Supplements: Which Ones Have Evidence and Which Do Not

You stand in the pharmacy aisle. There are hundreds of bottles that promise better energy, stronger immunity, a healthier heart, and sharper memory. Some cost more than your prescriptions. You want to know which ones are worth it.

This guide sorts supplements by the strength of the evidence. It also explains how supplements are regulated in Canada and the US, and how they can cause harm.

How supplements are regulated

The rules are different from prescription drugs.

• In the US, supplements are regulated as a type of food. The FDA does not approve them for safety or effectiveness before they are sold. Companies are responsible for making sure their products are safe and their labels are truthful.[4]
• In Canada, vitamins, minerals, and herbal products are called natural health products. They need a product licence from Health Canada before sale. Approved products show an 8-digit NPN (Natural Product Number) or DIN-HM (Homeopathic Medicine Number) on the label.
• In both countries, a licence or label claim is not the same as proof from large clinical trials.

Third-party seals from independent testing groups can show that a product contains what the label says. They do not show that it works.

What your doctor looks at

Clinicians ask two questions. Do you have a deficiency or a specific need? And do trials show a benefit for people like you?

Strong evidence in specific situations

• Folic acid before pregnancy. The USPSTF recommends that anyone who plans to or could become pregnant take a daily supplement with 0.4 to 0.8 mg (400 to 800 micrograms) of folic acid. This lowers the risk of neural tube defects, which are serious birth defects of the brain and spine.[2] Health Canada also recommends a daily multivitamin with folic acid for anyone who could become pregnant.
• Proven deficiency. Vitamin B12, iron, and vitamin D supplements help when a blood test shows you are low. People who eat no animal foods, people with some stomach or bowel conditions, and some people who take metformin long term are at higher risk of low B12.
• Specific medical uses. Some clinicians recommend fiber supplements such as psyllium for constipation, or specific supplements for certain eye, bone, or blood conditions. These uses depend on your diagnosis.

Little or no evidence for prevention in healthy adults

In 2022, the USPSTF reviewed trials of vitamins and minerals taken to prevent heart disease and cancer.[1]

• Multivitamins: the evidence was insufficient to recommend for or against them.
• Single vitamins and pairs, such as vitamin C, vitamin D, calcium, and selenium: the evidence was also insufficient.
• Beta-carotene: the USPSTF recommends against it. In trials, it raised lung cancer risk in people who smoke or had asbestos exposure.[1]
• Vitamin E: the USPSTF recommends against it, because it showed no benefit.[1]

These recommendations are for healthy adults who are not pregnant. They do not apply to people with a known deficiency.

Vitamin D and fish oil: the VITAL trial

VITAL was a large US trial of about 25,900 adults without known heart disease or cancer. Participants took vitamin D (2,000 IU a day) or a placebo, and also fish oil (omega-3) or a placebo, for a median of about 5 years.[3]

• Vitamin D did not lower the rate of invasive cancer or major heart and blood vessel events.[3]
• Fish oil also did not lower the main heart outcome in this healthy group.

Vitamin D is still important for people who are deficient and for bone health in some groups. The trial shows that extra vitamin D does not prevent these diseases in people who are not deficient.

Popular products with weak or mixed evidence

Many products sold for immunity, energy, memory, joint health, or weight loss have small, mixed, or no trial evidence. NIH experts advise asking for proof from good studies, not from testimonials or advertising.[5]

How supplements can harm

• Interactions: St. John's wort can make birth control, blood thinners, HIV drugs, transplant drugs, and some heart drugs less effective.[6]
• Bleeding risk: high doses of fish oil, vitamin E, and ginkgo may add to the effect of blood thinners.
• Toxic doses: too much vitamin A, vitamin D, or iron can cause harm.
• Surgery: some supplements need to stop before surgery. Tell your surgical team about everything you take.[5]
• Hidden ingredients: some products, especially for weight loss, muscle building, and sexual performance, have been found to contain prescription drugs not listed on the label.[4]

Questions to ask your clinician

• Do I have a deficiency that a supplement would treat?
• Is there good trial evidence for this supplement for someone like me?
• Could this supplement interact with my medicines?
• What dose is safe for me, and what is too much?
• Should I take folic acid or a prenatal vitamin now?
• Should I stop any supplements before surgery or a procedure?

When to get care quickly

Call 911 or go to the emergency department if, after taking a supplement, you have swelling of the face or throat, trouble breathing, chest pain, a very fast heartbeat, yellow skin or eyes, or signs of bleeding such as vomiting blood or black stools. If a child swallows an iron product or adult vitamins, call a poison control center right away.

Bottom line

A few supplements have strong evidence: folic acid before pregnancy, and vitamins or minerals that treat a proven deficiency. For healthy adults, trials show little benefit from multivitamins, vitamin D, or fish oil for preventing heart disease or cancer. Beta-carotene and vitamin E are not recommended for that purpose. Treat supplements like medicines, and tell your pharmacist about all of them.

Primary AI can show you the guideline and study sources behind this topic in plain language, so you can bring better questions to your appointment.