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Howes M.D., PhD., R. (2007). Antioxidant Vitamins A, C and E:  Assessing Potential for Harm. PHILICA.COM Article number 83.

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Antioxidant Vitamins A, C and E: Assessing Potential for Harm

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

Published in medi.philica.com

The overwhelming preponderance of the lay and scientific literature speculates that so-called antioxidants are allegedly the cure-all for purported oxygen free radical induced human pathophysiologies, inclusive of aging. For the free radical theory, as applied to oxidative stress and aging to be correct, antioxidant usage should prevent, reverse or eliminate these scourges of mankind. To the contrary, large, randomized, controlled, double blind studies in man have repeatedly failed to confirm the predictions of the free radical theory as it relates to possible disease prevention or reversal. Actually, meta-analysis studies have shown that some antioxidants appear to increase the incidence of cancer, cardiovascular disease, stroke and overall mortality. As a consequence of their lack of effectiveness, many major health-related organizations do not recommend the use of antioxidant vitamins A, C and E. Epidemiologic studies, observational studies and in vitro studies have been particularly confusing, when compared with randomized, controlled trials. Although significant harm has been suggested, data inconsistencies and diametrically opposed experimental results indicate that more research is needed before reliably clear conclusions can be made as regards the efficacy, safety or potential harm of the antioxidant vitamins A, C and E. Mounting evidence from the overall data highlights the lack of the predicted benefits of the antioxidant vitamins in disease prevention and indicates their potential to do harm.

Article body


Over 50 years ago, Denham Harman1 proposed the "free radical theory," which conjectured that widespread damage to cellular macromolecules could occur by exposure to environmental or metabolic production of free radicals in aerobic organisms.

Oxygen free radicals were believed to be causative of prevalent human pathophysiologies, such as cancer, atherosclerosis and diabetes. Therefore, these common diseases were 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 clinical trials (RCTs) 2-7.  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. 2-7

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).

There is no clear evidence of benefit from antioxidant supplementation in people who do not have underlying deficiencies. Studies have shown that electronically modified oxygen derivatives (EMODs) have tumoricidal activity, which can induce apoptosis of neoplastic cells and that apoptosis and the action of chemotherapeutic drugs can be blocked by antioxidants. 2-7  This action has extreme harmful ramifications as regards cancer proliferation.

Of even greater concern is the fact that many of these large studies indicate that antioxidant vitamins are causing increases in cardiovascular diseases, strokes, cancer and overall mortality.  Nonetheless, following huge marketing campaigns, many patients have taken antioxidant vitamins to assure good health and have nonchalantly assumed that these antioxidant vitamins would not cause them any harm, even if it did not prevent disease. Consequently, 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.  Nonetheless, certain vitamin supplements may be beneficial for some people, such as pregnant women, women of childbearing age, and people with restricted dietary intakes.


Indications of adverse or harmful effects resulting from the use of the antioxidant vitamins A, C and E have surfaced in a number of large RCTs.  To wit:

α-Tocopherol, β-Carotene Cancer Prevention Study 8 (ATBC Cancer Prevention Group, 1994);  Country:  Finland; Study Type:  Primary prevention; randomized, double-blind, placebo-controlled intervention; Study Population:  29,133 male cigarette smokers, aged 50-69 years; Duration of Treatment Years:  6; Daily Dose:  50 mg α-tocopherol and/or 20 mg β-carotene; Primary Disease Outcome:  Lung cancer; Results:  50% increase in hemorrhagic stroke deaths among vitamin E group; 11% increase in ischemic heart disease deaths among β-carotene group; 18% increase in lung cancer among β-carotene group; no effect of vitamin E on lung cancer. Men with known coronary artery disease given 50 mg of a synthetic vitamin E had no reduction in fatal heart attacks.  There was an increase in overall mortality and the study was stopped early.

A 2004 article by Kris-Etherton et al.9 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

The β-Carotene and Retinol Efficacy Trial (CARET) (Omenn et al., 1996) 10; Country:  US; Study Type:  Primary prevention; randomized, double-blind, placebo-controlled intervention;  Study Population:  14,254 heavy smokers and 4,060 asbestos workers, aged 45-69 years; Duration of Treatment Years:  4; Daily Dose:  30 mg β-carotene, 25,000 IU retinol (as retinyl palmitate); Primary Disease Outcome:  Lung cancer; Results:  28% increase in lung cancer; 26% increase in CVD (nonsignificant); 17% increase in total mortality among treatment group. Also, there was no effect on CVD mortality. This study was also stopped early.

Note:  A 6-year follow-up of a large, randomized trial in people with a history of smoking has found that the overall harm associated with beta-carotene supplementation on cardiovascular disease mortality disappeared quickly after participants stopped taking the supplements. However, the risk of lung cancer may persist, especially in females and former smokers, according to the study in the December 1, 2004 issue of the Journal of the National Cancer Institute. 11  Gary E. Goodman, M.D., of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues followed the more than 18,000 participants in CARET for 6 years after the trial was stopped, until the end of 2001.The increased risk of cardiovascular disease mortality quickly disappeared after participants stopped taking the supplements. However, women had a higher risk of death from cardiovascular disease or from any cause than men. In addition, the incidence of lung cancer and deaths from all causes decreased but did not disappear completely after the supplementation ceased. The excess risk of lung cancer was restricted primarily to females and former smokers. The results of CARET and ATBC emphasize that chemoprevention trials require careful monitoring of all disease endpoints … even after the study intervention is discontinued."

ATBC Sub-Study Shows Increased CVD Deaths (Rapola, 1997)12: 1,862 men, with prior myocardial infarction, 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 Alpha Tocopherol Beta Carotene Cancer Prevention Trial reported an increase in cerebral hemorrhage for participants who were taking 50 mg of vitamin E daily compared with placebo. 13

The Iowa Women's Health Study 14 by Duk-Hee Lee et al. 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. 

In the secondary prevention HDL Atherosclerosis Treatment study (HATS) 15, In a three-year, double-blind trial, 160 patients with coronary disease, subjects were randomized to simvastatin (lipid-lowering) plus niacin treatment, or antioxidants (vitamin C, α-TOH, β-carotene, and selenium) or a combination of both. Compared with no treatment, only simvastatin/niacin significantly lowered stenosis progression rate and favorably altered plasma lipid profiles. Antioxidant supplementation alone had no significant effect on clinical end points but, notably, when used in combination with simvastatin/niacin, antioxidants negated the benefit of the latter on plasma lipid profile and stenosis progression.  Simvastatin/niacin alone induced 0.4% atheroregression, whereas adding antioxidant cocktail resulted in a stenosis progression of 0.7%.

The Vitamin E Atherosclerosis Prevention Study (VEAPS) 16 examined the effect of 400 IU/day D,L-α-TOH on the progression of carotid artery intima-to-media thickness in men and women with LDL cholesterol 3.37 mM (130 mg/dl) and no clinical signs or symptoms of cardiovascular disease. A total of 353 participants were recruited to accommodate the anticipated dropout rate (353 were randomized (176 placebo, 177 vitamin E). Vitamin E supplements for 3 years did not reduce the progression of atherosclerosis compared with subjects randomized to placebo; rather, there was a borderline disease-promoting effect of α-TOH supplements.

Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study 17 of antioxidant vitamin supplementation in 20,536 high-risk men and women, aged 40-80 years; found that vitamin E, vitamin C, and beta-carotene supplementation resulted in small but significant increases in plasma Tchol (serum total cholesterol), LDL-C (low density lipoprotein-cholesterol), and TG (triglyceride) concentrations.

The Women's Angiographic Vitamin and Estrogen (WAVE) Trial: 18  This was a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. Patients received 800 IU of vitamin E and 1000 mg of vitamin C plus HRT.  In postmenopausal women with coronary disease, neither 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 Meta-analysis: 19  High-dosage vitamin E supplementation may increase all-cause mortality.  (Miller et al. 2004) Meta-analysis, including more than 135,000 subjects, concluded that high doses of vitamin E increased mortality. Researchers said the current U.S. dietary guidelines do not recommend vitamin E supplementation, but indicate that the upper tolerable limit of intake is 1000 IU per day. "These results parallel the findings of beta carotene supplementation trials. Two major studies showed that beta carotene supplementation results in an increased risk for lung cancer and death. And, as a result, you will never see beta carotene supplements recommended again," Miller said.

Miller et al. 19 reported the results of a carefully conducted meta-analysis of clinical trials of vitamin E supplementation concluding that high doses of this agent increase the risk for death. Their meta-analysis involved data from 19 randomized trials, which recorded 12,504 deaths. Overall, being randomly assigned to receive vitamin E had no effect, either positive or negative. However, the data suggested a decreased risk for death associated with vitamin E in trials that used lower doses (<400 IU) and showed a statistically significant trend towards increased risk at doses of 400 IU and above. Thus, it may be wrong to focus on a single element of the diet; guidelines from some professional or governmental panels recommend attempting to obtain vitamins and minerals from food sources rather than from supplements. 20

Recent studies repeatedly question the benefits of antioxidant vitamins and acknowledge their harmful potential. 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. 21

Of particular concern, more evidence for an elevated mortality risk at high doses of vitamin E comes from 2 other trials that administered vitamin E together with ß-carotene, a supplement previously associated with an increased risk for death. 17, 22

Raymond Gibbons, MD, a professor of medicine at the Mayo Clinic in Rochester, Minnesota, said he has been urging his patients to stop taking vitamin E for years. Dr. Gibbons said that cardiovascular disease prevention guidelines from "vitamin E is ‘not recommended'. It doesn't get clearer than that - don't take it." In an interview, Dr. Gibbons said he hopes this latest report will finally debunk the vitamin E myth.

Dr. Gibbons said, "In the British Heart Protection Study, 17 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 (MRC/BHF Heart Protection Study), 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.

In a Trial of Antioxidant Vitamins to Prevent Second Primary Cancers in Head and Neck Cancer, 23 Canadian researchers reported that taking vitamin E doesn't protect head and neck cancer patients from developing new tumors and in fact, it may actually raise the risk of developing a second cancer. 21  The study, published in the Journal of the National Cancer Institute, is the second recent piece of research to cast doubt on the use of vitamin E against cancer. A team of international researchers recently said vitamin E supplements don't offer any protection against cancer but may well raise the risk of heart failure in some patients.

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 new study, led by researchers at L'Universite Laval in Quebec, involved 540 patients with stage 1 or 2 head and neck cancer (oral cavity, pharynx and larynx). During radiation therapy and for 3 years after, half the patients took daily vitamin E supplements (400 IU, or international units), while the other half took a placebo. (Some of the vitamin E patients were also given beta carotene supplements, but these were stopped after about 1 year, when another study, the CARET study, showed beta carotene could increase the risk of lung cancer in smokers.).

People who took the vitamin E had a significantly higher rate of second cancers than people who took the dummy pill. In the years they were taking the pill, vitamin E appeared to more than double the risk of developing a second cancer. Once they stopped, however, their rate of second cancers was lower than that of people on the placebo. And after 8 years of follow up, the rate of second cancers in both groups was the same. The rates at which the initial cancers came back followed the same pattern.

"Nevertheless," 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. 22

In an editorial published in the same issue of the journal, 24 two head and neck cancer specialists from M.D. Anderson Cancer Center in Houston said future studies must use genetic clues called biomarkers to carefully select a substance that's likely to have an effect against this type of cancer, and to find the patients most likely to benefit from it.

Vitamin E supplements may increase heart failure risk. In 2005, the Heart Outcomes Prevention Evaluation (HOPE) investigators report an extension of the 9541-patient HOPE Vitamin E trial. 25  Eva Lonn, M.D., of the Population Health Research Institute and McMaster University, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada, and colleagues conducted a study to evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. The randomized, double-blind, placebo-controlled trial (Heart Outcomes Prevention Evaluation [HOPE]) was initially conducted between December 21, 1993, and April 15, 1999, and included patients at least 55 years old with vascular disease or diabetes mellitus. This trial was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) to between April 16, 1999, and May 26, 2003.

In the 2.5-year extension of HOPE (HOPE-TOO) 174 of the original 267 centers continued an extended follow-up. From these centers, 3994 of the 7030 original study enrollees who were still alive elected to continue the randomized vitamin E/placebo drug assignment. After a mean of 7.2 years of follow-up, vitamin E did not significantly reduce the relative risk (RR) of total cancer incidence, of cancer death, or a composite of cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and stroke, or of individual components of this composite end point. These findings of lack of benefit from vitamin E (natural source, 400 IU -tocopheryl acetate) during the extended study are consistent with the original HOPE report and with recent meta-analyses of Vivekananthan 26 and Miller. 19  Another subgroup finding in HOPE-TOO was a vitamin E-associated increased risk of heart failure incidence that appeared in a secondary end point analysis in the 4.5-year report and persisted in the 7-year extended follow-up, as did the risk of hospitalization for heart failure. 

The researchers reported the following: "In the HOPE and HOPE-TOO trials, the daily administration of 400 IU of natural source vitamin E for a median of 7.0 years had no clear impact on fatal and nonfatal cancers, major cardiovascular events, or deaths. We observed an increase in the risk of heart failure, which is of concern. Although this adverse effect of vitamin E was unexpected and cannot be confirmed at this time by other trials, our data are internally consistent. Therefore, a meta-analysis of heart failure events including all completed large vitamin E trials is strongly recommended."

"In conjunction with its lack of efficacy, the potential for harm suggested by our findings strongly supports the view that vitamin E supplements should not be used in patients with vascular disease or diabetes mellitus," the authors write. "Our study also has wider implications. There is a tendency to accept 'natural products' (e.g., vitamins) as being safe, even if they have not been proven to be effective. However, our findings emphasize the need to thoroughly evaluate all vitamins, other natural products, and complementary medicines in appropriately designed trials before they are widely used for presumed health benefits." These authors concluded that in patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.

A recent author questions whether or not there is any hope for vitamin E. In an accompanying editorial, 27 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, discuss the findings of the HOPE-TOO trial.

"Why is this report important? First, by extending HOPE 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. Second, in doing so, 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."

They conclude that, "The hopes for vitamin E alone or in combination with vitamin C and beta carotene have been diminished by a compelling body of clinical trial evidence, and by certain adverse effects with plausible biological explanation. These hopes are now confined to modest expectations for specific disorders and there are concerns about adverse effects."

Madamanchi et al. 28 state 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, when most use of vitamins occurs, has no favorable health effects, and meta-analysis studies and randomized controlled clinical trials raise the serious possibility of harm. If harmful manifestations of antioxidant vitamins occur, they would be expected to present with a prolonged and gradual onset and not as an acute toxicity.  Curiously, many users of nutritional supplements report that they would continue to take the supplements even if they were shown to be ineffective in scientific clinical studies. 29

With all of the above said, a new study is being cited which somewhat confounds the whole issue of antioxidant vitamin safety, especially for vitamin E. Many studies are at complete odds with the conclusions drawn by many other studies.  A Blomhoff 30 review stated that, "Although initial studies have indicated that antioxidants may reduce oxidative stress, human intervention studies do not support a beneficial effect of antioxidant supplements." Yet, unbelievably favorable results were presented in a recent 2006 report by Wright et al. 31 published in the American Journal of Clinical Nutrition, which found that male smokers in the ATBC study population, who had the highest blood levels of vitamin E, suffered significantly fewer deaths than comparable male smokers who had lower blood levels of this essential vitamin. Almost miraculously, there was an 18% lower risk of deaths from all causes. Included in this figure are results relating to specific causes of death, including a 21% reduction in deaths from cancer, a 19% reduction in deaths from cardiovascular disease and an incredible 30% reduction in deaths from all other causes. Wright et al. make the astounding claim that high blood levels of vitamin E reduced the risk of dying from prostate cancer by 32%, lung cancer 21%, ischemic stroke 37%, hemorrhagic stroke 35% and respiratory disease 42%. Wright's results are so out of line with other large RCTs that they seem similar to those studies previously sponsored by supplement manufacturers or marketers and thus, they beg for closer scientific and analytical scrutiny.

Less serious adverse effects of antioxidant vitamins, such as yellowing of the skin or cutaneous abnormalities, were not covered in this paper but have been addressed in other studies, i.e., AREDS, 2001 32; MONMD, 1996 33; Xuan et al., 1991 34; Grouhi and Sussman, 2002 35; Gulati et al., 1999 36; and Ohtake et al., 2005. 37   Also, adverse effects of hypervitaminosis, which are well known and documented, with the antioxidant vitamins A, C and E were not addressed here.

Thus, the answer to the question, "Can antioxidant vitamins cause harm?" is likely to be, "Yes.' ‘No.' and ‘It depends."  The answer is that there is currently no clear, resounding, categorical, unambiguous answer. Criticisms abound as regards study designs and analytical techniques for both proponents of the safety of antioxidant vitamins and for those who suggest the potential harmful aspects of the antioxidant vitamins. The finding of possible harm (death) 8,19, 38 with higher doses of vitamin E was surprising to physicians and nutritionists and has serious implications for the tens of millions of people who regularly use vitamin E supplements, even in view of the Wright et al. 31 publication.

Additionally, Wright's results are theoretically completely counter to the experimental results of Salganik et al. 39, who observed a reduction in brain tumor size in the TgT  transgenic mouse model, which spontaneously develops brain cancer, when these mice were fed diets depleted of antioxidants. 40  There was enhanced apoptosis within tumors of antioxidant depleted mice.  Recently, colleagues extended this observation to another cancer type, breast cancer. 41 

Using a transgenic mouse model of mammary tumorigenesis with defined rates of tumor growth and lung-targeted metastasis, Salganik et al. 39 determined that dietary antioxidant depletion inhibited tumor growth and diminished metastasis. Compared with control mice fed a standard diet, mice fed an antioxidant-depleted diet exhibited tumor-targeted generation of reactive oxygen species; the number of apoptotic cells in tumors increased 5-fold, and the percentage of tumor cells undergoing mitosis decreased by half. The mice fed the antioxidant-depleted diet had more small primary tumors and fewer large primary tumors than did controls, and they also had <30% of the number of lung metastatic tumor foci compared with mice fed the control diet.

Huang et al. 42 reported that 2-methoxyestradiol (2-ME), which generates EMODs, kills cancer cells taken from patients with several types of leukemia (chronic lymphocytic, chronic myelogenous, acute lymphocytic, acute myelogenous) as well as five different tumor cell lines. The administration of EMOD antioxidant scavengers in combination with 2-ME prevented the accumulation of superoxide and scavengers blocked EMOD induced apoptosis. 43

One has to look at the data and draw their own conclusions as regards relative safety or danger of the antioxidant vitamins. One can select data to support either of these opposing viewpoints or to argue that the antioxidant vitamins have little or no effect on disease prevention or delaying aging. Hopefully, the quality of individual studies and the preponderant suggestions of the data may give future insights into the issue of antioxidant vitamin safety or danger.

Many of the major health-related organizations do not recommend the use of antioxidant vitamins because of their purported harmful potential. I have proposed new theoretical paradigms to provide a better understanding of the role of EMODs and antioxidant vitamins in homeostatic health and disease, 2,3 which are available at www.thepundit.com. It is my belief that EMODs are of low toxicity, that they are essential secondary cellular messengers and that antioxidants may serve as co-oxidants to promote electron and proton flow, to regulate cellular redox status and to aid prooxidant protection. 2-7


Of significant current concern is the common and widespread practice of antioxidant food fortification and genetic engineering, which also is presently being done to artificially increase the antioxidant content of fruits and vegetables. Yet, few, if any, of these manufacturers point out the potential dangers of the antioxidant vitamins.  Our single most important obligation is to provide the public with the best current state of our knowledge with respect to the risk and benefits associated with these agents and to provide consumers with products of utmost safety. Since the data is so inconsistent and since there is now the widespread ingestion of fortified foods, consumer safety is of paramount importance. Informed consumers will have to make their own decisions as regards personal antioxidant vitamin supplementation. Caveat emptor.

When considered in its totality, the above data presents a compelling argument that antioxidant vitamins have considerable potential to do harm.  In the absence of vitamin deficiency states, one should consider refraining from the injudicious use of antioxidant vitamins.  Even considering the glowing recent report regarding vitamin E, there is an obligation to bring these possible antioxidant dangers to the attention of the general public and to create an awareness of the increased potential risk of developing cardiovascular disease, cancer, strokes and overall mortality by the unsupervised use of antioxidant vitamins. However, it is clear that considerable additional research is needed to arrive at a credible conclusion as regards the overall efficacy, safety or harm of the antioxidant vitamins A, C and E.


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Contact information:

Prof. Hon. Randolph M. Howes, M.D., Ph.D.

Adjunct Assistant Professor of Plastic Surgery, The Johns Hopkins Hospital, Baltimore, Md., U.S.A. and Espaldon Professor of Plastic and Reconstructive Surgery, University of Santo Tomas, Manila, Philippines.

Address for communication: 27439 Highway 441, Kentwood, Louisiana 70444-8152, USA. Email: rhowesmd@hughes.net


Information about this Article
Peer-review ratings (from 1 review, where a score of 100 represents the ‘average’ level):
Originality = 25.00, importance = 50.00, overall quality = 50.00
This Article was published on 15th February, 2007 at 16:30:55 and has been viewed 9311 times.

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The full citation for this Article is:
Howes M.D., PhD., R. (2007). Antioxidant Vitamins A, C and E: Assessing Potential for Harm. PHILICA.COM Article number 83.

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1 Peer review [reviewer #47336unconfirmed user] added 30th September, 2011 at 14:45:37

For the main point of the article to be valid one needs to specify antioxidant and/or vitamin doses and compare these with FDA recommendations. Without such specifications one might conclude from the article that any intake of vitamins would be detrimental, which is obviously false. One knows that the contrary is true: that severe vitamin deficiency does have undesirable health consequences for humans—and this is why they are called ‘vitamins’-meaning ‘vital’ compounds for human survival that human metabolism does not synthesize. Therefore, a specification of the high levels, or ‘megadoses’, at which antioxidants and/or vitamins would have detrimental effects to human health should be specified. Higher vitamin E doses were mentioned in the article but no numbers or dose ranges were specified. Without such high dose specifications the article remains much too vague to be useful. Clearly references cited contain the implied doses, but their elimination from this part-review article does not help the reader and diminishes tremendously the value of this article. Perhaps in a follow-up article, or an improved version of this first article, such numbers/specific doses or ranges would be specified along with the most relevant details of the patient populations on which the studies were made, as well as the methodology, etc.

Moreover, such ‘higher doses’ are known to have effects that vary both with age and gender, etc. Not to mention the balancing of B-vitamins, etc.

Although coenzyme coQ10 is not classified as a ‘vitamin’ because it is synthesized in the human body, daily recommended doses of coQ10 of 10 to 20 mg/day are being recommended by many Japanese physicians for ‘improving the quality of life and health’ of tens of millions of patients diagnosed with heart diseases. Does the author also consider coQ10 at such doses to be detrimental to the health of patients diagnosed with heart diseases, such as CHD.

Clearly, as stated by the author, there are problems with the correct understanding of the *in vivo* redox balance in humans, as well as in animals. It would have been therefore desirable to at least suggest in this article how our understanding of the *in vivo redox potential* might be improved, or even approached.

Originality: 1, Importance: 2, Overall quality: 2

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