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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.

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."

Vitamins 'could shorten lifespan' and Antioxidants Don't Mean Longer Life are the titles of some typical articles discussing the findings of a recent Cochrane review of clinical trials involving beta carotene, vitamin A and vitamin E. The results - a slight increase in mortality in those taking the pills - seem to contradict 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 - they are not even using the real thing! Most pharmaceutical studies rely on synthetic versions or artificial analogs of these natural biomolecules.

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.

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Beldeu Singh

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.