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Taking Supplementation Seriously Part II:

Last month, we started a dialogue on whether supplementation is the appropriate course for insuring a nutritionally complete diet. We examined a very simple case, the multivitamin: a supplement designed to provide the base set of essential nutrients that are requisite for normal human metabolism. In response to the case against multivitamin usage (“proper diet alone should be adequate in providing essential nutrients”), we considered how 1) widespread deficiency of several nutrients in the U.S. diet, 2) the demonstrated reduction in nutrient availability in the modern food supply, and 3) the subclinical deficiencies in several nutrients that can result from caloric restriction and exercise, suggest that supplementation of essential nutrients may be warranted in some individuals. Here we expand the list of observations to consider when making the decision whether to include a multivitamin in your daily health regimen.

Supplemental vitamins and minerals may reduce disease risk There is little debate that proper nutrition reduces the risk of some diseases; indeed, the discovery of vitamins and essential trace elements was due in no small part to their ability to cure the diseases of their deficiency. Of course, deficiency diseases like beriberi, scurvy, and pellagra are almost unheard nowadays in developed countries, but the incidence and progression of diseases like cardiovascular disease and cancer, are also likely influenced in part by the amount and composition of dietary macronutrients and micronutrients.

Given that essential nutrients are indispensable for proper function of the body and the reduction of disease risk, one might assume supplemental vitamins and minerals themselves might reduce disease risk. It seems a logical argument, although the data must be interpreted carefully. There are certainly peer-reviewed, published studies which do suggest supplementation may not be appropriate or effective in all contexts. You many be familiar with the media reports that multivitamin usage may increase prostate cancer risk, or that supplemental vitamin E increases the risk of cardiovascular mortality, or that calcium and vitamin D have no effect on reducing hip fracture risk. (Although the last statement, which was based on the results of the Women’s Health Initiative is not entirely correct: women who adhered to the study protocol actually had a 29 percent reduction in fracture risk.)

However, there are also many examples in which vitamins and minerals, taken as dietary supplements, reduced the risks of certain diseases. Several recent meta-analyses (pooled data from several individual studies that sometime allows a more rigorous analysis of associations) have demonstrated several positive effects of supplemental vitamins at low to moderate doses. Notable examples include: niacin significantly reduced cardiovascular events and demonstrated non-significant decreases in cardiovascular mortality; adequate serum vitamin D levels are associated with significant reductions in cardiovascular and breast cancer risks; vitamin E reduced total and ischemic stroke incidence (although increased risk of hemorrhagic stroke); multivitamins, supplemental vitamin C, and vitamin E were all associated with lower colon cancer risk (vitamin C and E from foods, however, had no effect). Several large individual studies have shown that long-term multivitamin usage reduced the risk of heart attack and hypertension in healthy individuals (the Swedish Mammography Cohort), lowered mortality rate from gastric cancer and all cancers (the Linxian General Population Trial and SU.VI.MAX trial), and slowed the risk of advanced macular degeneration in high-risk individuals (the AREDS trial).

How can we resolve these seemingly contradictory findings? Vitamins as “treatments” have been met with mixed results, which may not be surprising considering they exist to facilitate healthy metabolism (i.e. at the right levels in the diet, they ensure that metabolism proceeds properly). To expect a vitamin or mineral to fix or reverse a problem after it has already occurred may be a tall order. (Even so, there have been several successes with nutrient interventions in controlled clinical settings, for example, folate, niacin, or high dose vitamin D for cardiovascular disease, calcium, vitamin D, vitamin K, silicon, for osteoporosis, amongst others.) In contrast, current evidence is consistent with the observations that taking supplemental vitamins to obtain adequate amounts of essential nutrients (as opposed to supra-physiological doses as “treatments”) may reduce the risk of some diseases in healthy people. In this case, the multivitamin is a good choice, as they are less likely to lead to excessive intakes. It is not always feasible to consume a diet with an adequate nutrient profile.

A healthy diet should be the primary approach for nutrient sufficiency, however, this is not always the most practical or feasible way for the body to obtain everything it needs. Eating well requires navigating a vast array of food choices and composing meals which satisfy individual metabolic needs; this requires a time investment many are unable or unwilling to make, hence the rising popularity of convenience foods and increased spending on food consumed away from home. (Ironically, even healthcare professionals may suffer from a “graband- go” mentality; surveys of physicians revealed that many have difficulties maintaining proper nutrition in the workplace.) Although nutrient labeling programs for prepared foods and restaurant menus are positive steps, they usually lack sufficient data on micronutrients to assess the overall nutritional value of a food choice, and most of us probably don’t have the degree of dietitian training to determine nutritional value of a meal by recall alone. It is probably no coincidence that many dietitians are also supplement users.

Limitations in food choices, whether involuntary (prohibitive costs of nutrient-dense foods; lack of availability, food allergy or dietary intolerance) or voluntary (veganism/vegetarianism), can also limit key nutrients. For example, strict vegetarian and vegan diets, despite conferring unique health benefits, are also lacking in some vitamins (B12 and D3, the more effective form of vitamin D), and can be deficient in minerals (iodine, zinc and highly bioavailable “heme” iron) and essential amino acids (methionine). Under these conditions, supplementation may be the only way to insure intake. “Biochemical individuality” dictates that everyone has unique nutrient needs.

Metabolic needs vary greatly between individuals, as does the metabolism of dietary nutrients (absorption, retention, and excretion). This is evident in any of the thousands of published nutrient absorption studies. There has been attempts to reconcile these differences by the establishment of “Reference” intakes for several (but not all) important micronutrients; the DRIs and EARs established by the Institute of Medicine recommend intakes that are meant to address the average nutrient requirements for the population. While a start, it is important to remember these guidelines are estimates for avoiding deficiencies at different life stages (they have also been criticized for lack of a transparent criteria in the assignment of intake values; in several cases, different scientific bodies have come up with dramatically different recommendations based on the same data).

There is potential for considerable variability in nutrient needs within these groups; the dietary requirements for an “adult” can differ depending on whether she is a trained athlete, taking prescription medications, consuming a vegetarian diet, under stress, or in poor health. Even time of year and location can have effects on nutrient needs; vitamin D deficiency during winter months at northern latitudes has already been mentioned (due to decreased UV irradiation reaching the earth), but circulating levels of folate, vitamin A, pro-vitamin A carotenoids (â- and á- carotene), vitamin E (and the related ã -tocopherol), lutein, and lycopene, can all experience seasonal fluctuations. Some of this variability likely corresponds to seasonal changes in food availability/consumption, but for some nutrients (vitamin A and lycopene), the reason for variability is unclear.

With biochemical individuality in mind, it is not unreasonable to consider supplementation as a means to help tailor individual nutrient intake. Ideally, an objective measurement of vitamin status (e.g. blood test) would be used to guide the supplement regimen.

When we considered the most basic case for supplementation (“is my diet adequate to provide the minimum amount of the essential nutrients to satisfy my metabolic needs?”), there were several cases that suggest a multivitamin supplement may be in order for some people. Based on the prevalence in deficiency of the officially-recognized essential nutrients, the “average” U.S. diet is lacking nutritional sufficiency; poor food choices are a likely cause, but declining food quality may have a small contribution. In view of these observations, supplementation of essential nutrients may be an important step towards mitigating disease risk. Supplemental essential nutrients also appear to have a role in maintaining nutrient status during dramatic diet and lifestyle changes; allowing us to safely reduce calories and increase energy expenditure without metabolic dysfunction.

It is important to note the examples provided only addressed the supplementation of essential nutrients to a “sufficient” level. We did not consider “optimal” intake of essential nutrients, nor did we touch upon the scores of non-essential nutrients (such as carnitine, CoQ10, carotenoids, phospholipids, flavonoids) and other dietary compounds that have demonstrated roles in improving a wide variety of health conditions. Suffice to say, the complexity of addressing the entirety of supplementation is beyond the scope of a single article, but some of the rationale applied to our appraisal of vitamin and mineral supplementation is applicable to other types of supplements as well.

Kevin M. Connolly, PhD

Kevin M. Connolly, PhD received his bachelor’s degree in anthropology from Brown University, and doctorate in biochemistry and molecular biology from UCLA. Before consulting for the dietary supplement industry, he spent 15 years in basic biochemistry research elucidating such diverse mechanisms as bacterial antibiotic resistance and collagen synthesis. He contributes to several online and print publications, and is a frequent guest on radio health programs throughout the country. When not writing, he teaches undergraduate biochemistry.