Health Supreme by Sepp Hasslberger

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February 28, 2007

Synthetic Antioxidants 'Can Harm Your Health'

Antioxidants are part of many plants and a myriad of foods we eat every day. Their health promoting effects have been well documented. Antioxidants work by donating an electron to a molecule that has been compromised by oxidation, bringing it back into a state of proper function. Having been "used up" in this way, the antioxidant molecule is then either re-charged by accepting an electron from another type of antioxidant or it is re-cycled into building material such as - in the case of vitamin C - collagen for purposes of tissue repair.


Veggies - Image: HealthyNJ

According to this Wikipedia entry,

"Antioxidants are widely used as ingredients in dietary supplements, which are used in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease. Although some studies have suggested antioxidant supplements have health benefits, other large clinical trials did not detect any benefit for the formulations tested, and excess supplementation may even be harmful."

Despite this warning and the campaign against antioxidants - don't throw out your supplements just yet.

Vitamins 'could shorten lifespan' and Antioxidants Don't Mean Longer Life are the titles of some typical articles discussing the findings of a Danish meta analysis of clinical trials involving beta carotene, vitamin A and vitamin E which was recently re-published by JAMA, the Journal of the American Medical Association. The results - a slight increase in mortality in those taking the pills - contradict both experience and good sense. They are opposed to the results of a large number of epidemiological studies, which have found positive effects of higher levels of intake of the natural antioxidants in fruits and vegetables.

The doubt being thrown on the healthful properties of antioxidants, says Beldeu Singh, is due to the fact that many studies designed to clinically test the effects of antioxidants do not take into account nutrient synergy - they are designed around the use of only one single substance. But what's even more important, when researching "antioxidants" - they are not even using the real thing! Most pharmaceutical studies rely on synthetic versions or artificial analogs of these healthy nutrients.

The difference seems to be that, contrary to the natural variety, the synthetic analogs cannot be recycled and re-used by the organism, once they have donated their electron. When they are "spent", they tend to turn into harmful metabolic byproducts that increase, rather than decreasing, the total load of oxidative stress on the organism. That may, according to Beldeu Singh, explain the apparently contradictory results.

There is another 'confounding' factor: The ease with which a meta analysis - a study that examines only the results of previous studies and re-interprets them - can be manipulated to say almost anything and the contrary of it. Meta analyses have previously been used by pharmaceutical interests to show how wonderful their products are, or how bad the (competing) non-patentable natural substances are.

In this case, the statistical 'cherry picking' seems to have been particularly egregious, according to an analysis of the analysis ... see Poor methodology in meta-analysis of vitamins (PDF)

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Beldeu Singh

We know that food and dietary sources contain antioxidants. Minerals and antioxidants are part of our nutritional intake and epidemiological studies show that populations with high antioxidant intake from dietary sources are at a lower risk to diseases such as cancers, hypertension cardiovascular disease, stroke etc more so in contrast with malnourished people.

We also know the role of antioxidants in our biochemistry is to scavenge free radicals or convert hydrogen peroxide formed during cell metabolism into water and oxygen as soon as it is formed and that ability is part of health.

Yet studies try to show that antioxidants are "harmful". If so, do not take fruits and vegetables for they are rich sources of natural antioxidants! Go on a diet that is low or devoid of that what these scientists want you to believe? Utter rubbish. But science does not spew such rubbish, only the conclusions of some scientists.

If your diet is low in natural antioxidants, free radicals begin to be in excess of your antioxidant ability to biochemically neutralize them (scavenge) and there will be oxidative damage and free radical chain reactions that will damage molecules and cell membranes and quickly lead to the development of disease states as well as impair the function of your immune system.

Oxidative stress is implicated in most human diseases because the superoxide can oxidatively damage molecules in the mammalian biological system. These oxidatively damaged molecules can initiate disease states. For instance, oxidatively damaged glucose and protein molecules form glycated proteins that can lead to cataracts etc. Oxidatively damaged glucose molecules cannot form conjugates to enter cell walls and pass into the cell where they can be used to produce ATP. Also, oxidatively damaged cell membranes lose their functional integrity that can lead to disease states. And there is a bigger problem with excess superoxide. Excess superoxide is the amount of superoxide that cannot be scavenged by the antioxidants or the antioxidant system in the cells and it can react with other useful molecules such as nitric oxide (NO) to produce the highly reactive secondary radical called the peroxynitrite radical that can damage cell membranes and lead to disease conditions such as cardiovascular disease, arthritis, ED etc. It is also well established that if the glutathione-catalase system cannot effectively convert hydrogen peroxide formed during cell metabolism, it can react with the excess superoxide to form the very deleterious hydroxyl radicals that can damage cell membranes, protein molecules, hormone molecules, enzyme molecules and even mDNA and DNA molecules and lead to the development of a host of disease states and cancers.

The biochemical mechanisms that point to the role of free radicals in the development of disease states and cancers and degenerative conditions as well as in the progress of aging became clear over the last two decades of research and are now well understood. From an implication, free radicals and free radical reactions and free radical-induced reactions are now understood as the cause of many diseases pointing to the biochemical origin of disease other than caused by pathogens. The biochemically harmful effects of free radicals are real and measurable and are not “alleged harmful effects” as stated in a recent report in JAMA (Goran Bjelakovic et al, Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention Systematic Review and Meta-analysis, JAMA, February 28, 2007—Vol 297, No. 8 847-857).

Only natural antioxidants can effectively scavenge free radicals in the mammalian biological system and do it safely

The antioxidants in mammalian biological systems work in an integrated network system. L-ascorbic acid can donate electrons to all the water-soluble antioxidant molecules in the system directly, a process that recharges or recycles them and it can also donate electrons to alpha-lipoic acid that can then donate electrons to both the water-soluble and fat-soluble antioxidant molecules of the mammalian biological system and any other natural antioxidant molecules (from food or edible sources) that can work within the natural antioxidant system of mammals. This is a critical factor in the antioxidant defense mechanism. Populations that consume a diet that offers natural antioxidant molecules from a variety of sources tend to have a lower risk of cardiovascular disease, arthritis, diabetes, hypertension and cancers. Hence, antioxidants from fruits, green leafy vegetables and fish oils and natural olive oil or sesame seed oil or coconut oil would prove to be better for health.

The mammalian biological system operates on the L-form antioxidants. These are antioxidants found in natural sources, excepting olive oil which occurs in the D-form in nature. Free radical biochemistry is harmful and can produce deleterious and lethal effects over time whereas natural antioxidants scavenge free radicals and prevent or minimize the harmful effects of free radical biochemistry in the body. That is not difficult to understand but there is another interesting point about antioxidants.

The healthy biochemical pathways of the mammalian biological system operating on L-form antioxidants involve the production and utilization of ATP molecules, production of antibodies, collagen, melatonin, hormones and other useful biomolecules - all of them dependent on antioxidant-driven biochemical processes that can be disrupted by excess free radicals. In such a system, the antioxidant molecules that donate electrons during the scavenging activity become “spent” but remain stable and may either be recharged and recycled for further scavenging activity or may be broken down and utilized in the synthesis of other useful biomolecules. For instance, L-ascorbic acid may be converted into collagen with the help of colloidal copper or colloidal gold after it is “spent”.

Natural antioxidants, therefore, actually prevent the development of disease states by preventing oxidative stress by excess free radicals and by preventing the development of secondary radicals. Otherwise, they decrease or diminish oxidative damage and its harmful effects. Now there is interest in tapping the potential of natural antioxidants from food or edible sources for inducing and promoting rapid free radical scavenging activity to study the antioxidant-driven effects for reversing the cellular and biochemical damage of excess.

Many people are taking antioxidant supplements to supplement the natural antioxidant intake from their diet to improve the free radical scavenging activity in their bodies as a way to prevent health problems and prevent the development of disease states or otherwise to slow down the aging process or slow down the progression of disease conditions that are free-radical induced. Yet, the authors of the report in JAMA titled “Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention Systematic Review and Meta-analysis” are not sure when they state “whether antioxidant supplements are beneficial or harmful is uncertain.”

Many primary or secondary prevention trials of antioxidant supplements have been conducted to prevent several diseases. They conclude that “antioxidant supplements, with the potential exception of selenium, were without significant effects on gastrointestinal cancers and increased all-cause mortality.”

“The methodological quality of some of the trials was assessed using the published reports, which may not reflect the actual design and bias risk of the trials. Some authors responded to our requests for further information. All available nonenzymatic antioxidants work differently in the human body and most of them exert effects that are nonantioxidant. We are not able to point to the specific biochemical mechanisms behind the detrimental effects” (Goran Bjelakovic et al, Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention Systematic Review and Meta-analysis, JAMA, February 28, 2007—Vol 297, No. 8 847-857).

They performed adjusted-rank vitamin C; vitamin A and vitamin C; vitamin C and vitamin E; vitamin E and selenium; selenium and zinc; beta carotene, vitamin C, and vitamin E; beta carotene, vitamin C, vitamin E, and selenium; beta carotene, vitamin C, vitamin E, selenium, and zinc; vitamin A, vitamin C, vitamin E, selenium, and zinc; vitamin A, vitamin C, vitamin E, selenium, methionine, and ubiquinone. In 11 trials, participants were supplemented with different mixtures of antioxidants as well as with vitamins and minerals without antioxidant properties.

The fact is that most antioxidants in the mammalian biological system also work in a synergistic fashion. For instance, L-ascorbic acid recycles melatonin and enhances its effects three fold. Melatonin is a brain-body antioxidant that has anti-cancer effects, primarily due to its ability to donate electrons to both the lipid and non-lipid part of the cell wall. This biochemical repair restores cell wall integrity and that in turn promotes aerobic respiration and consequently prevents the cell wall from acquiring a strong positive charge {positive cell membrane potential (CMP)} a key factor in the transformation to from aerobic respiration to anaerobic respiration which initiates the formation of cancer cells.

It has been suggested that antioxidant supplements may show interdependency and may have effects only if given in combination (Hercberg et al, The potential role of antioxidant vitamins in preventing cardiovascular diseases and cancers, Nutrition. 1998;14:513-520). That is clearly a logical suggestion within the working of the mammalian biological system and the fact that the natural antioxidant molecules work in an integrated fashion in a network and also in synergistic roles. Most of the studies on vitamins are designed around the administration of one vitamin and many of these studies use analogues or synthetics instead of the L-form molecules from food sources.

Synthetic vitamins are like any other synthetic molecules but because of their antioxidant nature, they are able to donate one electron, after which they do not remain stable but are broken down in a metabolic process that yields hydrogen peroxide. Administering synthetic vitamins in persons with disease states can thus be counter-productive. These people already have a problem associated with or directly caused by excess free radicals, including hydroxyl radicals. Adding substances into their biological system that can lead to the formation or more hydroxyl radicals only exacerbates their free radical biochemistry. There are several studies that show that synthetic vitamins are harmful. For a therapeutic purpose, there is a need to enhance the free radical scavenging potential in patients with disease states that successfully converts all the hydroxyl radicals and hydrogen peroxide into water and oxygen as soon as they are formed – something that occurs during the prime of youth.

The aim of the review in the JAMA study (Goran Bjelakovic et al, Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention Systematic Review and Meta-analysis, JAMA, February 28, 2007—Vol 297, No. 8 847-857) was to analyze the effects of antioxidant supplements (beta carotene, vitamins A and E, vitamin C [ascorbic acid], and selenium) on all-cause mortality of adults included in primary and secondary prevention trials. The authors “found that antioxidant supplements, with the potential exception of selenium, were without significant effects on gastrointestinal cancers and increased all-cause mortality”. That would be quite the natural expectation if synthetic antioxidants were used as supplements in patients with cancers. Cancer patients have high amounts of excess superoxide and a large number of hydroxyl radicals.

Several new review studies on nutrients, called meta-analysis, seem to contradict either what we know from previous research, or what our intelligence tells us should be true. You only have to scan the headlines and pay attention to the "newly found" dangers of this or that natural substance. From St. John's Wort to Kava Kava, from vitamin C to vitamin E, we hear that they are "not effective" or worse - that they may be dangerous.

We know one fundamental truth – and that is nutrition and nutritional intake through food is what makes us grow and is essential for health. And we also know that by increasing our natural antioxidant intake through supplements made from food substances, but not in undue excess, we increase the free radical scavenging potential in our bodies and tend to improve health. That is basic health science or food science. Yet a new field of study called meta-analysis may be used to discredit the role and function of natural supplements or does it prove one fact very bluntly – synthetic vitamins are harmful.

Fish oils "don't work"?

On 24 March 2006, The British Medical Journal published a meta-analysis (a study of other studies) on omega-3 fatty acids that prompted headlines around the world to the effect that “fish oils don’t work”. This is not the first time a meta-analysis has triggered headlines that discredit natural health supplements (see: Health Supreme, Meta-analyses Used To Discredit Supplements, April 24, 2006). These meta-analyses are a funny piece of work that is made out to look like sophisticated science, probably targeted at lay people. Dr Robert Verkerk of the Alliance for Natural Health says, those studies are manipulated. This is a new kind of study that is highly regarded these days, but it is based on a choose-and-pick approach where older studies are reviewed and analyzed to combine their wisdom. The criteria of inclusion/exclusion of previous studies in the analysis, and the decision of how to give different weights to different results are so rubbery that almost any conclusion becomes possible. One of the more recent studies that attempts to trash nutrients takes on the health benefits of fish oils... and may be used to coincide with a launch of a synthetic …making such studies more of a marketing gimmick rather than a real scientific study.

And such a coincidence has indeed happened. The fact that the meta-analysis throwing doubt on omega-3 fish oils coincides with the launch of a pharmaceutical version of the same type of fats made by chemical giant Solvay (see: Health Supreme, Meta-analyses Used To Discredit Supplements, April 24, 2006) and it reminds me of the tryptophan disaster of more than a decade ago (see: The FDA Ban of L-Tryptophan: Politics, Profits and Prozac, Life Extension Foundation, April 6 1998).

In meta-analyses there is a big catch, like a mathematical fallacy in which one tries to divide by zero. The “trick” lies in assessing “all-cause mortality.” Take for instance, the study on vitamin E. The overall conclusion that high-dose vitamin E causes increased mortality could also have been a statistical artefact, with no biological relevance. Since the study assessed all-cause mortality, and not just cardiovascular mortality, any other cause of mortality is included. Other factors could easily have contributed to the greater death rate in the higher dose vitamin E group found when trials were pooled. The pooling of risks to mortality creates the desired warp and twisting. It is a strange science.

Meta-analysis can make a nutrient into a factor that increases mortality or it can "show" that beta-carotene, vitamin A and other antioxidant vitamins such as vitamin E are harmful. It can make people doubt the benefits of omega-3 oils by making headlines like “fish oils don’t work”. On the other hand, it can be used to investigate the effect on heart disease risk of a Unilever margarine enriched with alpha-linolenic acid (ALA), an important short-chain omega-3 found to be rich in Mediterranean diets, well known for its health promoting properties, and conclude clearly the beneficial effects of ALA-enriched margarine on reducing heart disease risk! In one meta-analysis, scientists can decry a natural antioxidant that promotes heart health while in another, it can promote the same class of natural antioxidant in a hydrogenated oil that introduces trans-fatty acids into the bloodstream as circulating fatty acids that promote plaque formation and heart disease and damage cell walls. A fishy tool that can be well adapted as a basis for promotional literature and published in peer review journals for marketing synthetic products unless the consumer knows the real science of natural antioxidants and their biochemical function in free radical biochemistry. But it is the headlines that influence consumer behavior rather than the research in scientific journals. Few read the actual studies.

Antioxidant omega-3 oils in cardiovascular disease

Dr. Alexander Leaf, a professor and his team of scientists at Harvard, had done extensive work on omega-3 fish oils and documented the beneficial effects of this natural oil on health and cardiovascular disease, and an experiment was designed to prove its anti-arrythmic role. Leaf and other researchers cultured neonatal heart cells from rats. Under the microscope, these cells clumped together which as a clump of heart cells beat spontaneously and rhythmically just like the heart as an organ. Toxic agents known to produce fatal arrhythmias in humans were added to the medium bathing the cultured cells, and the effects of adding the omega-3 fatty acids were observed. Increased extracellular Ca2+, the cardiac glycoside ouabain, isoproterenol, lysophosphatidylcholine and acylcarnitine, thromboxane, and even the Ca2+ ionophore A23187 were tested. All of these agents induced tachyarrhythmias in the isolated myocytes (Leaf A Circulation. 2003;107:2646, 2003 American Heart Association, Inc.)

Of particular interest are the effects of elevated perfusate Ca2+ and ouabain on the myocytes. Both agents induced rapid contractions, contractures and fibrillation of the myocytes. When EPA was added to the superfusate, the beating rate slowed, and when the high Ca2+ or ouabain was added in the presence of the EPA, no arrhythmia was induced. Furthermore, after a violent fibrillation was induced in the cells by both elevated calcium and ouabain, addition of EPA stopped the arrhythmias, and the cells resumed their fairly regular contractions. The addition of the dilipidated BSA to remove the free fatty acid from the myocytes resulted in recurrence of the arrhythmia.

This indicated two important facts as outlined by Dr. Leaf. First, the EPA could be extracted from the cells in the continued presence of the toxins, and the arrhythmia would return, which indicated that the fatty acids were acting without strong ionic or covalent binding to any constituent in the cell membrane. If they had such binding, we would not have been able to extract the EPA from the cells with the albumin. It appears the free fatty acids act directly on the heart cells and need only partition (dissolve) into the hospitable hydrophobic interior of phospholipids of the plasma membranes of myocytes to elicit their antiarrhythmic actions. Second, when we tested the ethyl ester of the EPA, it had no prompt antiarrhythmic action; only the free fatty acid with its negative carboxyl charge was antiarrhythmic. Herein lies the key in understanding the role of omega-3 oil - its role as an antioxidant (see": WHY OMEGA-3 FISH OIL PROTECTS YOUR HEART AND BRAIN; Health Supreme).

Another study reported in the Annals of Internal Medicine concluded that omega-3 fatty acids can slow the course of atherosclerosis and may reduce the risk of further heart disease. Many studies have come to a similar conclusion.

After several population studies that noted the positive effects of omega-3 fish oils and laboratory evidence, I explained their role as an antioxidant in an article. Now, it was within mainstream science and the growing understanding and popularity of natural biomolecules that are integrated into normal and healthy cellular function and at the same time more people have became aware of drug toxicities, I was expecting "studies" to contradict omega-3 fish oil studies, but I expected something subtle like casting a doubt at first and then discrediting it. I did not expected a foolhardy and blatant “fish oils don’t work” in a British Medical Journal.

The fact remains that natural omega-3 fish oil, like many other natural oils are antioxidants that scavenge free radicals in the cell wall and biomembranes and provide an electron to the lipid part of the molecules in biomembranes, that was lost to a free radical and that restores stability and functional integrity to the biomembranes. That sums up, in a nutshell, the antioxidant role of such oils (and) fat soluble antioxidants in restoring healthy function of cells and tissues. These natural antioxidants are an integral part of our evolutionary history whereas synthetic molecules are not.
Please note the use of synthetic vitamin E in the Miller study, and this could have explained the negative results found by Miller et al (Ann Intern Med. 2005 Jan 4;142(1):37-46), as well as those found earlier by Dr Marc Penn and colleagues from the Cleveland Clinic, published in The Lancet. Again, note the negative results from a very small clutch of studies on synthetic vitamins like synthetic beta-carotene and vitamin E, which were administered to diseased or high risk subjects. These authors asserted that beta-carotene, vitamin A and other antioxidant vitamins such as vitamin E were harmful. That conclusion in Lancet, by Dr Marc Penn and colleagues from the Cleveland Clinic is correct and wholly supports what we have been saying - that synthetic molecules are harmful and cannot be incorporated into therapies and diet. Synthetic biomolecules can suppress the immune system or disrupt the production of natural antioxidants in the body or disrupt normal biochemical pathways in the body, a problem mediated through the production of hydrogen peroxide during the cell metabolic breakdown of synthetics under oxidative stress leading to the formation of more hydroxyl radicals. So, while L-ascorbic acid intake improves collagen formation in the body and improves elasticity of blood vessels, the D-form may produce bleeding in patients.

Synthetic antioxidants for smokers

The report of the study in Finland of Vitamin E and beta carotene on the incidence of cancer in male smokers is important because it drives home the message that vitamins may increase cancer (Heinonen OP et al, The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers, New England J of Med 330:1029-1035, 1994). Synthetic vitamins, that is. Synthetic vitamins are not food. They are synthetic chemicals. Only vitamins from dietary sources or edible plants can be considered nutrients for the body.

The first study in question was the 1994 Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC) involving Finnish men who were heavy smokers and alcohol drinkers. The volunteers were either given 20 milligrams of synthetic beta carotene, vitamin E, a combination of the two, or a placebo. The expected outcome suggested that there was an 18 percent increase in lung cancer rates in the beta carotene-only group. Cigarette smoke contains about 4000 toxic chemicals, of which 40 are known carcinogens. The metabolic breakdown of synthetic chemicals and alcohol yields toxic metabolites that yield the superoxide radical and hydrogen peroxide. Similarly, the breakdown of synthetic beta carotene and synthetic vitamin E also results in the same biochemical problem in the liver and that simply adds to creating excess free radicals and oxidative stress from hydroxyl radicals. Hydroxyl radicals can cause damage to membranes and DNA molecules and transform normal cells into cancer cells. In other words, synthetics accelerate free radical biochemistry.

The second trial was the 1996 Carotenoid and Retinol Efficacy Trial (CARET), which was a lung cancer prevention study involving a combination of 30 mg of synthetic beta carotene and 25,000 iu of retinol (synthetic formed vitamin A) versus placebo. The volunteers were either smokers or asbestos workers. This study was stopped early due to the fact that preliminary findings suggested that there was a 28 percent increase in cancer rates in the beta carotene/vitamin A group, compared to placebo. Asbestos in the human body can create biochemical problems. The findings in this study are consistent with the expectation of higher rates of cancers as would be with all other studies that test synthetics. The correct conclusion is that synthetic vitamins contribute to free radical biochemistry in the human biological system and in people who introduce other substances into the body that also generate free radicals, the risk of generating hydroxyl radicals increases while in some people it becomes excess, leading to the development of cancers. Much of the outcome depends on the intake of antioxidants from dietary sources.

The most critical fact that deserves special scrutiny in the Finnish studies is that the beta carotene and vitamins used in these studies are synthetic and not from dietary sources. It is interesting to note that dietary intake of various antioxidants such as carbonyl from broccoli or olive oil other carotenoids (such as lycopene and cryptoxanthin) is far more strongly associated with lower cancer risk while intake of synthetic antioxidants tend to raise that risk, especially in smokers and those who consume alcohol or those who are already have cancers in them.

Recycling vs. metabolic breakdown

People who have cancers and those who smoke and consume alcohol, in general, have lower levels of natural vitamin C. That by itself is a compromising factor for the immune function of white blood cells and T4 cells. These lower levels of natural vitamin C are insufficient to fully recycle other antioxidants directly or through alpha-lipoic acid. Recycling the fat-soluble antioxidants through alpha-lipoic acid becomes critical in cancer patients because of the greater amounts of fat-soluble antioxidants required to biochemically repair the cell membranes (by donating electrons and reducing their positive potential) in order to restore their functional integrity. And natural vitamin C cannot recycle synthetic vitamins. The synthetic vitamins are targeted for metabolic breakdown once they have donated their electron.

Natural molecules, such as natural oils, fat soluble antioxidants and natural vitamins have been part of the mammalian diet for 65 million years and primate diets for 15 million years of hominid evolution. We read in our primary schools how effective vitamin C was in curing scurvy in sailors. Research in free radical science has already contributed so much knowledge to mainstream science. Yet we have researchers who dare state that natural antioxidants "don't work" and are harmful while synthetic molecules work and are safer?

History of science is important

History of the use of oils is a part of that history as well as part of the history of marketing. A few decades ago, a particular association began lobbying and commenced a media campaign against natural tropical oils saying that these oils are highly saturated. Their campaign was designed to get people to switch to vegetable oils that they did not say were in fact, hydrogenated oils. In the body, these long chain fatty acids become converted to circulating lipoproteins and hence contribute to the artery-clogging factor. Their campaign succeeded, in spite of the fact that tropical oils are not long chain fatty acids but are medium chain fatty acids which are readily broken down in the liver to produce energy, do not become circulating fat molecules and do not contribute to artery-clogging. Other positive information on medium chain fatty acids was never brought to light, including their anti-inflammatory properties and that they are used by the body to produce antimicrobial and antiviral molecules and have cardio-protective function, as well as that they may be used to synthesize other molecules that have anti-inflammatory or anti-bacterial properties.

The success of that campaign against tropical oils contributed to rising rates of obesity, cardiovascular disease and cancers and created an expanded market for a wider range of drugs.

It can be speculated that, as a general rule, the synthetic oil starts as a prescripitory medication in order to gain a foothold in the market and that later it may be 'moved' into the supplement category to broaden its market. However, the war on natural fish oil is being fought differently. Meta-studies appear to be used as a tool to discredit the natural oil which is already part of the diet as well as other scientific works in reputable journals for purposes of possibly altering consumer buying behavior in favor of the synthetic oil.

People are more educated than before and too many people know how science is manipulated. These people will not put "prescripitory health" above natural health. Health is a result of nutrients from food sources and it cannot be an outcome of prescriptions that contain synthetics or analogues. Consumers should know the difference between the two. This points to the need to improve science literacy in Congress and Parliaments and the need to scrutinize the media that attempt to promote synthetic stuff as superior and better than natural biomolecules, while at the same time discrediting other scientific studies that prove or note the beneficial function of natural biomolecules in the human body. It also points to the need for a sound health education in primary and secondary schools and as a subsidiary subject in colleges and universities.

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See also:

Poor methodology in meta-analysis of vitamins (PDF)
Scientific papers often reveal more than is apparent from the reported results. A recent review of clinical trials by Bjelakovic et al. claimed to show that certain antioxidant vitamins increased the risk of death. Superficially, this study appears to have a degree of scientific rigour because of a detailed and extensive use of statistics. However, the statistics were inappropriately applied to poorly selected data, thus the conclusions are invalid. Researchers need to remember the fundamentals of the scientific method to avoid introducing experimenter bias. In this case, experimenter bias was compounded by a basic misuse of statistical testing.

Analysis of antioxidant pills' benefits may be hard to swallow
Balz Frei, a biochemist who studies antioxidants at Linus Pauling Institute at Oregon State University in Corvallis, says Gluud's technique inherently was biased against antioxidants. "The high-bias papers show a 9% decrease in deaths, and the low bias papers find a 5% increase. The scientific way would have been to include all the studies they reviewed."

Experts Rebuke "Vitamins Kill" Theory
SHANGHAI: A panel of medical and nutritional professionals has rebuked an essay published in the February 28 issue of the JAMA (Journal of the American Medical Association), which claimed that taking vitamins increases the risk of death. Gathered at a recent symposium on vitamin C, the experts agreed that a balanced intake of vitamins and minerals is actually beneficial, not harmful, to one's well-being. The group said that the study by Serbian doctor Goran Bjelakovicon was "biased and selective".


posted by Sepp Hasslberger on Wednesday February 28 2007
updated on Tuesday December 21 2010

URL of this article:


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Readers' Comments


Antioxidants are widely used as ingredients in dietary supplements, which are used in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease (see above).

According to this Wikipedia entry,

Although some studies have suggested antioxidant supplements have health benefits, other large clinical trials did not detect any benefit for the formulations tested, and excess supplementation may even be harmful."

We know that food and dietary sources contain antioxidants. Minerals and antioxidants are part of our nutritional intake and epidemiological studies show that populations with high antioxidant intake from dietary sources are at a lower risk to diseases such as cancers, hypertension cardiovascular disease, stroke etc more so in contrast with malnourished people.

We also know the role of antioxidants in our biochemistry is to scavenge free radicals or convert hydrogen peroxide formed during cell metabolism into water and oxygen as soon as it is formed and that ability is part of health.

Yet studies try to show that antioxidants are "harmful". If so, do not take fruits and vegetables for they are rich sources of natural antioxidants! Go on a diet that is low or devoid of that what these scientists want you to believe? Utter rubbish. But science does not spew such rubbish, only the conclusions of some scientists.

If your diet is low in natural antioxidants, free radicals begin to be in excess of your antioxidant ability to biochemically neutralize them (scavenge) and there will be oxidative damage and free radical chain reactions that will damage molecules and cell membranes and quickly lead to the development of disease states as well as impair the function of your immune system


Posted by: BELDEU SINGH on March 1, 2007 02:22 AM


Garlic has also just been studied and found wanting:

It seems the NIH complementary medicine studies are either set up to disprove the value of supplements and herbs or if they discover a benefit, to bury it. Someone I know worked with a researcher in the Complementary Medicine division on her daughter's autism. The little girl was semi-paralyzed and diagnosed as autistic when she began. She is learning ballet and completely healthy today. Shouldn't that have made headlines?

Posted by: Elizabeth Nobbe on March 1, 2007 05:07 PM


A comment on the JAMA-study by the ANH - Alliance for Natural Health - team:

5 March 2007

On 28th February we saw headlines around the world once again condemning vitamin supplements. The stimulus? A Serbian doctor, Goran Bjelakovic, who was involved in an earlier canning job on vitamins – in 2004 on vitamin supplements for reducing risk of gastrointestinal cancers (Lancet 2004; 364: 1219–28) – somehow found himself doing it all over again. This time he published in the US-based Journal of the American Medical Association (JAMA). On both occasions, his papers triggered headlines around the world which appeared to have just one purpose: getting people to stop taking vitamin supplements.

Interestingly, in a bout of apparent schizophrenia for JAMA, Bjelakovic and colleagues’ views are fundamentally opposed to those of Fairfield and Fletcher published in the same journal some two years earlier (JAMA 2002; 287:3116-3126). Fairfield and Fletcher broke the long-standing anti-supplement agenda of the JAMA by supporting supplementation as a means of reducing risk of key chronic diseases. But it seems it’s now back to business as usual for JAMA.

On the top of the Serbian’s hit list were the favourites: vitamin E and beta-carotene. Dr Bjelakovic, given his previous work, appears to have a bit of thing for antioxidant supplements which he considers to be beta-carotene, vitamin A, vitamin C, vitamin E and selenium. From the point of view of any informed scientist, this is a peculiarly narrow perspective on what is meant by ‘antioxidant supplements’. First of all the vitamins in question are not automatically antioxidants. In certain forms (especially as synthetic, isolated forms) and dosages, they can actually have the reverse effect – and act as pro-oxidants. Secondly, the dose and form of the vitamin are critical to determining how the vitamin will behave in the body, as are the other nutrients which are consumed at the same time.

To give an example, high doses of vitamin E (the very forms that have swayed Bjelakovic’s analysis) actually reduce the body’s absorption of the more important antioxidant form of vitamin E, gamma-tocopherol, the predominant form in foods and high quality vitamin E supplements.

It was seriously remiss of Bjelakovic and his team to not emphasise that; a) the studies they used to condemn these vitamins were nearly all performed using synthetic forms of the vitamins that behave in the body in remarkably different ways to the natural forms and b) to not make clear the effects their study selection approach would have on the final results.

Looking further at this second, crucially important point, Bjelakovic’s team found 815 trials that were potentially relevant. But they culled out a massive 747 (yes – a jumbo jet load!) of these trials, leaving just 8 of the total number for the number crunching! The most important reason given by the authors themselves for the exclusion of studies (responsible for 50 of the exclusions – a total of 405 trials) was “mortality was 0 in both study groups.??

Consider what effect this might have on bias. If you remove 50 of the studies because they didn’t cause any increased risk of death – how can you say that vitamin supplements overall cause a 5 increase in risk of death….it simply beggars belief that the JAMA can tolerate this type of science.

This is just one of the stunning problems with Bjelakovic’s study. Dr Steve Hickey (of the ANH Expert Committee) and colleagues reveal more reasons for the flawed nature of the Bjelakovic’s meta-analysis – click here to view their rebuttal submitted and approved for publication in the Journal of Orthomolecular Medicine.

Bjelakovic’s specialty appears to be meta-analyses (statistical study of studies). The application of a lot of statistics to a given data set does not change the quality of the data set. In fact it can often magnify inherent problems in the data. Bjelakovic’s data set is poorly selected and severely compromised – and the results of his analyses do not provide any reflection on the risk of supplementing with vitamin A, beta-carotene, vitamin C, vitamin E or selenium, the targets of the meta-analysis. In fact, the results tell you absolutely nothing about taking, either the natural forms of these supplements, or the effects of taking all these nutrients together, the common way they are taken by most people – as multivitamin/mineral supplements.

Newspaper headlines on 28 February were as dire as “Supplements ‘raise death rate by 5’?? (The Times, UK), “Vitamins ‘could shorten lifespan’?? (BBC News, UK), “Des vitamines dangereuses pour la santé??? (Le Soir, France) and “Another knock on antioxidants?? (Los Angeles Times, USA). But they may not have had the impact that was hoped for by certain interest groups. Judging by the vehement and often irrational hatred for vitamin supplements shown by elements of the orthodox medical profession closely aligned with the pharmaceutical industry, it seems likely that the main objective both of Bjelakovic’s meta-analysis and the resultant articles was to stimulate a turn-around in the increasing numbers of people who are side-stepping pharmaceutical medicine in their quest for health.

Just like all the other factors Bjelakovic and his colleagues failed to consider, clarify or include in their meta-analysis, it seems that another important factor has been ignored. And that’s the millions of people who have derived benefits from taking supplements, combined with other aspects of a healthy lifestyle. These people will need a little more than a computer-generated, reductionist, flawed analysis of past studies of pharmaceutical forms of vitamins to put them off.

So will we.


Journal of the American Medical Association, Bjelakovic et al
(link no longer active)

BBC News, Vitamins 'could shorten lifespan', 28 Feb 2007

Rebuttal by Dr Steve Hickey, ANH Scientific Expert Committee

Posted by: Sepp on March 7, 2007 04:15 AM


Here is a recent communication by email from Denmark:

New slander against antioxidants

By THE VITALITY COUNCIL / 13 MARCH 2007 - 09:00 A.M.

A new article maintains that antioxidants cause death, but the article is based on a comparison of results from incomparable studies.

Once again a scientific article has created a commotion regarding antioxidants. It claims that they cause death. This has been heard, and disproved, before. Because of the common uncertainty regarding this subject, we are nonetheless forced to take a stand regarding this claim.

The man behind this claim is a Serbian professor from a university located in the town of Nis. One of the co-authors is a Danish physician who has, among other things, declared antioxidants to be poisonous and cancer causing on Danish TV. He even suggested that they are poisonous in the amounts found in vegetables.

The study is a so called Meta analysis. It combines as many old studies on antioxidants as possible and extracts a kind of average from their results. Small four week studies are blended up with larger studies which have gone on for up to 12 years. Studies where very small doses were used are blended up with studies on mega doses, studies using one antioxidant are blended up with studies on combinations of antioxidants (e.g. vitamin E, vitamin C, and selenium), and so on. Among the studies used, there are at least eight different combination treatments using vitamin E. This enormous mess alone causes the study to be somewhat questionable. One cannot calculate an average between apples and oranges.

This is not even the worst part. In an attempt to prove that vitamin E increases risk of death (the articles primary claim), they ignored studies where selenium was used together with vitamin E. The selenium studies often showed reduced mortality and lowered cancer risk. This was not good for the Meta analysis authors, it disturbed their theory. They eliminated 11 essential studies on vitamin E and selenium from the analysis.

Selenium was ignored, but that wasn’t enough. The still couldn’t prove that vitamin E is harmful. The numbers would not work. To solve this, the article uses the fact that the antioxidant beta-carotene, the yellow colouring in carrots, increases death rates in smokers. This is commonly accepted (although not completely certain). In two of the largest studies conducted on antioxidants, a very slightly increased death rate was found due to a combination of beta-carotene and vitamin E.

More peculiarities

Common sense lends to the conclusion that beta-carotene is the villain in these studies. This was known in advance. Combinations of vitamin E with e.g. vitamin C and/or selenium do not increase mortality. More likely the opposite is true. In the large and very thorough French SU.VI.MAX study, death rates in men fell by over a third when they received vitamin E and vitamin C as well as selenium (besides zinc and beta-carotene!). This introduced a new era because this was the first time in our part of the world that a large array of antioxidants was used in study; which is what most people recommend. The antioxidants in our food are an orchestra, not solo instruments. They must play together to work. In a Chinese study from Linxian the same thing was found: lower mortality after supplements of vitamins E and C, selenium, beta-carotene, and vitamin A.

But the article in question maintains that vitamin E causes death. The claim is built, along with the discussed "manoeuvres," on the two aforementioned studies, because the other vitamin E studies are insignificantly small in comparison. In these studies vitamin E was used with beta-carotene, and vitamin E was blamed in the Meta analysis for the poor results.

This is like claiming that mineral water is deadly if someone dies after drinking water mixed with arsenic. This conclusion is insane. The arsenic is deadly, not the water. Even though A+B is dangerous, it can naturally not be claimed that both A and B are dangerous alone.

There are other peculiarities in the article. Among other things, in at least two of the studies used, mortality was calculated many years after the end of the study. This is comparable to blaming a traffic accident for back pain when the pain became apparent eight years after the traffic accident. This type of measure was apparently necessary to get the desired results.

It is very easy to make these arguments in a scientific journal. If not for the press, it would be ignored. The article is based on a comparison of a number of incomparable articles, and this makes it hardly worth the effort it takes to make it better. It has also been exposed to sharp criticism. It has been clearly dismissed by two unrelated statisticians and by a professor of nutrition at Harvard University, Meir Stampfer. Stampfer is world renown and among the leading figures in nutrition studies encompassing over 300,000 people. He says that he will continue taking his vitamin supplements, unfazed by the article. But he adds that the article can lead to misinterpretation of the information that we have.

This is unfortunately an all too real possibility. Not in the least because the analysis’s authors insistently do the same.

Niels Hertz M.D.
The Vitality Council
Lyngby, Denmark


1. Bjelakovic G, Nikolova D, Gluud LL et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention trials. JAMA 2007;297:842-857.

2. Virtamo J et al. ATBC Study Group. Incidence of cancer and mortality following alpha-tocoferol and beta carotene supplementation: A postintervention follow up. JAMA 2003;290:476-485.

3. Lee IM et al. Vitamin E in the primary prevention of cardiovascular disease and cancer. The Women’s Health Study. A randomized, controlled trial. JAMA 2005;294:56-65.



Tamara Theresa Mosegaard
Chairwoman and web editor
MayDay Civil Health Rights Movement
Rundforbivej 2, Troeroed
DK - 2950 Vedbaek
Main website:
DK campaign website:

Health Freedom; Freedom of Choice

MAY you have a happy and healthy DAY!

Posted by: Sepp on March 23, 2007 06:51 AM


Erica sends this comment by Patrick Holford on the antioxidant review, published in the Irish Times:


Madam, - William Reville's article entitled "Why you don't need vitamin supplements" ( Science Today, March 15th) does not accurately reflect what the recent US study on antioxidants shows. Three classic tests for publication bias are: (a) to check if the study summary agrees with the results; (b) to check the basis for inclusion or exclusion of trials; (c) to check and if the studies cited as negative were actually negative. This study fails on all counts.

The conclusion of the study says that "treatment with beta-carotene, vitamin A, and vitamin E may increase mortality", creating the impression that these antioxidants are no good. What it fails to say, yet what is clearly shown in the results, is that "vitamin C given singly, or in combination with other antioxidants did not affect mortality, and selenium given singly or in combination with other antioxidant supplements may reduce mortality".

The summary also fails to say that "beta-carotene or vitamin A did not show an increase in mortality if given in combination with other antioxidants", or that "vitamin E given singly or combined with four other antioxidants did not significantly influence mortality". The obvious take-home message is that antioxidants are team players and that vitamin C and selenium are more beneficial than beta-carotene or vitamin A.

The summary goes on further to degrade antioxidants by deciding which trials (usually the positive ones) are high bias, then excluding them, and which are low bias (usually the negative ones) and only adding these together. For example, it is well known that taking statin drugs, which lower cholesterol and induce CoQ10 deficiency, make vitamin E harmful by turning it into an oxidant. This is an obvious bias but the authors don't even mention this. Once you exclude these trials vitamin E has a positive effect overall.

The final test is to see if the most negative studies were actually negative. One study that skews the results is that of Dr Correa et al from the pathology department at the Louisiana State University Health Sciences Centre in New Orleans. I contacted him and he was "amazed", he said, because his research, "far from being negative, had shown clear benefit from taking vitamins". Correa told us there was no way the study could show anything about mortality. "Our study was designed for evaluation of the progress of precancerous lesions," he said. "It did not intend, and did not have the power, to study mortality and has no value to examine mortality of cancer." Without this study the main conclusion, that antioxidants may increase gastrointestinal cancer, becomes invalid.

Prof Reville's comments that "pregnant women need to be careful that they are getting enough folic acid and should talk to their GP about this. Otherwise we needn't worry." This particularly worrying. The RDA (recommended daily allowance) for zinc is 15mg, and 20mg is recommended in pregnancy since zinc deficiency is linked to growth defects.

According to the Irish Food Consumption Survey the average Irish woman achieves 8.5mg. Zinc deficiency in pregnancy is exceedingly common, so why not supplement it? The blanket statement that "you don't need supplements" ignores the fact that the average intake of vitamin D is 3.7mcg, compared with the RDA of 10mcg, yet a large body of research concludes that intakes of 25mcg per day can halve the risk of some common cancers. Moreover, proper clinical trials show that large amounts of B3 (niacin) lower cholesterol; chromium reverses diabetes; vitamin C reduces the severity and duration of infections; folic acid improves memory and cuts stroke risk by a quarter; and multivitamins raise children's IQ in eight out of 11 trials.

The amounts of nutrients that produce these effects are above the basic RDA levels and certainly above what you will achieve by eating what most people consider a well balanced diet. Of course, diet is the first place to start, but I for one will keep recommending people to supplement their diet with a combination of antioxidants, including selenium and vitamin C, as well as zinc, vitamin D and B vitamins - all found in a high strength multivitamin - because the majority of the trials, including those reviewed in this meta-analysis show benefit, not harm. - Yours, etc,

PATRICK HOLFORD, Founder, Institute for Optimum Nutrition, London SW15.

Posted by: Erica on March 26, 2007 09:45 AM


Another comment (to the Irish Times, but always on the subject of the antioxidant meta-analysis) sent in by Erica:

Dear Editor,

Professor William Reville's arguments on why people should not take supplements [Irish Times, 15th March 2007] are presumably well-meaning, but lack scientific merit.

Firstly, he incorrectly described James Lind's famous experiment as having two groups (there were six). Furthermore, he uses a recent paper in the Journal of the American Medical Association (JAMA) to support his claims. Unfortunately, the methodology of this paper is seriously flawed, as described in a response paper published in the Journal of Orthomolecular Medicine [22(1), March 23, 2007]. We have also submitted a rebuttal to JAMA, but this may take weeks, if not months, to be published; meanwhile, Professor Reville and others will continue to promote the error.

Briefly, the JAMA authors selected data for their meta-analysis with prior knowledge of the results, which is a fundamental experimental error. Consequently, the paper suffers from selection bias, and reflects little more than its authors' prejudices.

We have issued an open challenge to any reputable group of scientists willing to defend the idea that people need only low (Recommended Dietary Allowance level) doses of vitamin C. So far, no group has accepted the challenge. Until scientists come forward to defend this idea, people should regard claims, such as those by Professor Reville, merely as statements of prejudice.

We publicly invite Professor Reville, and any group of scientists that he can gather to support his low dose ideas, to take up this challenge. If he does not, perhaps it is reasonable to say that his comments can be ignored.

Dr Steve Hickey
Dr Hilary Roberts

Posted by: Erica on March 27, 2007 06:07 AM


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