Vitamins and Minerals

Vitamins (e.g., vitamin A, C, D, E, K, and the B vitamins) are groups of chemically diverse organic compounds that are essential or conditionally essential to maintaining normal metabolism.² Minerals are inorganic substances that humans also need to maintain function (e.g., calcium, iron, zinc).³ Vitamins and minerals are primarily obtained from nutrient-dense foods and beverages, but are also available in the form of supplements.⁴ Vitamins and minerals can be combined, with or without other substances, in multivitamin or multimineral supplements. In the United States, there is no standardized or regulatory definition for multivitamins or multiminerals with respect to required components or doses, thus these terms can refer to a wide variety of products available on the market.⁵ For the purposes of this review, we use the term multivitamin to refer to any three or more vitamins or minerals, with minimal added herbs, hormones, enzymes, or drugs, each at a dose less than the tolerable upper intake level, as determined by the Food and Nutrition Board.⁶ Upper intake levels are the maximum daily intake unlikely to cause adverse health effects.^{7, 8} While supplements can be taken to combat various vitamin or mineral deficiencies, this report specifically evaluates vitamin and mineral supplementation in populations without known chronic disease or known nutritional deficiencies.

Use of Vitamin and Mineral Supplements in the United States

Dietary supplementation is a $30 billion industry in the United States, with over 90,000 products on the market.⁹ In the United States, the regulation of dietary supplements is less stringent than for over-the-counter or prescription drugs. According to the Food and Drug Administration (FDA), supplements—unlike drugs—are not intended to treat, diagnose, prevent, or cure diseases.¹⁰ The FDA requires that manufacturers submit safety data only for ingredients introduced in the US as a dietary supplement after 1993, but otherwise does not review dietary supplements for safety and effectiveness prior to marketing.¹¹ Additionally, studies have found that the content of vitamins and minerals may not be accurate to the package labeling.¹²

According to 2011–2014 National Health and Nutrition Examination Survey (NHANES) data, over half (52%) of surveyed US adults (n=11,024) reported using at least one dietary supplement in the past 30 days with 31 percent reported using a multivitamin-mineral supplement.¹³ Dietary supplement use varies by age, gender, race, and ethnicity, as well as socioeconomic characteristics, such as educational attainment and income (Table 1). The prevalence of dietary supplement use increases with age, with 36 percent of adults aged 19–30 years, 45 percent of adults aged 31–50 years, 63 percent of adults aged 51–70 years, and 75 percent of adults aged 71 years or older reporting supplement use in the past 30 days. Women are more likely to report using dietary supplements than men (59% vs. 45%, respectively), and White people are more likely to report using dietary supplements than people of other racial and ethnic background (58%, vs. 40% of Black, 35% of Hispanic, and 54% of Asian American persons). Dietary supplement use increases with education and income (Table 1).⁹ Older data (2007-2011) from a trade group report that the reasons most often cited for supplement use were for overall health and wellness (58%) and to fill nutrient gaps in the diet (42%).¹⁴

Table 1

Past 30-Day Use of Any Dietary Supplement or Multivitamin-Minerals by Demographic and Socioeconomic Characteristics (NHANES 2011–2014; N=11,024).

Prevalence and Burden of CVD and Cancer in the United States

Cardiovascular disease and cancer are the two leading causes of death¹⁵ and combined account for approximately half of deaths in the US annually.¹⁶ According to 2015-2018 NHANES data, 26.1 million persons in the U.S. have some form of cardiovascular disease (excluding hypertension).¹⁷ Cardiovascular disease accounted for 803,191 deaths in the U.S. in 2018, approximately one of every three deaths.¹⁶ The prevalence of and mortality from cardiovascular disease (CVD) varies substantially by age, race/ethnicity, and socioeconomic factors.¹⁸ As shown in Table 2, heart disease and stroke are most common among older adults, males, and low socioeconomic status groups. The prevalence rates of CVD, and notably stroke, are particularly high among Black Americans and American Indian/Alaska Native compared to other races and ethnicities.^{16, 18, 19} Similar to CVD morbidity, mortality from CVD is more common in men than women (age-adjusted mortality rate of 261.9 vs. 177.5 per 100,000 population, respectively), and varies by race, with the highest mortality rate among Black Americans (290.1), followed by Pacific Islander Americans (225.3), White Americans (218.4), Native North Americans (188.8), Hispanic Americans (156.7), and Asian Americans (122.8).¹⁶

Table 2

Age-Adjusted Prevalence (Percentage) of Participant-Reported Cancers and Cardiovascular Disease (NHIS 2018).

In 2018, an estimated 1.7 million individuals were diagnosed with cancer in the United States.²⁰ The annual age-adjusted incidence rate for any cancer was 447.9 per 100,000 individuals. Cancer is the second leading cause of death in the United States, accounting for 21.1 percent of all deaths in 2018.¹⁶ The overall age-adjusted mortality rate for any cancer was 158.2 per 100,000 individuals, with a median age at death of 72 years in 2013–2017.²¹ Black men have the highest rates of cancer incidence in any gender and racial/ethnic group (547.6 per 100,000 population) (Table 3).²² Rates of cancer incidence are lowest in Asian American and Pacific Islander men and women (combined, 296.5 and 295.7 per 100,000 population, respectively).²² The leading incident cancers in men are prostate (108.1 per 100,000), lung (69.5 per 100,000), and colorectal (45.1 per 100,000) and in women are breast (126.8 per 100,000), lung (51.8 per 100,000), and colorectal (34.4 per 100,000).²² Similarly, cancer mortality rates differ by gender, with men being more likely to die from cancer than women.¹⁶ Black men and women have the highest total cancer mortality and the highest mortality rates for most major cancer sites.²²

Table 3

Age-Standardized Cancer Incidence and Mortality per 100,000 Population by Sex and Race/Ethnicity (SEER 2012–2016 for Incidence and 2013–2017 for Mortality).

Role of Vitamins and Minerals in the Prevention of CVD and Cancer

Despite the differences in their clinical manifestations, CVD and cancer share several risk and etiologic factors, including age, alcohol use, smoking status, poor nutrition, sedentary behavior, and obesity.²³ Inflammation and oxidative stress, both prime targets of vitamin and mineral supplements, appear to account for at least part of this overlap in risk factors between diseases.²⁴ Another possible common pathway for CVD and cancer etiology is impaired regulation of methionine metabolism and methylation of a variety of biochemical targets.^25–29 Several dietary supplements are known to have antioxidant and anti-inflammatory effects or influence methionine metabolism. This has served as the rationale for proposing dietary supplements as an effective means to prevent both CVD and cancer.

Vitamins and minerals might protect against oxidative damage by neutralizing free radicals and other reactive species and thus reduce both CVD and cancer risk. Fat-soluble antioxidant vitamins such as vitamin E circulate principally in lipoproteins, especially LDL. Oxidized LDL is highly atherogenic and vitamin E protects against this oxidation.³⁰ To maintain vitamin E in its antioxidant or reduced state, however, circulating, water-soluble antioxidants such as vitamin C are required. Natural, enzymatic antioxidants catalyze the reactions that suppress free radicals and peroxide, and contain copper, zinc, and manganese as integral parts of their structure, providing a rationale for supplementing with minerals. Low levels of vitamin B12 and folate that participate in DNA synthesis may result in deficiency of methionine and contribute to aberrant DNA synthesis and carcinogenesis.^31–33 Also, it has been demonstrated that increased levels of homocysteine, an amino acid formed by demethylation of methionine, is associated with increased risk of coronary heart disease events.³⁴ Vitamin E (alpha-tocopherol), zinc, and vitamin A are supplements that are thought to inhibit inflammation. Beta-carotene is a precursor vitamin, or provitamin, that the body converts into vitamin A. While vitamin A has an upper limit due to the risk of toxicity at high doses, beta-carotene has not been shown to cause toxicity and therefore does not have a defined upper limit.⁷

Regular human exposure to vitamins and minerals is through diet,⁴ which includes a vast array of micronutrients that interact in complex ways with each other and with macronutrients such as fiber and fatty acids.^35–37 The existence of such interactions, their mechanisms, and effects are often unknown or understudied.³³ In addition, variability in individuals’ absorption and metabolization of food may influence the effects of these nutrients. As such, multivitamins cannot mimic the content of a healthful diet that includes a wide variety of unprocessed foods. Additionally, the chemical structure of single vitamin supplements may vary substantially from what is found in whole foods, which could alter biological impacts.^{38, 39} The importance of a supplement’s chemical form and potential vitamin-vitamin interactions can be exponentially expanded when we consider a supplement’s potential interactions with other nutrients, supplements, and medications.

Current Clinical Practice in the United States and Recommendations of Other Organizations

The 2020–2025 US Dietary Guidelines recommend that nutrient needs be met primarily from nutrient-dense foods and beverages because, in addition to vitamins and minerals, they contain other health-promoting components with no or little added sugars, saturated fat, and sodium.⁴ It is further noted that in some cases, fortified foods and dietary supplements may be useful in providing one or more nutrients that otherwise may be consumed in less than recommended amounts. Similarly, other organizations including the Academy of Nutrition and Dietetics (2018);⁴⁰ World Cancer Research Fund and American Institute for Cancer Research (2018);⁴¹ National Osteoporosis Foundation and American Society for Preventive Cardiology (2017);⁴² and the American Heart Association (2014)⁴³ have guidelines or positions recommending that healthy adults meet their nutrient needs primarily through a healthy diet, and that vitamins should not be used for CVD or cancer prevention (Table 4). Varying slightly, the Canadian Cancer Society (2018) recommends that nutritional needs be met by a healthy diet with the exception of vitamin D, for which individuals should discuss supplementation during the fall and winter months with their physician, noting a possible role of vitamin D in cancer prevention.⁴⁴

Table 4

Recommendations From Other Organizations.

Contemporary and independently collected data on the prevalence with which health care professionals recommend vitamins and minerals for CVD and cancer prevention are sparse. Older data collected by a trade group suggest that it is common for a variety of health care providers to recommend vitamin and mineral supplements to their patients. A 2007 survey found that 72 percent of surveyed physicians (n=900), 82 percent of nurses (n=277), and 97 percent of registered dietitians (n=300) reported recommending supplemental vitamins and minerals to patients.^{45, 46} The most common reason physicians and nurses reported recommending supplements was for overall health and wellness (41% of physicians and 62% of nurses).⁴⁶ Supplements were also recommended for reasons related to bone health (41% of physicians and 58% of nurses, respectively), joint health (37% and 36%), flu or colds (24% and 39%), heart health (33% and 26%), immune health (19% and 36%), musculoskeletal pain (26% for both), and energy (19% and 25%).⁴⁴

Previous and Related USPSTF Recommendations

In 2014, the USPSTF concluded that there was insufficient evidence to assess the balance of benefits and harms associated with the use of multivitamins (I statement⁴⁷) and many single- or paired-nutrient supplements for the prevention of CVD or cancer (I statement).¹ The USPSTF recommended against supplementation with beta-carotene or vitamin E for the prevention of cardiovascular disease or cancer (Grade D recommendation).¹ The USPSTF found that there was adequate evidence that beta-carotene and vitamin E do not reduce the risk of cancer or CVD in healthy populations without known nutritional deficiencies, and that beta-carotene increases the risk of lung cancer and persons at increased risk for this condition.

The USPSTF has published other recommendations related to supplements for aims other than cancer or CVD prevention. Taken together, these are statements of evidence insufficiency or recommendations against supplementation with vitamin D. Specifically, the USPSTF conclusions include:

• For the prevention of fractures:⁴⁸

  • Insufficient evidence to recommend the use of any level of vitamin D and calcium for men and premenopausal women (I statement)
  • Insufficient evidence to recommend daily supplementation at doses greater than 400 IU for vitamin D and 1000 mg for calcium for postmenopausal women (I statement).
  • Adequate evidence that daily supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium is not effective for the primary prevention of fractures in postmenopausal women (Grade D recommendation).⁴⁸
• For the prevention of falls:⁴⁹ Adequate evidence that vitamin D supplementation in community-dwelling adults age 65 and older is not effective in preventing falls (Grade D recommendation).
• Screening of vitamin D deficiency in asymptomatic adults:⁵⁰ Insufficient evidence to recommend for or against screening for vitamin D deficiency in asymptomatic adults (I statement).
• For the prevention of cognitive decline in people with mild to moderate dementia or mild cognitive impairment:⁵¹ The systematic review supporting the 2020 recommendation for screening for cognitive impairment concluded that vitamin supplements did not improve global cognition or physical function in persons with mild to moderate dementia or mild cognitive impairment, with no clear increase in harms.

For the prevention of neural tube defects: The USPSTF found convincing evidence that folic acid supplementation in the periconceptional period provides substantial benefits in reducing the risk of neural tube defects in the developing fetus and recommends that women who are planning or capable of pregnancy take a daily supplement of 0.4 to 0.8 mg of folic acid daily for the prevention of congenital neural tube defects (Grade A recommendation).⁵²