Jan 9, 2019

How Multivitamins Affect Cancer and Heart Disease Risk

Does daily multivitamin use help prevent diseases like cancer and heart disease?

October 2018 Issue

Multivitamin & Mineral Supplements
By Jessica Levings, MS, RD
Today’s Dietitian
Vol. 20, No. 10, P. 32

Learn what the research says about their ability to reduce CVD, cancer, and all-cause premature mortality risk.

Americans have been taking multivitamin/mineral supplements (MVMs) to help treat vitamin deficiencies for nearly 80 years since they first hit the market in the early 1940s.1 However, MVMs have become increasingly popular over the past few decades as marketing claims have suggested they not only correct deficiencies but also help improve health. Between 2003 and 2006, 39% of US adults reported taking MVMs,2 compared with 76% of US adults in 2017.3 Sales of MVMs totaled $5.7 billion in 2014, accounting for 40% of all dietary supplement sales.4

Vitamins can be grouped into the following two categories: Fat-soluble vitamins, including vitamins A, D, E, and K, and water-soluble vitamins, including vitamins C, B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), and B12 (cyanocobalamin).5 Similarly, minerals are grouped into two categories. Macrominerals are needed in larger amounts and include calcium, phosphorus, magnesium, sodium, potassium, chloride, and sulfur. Trace minerals are needed in lesser amounts and include iron, manganese, copper, iodine, zinc, cobalt, fluoride, and selenium.6

According to the National Institutes of Health Office of Dietary Supplements, there’s no standard or regulatory definition for MVMs, including what nutrients they must contain and at what levels.7 Manufacturers determine the types and quantities of ingredients including vitamins and minerals, and because of this MVMs vary widely in their compositions and quality. Dietary supplements are available over the counter and typically come in pill, powder, or liquid form. Most MVMs are taken once daily and contain all or most essential vitamins and minerals, with labeled quantities at or near 100% of the recommended intake level. However, some MVMs contain vitamins and minerals in quantities significantly higher than what’s recommended, and some varieties even exceed the Tolerable Upper Intake Level that’s considered safe. In the United States, the FDA regulates dietary supplement products and their ingredients, but these products are regulated differently than conventional food and drug products. Under the Dietary Supplement Health and Education Act of 1994, manufacturers and distributors of dietary supplements and dietary ingredients are responsible for the safety and labeling of their products before they hit the market to ensure they meet all of the act’s requirements. Once a product is on the market, any issues with misbranding are the FDA’s responsibility.

According to a 2017 survey by the Council on Responsible Nutrition, multivitamins are the most commonly consumed dietary supplement (73%), followed by vitamin D (37%), vitamin C (32%), calcium (26%), and a vitamin B complex (24%). Reported reasons for taking dietary supplements among men and women are similar, with both listing overall health and wellness benefits as the number one reason for usage (50% of female users and 42% of male users).3 However, whether MVMs confer health benefits in the generally healthy population has been the subject of debate for some time.

What Does the Research Say?
The evidence is mixed and inconclusive regarding myriad potential health benefits of MVMs, with the most recent data suggesting MVMs don’t significantly improve CVD outcomes specifically. A 2018 systematic review and meta-analysis of existing systematic reviews and meta-analyses and single randomized controlled trials conducted between January 2012 and October 2017 found no consistent benefit between MVM use and the prevention of CVD, myocardial infarction, stroke, or all-cause mortality during the study period.8 However, the researchers noted that long-term studies may be required to detect reductions in CVD risk since chronic disease takes longer to develop compared with typical study follow-up periods, and that the impact of any risk reduction in these diseases may be too low to be reflected in all-cause mortality. The study authors concluded that “In the absence of further studies, the current data on supplement use reinforce advice to focus on healthy dietary patterns, with an increased proportion of plant foods in which many of these required vitamins and minerals can be found.”

Another 2018 systematic review and meta-analysis assessed associations between MVMs and CVD outcomes and found no association between MVMs and CVD mortality, coronary heart disease mortality, or stroke incidence.9 The analysis included 18 studies with an average participant age of 57.8 years. Only five of the studies reported the type and ingredients used in the MVMs, and only 11 of the 18 studies were from the United States, with an average follow-up period of 11.6 years. Interestingly, the analysis found that MVMs were associated with lower risk of coronary heart disease incidence in the studies outside the United States, but no benefit was found among studies inside the United States. This could be due to the varying lifestyle habits and dietary patterns of Americans compared with those from other countries included in the analysis. Study authors also noted that most of the studies used questionnaires to assess MVM use, which couldn’t accurately analyze frequency, dosage, and compliance.9

A 2013 systematic review by the US Preventive Services Task Force10 assessed MVM use in the prevention of CVD in nutrient-sufficient adults and concluded that limited evidence supports any benefit from MVMs for the prevention of cancer and CVD in general, but some evidence does suggest a small benefit in cancer prevention in men (of the individual trials analyzed, two found lower overall cancer incidence in men).11,12 The review included four trials and one cohort analysis examining MVM use’s effect on CVD, cancer, and mortality outcomes and harms. MVM content ranged anywhere from three vitamins to 14 vitamins and 12 minerals, and the average age range was older than 50 in most studies, with follow-up periods ranging from six months to 16 years. While study authors found no evidence of an effect of nutritional doses of vitamins or minerals on CVD, cancer, or mortality in healthy people without known nutrient deficiencies, they also noted that in most cases data were insufficient to draw any conclusions. Study authors also found that the only multivitamin trial to include women used a supplement with only five ingredients, and that future studies of MVMs should be representative of the general population including multiple minority groups, both sexes, and use of MVMs similar to brands most commonly purchased in the marketplace. Lastly, study authors suggested that follow-up periods in future studies continue for at least a decade and include a large enough participant population to adequately analyze benefits and harms. While findings in the present study don’t indicate harm associated with MVM use, study authors didn’t examine harms from doses higher than the Tolerable Upper Intake Level set by the Institute of Medicine.

The conclusions drawn from research findings to date on potential benefits or lack thereof of MVMs are limited by certain considerations. In many studies, participants could continue taking additional supplements on their own outside of the study design, with these data not being reported. Furthermore, many of the studies were done in other countries, which are difficult to apply to the US population. The average age of study participants was typically older with a lack of research examining the effects of routine use of MVMs in younger, healthy populations over time. Lastly, potential adverse effects of different doses of MVMs weren’t systematically determined, and no data are available on optimal doses and composition of MVMs.

Recommendations for Dietitians
According to the 2015–2020 Dietary Guidelines for Americans, “Nutritional needs should be met primarily from foods. Individuals should aim to meet their nutrient needs through healthy eating patterns that include nutrient-dense foods … [that] contain essential vitamins and minerals and also dietary fiber and other naturally occurring substances that may have positive health effects.”13 The guidelines also reported that the US population consumes insufficient amounts of green leafy vegetables, fresh fruits, whole grains, and fiber, and excessive amounts of refined carbohydrates, saturated fat, and sodium. In fact, according to self-reported data from the Centers for Disease Control and Prevention, only 13.1% of US adults meet fruit intake recommendations and only 8.9% meet vegetable intake recommendations.14 Unlike data on MVM use, existing research on fruit and vegetable intake consistently has shown that eating patterns rich in fruits and vegetables can help lower blood pressure and reduce the risk of heart disease, stroke, and certain cancers, as well as improve digestion and benefit blood sugar. Dietitians speaking with clients concerned about nutrient inadequacies should brief them on the research comparing benefits of MVMs vs improving dietary patterns from food and help them identify food sources of essential vitamins and minerals.

It’s also important that clients understand the difference between a nutrient “inadequacy” and true nutrient “deficiency.” While many in the US population may have inadequate intakes of potassium, for example, this doesn’t necessarily mean they’re truly deficient. An inadequacy likely can be corrected by changes to one’s eating pattern, whereas a true deficiency may be linked to an underlying disease state that would need to be corrected with medication and/or a supplement. Dietitians can recommend clients be tested for true nutrient deficiencies to determine whether a supplement is warranted. In most cases, counseling regarding changes in dietary patterns, if followed, should be enough to correct nutrient inadequacies. Food frequency questionnaires can help dietitians assess whether clients’ diets are lacking in essential vitamins and minerals, and counseling can be provided to encourage them to make beneficial changes.

According to the Academy of Nutrition and Dietetics, while widespread recommendations for MVMs in generally healthy people aren’t necessary, some members of the population are limited in their food choices due to allergies, medical conditions, or dietary preferences such as vegetarian or vegan eating patterns. In certain populations such as these, MVMs may be warranted.15 Learning about clients’ medical conditions, allergies, and food choices also is important when helping them decide whether MVMs are right for them. Some clients whose life stage may dictate the need for MVMs include women who are planning to become or are pregnant, postmenopausal women, and people with an underlying disease state interfering with nutrient absorption.

When recommending MVMs to clients, dietitians vary in their approach. Kelli Shallal, MPH, RD, owner of Hungry Hobby, LLC, a nutrition consulting and communications business in Phoenix, likens MVMs to insurance. “I think of a multivitamin like an insurance policy. Do you absolutely need it to survive or even thrive? No, you don’t. However, if you are highly active, have a fast-paced lifestyle, or are human, chances are you aren’t 100% perfect all the time. I try to educate my clients on what to look for in a multivitamin. I tell them to look for divided doses (to increase nutrient absorption), avoid herbal additives, and take them with food.”

Chicago-based dietitian Amanda Baker Lemein, MS, RD, takes a more prescribed approach: “The types of supplements I often recommend are prenatal vitamins and vitamin D. Living in Chicago, many of my clients have very low levels of vitamin D, so I recommend a food-based supplement with at least 1,000 IU to those clients.”

Dietitians also should remind clients that there is such a thing as taking too much of a good thing when it comes to vitamin and mineral supplementation, and what’s on the label isn’t always what’s in the bottle. A 2017 study compared the labeled value of nearly 400 samples of over-the-counter MVMs with the chemical composition, and the lab analysis found that quantities of all ingredients except thiamin exceeded what was listed on the label.16 Certain health issues including chronic kidney disease warrant limiting certain minerals, such as potassium. Furthermore, while excess water-soluble vitamins (other than B12) are excreted in the urine instead of stored in the body, large amounts of fat-soluble vitamin supplements are stored in fat cells, which can build up in the body and possibly cause harm.5

While the bulk of research suggests that taking MVMs is unlikely to be harmful, it’s important to consider food sources of vitamins and minerals, including fortified foods and drinks such as cereals and beverages with added vitamins and minerals. If a client wants to begin taking MVMs, suggest a basic, well-known brand whose ingredients don’t exceed 100% of the recommended intake. According to the National Institutes of Health, MVMs containing recommended intake levels of nutrients usually don’t interact with medications, except medicines that reduce blood clotting (eg, warfarin). RDs should remind clients to always tell their health care providers what over-the-counter MVMs they’re taking when asked about medication use.

Lastly, dietitians should focus on a food-first strategy as recommended by the Dietary Guidelines by encouraging consumption of a variety of fruits, vegetables, fortified dairy foods, legumes, and whole grains, and tell clients that MVMs don’t take the place of a healthful diet. And while research has confirmed that healthful eating patterns overall help prevent CVD and other chronic diseases, these results have yet to consistently carry over to MVMs.

— Jessica Levings, MS, RD, realtor, is a freelance writer and food industry consultant helping consumers Home in on Health with evidence-based resources. Dietitians can read more of her articles at BalancedPantry.com and follow her on Twitter and Facebook @BalancedPantry.

References
1. National Institutes of Health State-of-the-Science Panel. NIH state-of-the-science conference statement: multivitamin/mineral supplements and chronic disease prevention. Am J Clin Nutr. 2007;85(1):257S-264S.

2. Gahche J, Bailey R, Burt V, et al. Dietary supplement use among U.S. adults has increased since NHANES III (1988-1994). NCHS Data Brief. 2011;(61):1-8.

3. Council for Responsible Nutrition. CRN 2017 Annual Survey on Dietary Supplements. https://www.crnusa.org/sites/default/files/images/CRN-2017-ConsumerSurvey-4-page-highlights.pdf

4. Nutrition Business Journal; New Hope Network. Supplement Business Report 2016. https://www.newhope.com/sites/newhope360.com/files/2016%20NBJ%20Supplement
%20Business%20report_lowres_TOC.pdf
. Published 2016.

5. Vitamins. MedlinePlus website. https://medlineplus.gov/ency/article/002399.htm

6. Minerals. MedlinePlus website. https://medlineplus.gov/minerals.html

7. Multivitamin/mineral supplements: fact sheet for health professionals. National Institutes of Health, Office of Dietary Supplements website. https://ods.od.nih.gov/factsheets/MVMS-HealthProfessional/. Updated July 8, 2015.

8. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol. 2018;71(22):2570-2584.

9. Kim J, Choi J, Kwon SY, et al. Association of multivitamin and mineral supplementation and risk of cardiovascular disease: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2018;11(7):e004224.

10. Fortmann SP, Burda BU, Senger CA, Lin JS, Whitlock EP. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013;159(12):824-834.

11. Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164(21):2335-2342.

12. Sesso HD, Christen WG, Bubes V, et al. Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2012;308(17):1751-1760.

13. US Department of Health & Human Services. Dietary Guidelines for Americans 2015–2020: Eighth Edition. http://health.gov/dietaryguidelines/2015/guidelines/. Published January 7, 2016.

14. Moore LV, Thompson F. Adults meeting fruit and vegetable intake recommendations — United States, 2013. MMWR Morb Mortal Wkly Rep. 2015:64(26);709-713.

15. Wolfram T. Vitamins, minerals and supplements: do you need to take them? Academy of Nutrition and Dietetics website. https://www.eatright.org/food/vitamins-and-supplements/dietary-supplements/vitamins-minerals-and-supplements-do-you-need-to-take-them. Published July 6, 2018.

16. Andrews KW, Roseland JM, Gusev PA, et al. Analytical ingredient content and variability of adult multivitamin/mineral products: national estimates for the Dietary Supplement Ingredient Database. Am J Clin Nutr. 2017;105(2):526-539.

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