Donald B. McCormick, Ph.D

Nutrition

(Article is in the forum section of Nutrition Reviews, April 2010; Vol. 68(4):207-213)

Vitamin/mineral supplements: of questionable benefit for the general population
Donald B. McCormick
Dept. of Biochemistry and Program in Nutrition & Health Sciences,
Emory University, Atlanta GA 30322, U.S.A.; e-mail: biocdbm@emory.edu

KEY WORDS: vitamins, trace minerals, micronutrients, supplements

ABSTRACT

In the United States today, there is a multi-billion dollar industry in dietary supplements with at least a third sold as vitamin/mineral pills and drinks. Though everyone requires small amounts of these essential micronutrients, and supplements are of benefit to some within the population, the considerable majority of people can fulfill their needs with the intake of healthy diets of mixed foods. In addition the fortification of some of our processed foods adds extra amounts of several micronutrients, especially those for which there is deemed to be a need in special segments of our population. In spite of this safe and adequate level of intake, there are many who have been led to believe that the frequent ingestion of supplements will be helpful in their efforts to maintain optimal health, live longer, and even prevent or cure non-deficiency diseases. It is the intent of this article to unravel the causes and misconceptions behind this practice and to emphasize that most of the money spent on unnecessary supplementation could be better used for other purposes.

     NATURE, OCCURRENCE, FUNCTION, AND NEED FOR MICRONUTRIENTS

     There are 13 vitamin groups1 and as many trace minerals2 that are essential but cannot be made in our bodies and are therefore derived exogenously, usually in the foods we eat. The discovery, isolation, characterization, functions, and nutritional requirements for these micronutrients were detailed during the past century. Understanding at the molecular level has revealed that most vitamins and trace minerals function after metabolic conversion to cofactors within enzyme systems that catalyze reactions necessary to sustain life, or they serve in important hormonal or epigenetic roles. Because of turnover in our body that results from catabolism, excretion, and secretion of the micronutrients and their functional forms, we need rather steady intakes of most. Without adequate and relatively frequent intakes, there is an eventual deficiency disease characteristic of each that, when protracted, can often lead to death. Also most of such micronutrients when chronically taken in excess, become toxic and, again, in some instances can be lethal. Hence, we need to consume those amounts, usually micro- to milligram quantities per day, that help us maintain growth, health, and normal reproductive function, but avoid such excesses as may be deleterious. Most of the peer-reviewed literature on this subject has been summarized in volumes that collate information within periodically updated chapters that are especially appropriate for nutritional professionals.3,4  For the considerable majority of individuals, the ingestion of readily available diets that are derived from edible plant and animal tissues wherein the micronutrients also function, is sufficient to supply our needs. A healthy mix of fruits, vegetables, cereals, dairy products, and meats is the usual and sufficient way to obtain the recommended dietary allowances (and intakes) that are meant to cover over 97% of our population. These numbers are periodically fine-tuned as new information on requirements for different age and gender groups is obtained and published as Dietary Reference Intakes.5,6 Given that some processed foods are now enriched with several of the micronutrients, some of which represent special needs for certain segments of our population, it is unlikely that all but a relatively small fraction of the population, such as suffer from abnormal absorption or metabolism that can result from single-nucleotide polymorphisms in genes, needs any further supplementation. In these cases, supplements may be recommended by health professionals trained to recognize and treat these relatively uncommon, sometimes genetic-based, causes.

        MAGNITUDE AND CAUSES OF MICRONUTRIENT SUPPLEMENT USE

There are, unfortunately, extensive writings and pronouncements that go beyond evidence-based science but claim that supplements may be a benefit for all. A review of the diverse substances taken as supplements has been made available in a two-volume encyclopedia put together at NIH.7 Advertisements in popular magazines and on TV abound. The impact on the often-vulnerable public has been huge. The expenditures for total supplements are now estimated to run in the range of 21 to 25 billion dollars per year with over 8 billion spent in the multivitamin/mineral category; this represents an ongoing increase from the 2000 level.8 One half to two thirds of the adult population in the United States is involved in some use of such supplements. The causes behind this public consumption of vitamin/mineral supplements are several.
     First, the lay public tends to trust "natural" treatments over "drug" treatments and want to take control of their own lives.
     Second, we should recognize the tendency of many to want to believe in any suggestion of how to stay young and attractive, even when no hard evidence has been presented for such an elixir. Sometimes our hopes and vanities outstrip common sense. When something has been shown helpful at one level or for one purpose, we tend to extrapolate from sense to nonsense. Apropos this foible of human nature and with specific regard to supplements, Dr. Edward Rynearson, a former Director of Mayo Clinic and President of the American Medical Association, stated over a generation ago: "Americans love hogwash. They think if a little is good, more is better."
     Third, we too often accept as authoritative, statements from people who are not really expert in what they claim. Misleading self-appointed "experts" have been described by Nobel Laureate Richard Feynman, first in his interview by the BBC and later, in 1999, in his posthumous book The Pleasure of Finding Things Out under a subdivision entitled "Science Which is Not Science".9 Not only are there those who have little or no specific knowledge of micronutrients yet proclaim their virtue beyond fact, but there are some who have a confabulation of some facts and false premises. Both types make dogmatic statements meant to convince the reader or listener and are especially convincing to those not educated in the subject. Sadly, some in our health profession, including physicians, have felt compelled to recommend the use of vitamin/mineral supplements when there was insufficient evidence of need or benefit. The US Poison Control Centers reported in 2005 that there were 62,562 cases of exposure to vitamin/mineral  preparations that led to 5,972 treatments at health care facilities; many were the result of too exuberant intake of supplements recommended by physicians; over 80 % were pediatric cases.10 It is certainly timely that Dr. Paul Blumenthal, an MD who is an editor of Medscape, has made a plea that his colleagues should practice evidence-based medicine as Dan Hurley has argued should apply to supplements.11
      Fourth, we are constantly bombarded by sales propagandists and company spokespersons who hope to garner money from a public that has sometimes opted to spend their wages entirely on themselves rather than such worthwhile matters as education and conservation.12

EPIDEMIOLOGICAL OBSERVATIONS VERSUS CONTROLLED CLINICAL TRIALS

A major problem with the information that has been interpreted by researchers who have meant to honestly report their conclusions on supplements has to do with methodology. There is both a conflict between how epidemiologists and biostatisticians evaluate the strength of their data and a general tendency to regard the former as having more weight than is warranted. This problem has been addressed recently by Andreas von Bubnoff in his article "Numbers Can Lie" that is in the 2008 volume of The Best American Science and Nature Writing.13 Conflicting reports typically arise and certainly can confuse the average person who does not know that epidemiological studies are observational whether categorized as of cohort, case-control (Retrospective), or cross-sectional type. They may indicate  possible associations but do not have the weight of randomized, double-blinded, placebo-controlled clinical trials that use sufficient numbers to provide clear answers of a positive or negative effect.  The randomized clinical trial is properly considered by most as the gold standard of medical research. In fairness to the continued use of epidemiological studies, however, it is impractical (and too expensive) to evaluate the roles of nutrients in clinical trials with slow-developing chronic diseases.

   UNLIKELY BENEFITS FROM MICRONUTRIENT SUPPLEMENTS FOR MOST

After a relative surge in publications ending with claims of positive findings from the use of individual micronutrients or combinations of such nutrients in vitamin/mineral supplements to prevent and even cure diseases not known to relate to nutrient deficiencies, there has been a notable reversal in such claims. Much of this is due to larger studies in which randomized clinical trials were done and where meta-analyses of more data have been possible. An illustrative example is the  meta-analysis of randomized controlled trials as relates to the progression of atherosclerosis14 and the editorial that emphasized the finding of no benefit of vitamin/mineral supplements in such cases.15 The Annual Bibliographies of Significant Advances in Dietary Supplement Research, published by the Office of Dietary Supplements at the National Institutes of Health, are compiled with the assistance of  numerous international reviewers of the general supplement literature.16 It is instructive to see the disclaimers of any certain benefit from numerous micronutrients, toward non-deficiency diseases such as cancers, cardiovascular diseases, respiratory infections, etc. A summary of these reports from the years 2004-2008,16 with full listings of authors and reference details, with full listings of authors and reference details, are given below.

Summary of select articles reporting disclaimers of any certain benefit from numerous micronutrients toward non-deficiency diseases such as cancers, cardiovascular diseases, and respiratory infections.
































































































                                               

Bjelakovic et al., The Lancet, Antioxidant supplements for prevention of gastrointestinal cancers: A systematic review and meta-analysis. - Antioxidant supplements (A, C, E, selenium, and -carotene) might not be helpful for prevention of gastrointestinal cancers and may increase overall mortality.
Lee et al., Am. J. Clin. Nutr., Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? - High doses of supplemental vitamin C could be potentially harmful to older women with diabetes.
Meydani et al., JAMA, Vitamin E and respiratory tract infections in elderly nursing home residents: A randomized controlled trial. -- Vitamin E had no significant effect on the incidence or number of days with infection for all upper or lower respiratory tract infections or antibiotic use.
Lange et al., N. Engl. J. Med., Folate therapy and in-stent restenosis after coronary stenting. - Individuals with coronary artery stents should not use folate therapy routinely to reduce the risk of restenosis.
Milner et al., Pediatrics, Early infant multivitamin supplementation is associated with increased risk for food allergy and asthma.


Heart Outcomes and Prevention Evaluation (HOPE 1 and 2) Trials, JAMA, Effects of long-term vitamin E supplementation on cardiovascular events and cancer: A randomized controlled trial. - Long-term vitamin E therapy does not prevent cancer or cardiovascular events and may increase the risk of heart failure in individuals with existing disease.
Lee et al., JAMA, Vitamin E in the primary prevention of cardiovascular disease and cancer. The women's health study: A randomized controlled trial. - Overall, this study with its large sample size and long duration does not support the use of vitamin E to prevent CV disease or cancer in women.


HOPE 2 Trial, N. Engl. J. Med., Homocysteine lowering with folic acid and B vitamins in vascular disease. - Findings do not support an association between B vitamin (folate, B12, and B6) supplementation, reduction in elevated homocysteine levels, and reduced risk for cardiovascular disease in individuals with existing disease.
Briefel et al., J. Am. Diet. Assoc., Feeding Infants and Toddlers Study; Do vitamin and mineral supplements contribute to nutrient adequacy or excess among US infants and toddlers? - Nutrient adequacy can be obtained from dietary intakes, and supplementation with multivitamin and/or multiminerals may not be necessary in infants and toddlers.
Rumbold et al., N. Engl. J. Med., Vitamins C and E and the risks of preeclampsia and complications. - Supplementation with the antioxidant vitamins C and E are not effective in preventing or reducing the risk of preeclampsia in women.
Close et al., Br. J. Nutr., Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process.


Cole et al., JAMA, Folic acid for the prevention of colorectal adenomas: A randomized clinical trial. - This study raises the concern that folic acid supplementation may increase the risk for colorectal cancer in those with a history of adenomas.
Ray et al., Ann. Intern. Med., Homocysteine-lowering therapy and risk of venous thromboembolism: A randomized trial. - B-Vitamin supplementation is not an effective regimen for the prevention of first or recurrent episodes of venous thromboembolism.
Cook et al., Arch. Intern. Med., A randomized factorial trial of vitamins C and E and beta-carotene in the secondary prevention of cardiovascular events in women: Results from the Women's Antioxidant Cardiovascular Study. - This study does not support the regular use of antioxidants in reducing the risk of cardiovascular disease outcomes among women with risk factors for cardiovascular disease.


Balk et al., Arch. Intern. Med., Vitamin B6, B12, and folic acid
supplementation and cognitive function. - Evidence does not yet provide adequate evidence of an effect of these vitamins alone or in combination on cognitive function testing in people with either normal or impaired cognitive function.
McMahon et al., J. Nutr., Lowering homocysteine with B vitamins has no effect on blood pressure in older adults.
Sawka et al., Arch. Intern. Med., Randomized clinical trial of homocysteine level-lowering therapy and fractures.  Though hyperhomocysteinemia is associated with an increased risk of skeletal fractures, findings do not support the use of routine supplementation with folic acid and B vitamins for the primary prevention of fractures among middle-aged and elderly community-dwelling adults.


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Data from the Annual Bibliography of Significant Advances in Dietary Supplement Research publications from the Office of Dietary Supplements at the National Institutes of Health16 expand upon the conclusions from the 2006 National Institutes of Health
State-of-the-Science Conference on "Multivitamin/Mineral Supplements and Chronic Disease Prevention",17 which are summarized as follows: "With few exceptions, the available evidence from RCTs [randomized clinical trials] of -carotene, vitamin E, vitamin A (in combination with zinc or -carotene) or combined riboflavin and niacin indicates no consistent, significant benefit of these single or paired nutrients in preventing cancer, cardiovascular disease, cataract, or age-related macular degeneration. --- [There is] no short-term benefit of folic acid (with or without vitamins B12 and B6) or vitamin B6 alone in preventing cognitive decline."
     In addition to these professional-level reports, it is encouraging to note the increasing numbers of statements aimed at the lay audience. An article on the "myth" of benefits from some of those vitamins and minerals often encountered in supplements was presented in "Reader's Digest" in sensible lay terms.18 Another example is the report by Rebecca Ruiz on the Netscape "Home & Living" site that included comments solicited from nutritionists.19 The bottom line was to declare that one could and should get their needed vitamins and minerals from their diet and not by taking supplements.



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