Vitamin and Mineral Supplements: What Clinicians Need to Know

Despite this enthusiasm, most randomized clinical trials of vitamin and mineral supplements have not demonstrated clear benefits for primary or secondary prevention of chronic diseases not related to nutritional deficiency. Indeed, some trials suggest that micronutrient supplementation in amounts that exceed the recommended dietary allowance (RDA)—eg, high doses of beta carotene, folic acid, vitamin E, or selenium—may have harmful effects, including increased mortality, cancer, and hemorrhagic stroke.²

In this Viewpoint, we provide information to help clinicians address frequently asked questions about micronutrient supplements from patients, as well as promote appropriate use and curb inappropriate use of such supplements among generally healthy individuals. Importantly, clinicians should counsel their patients that such supplementation is not a substitute for a healthful and balanced diet and, in most cases, provides little if any benefit beyond that conferred by such a diet.

Clinicians should also highlight the many advantages of obtaining vitamins and minerals from food instead of from supplements. Micronutrients in food are typically better absorbed by the body and are associated with fewer potential adverse effects.^2,3 A healthful diet provides an array of nutritionally important substances in biologically optimal ratios as opposed to isolated compounds in highly concentrated form. Indeed, research shows that positive health outcomes are more strongly related to dietary patterns and specific food types than to individual micronutrient or nutrient intakes.³

Although routine micronutrient supplementation is not recommended for the general population, targeted supplementation may be warranted in high-risk groups for whom nutritional requirements may not be met through diet alone, including people at certain life stages and those with specific risk factors

The evidence is clear that women who may become pregnant or who are in the first trimester of pregnancy should be advised to consume adequate folic acid (0.4-0.8 mg/d) to prevent neural tube defects. Folic acid is one of the few micronutrients more bioavailable in synthetic form from supplements or fortified foods than in the naturally occurring dietary form (folate).² Prenatal multivitamin/multimineral supplements will provide folic acid as well as vitamin D and many other essential micronutrients during pregnancy. Pregnant women should also be advised to eat an iron-rich diet. Although it may also be prudent to prescribe supplemental iron for pregnant women with low levels of hemoglobin or ferritin to prevent and treat iron-deficiency anemia, the benefit-risk balance of screening for anemia and routine iron supplementation during pregnancy is not well characterized.²

Supplemental calcium may reduce the risk of gestational hypertension and preeclampsia, but confirmatory large trials are needed.² Use of high-dose vitamin D supplements during pregnancy also warrants further study.² The American College of Obstetricians and Gynecologists has developed a useful patient handout on micronutrient nutrition during pregnancy.⁴

The American Academy of Pediatrics recommends that exclusively or partially breastfed infants receive (1) supplemental vitamin D (400 IU/d) starting soon after birth and continuing until weaning to vitamin D–fortified whole milk (≥1 L/d) and (2) supplemental iron (1 mg/kg/d) from 4 months until the introduction of iron-containing foods, usually at 6 months.⁵ Infants who receive formula, which is fortified with vitamin D and (often) iron, do not typically require additional supplementation. All children should be screened at 1 year for iron deficiency and iron-deficiency anemia.

Healthy children consuming a well-balanced diet do not need multivitamin/multimineral supplements, and they should avoid those containing micronutrient doses that exceed the RDA. In recent years, ω-3 fatty acid supplementation has been viewed as a potential strategy for reducing the risk of autism spectrum disorder or attention-deficit/hyperactivity disorder in children, but evidence from large randomized trials is lacking.²

With respect to vitamin B₁₂, adults aged 50 years and older may not adequately absorb the naturally occurring, protein-bound form of this nutrient and thus should be advised to meet the RDA (2.4 μg/d) with synthetic B₁₂found in fortified foods or supplements.⁶ Patients with pernicious anemia will require higher doses.

Regarding vitamin D, currently recommended intakes (from food or supplements) to maintain bone health are 600 IU/d for adults up to age 70 years and 800 IU/d for those aged older than 70 years.⁷ Some professional organizations recommend 1000 to 2000 IU/d, but it has been widely debated whether doses above the RDA offer additional benefits. Ongoing large-scale randomized trials (NCT01169259 and ACTRN12613000743763) should help to resolve continuing uncertainties soon.

With respect to calcium, current RDAs are 1000 mg/d for men aged 51 to 70 years and 1200 mg/d for women aged 51 to 70 years and for all adults aged older than 70 years.⁷ Given recent concerns that calcium supplements may increase the risk for kidney stones and possibly cardiovascular disease, patients should aim to meet this recommendation primarily by eating a calcium-rich diet and take calcium supplements only if needed to reach the RDA goal (often only about 500 mg/d in supplements is required).² A recent meta-analysis suggested that supplementation with moderate-dose calcium (<1000 mg/d) plus vitamin D (≥800 IU/d) might reduce the risk of fractures and loss of bone mass density among postmenopausal women and men aged 65 years and older.²

Multivitamin/multimineral supplementation is not recommended for generally healthy adults.⁸ One large trial in US men found a modest lowering of cancer risk,⁹ but the results require replication in large trials that include women and allow for analysis by baseline nutrient status, a potentially important modifier of the treatment effect. An ongoing large-scale 4-year trial (NCT02422745) is expected to clarify the benefit-risk balance of multivitamin/multimineral supplements taken for primary prevention of cancer and cardiovascular disease.

When reviewing medications with patients, clinicians should ask about use of micronutrient (and botanical or other dietary) supplements in counseling about potential interactions. For example, supplemental vitamin K can decrease the effectiveness of warfarin, and biotin (vitamin B₇) can interfere with the accuracy of cardiac troponin and other laboratory tests. Patient-friendly interaction checkers are available free of charge online (search forinteraction checkers on drugs.com, WebMD, or pharmacy websites).

Clinicians and patients should also be aware that the US Food and Drug Administration is not authorized to review dietary supplements for safety and efficacy prior to marketing. Although supplement makers are required to adhere to the agency’s Good Manufacturing Practice regulations, compliance monitoring is less than optimal. Thus, clinicians may wish to favor prescription products, when available, or advise patients to consider selecting a supplement that has been certified by independent testers (ConsumerLab.com, US Pharmacopeia, NSF International, or UL) to contain the labeled dose(s) of the active ingredient(s) and not to contain microbes, heavy metals, or other toxins. Clinicians (or patients) should report suspected supplement-related adverse effects to the Food and Drug Administration via MedWatch, the online safety reporting portal. An excellent source of information on micronutrient and other dietary supplements for both clinicians and patients is the website of the Office of Dietary Supplements of the National Institutes of Health

Conflict of Interest Disclosures: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Manson and Bassuk reported that their research division conducts randomized clinical trials of several vitamins and minerals. The Vitamin D and Omega-3 Trial (VITAL) is sponsored by the National Institutes of Health but the vitamin D is donated by Pharmavite. In COSMOS, the multivitamins are donated by Pfizer. Both authors collaborate on these studies.