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.