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Aging and anti-aging claims: a review on antioxidant vitamins A, C & E

Randolph Michael Howes M.D., PhD. (Plastic surgery, Johns Hopkins Hospital, Baltimore)

Published in medi.philica.com

Abstract
Considerable effort has been put forth throughout man’s history attempting to find an effective anti-aging supplement, a so-called “elixir of life.” There are several classes of anti-aging supplements: antioxidants, phytochemicals, hormones and fatty acids. Antioxidant vitamins (especially vitamin E, vitamin C and beta carotene) are by far the most popular alleged anti-aging agents. The free radical theory and the use of free radical scavengers (antioxidants which claim to break chain reactions of free radicals) have somehow evolved as the most widely accepted theory of aging and age prevention. Clearly, it has not been proven that supplementation with antioxidant vitamins, alone or in combinations, retards or reverses aging. It is evident that antioxidant vitamins have failed to raise the life expectancy barrier. To the contrary, some studies indicate that they increase the risk of mortality. Thus, the free radical theory needs to be seriously questioned, due to the failure of antioxidant vitamins in disease and aging prevention. Further, it has been shown in many randomized controlled trials (RCTs) that antioxidant vitamins are associated with increased risk of prevalent diseases. Thus, their use must certainly be carefully scrutinized for patient safety and with caution before being recommended for a health promoting or anti-aging diet. Remember, physician, “First, do no harm.”

Article body

Introduction

There is little doubt that vitamin supplements have benefited those with vitamin deficiencies, but before recommending their use in healthy individuals or in attempts to block aging, one should review the research data as regards fact versus speculation.

So-called "Fountain of Youth" clinics and self-appointed anti-aging experts are commonplace.  Many of these advocate the use of antioxidant vitamins with their scheme.

Most evidence about the benefits of antioxidant vitamin supplements is epidemiological, including observations and uncontrolled studies, and has been fraught with misinterpretation and conclusions with unsubstantiated claims. For example, it has been observed that a diet with a high intake of fruit results in less incidence of cardiovascular disease. Once there is an observation, scientists start by "guessing" which substance, out of the thousands contained therein, in fruits is responsible for this effect, isolating it and conducting tests on it, testing it on animals and if the results are encouraging, proceeding with a prospective human study.

The "official" viewpoint on dietary supplementation is expressed in the determination of the Recommended Daily Allowances (RDAs). In deciding on their values, there are six major criteria which are included: amount people consume normally of the nutrient; amount needed to avoid a particular disease; the adequacy of the physiological function in relation to the nutrient intake; amount of nutrient absorbed; studies determining the nutrient deficiency characteristics; and results from animal experiments.

Experts urge caution

Experts urge caution with dietary supplements because anticipated benefits of antioxidant vitamin use, once widely thought to prevent cancer, heart disease and strokes, have failed to live up to their expectations when put to rigorous testing.

Many health-related committees and major health organizations, such as the American College of Cardiology, the American Heart Association (AHA), the AHA Nutrition Committee, the US Preventive Services Task Force, the Institute of Medicine, and the American Heart Association Science Advisory statement, do not recommend that individuals take these vitamin and antioxidant supplements, in the absence of a vitamin deficiency.  Frequently, current medical specialists over-recommend the use of certain drugs and antioxidant vitamin supplements that have not stood up to scientific inquiry and they ascribe to and promote unproven theories, rather than scientifically acquired facts.

The World Cancer Research Fund (WCRF) conducted a landmark study on cancer prevention that Professor Martin Wiseman, project director, said "represents the most definitive advice on preventing cancer that has ever been available anywhere in the world."   The 10/31/07 report, which selected 7,000 studies from a worldwide pool of 500,000 written since records began in the 1960s, produced five key findings. One of those findings, that is particularly important and relevant, is that, "It did not recommend dietary supplements as (cancer) prevention."  The production of the second expert report was a huge undertaking for the WCRF global network, involving over 100 scientists from 30 different countries. WCRF/AICR commissioned and funded the report, but the content has been driven by an independent panel of 21 world renowned scientists. The Expert Panel worked for five years to assess the research and their conclusions and recommendations are firmly based on the scientific evidence.

According to the website for the Harvard School of Public Health, "The evidence accumulated thus far on antioxidant vitamins isn't promising. Randomized trials of vitamin C, vitamin E, and beta-carotene haven't revealed much in the way of protection from heart disease, cancer, or aging-related eye diseases (website accessed 2/09/06).

Dr. Gibbons, a professor of medicine at the Mayo Clinic, said, "In the British Heart Protection Study, the patients taking vitamin E ended up on the wrong side of the survival line. It was not a statistical glitch; it was a clear indication of increased mortality." The Medical Research Council/British Heart Foundation Heart Protection Study, 1 which is the study cited by Dr. Gibbons, randomized 10,269 patients to 660 IU/day of vitamin E and 10,267 to placebo control. The vitamin E group was associated with about a 10% increase in mortality.

The Heart and Vascular Institute of the Cleveland Clinic states the following:  "Natural products, herbal supplements, alternative dietary therapies, antioxidants, micronutrients or plain old vitamin pills…No matter what you call them, if you take these products prior to a heart operation, they can cause real problems during or after your surgery. Previous studies of these and other natural or alternative therapies such as ginger, coenzyme Q-10, and vitamin E, have found that side effects from natural agents can be as serious as a heart attack, stroke or excess internal bleeding."

Despite the proliferation of skin-care products containing antioxidants, according to Dr. Jeffrey Blumberg, chief of antioxidants research at Tufts University, "There is no conclusive scientific evidence that antioxidants really prevent wrinkles, nor is there any information about how much antioxidant(s) or exactly which one(s) has to be present in a product to have an effect."

Investigators from the University of Pennsylvania Medical Center recently, said, "There are no large-scale controlled trials indicating that healthy people derive any benefit from vitamin E supplements. It would seem therapeutically judicious and economically prudent for such individuals to abstain from vitamin E consumption and await the evidence." 2

To determine whether antioxidant supplementation could reduce the risk of second primary cancers in head and neck cancer patients (oral cavity, pharynx and larynx), Isabelle Bairati, M.D., Ph.D., of the Université Laval in Québec City, Québec, and colleagues conducted a multicenter, double-blind, placebo-controlled, randomized trial among 540 patients with stage I or II head and neck cancer who had been treated with radiation therapy between 1994 and 2000.  The researchers wrote, "Our results suggest that caution should be advised regarding the use of high-dose [vitamin E] supplements for cancer prevention." The results came as a bit of a surprise, because some earlier studies had suggested a lower rate of new cancers in groups taking vitamin E. Instead, the vitamin E appeared to speed up the progression of cancer. 3

Brown and Crowley 4 questioned whether or not there is any hope for vitamin E.  B. Greg Brown, M.D., Ph.D., of the University of Washington School of Medicine, and John Crowley, Ph.D., of the University of Washington School of Public Health and Community Medicine, Seattle, discussed the findings of the HOPE-TOO trial.  By extending HOPE 34 and adding to the growing list of neutral prospective vitamin E trials, this report effectively closes the door on the prospect of a major protective effect of long-term exposure to this supplement, taken in moderately high dosage, against complications of atherosclerosis and overall cancer incidence.  HOPE-TOO reemphasizes the importance of controlled clinical trials for testing important hypotheses deriving from basic biological findings or from epidemiological observations. The latter can mislead; well-designed clinical trials rarely do."

Madamanchi et al. 5 stated that antioxidants are ineffective in reducing cardiovascular death despite evidence for so-called oxidative stress (OS) in cardiovascular diseases (CVD) from animal and human investigations. Ample evidence indicates that taking high-dose vitamin E in later adult life has no favorable health effects, and meta-analysis studies and randomized controlled clinical trials raise the serious possibility of harm.

In March 2007, Fox News.com presented a report entitled, "The Mega-vitamin Mega-myth," in which they stated, "The conclusion that antioxidant supplements don't appear to help you live longer is likely on a sound footing. Even without statistically combining the studies through meta-analysis, it's fairly clear that antioxidant supplements are ineffective for increasing longevity."  In a Journal of the American Medical Association (JAMA) published a review of 68 studies, containing 232,606 subjects, investigators found 66 studies reported no statistically significant association between supplement use and longevity. The remaining two studies actually reported statistical increases in premature death with supplement use.  25 Further, they said, "Antioxidants have been hypothesized to reduce alleged oxidative damage to the body caused by so-called "free radicals.  Some have suggested that antioxidant supplements may reduce the risk of cancer and heart disease. Such claims helped fuel the growth of the multi-billion dollar nutritional supplement industry."  However, there is a convincing preponderance of data which shows that the antioxidant vitamins A and E and to a lesser extent, vitamin C, increase the risks for cancer, heart disease, strokes and overall mortality.

In 2007, Dr. Michael Sporn, past Head of the National Cancer Institute Chemoprevention Laboratory and current professor of pharmacology and toxicology at Dartmouth Medical School and Eminent Scholar, NCI's Center for Cancer Research, said  that, "The use of dietary substances, like the antioxidant vitamins C and E, has been pretty much a colossal failure for protection against almost any kind of human disease."

The antioxidant vitamins A, C & E, which have been strongly recommended in anti-aging programs, have been studied extensively as regards their relationship to common disease, longevity and overall mortality.  Thus, "Are antioxidant vitamins effective in retarding or reversing aging?"  Modern scientific data indicates that, with a high order of probability, we can answer on this question, "No."

Discussion

Aging: definition

In my opinion, aging, as it relates to humans, is the usual chronological manifestation of preprogrammed complex biochemical organic alterations occurring in living matter.  The rate and type of these biochemical changes depends on the impact of localized specificities (cytoplasmic, organelle, cellular, tissue, organ, organismal, etc.), genetic sway and environmental influences.  As commonly used, aging is the cumulative phenotypic expression of these changes and which is associated with an increased risk of mortality.  Aging refers to functional and physiological deterioration and not just to the passage of time.

Theories on aging

Theories on aging have been plentiful, although none are currently proven.  Historically, a few of the more familiar ones are as follows:

The Rate of Living theory of Aging proposed in 1928 by Pearl 6

The Free Radical theory of Aging proposed in 1956 by Harman 7

The Pleiotropic gene theory of Aging proposed in 1957 by Williams 8

The Somatic Mutation theory proposed in 1959 by Szilard 9

The Error Catastrophe theory proposed in 1963 by Orgel 10

The Cross-linkage theory proposed in 1968 by Bjorksten 11

The Genetically Programmed theory of Aging proposed in 1968 by Hayflick 12

The Glycation theory of Aging proposed in 1985 by Cerami 13

The Disposable Soma theory of Aging proposed in 1990 by Kirkwood 14

The Free Radical theory of Aging

Some have estimated that there are over 300 theories on aging, none of which have been proven.  Half a century ago, Denham Harman proposed the "free radical theory," 15 which conjectured that widespread damage to cellular macromolecules could occur by exposure to environmental or metabolic production of free radicals in oxygen-requiring organisms.

Oxygen free radicals were believed to be causative of prevalent human pathophysiologies, such as cancer, atherosclerosis and diabetes. Therefore, these common diseases should be theoretically amenable to cure, prevention or reversal by the use of antioxidants. These predictions, based on the free radical theory, have repeatedly failed to be supported by large randomized, controlled trials (RCTs). 16-21  Redox chemistry is teeming with misnomers, misinformation, misrepresentations and half-truths.  Erroneously grouping oxidants as being bad and antioxidants as being good, serves no useful purpose and is an out dated concept.

The most widely accepted theory is that of Harman, 7 but the complex mechanisms that cause the deterioration of cellular functions during the aging process are extremely controversial and unproven. The hypothesis that senescent changes are caused primarily by ROS (reactive oxygen species) and the accumulation of macromolecular oxidative damage generated by reactive oxygen species (ROS), is touted as being supported by a considerable body of correlative evidence.  Although some research using animals has found an inverse correlation between levels of mitochondrial ROS and life span, a causative effect of ROS-promoted oxidation in limiting life span has not been established because of the inconsistent and/or nonexistent effects of antioxidants. 22, 23

The free radical theory has been so ingrained into the global orthodoxy that studies showing the failures of antioxidant vitamins have been met with "disappointment, surprise and denial."

The promises that antioxidant vitamins held for the control or even elimination of a wide variety of diseases have come up empty due to the fact that their anticipated benefits were based on the invalidated free radical theory. 24 This issue is discussed in great detail and is available in "The Howes Selective World Library of Oxygen Metabolism" at the www.thepundit.com website.

Fortunately, Harman's free radical theory 7 is a testable theory.  Unfortunately, it has failed to deliver on its claims of disease and aging prevention.

A half century of data has demonstrated its lack of predictability and inconsistencies.  Consequently, it has been discredited by the scientific method and widespread use of antioxidants has failed to quell the current pandemic of cancer, diabetes, and cardiovascular disease or to stop or reverse the aging process. 24

Danish researchers 25 have warned that consumers should be cautious about taking supplements containing nutrients. Supplements that millions of North Americans take to stave off disease and slow the aging process do not boost longevity and appear to actually increase the risk of dying.  Bjelakovic's analysis, which pooled data from 68 studies involving more than 232,000 people, found no evidence that taking beta-carotene, vitamin A or vitamin E extends life span.

In fact, Bjelakovic's analysis 25 found that beta carotene, vitamin A and vitamin E, taken singly or combined with other antioxidant supplements, were associated with increased all-cause mortality. Conservatively, the supplements increase the likelihood of dying by about 5 percent.  Vitamin C and selenium appeared to have no impact on longevity.  Antioxidants are marketed as health-promoting anti-aging products because they were thought to prevent disease and to slow down the aging process but this is not supported by current scientific studies in man. To the contrary, antioxidant vitamins have proven to have many undesirable and potentially harmful effects.

Summary of antioxidant vitamin studies showing 1) benefits, 2) no effects, 3) harmful effects and 4) increased mortality:

Antioxidant vitamin supplement effectiveness has been hotly debated.  Some critics claim benefits but others believe that they have no effect; whereas, others say that they are harmful.  Selective "cherry picking" of the data can be "manipulated" to support any of these four positions but I am convinced that the preponderance of the data indicates either a harmful effect or no effect at all.  The lack of predictability and inconsistency of results has effectively nullified the free radical theory of Harman.

I have reviewed studies on over 1 million participants and I have focused on studies showing either no benefits or harmful consequences secondary to antioxidant vitamin useage.  However, a balanced review requires that I also include studies showing the benefits of the antioxidant vitamins.  Also, the potential for harmful effects differs between the antioxidant vitamins, as does their chemical reactivity and is much less for vitamin C, which has prooxidant capability.  These are the best scientific studies available but inherent variables are numerous.

(Note:  These studies occurred at differing times, lengths of study, concentrations of vitamins, combinations of vitamins, source of vitamins, types of participants, varying states of health of participants, varying diets of participants, varying methods of statistical analysis, countries of origin, gender of participants, smoking and drinking habits of participants, varying body weights and BMIs, levels of daily exercise, varying levels of stress or depression of participants, types of questionaires used, varying study end points, genetic sway, environmental conditions, etc. Published details of these studies, as they were presented in the literature, can be found at www.thepundit.com.)

1) Studies suggesting benefits from antioxidant vitamin ingestion:

Vitamin E

CHAOS (1996) 26

ATBC (1997) 27

SPACE (2000) 28

Vitamins E & C

ASAP (2000) 29

IVUS (2002) 30

Papers by Wright 31 and Tribble 32 also indicated benefits with antioxidant vitamins but not increased longevity.

2) Studies showing no effect for the use of antioxidant vitamins either alone or in combination:

Vitamin E

GISSI (1999) 33

HOPE (2000) 34

PPP (2001) 35

MICRO-HOPE (2002) 36

VEAPS (2002) 37

Beta carotene

ATBC (1998) 38

SCPS (1996) 39

PHS (1996) 40

The Women's Health Study (1999) 41

Antioxidant vitamin combinations

ATBC (1998) 38

HPS (2002) 42

Current results from the Heart Outcomes Prevention Evaluation (HOPE) and Heart Outcomes Prevention Evaluation-The Ongoing Outcomes (HOPE-TOO) followed subjects over a mean duration of 7.0 years and vitamin E was not superior to placebo in terms of incident cancer, cancer deaths, major vascular events, or cardiovascular deaths.  Stringent statistical evaluation showed an increased risk of heart failure associated with vitamin E supplementation in multiple analyses, including a 19% increased risk of all heart failure events and a 40% increase in the risk of hospital admission due to heart failure. 34

Also, prospective, RCTs and meta analysis of various trials, (such as Vivekananthan's meta-study, 43 and Brown's study, 44) evaluating the effect of vitamin E and other antioxidant vitamins or their combinations on clinical manifestations of cardiovascular disease, cancer and diabetes, have consistently shown that commonly used antioxidant vitamin regimens (vitamins E, C, beta carotene, or a combination thereof) do not significantly reduce overall cardiovascular events, diabetes or cancer.

3) However, more recent studies utilizing RCTs show an alarming potential for harm:

Vitamin E

ATBC (1994) 45

Beta carotene

ATBC (1994) 45

Antioxidant vitamin combinations

CARET (1996) 46

HATS (2001) 44

WAVE (2002) 47

Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study (2002) 1

Scientific evidence recommends the consumption of a nutritious diet high in food sources of antioxidants and other cardioprotective nutrients, such as fruits, vegetables, whole grains, and nuts, instead of antioxidant supplements to decrease the risk of CVD. 48, 49 It does not support the use of antioxidant vitamin dietary supplements.

Additionally, "Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women" concludes that synthetic antioxidant vitamin supplements should not be used to prevent CVD (Class III, Level A Evidence). 50

4) RCTs showing an increase in overall MORTALITY:

ATBC (1994) 45 There was an increase in overall mortality and the study was stopped early.

A 2004 article by Kris-Etherton et al. 51 states that the ATBC study shows:

- Increase in overall mortality (vitamin E)

- Increase in hemorrhagic stroke (β-carotene) with more deaths due to:  ischemic heart disease, hemorrhagic stroke and ischemic stroke.

ATBC Sub-Study Shows Increased CVD Deaths 27 while studying 1,862 men, with prior myocardial infarction, who took α-tocopherol and β-carotene for 5.3 years. There were no significant differences in major coronary events but significantly more deaths from fatal coronary heart disease.

The Beta-Carotene and Retinol Efficacy Trial (CARET) (1996) 46 had 18,314 smokers, former smokers, and workers exposed to asbestos, were given β-carotene and vitamin A for 4.0 years, and they had a 28% increase in lung cancer incidence.  The trial was stopped 21 months early.  They particularly noted that the incidence of lung cancer and deaths from all causes decreased but did not disappear completely after the supplementation ceased.  The results of CARET and ATBC emphasize that chemoprevention trials require careful monitoring of all disease endpoints … even after the study intervention is discontinued."

The Iowa Women's Health Study (2004) by Duk-Hee Lee et al. 52 in the Nov. 2004 issue of American Journal of Clinical Nutrition, found that such supplements may actually promote the clogging of arteries.  They evaluated cardiovascular disease in 1,923 post-menopausal women with diabetes, part of the Iowa Women's Health Study, which collected data in 1986 about diets and vitamin C consumption in nearly 35,000 recruits.  The researchers found that women with diabetes consuming at least 300 milligrams of vitamin C per day faced 2.3 times the risk of death from stroke and 2 times the risk of dying from coronary artery disease as did diabetic women who took in less of the vitamin C.

The Women's Angiographic Vitamin and Estrogen (WAVE) Trial: 47 In postmenopausal women with coronary disease, neither hormone replacement therapy (HRT) nor antioxidant vitamin supplements (vitamins C & E) provide cardiovascular benefit. Instead, a potential for harm was suggested and seen with each treatment.  All-cause mortality was higher in the antioxidant group + HRT vs (hazard ratio) vitamin placebo group.

Miller's Meta-analysis (2004):  53 High-dosage vitamin E supplementation may increase all-cause mortality.  Johns Hopkins' investigator, Miller et al. performed a meta-analysis, including more than 135,000 subjects, and concluded that high doses of vitamin E increased mortality.

The authors of a meta-analysis of clinical trials of antioxidant supplements and gastrointestinal cancer concluded that random assignment to supplements may have increased overall mortality.  54 Among the seven high-quality trials reporting on mortality (131,727 participants), the fixed effect unlike the random effects meta-analysis showed that antioxidant supplements significantly increased mortality. They could not find evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, they seem to increase overall mortality.

Even though Harman has continued to revise and promote the free radical theory of aging for over half a century, 55-62 reliable scientific studies have found it to be unproven and at best, merely speculative.  Unfortunately, the use of antioxidant vitamins, as health promoting, disease-preventing and anti-aging agents, is based on a flawed theory.

CONCLUSION

Aging is an incredibly complex subject.  We barely have clues as to its cause, its meaning and its control.  Aging rates and processes vary widely between and within varying species. All 100 billion people who ever lived, aged and died.  Predictably, this pattern will be repeated for some distance into the foreseeable future.  Although it has serious adverse effects, caloric restriction without malnutrition holds some promise for slight increases in longevity in man but the jury is still out.

Randomized, double-blind controlled trials in humans, which are the clinical "gold standard," have repeatedly shown that the free radical theory lacks predictability and fails to be validated by the scientific method.  Yet, the lucrative multi-billion dollar market, which peddles antioxidant vitamins, as "health miracles and fountains of youth," has overtones of medical quackery.

Relative to the antioxidant vitamin studies, a co-author with Bjelakovic, Dr. Gluud, said these observations (i.e., that antioxidant vitamins are harmful) were "a huge disappointment," but added that at least it has been discovered. "We must see the positives in this. The question has been thoroughly addressed and we now know the answer - these agents (i.e., antioxidant vitamins) are harmful. The companies selling these anti-oxidant vitamins have been able to dodge the issue for a long time, saying that any negative data has not been comprehensive. They cannot do this any longer. There are lessons to be learnt here, for example, the importance of conducting trials with these agents and publishing the results."

Dr. Gluud feels that food supplements should be regulated in the same way as medical products. "The governments of the world now have the responsibility to inform people of these results. They have been too slow in the past in requesting that health supplements are properly evaluated, and allowing these products to be added to foods. People have been buying these supplements and foods advertised as having these supplements added under the impression that they are good for them, when in actual fact they are harmful. Any potential health supplements should not be allowed to be added to foods unless they have been shown to be beneficial, or at least proven not to be harmful."

I feel strongly that caution should be advocated for the use of antioxidant vitamins as elixirs of health and as anti-aging agents.  To my knowledge, there are no human studies which prove that the antioxidant vitamins can meaningfully increase the lifespan; whereas, studies have repeatedly shown that they have significant potential for producing harmful adverse effects and/or predisposing to increased risks of cancer, heart disease and strokes.  The harmful aspect of antioxidant vitamins is based on the premise that they counteract crucial protective oxidative biochemical mechanisms for normal pathogen and neoplasia protection.  Even worse, they have been shown to be responsible for increased mortality rates and shortened life spans.  It is time to acknowledge the fact that the free radical theory has fallen and creative new ways to combat disease and aging are needed.

In the end, once the data has been presented and reviewed, one has to draw their own conclusions as regards recommending, prescribing or using antioxidant vitamins for so-called aging and disease prevention.  Ultimately, patient safety should remain the priority.

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Peer-review ratings (from 1 review, where a score of 100 represents the ‘average’ level):
Originality = 50.00, importance = 125.00, overall quality = 100.00
This Article was published on 12th January, 2008 at 15:54:58 and has been viewed 7225 times.

1 Peer review [reviewer #47336] added 19th November, 2011 at 03:35:02

There are already very explicit and well-documented, official guidelines in place for the intake of vitamins and anti-oxidants:
http://ods.od.nih.gov/HealthInformation/DS_WhatYouNeedToKnow.aspx

The statements form this source agree with some of the views expressed in this article, but are often more specific, such as the following citation:
“Dietary Supplements: What You Need to Know- An assortment of dietary supplement pills and tablets:

The majority of adults in the United States take one or more dietary supplements either every day or occasionally. Today’s dietary supplements include vitamins, minerals, herbals and botanicals, amino acids, enzymes, and many other products. Dietary supplements come in a variety of forms: traditional tablets, capsules, and powders, as well as drinks and energy bars. Popular supplements include vitamins D and E; minerals like calcium and iron; herbs such as echinacea and garlic; and specialty products like glucosamine, probiotics, and fish oils.
==The Dietary Supplement Label==

All products labeled as a dietary supplement carry a Supplement Facts panel that lists the contents, amount of active ingredients per serving, and other added ingredients (like fillers, binders, and flavorings). The manufacturer suggests the serving size, but you or your health care provider might decide that a different amount is more appropriate for you.
==Effectiveness==

If you don’t eat a nutritious variety of foods, some supplements might help you get adequate amounts of essential nutrients. However, supplements can’t take the place of the variety of foods that are important to a healthy diet. Good sources of information on eating well include the Dietary Guidelines for Americans and MyPlate.

Scientific evidence shows that some dietary supplements are beneficial for overall health and for managing some health conditions. For example, calcium and vitamin D are important for keeping bones strong and reducing bone loss; folic acid decreases the risk of certain birth defects; and omega-3 fatty acids from fish oils might help some people with heart disease. Other supplements need more study to determine their value. The U.S. Food and Drug Administration (FDA) does not determine whether dietary supplements are effective before they are marketed.

==Safety and Risk==

Many supplements contain active ingredients that can have strong effects in the body. Always be alert to the possibility of unexpected side effects, especially when taking a new product.

Supplements are most likely to cause side effects or harm when people take them instead of prescribed medicines or when people take many supplements in combination. Some supplements can increase the risk of bleeding or, if a person takes them before or after surgery, they can affect the person’s response to anesthesia. Dietary supplements can also interact with certain prescription drugs in ways that might cause problems. Here are just a few examples:

- Vitamin K can reduce the ability of the blood thinner Coumadin® to prevent blood from clotting.
- St. John’s wort can speed the breakdown of many drugs (including antidepressants and birth control pills) and thereby reduce these drugs’ effectiveness.
- Antioxidant supplements, like vitamins C and E, might reduce the effectiveness of some types of cancer chemotherapy.

Keep in mind that some ingredients found in dietary supplements are added to a growing number of foods, including breakfast cereals and beverages. As a result, you may be getting more of these ingredients than you think, and more might not be better. Taking more than you need is always more expensive and can also raise your risk of experiencing side effects. For example, getting too much vitamin A can cause headaches and liver damage, reduce bone strength, and cause birth defects.

—Excess iron causes nausea and vomiting and may damage the liver and other organs.

Be cautious about taking dietary supplements if you are pregnant or nursing. Also, be careful about giving them (beyond a basic multivitamin/mineral product) to a child. Most dietary supplements have not been well tested for safety in pregnant women, nursing mothers, or children.

If you suspect that you have had a serious reaction from a dietary supplement, let your health care provider know. He or she may report your experience to the FDA. You may also submit a report to the FDA by calling $\bf 800-FDA-1088$ or completing a form online. In addition, report your reaction to the dietary supplement company by using the contact information on the product label.”

Originality: 2, Importance: 5, Overall quality: 4

2 Additional peer comment [reviewer #47336] added 19th November, 2011 at 03:43:38

A second comment concerns the RDA discussed in the article. A more significant index than the RDAs is known as the Daily Value or DV:
” $$\em Daily Values Recommended intakes of nutrients vary by age and gender and are known as Recommended Dietary Allowances (RDAs) and Adequate Intakes (AIs). However, one value for each nutrient, known as the Daily Value (DV), is selected for the labels of dietary supplements and foods. A DV is often, but not always, similar to one’s RDA or AI for that nutrient. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers determine the level of various nutrients in a standard serving of food in relation to their approximate requirement for it. The label actually provides the %DV so that you can see how much (what percentage) a serving of the product contributes to reaching the DV. DV Tables 14. Appendix F: Calculate the Percent Daily Value for the Appropriate Nutrients Guidance for Industry: A Food Labeling Guide This document also available en Español (Spanish) , ???? (Arabic PDF, 1.29MB), ????? (Hindi PDF, 1.46 MB), ???? (Simplified Chinese PDF, 2.85MB), ?? (Japanese PDF, 1.23MB) The document below is available in several foreign language(s). FDA offers these translations as a service to a broad international audience. We hope that you find these translations useful. While the agency has attempted to obtain translations that are as faithful as possible to the English version, we recognize that the translated versions may not be as precise, clear, or complete as the English version. The official version of this document is the English version. *Contains Nonbinding Recommendations*. There are two sets of reference values for reporting nutrients in nutrition labeling: 1) Daily Reference Values (DRVs) and 2) Reference Daily Intakes (RDIs). These values assist consumers in interpreting information about the amount of a nutrient that is present in a food and in comparing nutritional values of food products. DRVs are established for adults and children four or more years of age, as are RDIs, with the exception of protein. DRVs are provided for total fat, saturated fat, cholesterol, total carbohydrate, dietary fiber, sodium, potassium, and protein. RDIs are provided for vitamins and minerals and for protein for children less than four years of age and for pregnant and lactating women. In order to limit consumer confusion, however, the label includes a single term (i.e., Daily Value (DV)), to designate both the DRVs and RDIs. Specifically, the label includes the % DV, except that the % DV for protein is not required unless a protein claim is made for the product or if the product is to be used by infants or children under four years of age. The following table lists the DVs based on a caloric intake of 2,000 calories, for adults and children four or more years of age. Food Component DV Total Fat 65 grams (g) Saturated Fat 20 g Cholesterol 300 milligrams (mg) Sodium 2,400 mg Potassium 3,500 mg Total Carbohydrate 300 g Dietary Fiber 25 g Protein 50 g Vitamin A 5,000 International Units (IU) Vitamin C 60 mg Calcium 1,000 mg Iron 18 mg Vitamin D 400 IU Vitamin E 30 IU Vitamin K 80 micrograms µg Thiamin 1.5 mg Riboflavin 1.7 mg Niacin 20 mg Vitamin B6 2 mg Folate 400 µg Vitamin B12 6 µg Biotin 300 µg Pantothenic acid 10 mg Phosphorus 1,000 mg Iodine 150 µg Magnesium 400 mg Zinc 15 mg Selenium 70 µg Copper 2 mg Manganese 2 mg Chromium 120 µg Molybdenum 75 µg Chloride 3,400 mg In order to calculate the % DV, determine the ratio between the amount of the nutrient in a serving of food and the DV for the nutrient. That is, divide either the actual (unrounded) quantitative amount or the declared (rounded) amount (see next section) by the appropriate DV. When deciding whether to use the unrounded or rounded value, consider the amount that will provide the greatest consistency on the food label and prevent unnecessary consumer confusion. The nutrients in the table above are listed in the order in which they are required to appear on a label in accordance with 21 CFR 101.9(c). This list includes only those nutrients for which a DRV has been established in 21 CFR 101.9(c)(9) or a RDI in 21 CFR 101.9(c)(8)(iv).”$$

(Source: http://ods.od.nih.gov/HealthInformation/dailyvalues.aspx Page Last Updated: 05/23/2011 )

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