Patient education · Evidence review
The 30 most popular supplements: what the evidence actually says
From creatine to collagen, we rated the research behind the supplements Americans take most and flagged the safety issues every patient should know about.
Reviewed by Dr. Zaid, D.O. · PrimeCare of Novi · Updated October 2026
The short version
Evidence quality varies enormously across these 30 products. A few have strong randomized-trial data behind them, like creatine, lutein and zeaxanthin for macular degeneration, and zinc for shortening colds. Others, such as greens powders, collagen, apple cider vinegar gummies, and lion’s mane, have essentially no controlled human efficacy data.
Large reviews from the US Preventive Services Task Force and the Journal of the American College of Cardiology reach a consistent conclusion: for generally healthy adults who are not deficient, most vitamins and minerals do not lower the risk of death, heart disease, or cancer. A few carry real harms, including beta-carotene in smokers, excess vitamin A or D, and kidney stones with high-dose vitamin C and calcium.
Bottom line: the strongest reason to take most vitamins and minerals is to correct a documented deficiency or to serve a defined high-risk group, not “general wellness.”
How to read the ratings
Evidence ratings for all 30 supplements
What the research shows, plus the monitoring and interaction concerns we discuss with patients. Reference numbers match the list at the bottom of this page.
| # | Supplement | Evidence | What the evidence shows | Monitoring and cautions | Refs |
|---|---|---|---|---|---|
| 1 | Multivitamin | Weak | No mortality or cardiovascular benefit in healthy adults; small possible reduction in cancer incidence, with important limitations. | Smokers should avoid formulas with beta-carotene (lung cancer risk). Not a substitute for diet. | 1, 2 |
| 2 | Vitamin D | Moderate for deficiency; weak otherwise | No reduction in death, heart disease, or cancer in adults with normal levels. Value lies in correcting low levels and supporting bone health. | Toxicity and high calcium at excessive doses. Check a level before high-dose repletion. | 1, 2, 4 |
| 3 | Magnesium (glycinate) | Weak–moderate | Dietary intake linked to slower macular degeneration progression; limited trial support for sleep and cramps. | Builds up with kidney impairment, so use caution in CKD. Diarrhea at high doses. | 4, 5 |
| 4 | Omega-3 / fish oil | Moderate | Reduces cardiovascular death, heart attack, and coronary events; lowers triglycerides. | Dose-dependent atrial fibrillation signal at high doses. Bleeding risk with anticoagulants. | 3 |
| 5 | Vitamin C | Weak | No benefit for heart disease, cancer, or mortality; minimal effect on colds. | Higher kidney stone risk at high doses. Increases iron absorption, so use caution in iron overload. | 1, 2, 6 |
| 6 | Protein powder | Moderate for protein targets | Supports building and preserving muscle when dietary protein falls short. | Caution in advanced CKD. Choose third-party-tested products to limit contaminants. | — |
| 7 | Creatine | Strong performance; emerging for aging and cognition | Large body of randomized trials showing a robust benefit for strength and performance. | Very favorable safety across 685 trials; no kidney harm in healthy people. Mild GI upset and water weight. Monohydrate is the best-studied form. | 7, 8 |
| 8 | Probiotics | Weak–moderate | Low-quality evidence for fewer colds and GI symptoms; effects are strain-specific. | Avoid in critically ill or immunocompromised patients (rare bloodstream infections). Results don’t carry over between strains. | 9 |
| 9 | Vitamin B12 / B-complex | Strong for deficiency | Clear benefit in true deficiency: vegans, metformin or PPI users, older adults, pernicious anemia. | No benefit if levels are normal. “Energy” claims are unsupported without a deficiency. | 2, 4 |
| 10 | Calcium | Moderate for bone; weak otherwise | Useful in the bone density and osteoporosis context; no heart or mortality benefit. | Higher kidney stone risk. Take apart from iron and levothyroxine. Cardiovascular effects are debated. | 1, 2, 4 |
| 11 | Zinc | Moderate | Lozenges at 75 mg/day or more shorten colds (not severity); results vary between trials. | Long-term high doses cause copper deficiency. Nasal zinc is linked to loss of smell. GI upset. | 6, 10, 11 |
| 12 | Melatonin | Moderate sleep onset; weak for arthritis | Modest help falling asleep and with jet lag; arthritis data are only preclinical. | Next-day grogginess. Actual content varies by product. Caution with sedatives. | 12, 13 |
| 13 | Fiber (psyllium) | Moderate moderate to strong | Improves regularity, modestly lowers LDL cholesterol, and helps with fullness. | Take apart from other medications (it can block absorption). Increase slowly to avoid bloating. | — |
| 14 | Collagen | Weak | Mostly small, industry-linked trials for skin and joints; no high-quality confirmation. | Generally safe. Efficacy claims are not established. | — |
| 15 | Turmeric / curcumin | Weak–moderate | Some systematic-review support for arthritis pain and lipids; underlying trials are low quality. | AAOS rates it “limited” for knee arthritis. Reports of liver injury. Poorly absorbed. | 14, 15 |
| 16 | Iron | Strong for deficiency | Clear benefit in iron-deficiency anemia. | Use only with confirmed deficiency; unexplained deficiency needs a GI workup. Constipation. Risk of iron overload. | 4 |
| 17 | Elderberry | Weak–moderate | Reviews suggest shorter cold and flu duration, based on small, low-quality trials. | Appears safe short-term. No evidence of harmful immune overstimulation. | 16, 17 |
| 18 | Green tea extract | Weak strong harm signal | Minimal weight-loss benefit. | Well-documented liver injury, a leading cause of supplement-related liver damage, worse when taken fasting. Reduces iron absorption. | 18–21 |
| 19 | CoQ10 | Weak–moderate | May reduce all-cause mortality in heart failure; statin muscle-ache data are mixed and unconfirmed in trials. | Generally safe. May weaken warfarin’s effect. Modest blood pressure lowering. | 3, 22–24 |
| 20 | Ashwagandha | Weak | Short-term signals for stress and sleep from small trials. | Reports of liver injury. Avoid in pregnancy, autoimmune disease, and hormone-sensitive prostate cancer. Affects thyroid; strengthens sedatives. Monitor liver and thyroid tests. | 25–28 |
| 21 | Prenatal / folic acid | Strong | Folic acid clearly prevents neural tube defects. | Standard of care before and during pregnancy. Make sure the dose is adequate. | 2, 4 |
| 22 | Glucosamine / chondroitin | Weak | Inconsistent, limited benefit for arthritis pain and function. | AAOS rates it “limited.” Glucosamine may strengthen warfarin’s effect. Usually well tolerated. | 15 |
| 23 | Electrolytes | Context-dependent | Useful for fluid losses from exertion, heat, or low-carb eating. | High-sodium formulas are risky with high blood pressure, heart failure, or CKD. | — |
| 24 | Vitamin K2 | Weak | Paired with vitamin D for bone and arterial calcium; limited outcome data. | Counteracts warfarin and can lower INR. Keep intake consistent if you take a blood thinner. | 29 |
| 25 | Apple cider vinegar (gummies) | Very weak | No robust evidence for weight or blood sugar benefit. | Tooth enamel erosion and GI upset. Gummies often contain added sugar. | — |
| 26 | Biotin | Weak unless deficient | Benefits hair and nails only in true biotin deficiency. | Interferes with many lab tests (troponin, TSH, thyroid, hormones) and can cause false results. Stop before blood work. | — |
| 27 | Lion’s mane | Very weak | Only small, preliminary cognition data; no confirmed benefit. | Safety data are limited. | — |
| 28 | Berberine | Moderate surrogate markers | An umbrella review found improved glucose, lipids, weight, and blood pressure versus control, from low-quality meta-analyses. | Adds to the effect of diabetes medicines (low blood sugar). Strongly inhibits drug-metabolizing enzymes, so many interactions. GI effects. Avoid in pregnancy. | 30, 31 |
| 29 | Greens powders | Very weak | No controlled efficacy data; not a substitute for vegetables. | May contain vitamin K (warfarin) and unstandardized ingredients. | — |
| 30 | Lutein / zeaxanthin | Strong for macular degeneration | AREDS2 showed slower progression to late macular degeneration; it replaced beta-carotene in the formula. | Proven only for intermediate or advanced macular degeneration, not general screen strain. Smokers must avoid beta-carotene. | 5, 32–34 |
Swipe sideways to see the full table on a phone. Ratings summarize published evidence for generally healthy adults and are not individual medical advice.
Six safety flags to know before you buy
“Natural” doesn’t mean harmless. These are the issues we screen for most often when patients bring in their supplements.
Liver injury
Green tea extract, especially in weight-loss products taken on an empty stomach, and ashwagandha are both documented causes of supplement-related liver injury. Stop and call us if you notice dark urine, yellowing skin, or abdominal pain.
Blood thinners
Vitamin K2, high-dose omega-3, glucosamine, CoQ10, greens powders, and berberine can all change how warfarin works or raise bleeding risk.
False lab results
High-dose biotin, common in hair, skin, and nail products, distorts many blood tests, including troponin, thyroid, and hormone panels. Tell us you take it and hold it before lab work.
Diabetes medications
Berberine, marketed as “nature’s Ozempic,” combined with sulfonylureas or insulin can cause low blood sugar. It also interacts with many drugs through liver enzymes.
Beta-carotene in smokers
Smokers should avoid beta-carotene because of a lung cancer signal in AREDS2 and USPSTF data. Check multivitamin and eye-vitamin labels.
Kidney and heart conditions
Magnesium and high-sodium electrolyte mixes need caution in kidney disease or heart failure. High-dose vitamin C and calcium raise kidney stone risk.
Protecting muscle as you age
Two supplements stand out
For preserving muscle, creatine and whey protein have the strongest combination of efficacy and safety on this list. Most “wellness” products, including greens powders, collagen, apple cider vinegar, and lion’s mane, have little supporting evidence.
Creatine monohydrate
Strong trial evidence for strength and performance, with emerging data for healthy aging. Safety has been reviewed across 685 clinical trials with no kidney harm in healthy people.
Whey protein
Helps you reach daily protein targets when food alone falls short. Choose a third-party-tested product, and talk with us first if you have advanced kidney disease.
Both work best alongside regular resistance training.
Frequently asked questions
Do healthy adults need a daily multivitamin?
For most healthy adults who are not deficient, no. A US Preventive Services Task Force review found no reduction in death or heart disease from multivitamins. The best reasons to supplement are a documented deficiency or a specific need, such as pregnancy.
Which supplements have the strongest evidence?
Creatine for strength and performance, folic acid before and during pregnancy, lutein and zeaxanthin for intermediate or advanced macular degeneration, and vitamin B12, iron, or vitamin D when a blood test shows a deficiency.
Which supplements can damage the liver?
Green tea extract, especially in weight-loss products taken on an empty stomach, and ashwagandha are both documented causes of supplement-related liver injury. Turmeric has also been linked to liver injury reports.
Can supplements affect my blood test results?
Yes. High-dose biotin can cause false results on many lab tests, including troponin, thyroid, and hormone tests. Tell your doctor you take it and stop it before blood work.
Which supplements interact with blood thinners?
Vitamin K2, high-dose omega-3, glucosamine, CoQ10, greens powders, and berberine can change how warfarin works or raise bleeding risk. Review every supplement with your doctor if you take an anticoagulant.
What are the best supplements to protect muscle as I age?
Creatine monohydrate and whey protein have the strongest combination of efficacy and safety for muscle preservation. Both work best alongside regular resistance training.
Is berberine really “nature’s Ozempic”?
No. Berberine modestly improves blood sugar, cholesterol, and weight in low-quality studies, but it is not equivalent to GLP-1 medications. It can cause low blood sugar with diabetes medicines and interacts with many other drugs.
References
- O’Connor EA, Evans CV, Ivlev I, et al. Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2022;327(23):2334-2347.
- Jin J. Vitamins and Minerals to Prevent Cardiovascular Disease and Cancer. JAMA. 2022;327(23):2364.
- An P, Wan S, Luo Y, et al. Micronutrient Supplementation to Reduce Cardiovascular Risk. J Am Coll Cardiol. 2022;80(24):2269-2285.
- Manson JE, Bassuk SS. Vitamin and Mineral Supplements: What Clinicians Need to Know. JAMA. 2018;319(9):859-860.
- Agrón E, Mares J, Clemons TE, et al. Dietary Nutrient Intake and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2. Ophthalmology. 2021;128(3):425-442.
- Wang MX, Win SS, Pang J. Zinc Supplementation Reduces Common Cold Duration Among Healthy Adults: A Systematic Review of Randomized Controlled Trials With Micronutrients Supplementation. Am J Trop Med Hyg. 2020;103(1):86-99.
- Kreider RB, Gonzalez DE, Hines K, Gil A, Bonilla DA. Safety of Creatine Supplementation: Analysis of the Prevalence of Reported Side Effects in Clinical Trials and Adverse Event Reports. J Int Soc Sports Nutr. 2025;22(sup1):2488937.
- Andres S, Ziegenhagen R, Trefflich I, et al. Creatine and Creatine Forms Intended for Sports Nutrition. Mol Nutr Food Res. 2017;61(6).
- Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med. 2019;25(5):716-729.
- Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013.
- Luan R, Ding D, Xue Q, et al. Protective role of zinc in the pathogenesis of respiratory diseases. Eur J Clin Nutr. 2023;77(4):427-435.
- Xiong Z, Peng G, Deng J, et al. Therapeutic Targets and Potential Delivery Systems of Melatonin in Osteoarthritis. Front Immunol. 2024;15:1331934.
- Lu KH, Lu PW, Lu EW, et al. The potential remedy of melatonin on osteoarthritis. J Pineal Res. 2021;71(3):e12762.
- Pagano E, Romano B, Izzo AA, Borrelli F. The Clinical Efficacy of Curcumin-Containing Nutraceuticals: An Overview of Systematic Reviews. Pharmacol Res. 2018;134:79-91.
- American Academy of Orthopaedic Surgeons. Management of Osteoarthritis of the Knee (Non-Arthroplasty): Evidence-Based Clinical Practice Guideline. 2021.
- Wieland LS, Piechotta V, Feinberg T, et al. Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review. BMC Complement Med Ther. 2021;21(1):112.
- 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.
- Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal Products and the Liver: A Review of Adverse Effects and Mechanisms. Gastroenterology. 2015;148(3):517-532.
- Ma ZT, Shi Z, Xiao XH, Wang JB. New Insights into Herb-Induced Liver Injury. Antioxid Redox Signal. 2023;38(16-18):1138-1149.
- Navarro VJ, Khan I, Björnsson E, et al. Liver Injury From Herbal and Dietary Supplements. Hepatology. 2017;65(1):363-373.
- Cladis DP, Weaver CM, Ferruzzi MG. (Poly)phenol toxicity in vivo following oral administration: A targeted narrative review of (poly)phenols from green tea, grape, and anthocyanin-rich extracts. Phytother Res. 2022;36(1):323-335.
- Gasmi A, Bjørklund G, Mujawdiya PK, et al. Coenzyme Q10 in Aging and Disease. Crit Rev Food Sci Nutr. 2024;64(12):3907-3919.
- Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P. Coenzyme Q10 Supplementation in Aging and Disease. Front Physiol. 2018;9:44.
- Saha SP, Whayne TF. Coenzyme Q-10 in Human Health: Supporting Evidence? South Med J. 2016;109(1):17-21.
- Kumar A, Sah BK, Ahmad F, Jamwal V, Sahu SK. Potential Adverse Effects of Ashwagandha: A Critical Review of Preclinical and Clinical Evidence. Phytother Res. 2026;40(8):4913-4931.
- Brendler T, Al-Mondhiry R, Lang L, et al. Ashwagandha: Is It Safe? Part 1: A Regulatory Review. Phytother Res. 2026;40(8):4845-4857.
- Li L, Zhang X, Hao J, et al. Evaluating the Safety of Ashwagandha as a Food Additive: A Focus on Reproductive, Thyroid, and Immune System Effects. Phytother Res. 2026;40(8):4862-4879.
- Nobari H, Parnian-Khajehdizaj N, Johnson K, Ramos-Álvarez JJ. Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health. Nutr Metab. 2026;23(1):39.
- Talasaz AH, McGonagle B, HajiQasemi M, et al. Pharmacokinetic and Pharmacodynamic Interactions Between Food or Herbal Products and Oral Anticoagulants: Evidence Review, Practical Recommendations, and Knowledge Gaps. Semin Thromb Hemost. 2025;51(5):560-571.
- Li Z, Wang Y, Xu Q, et al. Berberine and health outcomes: An umbrella review. Phytother Res. 2023;37(5):2051-2066.
- Sanlier N, Ozler E, Karanfil N. Potential Health Effects of the Natural Alkaloid Berberine: A Narrative Review. Nutr Rev. 2026;84(10):2086-2105.
- Fleckenstein M, Keenan TDL, Guymer RH, et al. Age-related macular degeneration. Nat Rev Dis Primers. 2021;7(1):31.
- Vemulakonda GA, Bailey ST, Kim SJ, et al. Age-Related Macular Degeneration Preferred Practice Pattern. Ophthalmology. 2025;132(4):P1-P74.
- Chew EY, Clemons TE, Agrón E, et al. Long-term Outcomes of Adding Lutein/Zeaxanthin and Omega-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28. JAMA Ophthalmol. 2022;140(7):692-698.
This page is for general education and is not a substitute for personal medical advice. Talk with your doctor before starting or stopping any supplement, especially if you are pregnant, take prescription medications, or have a chronic condition.