsidis G, Lodge JK, et al. Tomato and lycopene supplementation and cardiovascular risk factors: A systematic review and meta-analysis. Atherosclerosis. 2017;257:100-108. View study →Note: In pooled trials, tomato products improved LDL and blood-vessel function, and lycopene supplements lowered systolic blood pressure.

Maca

  1. Shin BC, Lee MS, Yang EJ, Lim HS, Ernst E. Maca (L. meyenii) for improving sexual function: a systematic review. BMC Complement Altern Med. 2010;10:44. View study →Note: Found limited evidence suggestive of a benefit for sexual function, but the trials were few and small.

Manganese

  1. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005;26(4-5):353-362. View study →Note: Reviews manganese as an essential nutrient, its food sources and absorption, and the harms of excess exposure.

MCT Oil

  1. Mumme K, Stonehouse W. Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials. J Acad Nutr Diet. 2015;115(2):249-263. View study →Note: Across 13 trials (749 adults), MCTs in place of other fats lowered body weight by about half a kilogram (roughly 1 lb) — real, but small.

Medicinal Mushrooms

  1. Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2016;(4):CD007731. View study →Note: Found poor-quality trials and no evidence to support reishi as a first-line cancer treatment; any add-on benefit alongside standard treatment was uncertain.
  2. Oba K, Teramukai S, Kobayashi M, et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother. 2007;56(6):905-911. View study →Note: Pooled Japanese trials of PSK, a pharmaceutical turkey-tail preparation given with chemotherapy after gastric cancer surgery. It doesn't apply to retail mushroom supplements.

MSM

  1. Brien S, Prescott P, Lewith G. Meta-analysis of the related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee. Evid Based Complement Alternat Med. 2011;2011:528403. View study →Note: Suggested a possible benefit for MSM in knee osteoarthritis, but the authors cautioned that the trials were small and of limited quality.

NAD+ Precursors (NR & NMN)

  1. Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. View study →Note: Six weeks of nicotinamide riboside was well tolerated and raised NAD+ in healthy middle-aged and older adults; physical benefits weren't established.
  2. Freeberg KA, Udovich CC, Martens CR, Seals DR, Craighead DH. Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions. J Gerontol A Biol Sci Med Sci. 2023;78(12):2435-2448. View study →Note: Reviews human trials: NAD+ precursors raise NAD+ levels, but small, varied studies limit conclusions about real-world benefits.

Olive Leaf Extract

  1. Lockyer S, Rowland I, Spencer JPE, Yaqoob P, Stonehouse W. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial. Eur J Nutr. 2017;56(4):1421-1432. View study →Note: Six weeks of olive leaf extract modestly lowered blood pressure and cholesterol in 60 men with slightly high blood pressure.
  2. Álvares AA, Garcêz A, Silva LT, Averbuch N, Garavaglia J. Olive leaf extract effect on cardiometabolic risk factors: a systematic review and meta-analysis of randomized clinical trials. Nutr Rev. 2024;82(12):1710-1725. View study →Note: Pooled trials gave inconsistent results for blood sugar, blood pressure, and lipids; the authors called for more consistent studies.

Oregano Oil

  1. Force M, Sparks WS, Ronzio RA. Inhibition of enteric parasites by emulsified oil of oregano in vivo. Phytother Res. 2000;14(3):213-214. View study →Note: A small uncontrolled study: six weeks of emulsified oregano oil cleared some intestinal parasites in several adults. There was no comparison group.
  2. Sharifi-Rad M, Varoni EM, Iriti M, et al. Carvacrol and human health: A comprehensive review. Phytother Res. 2018;32(9):1675-1687. View study →Note: Reviews mostly lab and animal research on carvacrol and notes that human trials are still lacking.

Panax Ginseng

  1. Arring NM, Millstine D, Marks LA, Nail LM. Ginseng as a Treatment for Fatigue: A Systematic Review. J Altern Complement Med. 2018;24(7):624-633. View study →Note: Found ginseng is a promising option for fatigue, particularly in people with chronic illness, but the evidence is limited.

Passionflower

  1. Miyasaka LS, Atallah AN, Soares BG. Passiflora for anxiety disorder. Cochrane Database Syst Rev. 2007;(1):CD004518. View study →Note: Only two small trials were available — too few to draw conclusions about passionflower for anxiety.
  2. Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality. Phytother Res. 2011;25(8):1153-1159. View study →Note: A week of passionflower tea modestly improved self-rated sleep quality in healthy adults.

Peppermint Oil

  1. Alammar N, Wang L, Saberi B, et al. The impact of peppermint oil on the irritable bowel syndrome: a meta-analysis of the pooled clinical data. BMC Complement Altern Med. 2019;19(1):21. View study →Note: Across 12 trials, peppermint oil improved overall IBS symptoms and abdominal pain versus placebo, with side effects similar to placebo.
  2. Weerts ZZRM, Masclee AAM, Witteman BJM, et al. Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome. Gastroenterology. 2020;158(1):123-136. View study →Note: Missed its main endpoint, but small-intestinal-release peppermint oil improved abdominal pain, discomfort, and IBS severity.

Phosphatidylserine

  1. Crook TH, Tinklenberg J, Yesavage J, et al. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41(5):644-649. View study →Note: Used the older bovine-derived form of phosphatidylserine, which is no longer sold; results for today's soy- or sunflower-derived forms are less established.

Pine Bark Extract (Pycnogenol)

  1. Robertson NU, Schoonees A, Brand A, Visser J. Pine bark (Pinus spp.) extract for treating chronic disorders. Cochrane Database Syst Rev. 2020;(9):CD008294. View study →Note: Across 27 small trials in 10 chronic conditions, the evidence was insufficient to support pine bark extract for any of them.

Potassium

  1. Aburto NJ, Hanson S, Gutierrez H, et al. Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ. 2013;346:f1378. View study →Note: Found higher potassium intake lowered blood pressure, especially in people with hypertension, and was linked to lower stroke risk.

PQQ

  1. Harris CB, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013;24(12):2076-2084. View study →Note: A very small study (10 adults) that measured blood and urine markers after PQQ; it didn't test energy or cognition.

Prebiotics

  1. Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients. 2013;5(4):1417-1435. View study →

Pregnenolone

  1. Naylor JC, Kilts JD, Shampine LJ, et al. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(3):e200287. View study →Note: A small trial in 94 military veterans found less low back pain with pregnenolone than placebo; it hasn't been replicated.
  2. Brown ES, Park J, Marx CE, et al. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014;39(12):2867-2873. View study →Note: A small trial suggested pregnenolone may ease depressive symptoms in bipolar depression; it was well tolerated but needs larger confirmation.

Quercetin

  1. Serban MC, Sahebkar A, Zanchetti A, et al. Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2016;5(7):e002713. View study →Note: Found a small drop in blood pressure at doses of 500 mg/day or more; it did not test immune, respiratory, or inflammation claims.

Resveratrol

  1. Semba RD, Ferrucci L, Bartali B, et al. Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med. 2014;174(7):1077-1084. View study →Note: In about 800 older adults followed for 9 years, resveratrol levels from diet were not linked to longer life, less inflammation, heart disease, or cancer.

Saccharomyces boulardii

  1. Szajewska H, Kołodziej M. Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2015;42(7):793-801. View study →Note: Across 21 trials (4,780 people), S. boulardii cut the risk of antibiotic-associated diarrhea roughly in half, from about 19% to 8.5%.
  2. Guo Q, Goldenberg JZ, Humphrey C, El Dib R, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2019;(4):CD004827. View study →Note: Probiotics, including Saccharomyces, reduced antibiotic-associated diarrhea in children, though many of the trials were at high risk of bias.

Saffron

  1. Tóth B, Hegyi P, Lantos T, et al. The Efficacy of Saffron in the Treatment of Mild to Moderate Depression: A Meta-analysis. Planta Med. 2019;85(1):24-31. View study →

SAM-e

  1. Rutjes AW, Nüesch E, Reichenbach S, Jüni P. S-Adenosylmethionine for osteoarthritis of the knee or hip. Cochrane Database Syst Rev. 2009;(4):CD007321. View study →Note: This Cochrane review found the evidence too limited and inconsistent to establish whether SAM-e relieves osteoarthritis symptoms.

Saw Palmetto

  1. MacDonald R, Tacklind JW, Rutks I, Wilt TJ. Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review. BJU Int. 2012;109(12):1756-1761. View study →Note: This updated Cochrane review found saw palmetto was no more effective than placebo for urinary symptoms of benign prostatic hyperplasia, even at higher doses.

Selenium

  1. Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256-1268. View study →Note: Explains that benefits depend on starting status: people who already get enough gain little, and extra selenium may raise type 2 diabetes risk.

Slippery Elm

  1. Hawrelak JA, Myers SP. Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study. J Altern Complement Med. 2010;16(10):1065-1071. View study →Note: An uncontrolled pilot study of two multi-herb IBS formulas that included slippery elm; it can't show what slippery elm does on its own.

Spirulina

  1. Osadnik T, Goławski M, Lewandowski P, et al. A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults. Pharmacol Res. 2022;183:106402. View study →Note: Among the nutraceuticals compared, spirulina ranked favorably for improving lipids, though head-to-head certainty is limited.

St. John's Wort

  1. Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008;(4):CD000448. View study →Note: Extracts beat placebo and matched standard antidepressants with fewer side effects in major depression, but results varied widely between trials and countries.
  2. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis. J Affect Disord. 2017;210:211-221. View study →Note: In mild-to-moderate depression, St. John's wort had response rates comparable to SSRIs with fewer dropouts; it didn't address severe depression.

Sulforaphane

  1. Axelsson AS, Tubbs E, Mecham B, et al. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Sci Transl Med. 2017;9(394):eaah4477. View study →Note: Mostly lab and animal work; in a small trial, broccoli sprout extract lowered fasting glucose and HbA1c in obese people with poorly controlled type 2 diabetes.
  2. Fahey JW, Holtzclaw WD, Wehage SL, et al. Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase. PLoS One. 2015;10(11):e0140963. View study →Note: Sulforaphane was about 3 to 4 times more available when the product included active myrosinase.

Tart Cherry

  1. Hill JA, Keane KM, Quinlan R, Howatson G. Tart Cherry Supplementation and Recovery From Strenuous Exercise: A Systematic Review and Meta-Analysis. Int J Sport Nutr Exerc Metab. 2021;31(2):154-167. View study →

Taurine

  1. Waldron M, Patterson SD, Tallent J, Jeffries O. The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis. Sports Med. 2018;48(5):1247-1253. View study →Note: Pooled 10 small studies and found a modest improvement in endurance performance.
  2. Waldron M, Patterson SD, Tallent J, Jeffries O. The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis. Curr Hypertens Rep. 2018;20(9):81. View study →Note: Pooled 7 small studies (103 people): blood pressure fell about 3 mmHg on average. The authors called the findings preliminary.

Valerian

  1. Bent S, Padula A, Moore D, Patterson M, Mehling W. Valerian for sleep: a systematic review and meta-analysis. Am J Med. 2006;119(12):1005-1012. View study →Note: Found valerian might improve sleep quality, but most of the 16 studies had significant methodological problems and there was evidence of publication bias.

Vitamin A

  1. Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006;83(2):191-201. View study →Note: Reviews the acute and chronic toxic effects of too much preformed vitamin A (retinol), including from supplements.

Vitamin B1 (Thiamine)

  1. Martin PR, Singleton CK, Hiller-Sturmhöfel S. The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health. 2003;27(2):134-142. View study →

Vitamin B12

  1. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. View study →Note: Clinical review of B12 deficiency, including at-risk groups (older adults, vegans, metformin and acid-reducer users) and treatment.

Vitamin B2 (Riboflavin)

  1. Chen YS, Lee HF, Tsai CH, et al. Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis. Nutr Neurosci. 2022;25(9):1801-1812. View study →

Vitamin B3 (Niacin)

  1. HPS2-THRIVE Collaborative Group; Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-212. View study →Note: In more than 25,000 high-risk patients already on statins, adding extended-release niacin didn't reduce major vascular events and increased serious side effects.
  2. AIM-HIGH Investigators; Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267. View study →Note: Adding niacin to statin therapy raised HDL but didn't reduce cardiovascular events; the trial was stopped early.

Vitamin B5 (Pantothenic Acid)

  1. Yang M, Moclair B, Hatcher V, et al. A randomized, double-blind, placebo-controlled study of a novel pantothenic Acid-based dietary supplement in subjects with mild to moderate facial acne. Dermatol Ther (Heidelb). 2014;4(1):93-101. View study →Note: A single 12-week trial (48 adults enrolled) found fewer acne lesions; it hasn't been confirmed by larger independent studies.

Vitamin B6

  1. Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999;318(7195):1375-1381. View study →Note: Found B6 up to 100 mg/day likely helps premenstrual symptoms, but the trials were small and of limited quality.

Vitamin E

  1. Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46. View study →Note: Pooled trials found high-dose vitamin E (400 IU/day or more) was associated with a small increase in deaths from any cause.

Vitamin K1

  1. Cheung AM, Tile L, Lee Y, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008;5(10):e196. View study →Note: Two years of vitamin K1 (5 mg/day) didn't protect against age-related bone loss; fewer fractures occurred in the vitamin K group, but the trial wasn't designed to test fractures.

Vitex (Chasteberry)

  1. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134-137. View study →Note: Vitex extract helped 52% of women with PMS, versus 24% on placebo, over three cycles.
  2. Verkaik S, Kamperman AM, van Westrhenen R, Schulte PFJ. The treatment of premenstrual syndrome with preparations of Vitex agnus castus: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017;217(2):150-166. View study →Note: Most trials reported benefit for PMS, but most were at high risk of bias and results varied widely.

Zinc Carnosine

  1. Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut. 2007;56(2):168-175. View study →Note: In healthy volunteers, zinc carnosine prevented the rise in gut permeability caused by an NSAID; lab and animal data suggested gut-repair effects.
  2. Mahmoud A, Abuelazm M, Ahmed AAS, et al. Efficacy and Safety of Polaprezinc-Based Therapy versus the Standard Triple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022;14(19):4126. View study →Note: Adding polaprezinc to standard H. pylori treatment improved eradication rates, but the authors said the evidence is still scarce.

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