What does science say about multivitamin and mineral supplementation?
Dietary supplement use is common in the United States, with more than half of the population using such products.,,, Similarly, a majority of health professionals, including physicians and dieticians, use dietary supplements themselves and recommend them to patients.,, Among supplement users, multivitamin and mineral supplements (MVMs) are the most commonly used type (71%) of dietary supplement.
Despite these trends, headlines seem to appear regularly over the question of whether taking MVMs will promote better health, with some articles purporting that supplements are a waste of money. Policy makers and many health professionals are often reluctant to recommend routine use of dietary supplements, in part because they are concerned that people will view the supplements as a substitute for a healthy diet, or that they will consume too much of a particular nutrient.
In this article, I get to the bottom of these controversies and present an array of data to help answer the question: are MVM supplements beneficial?
Clinical trials must consider nutrient status
The skeptics of dietary supplements often cite “null” studies that failed to show an effect of supplementation on a desired health outcome. In many cases, such studies also failed to assess the nutritional status of subjects at the beginning of the study. As Dr. Robert Heaney (Creighton University) notes, “Literally hundreds of studies of nutrient effects have reported null, or even adverse outcomes of nutrient interventions, almost always without reference to the basal status that prevailed in the study sample.” In other words, vitamin or mineral supplements may not be effective in these trials because nutrient intakes among the participants are already at adequate levels.,,
The National Institute of Health (NIH) Women’s Health Initiative (WHI) is an example of such a “null” study. Researchers, who were interested in studying the effects of calcium and vitamin D on the risk of bone fractures, randomly assigned women over the age of 50 to receive 1000 mg of calcium and 400 IU of vitamin D3 daily, or a placebo, for an average of seven years. They reported that “supplementation resulted in a small but significant improvement in hip bone density, but did not significantly reduce hip fracture.” While this study is still widely cited, there’s more to the story than meets the eye.
Digging into the WHI study, the authors disclose that the participants were allowed to continue personal supplementation with calcium and vitamin D throughout the study, whether they were in the placebo or the intervention group. In fact, the average calcium intake of participants at baseline exceeded 1000 mg per day, close to the recommended dietary allowance (RDA) of 1200 mg for women age 50 and up. It’s no wonder, then, that additional calcium and vitamin D had no significant effect.
When a subsequent analysis was confined to women who were not already taking calcium and vitamin D, quite a different conclusion was reached: daily supplementation reduced the risk of hip fracture by 40% after five years. Therefore, “Long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women.”
Considering eight different randomized controlled trials, the National Osteoporosis Foundation (NOF) stated that “Calcium and vitamin D supplements are highly cost effective, and expanded use could considerably reduce fractures and related costs.” The NOF also notes that “It is very difficult to get all the vitamin D you need from food alone. Most people must take vitamin D supplements to get enough to support bone health.”
“It is very difficult to get all the vitamin D you need from food alone. Most people must take vitamin D supplements to get enough to support bone health.”
B-vitamin levels, aging, and cognition
B vitamins (folate, vitamin B12, and vitamin B6) are important for the metabolism of homocysteine (Hcy), an amino acid derived from methionine. If folate and other B vitamins are inadequate, Hcy accumulates in the blood. This condition (known as hyperhomocysteinemia, or HHcy) is associated with an increased risk for many age-related diseases, including cognitive decline and dementia,,, which we all want to avoid! Thus there is great interest in determining whether B-vitamin supplementation helps lower Hcy and preserve cognitive function with age.
Folate deficiency is the most common cause of HHcy. The benefits of folate supplementation were clearly shown in a clinical study of men and women aged 50 to 70 years (with known HHcy) who were not already taking B-vitamin-containing supplements. Subjects with low serum vitamin B12 levels were excluded in order to focus on folate in this study. Individuals who met these criteria were randomized to receive folic acid (800 mg per day), or a placebo, for three years. Serum folate concentrations increased fivefold, and plasma Hcy levels decreased by 26%, in the supplemented group.
The outcomes of this study were striking. Compared with placebo, the group supplemented with folic acid had slower rates of decline in memory and cognitive function as measured by standardized tests. Remarkably, the memory performance of individuals who consumed the folic acid supplements was equivalent, on average, to that of someone who was 4.7 years younger! The researchers concluded that “Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.”
Remarkably, the memory performance of individuals who consumed the folic acid supplements was equivalent, on average, to that of someone who was 4.7 years younger !
Although folic acid improved memory in this study, the results did not imply that folate supplementation could reduce the risk of Alzheimer’s disease. But in studies of individuals over the age of 70 with HHcy who already had mild cognitive impairment, daily high-dose B-vitamin supplementation (800 mg folic acid, 500 mg vitamin B12, 20 mg vitamin B6) not only improved cognitive function, but also slowed the atrophy of specific brain regions that are a key component of the Alzheimer’s disease process.,,
Even with a balanced diet, it may be difficult to meet the RDA for folate (400 mg per day). The regular use of MVMs containing 400 mg folic acid, along with vitamins B6, B12, and other micronutrients, has been shown to help maintain normal Hcy levels in healthy adults.,, In fact, a recently-published study showed that folate and vitamin B12 supplementation in older adults was associated with a higher ratio of blood methionine to homocysteine, which in turn correlated with a reduced risk of brain atrophy and dementia.
Are you really getting enough nutrients from your diet?
The U.S. Dietary Guidelines recommend that individuals obtain essential nutrients by consuming a balanced and varied diet including plenty of fruits, vegetables, whole grains, and low-fat dairy products. In actuality, many of us do not achieve this goal on a daily basis. Let’s face it: the demands of modern life, including work, travel, stress, and family responsibilities, often make it difficult to achieve an optimal diet every day.
Nationwide surveys show that, although U.S. diets have improved slightly over the last decade,, fewer than one in 10 Americans meet the recommendations for fruit and vegetable consumption, and nutritional gaps are common. The U.S. Dietary Guidelines Advisory Committee specifically identified vitamins A, C, D, and E, calcium, magnesium, iron, potassium, and choline as “underconsumed nutrients” in the U.S. population.
Diets that eliminate or restrict entire food groups pose risks for micronutrient insufficiencies. Gluten-free diets, which eliminate wheat, rye, and barley, often have inadequate levels of vitamins B1, B12, and D, folate, calcium, iron, magnesium, and/or zinc.,, The Paleolithic (“Paleo”) diet, which eliminates dairy, grains, and legumes, may provide insufficient levels of B vitamins, calcium, iodine, and magnesium., Vegetarians, and especially vegans who eliminate dairy, eggs, and meat products, may have inadequate intakes of vitamins B12 and D, calcium, choline, iodine, iron, and zinc.,,,, Due to low calcium and vitamin D intake, vegans have an increased risk of osteoporosis and fractures, and may benefit from supplementation. Scientists also advise that vegans, and anyone who significantly limits their intake of animal-based foods, should consider vitamin B12 supplementation.
Inadequate micronutrient levels have been observed for popular weight loss diets,, including the Atkins, Ornish, South Beach, and DASH diets., Ketogenic (Keto) diets provide inadequate levels of the majority of essential micronutrients. MVMs can help adults satisfy their micronutrient needs in conjunction with various food patterns and diet plans.,,,
Pregnancy poses additional nutrient demands to support the health of the mother and fetus. Approximately 30% of pregnant women do not take MVMs or folate-containing supplements, and may suffer from micronutrient insufficiencies.,, Insufficient folate during pregnancy increases the risk of neural tube defects (NTDs) such as spina bifida,,,, and the intake of sufficient folic acid reduces the incidence of NTDs by 50 to 70% if taken before conception and during the first trimester of pregnancy. Thus the U.S. Preventive Services Task Force recommends that all women who are planning or capable of pregnancy take a daily supplement containing 400 to 800 μg of folic acid. A review of this recommendation notes that “habitual use of folic acid supplements is a more reliable method of ensuring adequate levels than diet.”
Adults who did not consume MVM supplements were found to have a 40% risk of any nutrient inadequacy, compared to only 14% of those who used full-spectrum MVMs.
Across the population, the use of MVMs has been shown to reduce the risk of insufficiency for most vitamins and minerals.,,,, Adults who did not consume MVM supplements were found to have a 40% risk of any nutrient inadequacy, compared to only 14% of those who used full-spectrum MVMs.
Is MVM supplementation safe?
A panel of 14 international experts in nutritional science and health care recently concluded that “Use of MVMs is one approach to ensure that adequate micronutrient needs are met in support of biological functions necessary to maintain health. Long-term use of MVMs, not exceeding the upper limit of recommended intakes, has been determined to be safe in healthy adults.”Click here to see References
 Dickinson A, et al. Consumer attitudes about the role of multivitamins and other dietary supplements: report of a survey. Nutr J. 2015 Jul 2;14:66.
 Gahche J, et al. Dietary supplement use among U.S. adults has increased since NHANES III (1988-1994). NCHS Data Brief. 2011 Apr;(61):1-8.
 Dickinson A, et al. Consumer usage and reasons for using dietary supplements: report of a series of surveys. J Am Coll Nutr. 2014;33(2):176-82.
 Kantor ED, et al. Trends in dietary supplement use among US adults from 1999-2012. JAMA. 2016 Oct 11;316(14):1464-74.
 Dickinson A, et al. Physicians and nurses use and recommend dietary supplements: report of a survey. Nutr J. 2009 Jul 1;8:29.
 Dickinson A, et al. Use of dietary supplements by cardiologists, dermatologists and orthopedists: report of a survey. Nutr J. 2011 Mar 3;10:20.
 Dickinson A, et al. Dietitians use and recommend dietary supplements: report of a survey. Nutr J. 2012 Mar 14;11:14.
 Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014 Jan;72(1):48-54.
 Morris MC, Tangney CC. A potential design flaw of randomized trials of vitamin supplements. JAMA. 2011 Apr 6;305(13):1348-9.
 Gröber U, Holick MF. Diabetes prevention: vitamin D supplementation may not provide any protection if there is no evidence of deficiency! Nutrients. 2019 Nov 4;11(11):2651.
 Jackson RD, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83.
 Prentice RL, et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int. 2013 Feb;24(2):567-80.
 Weaver CM, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 2016 Jan;27(1):367-76.
 Weaver CM, et al. Cost-benefit analysis of calcium and vitamin D supplements. Arch Osteoporos. 2019 Apr 30;14(1):50.
 National Osteoporosis Foundation. Calcium and vitamin D [Internet]. Arlington (VA): National Osteoporosis Foundation; 2018 [cited 2020 Jan 1]. Available from: https://www.nof.org/patients/treatment/calciumvitamin-d/
 de Jager CA. Critical levels of brain atrophy associated with homocysteine and cognitive decline. Neurobiol Aging. 2014 Sep;35 Suppl 2:S35-9.
 Agnew-Blais JC, et al. Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women’s Health Initiative Memory Study. J Acad Nutr Diet. 2015 Feb;115(2):231-41.
 Hughes CF, et al. B-vitamin intake and biomarker status in relation to cognitive decline in healthy older adults in a 4-year follow-up study. Nutrients. 2017 Jan 10;9(1):53.
 Durga J, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16.
 Douaud G, et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9523-8.
 Smith AD, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010 Sep 8;5(9):e12244.
 de Jager CA, et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600.
 Stanger O, et al. Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases. Z Kardiol. 2004 Jun;93(6):439-53.
 White DJ, et al. Effects of four-week supplementation with a multi-vitamin/mineral preparation on mood and blood biomarkers in young adults: a randomised, double-blind, placebo-controlled trial. Nutrients. 2015 Oct 30;7(11):9005-17.
 Wolters M, et al. Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years. Eur J Nutr. 2005 Mar;44(3):183-92.
 Van Oort FV, et al. Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am J Clin Nutr. 2003 May;77(5):1318-23.
 Hooshmand B, et al. Association of methionine to homocysteine status with brain magnetic resonance imaging measures and risk of dementia. JAMA psychiatry. 2019 Nov 1;76(11):1198-205.
 U S Department of Health and Human Services and U S Department of Agriculture. 2015-2020 Dietary Guidelines for Americans [Internet]. Washington (DC): U S Department of Health and Human Services; 2016 [cited 2020 Jan 1]. Available from: http://health.gov/dietaryguidelines/2015/
 Rehm CD, et al. Dietary intake among US adults, 1999-2012. JAMA. 2016 Jun 21;315(23):2542-53.
 Wang DD, et al. Trends in dietary quality among adults in the United States, 1999 through 2010. JAMA Intern Med. 2014 Oct;174(10):1587-95.
 Lee-Kwan SH, et al. Disparities in state-specific adult fruit and vegetable consumption – United States, 2015. MMWR Morb Mortal Wkly Rep. 2017 Nov 17;66(45):1241-7.
 Bird JK, et al. Risk of deficiency in multiple concurrent micronutrients in children and adults in the United States. Nutrients. 2017 Jun 24;9(7):655.
 Blumberg JB, et al. Contribution of dietary supplements to nutritional adequacy in various adult age groups. Nutrients. 2017 Dec 6;9(12):1325.
 Shepherd SJ, Gibson PR. Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease. J Hum Nutr Diet. 2013 Aug;26(4):349-58.
 Diez-Sampedro A, et al. A gluten-free diet, not an appropriate choice without a medical diagnosis. J Nutr Metab. 2019 Jul 1;2019:2438934.
 Rondanelli M, et al. Micronutrients dietary supplementation advices for celiac patients on long-term gluten-free diet with good compliance: a review. Medicina (Kaunas). 2019 Jul 3;55(7):337.
 Manousou S, et al. A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women. Eur J Clin Nutr. 2018 Jan;72(1):124-9.
 Churuangsuk C, et al. Impacts of carbohydrate-restricted diets on micronutrient intakes and status: a systematic review. Obes Rev. 2019 Aug;20(8):1132-47.
 Farmer B. Nutritional adequacy of plant-based diets for weight management: observations from the NHANES. Am J Clin Nutr. 2014 Jul;100 Suppl 1:365S-8S.
 Clarys P, et al. Comparison of nutritional quality of the vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diet. Nutrients. 2014 Mar 24;6(3):1318-32.
 Karlsen MC, et al. Theoretical food and nutrient composition of whole-food plant-based and vegan diets compared to current dietary recommendations. Nutrients. 2019 Mar 14;11(3):625.
 Foster M, Samman S. Vegetarian diets across the lifecycle: impact on zinc intake and status. Adv Food Nutr Res. 2015;74:93-131.
 Krajcovicová-Kudlácková M, et al. Iodine deficiency in vegetarians and vegans. Ann Nutr Metab. 2003;47(5):183-5.
 Iguacel I, et al. Veganism, vegetarianism, bone mineral density, and fracture risk: a systematic review and meta-analysis. Nutr Rev. 2019 Jan 1;77(1):1-18.
 Pawlak R, et al. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. Eur J Clin Nutr. 2014 May;68(5):541-8.
 G Engel M, et al. Micronutrient gaps in three commercial weight-loss diet plans. Nutrients. 2018 Jan 20;10(1):108.
 Kuriti M, et al. Iodine content of U.S. weight-loss food. Endocr Pract. 2014 Mar;20(3):232-5.
 Gardner CD, et al. Micronutrient quality of weight-loss diets that focus on macronutrients: results from the A TO Z study. Am J Clin Nutr. 2010 Aug;92(2):304-12.
 Calton JB. Prevalence of micronutrient deficiency in popular diet plans. J Int Soc Sports Nutr. 2010 Jun 10;7:24.
 Zupec-Kania B, Zupanc ML. Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation. Epilepsia. 2008 Nov;49 Suppl 8:23-6.
 American Dietetic Association. Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. J Acad Nutr Diet. 2003 Jun 1;103(6):748.
 Fabian E, et al. Vitamin status in elderly people in relation to the use of nutritional supplements. J Nutr Health Aging. 2012 Mar;16(3):206-12.
 Schüpbach R, et al. Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland. Eur J Nutr. 2017 Feb;56(1):283-93.
 Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32.
 Bailey RL, et al. Estimation of total usual dietary intakes of pregnant women in the United States. JAMA Netw Open. 2019 Jun 5;2(6):e195967.
 Branum AM, et al. Dietary supplement use and folate status during pregnancy in the United States. J Nutr. 2013 Apr;143(4):486-92.
 National Institutes of Health (NIH). Folate: fact sheet for health professionals [Internet]. Bethesda (MD): US Department of Health and Human Services; 2019 [cited 2020 Jan 1]. Available from: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
 American College of Obstetricians and Gynecologists (ACOG). Nutrition during pregnancy [Internet]. Washington (DC): ACOG; 2018 [cited 2020 Jan 1]. Available from: https://www.acog.org/Patients/FAQs/Nutrition-During-Pregnancy
 De-Regil LM, et al. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD007950.
 Mills JL. Strategies for preventing folate-related neural tube defects: supplements, fortified foods, or both? JAMA. 2017 Jan 10;317(2):144-5.
 Green-Raleigh K, et al. Trends in folic acid awareness and behavior in the United States: the Gallup Organization for the March of Dimes Foundation surveys, 1995-2005. Matern Child Health J. 2006 Sep;10(5 Suppl):S177-82.
 US Preventive Services Task Force, et al. Folic acid supplementation for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement. JAMA. 2017 Jan 10;317(2):183-9.
 Frankenfeld CL, Wallace TC. Multivitamins and nutritional adequacy in middle-aged to older Americans by obesity status. J Diet Suppl. 2019 Aug 5:1-14.
 Angelo G, et al. Efficacy of multivitamin/mineral supplementation to reduce chronic disease risk: a critical review of the evidence from observational studies and randomized controlled trials. Crit Rev Food Sci Nutr. 2015;55(14):1968-91.
 Sebastian RS, et al. Older adults who use vitamin/mineral supplements differ from nonusers in nutrient intake adequacy and dietary attitudes. J Am Diet Assoc. 2007 Aug;107(8):1322-32.
 Wallace TC, et al. Multivitamin/multimineral supplement use is associated with increased micronutrient intakes and biomarkers and decreased prevalence of inadequacies and deficiencies in middle-aged and older adults in the United States. J Nutr Gerontol Geriatr. 2019 Oct-Dec;38(4):307-28.
 Blumberg JB, et al. The use of multivitamin/multimineral supplements: a modified Delphi consensus panel report. Clin Ther. 2018 Apr;40(4):640-57.