Most vitamin studies are flawed by poor methodology

In a new published analysis, researchers at the Linus Pauling Institute of Oregon State University report that many large clinical trials of vitamin supplements, especially antioxidants like vitamin C, have flawed methodologies that make them 'useless' in determining the real value of such nutrients.

It is on the basis of such flawed studies created by researchers that are uninformed as to the nature of nutrients that their studies may conclude that vitamins are of no value or may even be harmful.

Of course, common sense tells us that essential nutrients cannot be inherently useless or harmful in reasonable doses, but those are messages that we repeatedly hear in the media reports.  Such flawed science leads to the equally flawed calls for vitamins to be regulated as drugs, adding a new logical error in failing to consider the vast difference in safety between nutrients and drugs.

Drugs are typically synthetic, isolated substances that are foreign to the body and don't act like nutrients, and it is this foreignness of drug properties that make them inherently toxic to the body. That toxicity is the legal basis of regulating drugs as controlled substances, and the failure to demonstrate toxicity of nutrients, except in studies with such flawed methodogies as we are discussing, makes calls to regulate vitamins as drugs hollow and illogical.

A report on that article:
http://www.nutraingredients.com/Research/Most-vitamin-studies-are-flawed-by-poor-methodology-say-Linus-Pauling-researchers

The original peer-reviewed publication in a peer-reviewed nutrition journal:
http://www.mdpi.com/2072-6643/5/12/5161

Supplements vs. Food to Obtain Key Nutrients

Supplements vs Food [Infographic] by the team at Supplement Centre

Antioxidants misunderstood

In “Radical thinking on antioxidants” (Chicago Tribune, Oct. 6) there is a useful discussion of the controversial role of antioxidant nutrients in our health. While much of the information presented was fair, there were omissions and inaccurate statements made that should be addressed.

To understand the controversy over antioxidant nutrition, it is important to remember that this particular class of nutrients consists of individual substances that, unlike drugs, do not operate independently in the body. The failure to respect that fact has caused many researchers, especially those assembling and publishing statistical models of supposedly similar already-published studies, to veer way off course from reality. The most common errors include the use of the so called “gold standard” model used for pharmaceutical studies that looks at the intake of an individual substance and is randomized, double-blinded, and placebo controlled. But that model often fails to produce meaningful or consistent results when antioxidant nutrients are involved. Why?

One big problem is that antioxidants are synergistic and depend on one another to survive in a healthy state. A classic example is vitamin C, with a half-life of about 30 minutes. We would all die of scurvy in a few hours if we didn’t have a mechanism for recycling and recharging that spent antioxidant vitamin. That mechanism is antioxidant synergy, where other antioxidants recharge the spent ones so they can continue their essential work in our bodies. Antioxidants that have used one of their electrons to stop a dangerous chain reaction of free radicals ripping electrons from healthy cells –an otherwise uncontrolled electrical spark - can themselves become a problem if they over-accumulate, which is a signal that we lack other types of antioxidants that could restore their antioxidant potential.

Another problem is the tendency of supplement critics to exaggerate their opinions. In this article, a cardiologist reportedly claimed that, “there is little to no data supporting the use of antioxidants to protect against disease.” That can be easily disproven by a cursory look at medical journals. For example, the American Journal of Cardiology reported evidence that “coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment... supplementation may offer an alternative to stopping treatment with these vital drugs.” Another issue of that journal noted that “coenzyme Q10 supplementation in patients with worsening diastolic function with statin therapy improved parameters of diastolic function.” And the Journal of the American College of Cardiology published a referenced Expert Consensus Document that listed evidence for cardiovascular health benefits of antioxidants CoQ10, hawthorn extract, and ginkgo leaf extract.

http://articles.chicagotribune.com/2011-10-06/health/ct-met-antioxidants-20111006_1_antioxidants-dietary-supplements-free-radicals

My Interview on Memory and Brain Health for a trade magazine

The brain must be intact and healthy in order for it to perform normal functions like thought and memory. There is evidence that chronic or acute inflammation, or other insults to brain cells/tissues from chemicals or other damaging agents, can provoke negative health effects. In essence, the brain is literally under attack on a daily basis, requiring a constant infusion of supporting protective nutrients to maintain proper brain health and functionality.

Antioxidants and magnesium are key nutrients needed to protect the brain from chemicals called excitotoxins, such as MSG, which are damaging to brain cells when levels of various nutrients are insufficient to control them. The physical damage to brain cells that can be caused by oxidation, sometimes in the form of a bio-electrical spark causing a chain reaction that rips electrons from a string of innocent cells until an antioxidant ‘electron donor’ puts an end to it, can be prevented or stopped by antioxidants. Antioxidants also protect fats from oxidizing (going rancid), and since the brain is nearly half fat it is dependent on both fatty acids and antioxidants to protect its structural integrity.

While it is normally not necessary to see a physician before taking a brain/memory support dietary supplement, people on medications should always check if there are known interactions before using any new supplement and it is wise to always bring a list of your supplements to share with your doctor at your annual check-up. Those with known memory problems should request a medical evaluation to set a baseline level in order to maintain their mental assets and be able to compare future mental performance.

To aid this preservation of our mental faculties, it is obviously best to consume adequate levels of relevant protective nutrients for many years, rather than waiting until the senility of old age creeps up on us and then trying to regain lost abilities. Otherwise, careful eating and appropriate supplementation may be started ‘too little, too late.’

The best mental/brain support nutrients include some surprisingly ordinary ingredients: Lecithin, Vitamins A-E, and Antioxidants. Lecithin provides essential phospholipids for the brain, nerves, and cell membranes; including Choline, Serine, and other brain nutrients that directly support neurotransmitter production and memory. Lecithin’s Phosphatidyl Choline (PC) is a precursor of the neurotransmitter acetylcholine; in the central nervous system acetylcholine is involved in learning, memory, and mood. Phosphatidylserine (PS) also affects the levels of neurotransmitters in the brain related to mood, memory, and mental function.

Lecithin, which is a highly processed extract of soybean oil, does not in itself contain protein (allergens) or genetic material (GMOs), which the original soybeans may have contained. Some Lecithin products are derived from certified non-GMO soybeans or even sunflower seeds.

Another way to get Lecithin’s benefits is in the form of Krill Oil. Krill has its Omega-3 fatty acids bonded to phospholipids similar to those found in soy or egg lecithin. So krill not only supplies EPA, DHA, and phospholipids for brain, nerve, and membrane health but also enhances their bioavailability and access to the brain due to the ability of phospholipids to cross the blood-brain barrier better than ordinary fish oils. Fish Oils providing EPA and DHA should also be considered brain nutrients, as DHA is a significant physical component of the brain.

Vitamin E and its related compounds (the tocotrienols) have been shown to protect neurons (brain and nerve cells) from being damaged or even killed off by excitotoxic chemicals. The antioxidant benefits of this essential vitamin’s “family” of compounds also help to prevent oxidative reactions that can damage brain tissues. Look for gamma-tocopherol along with the usual alpha-tocopherol plus higher amounts of gamma- and delta- form tocotrienols.

Vitamin C directly pumps excitotoxins from neurons, protecting the brain and nerve cells from being damaged by these potentially toxic chemicals. There are several populations with impaired ascorbate absorption; including those with poor insulin sensitivity, those with gut inflammation, those who take aspirin, and those on low sodium diets; all situations where normal vitamin C uptake and utilization is often suboptimal.

Other antioxidants of benefit for brain health include Alpha Lipoic Acid, various carotenoids including Astaxanthin (also found in Krill oil), and Pycnogenol®. In addition to supplementation, it always helps to consume a variety of antioxidants from fruits and vegetables to maintain a good level and balance of antioxidants.

The formation of abnormal structures in the brain may in part be due to oxidative damage that perhaps can be kept within normal acceptable ranges by having a variety of antioxidant nutrients available. Genes in the subject cells are controlled by “switches,” that are in turn modulated by environmental “triggers.” The presence of various protective nutrients helps to maintain proper cellular health; whereas the deficiency of adequate protective nutrients can allow potentially damaging effects, leading to cell death and the subsequent formation of abnormal brain structures.

The presence of excessive amounts of saturated fats in the diet, especially if from an excess of processed foods, inevitably reduces the amount of available long-chain fatty acids EPA and DHA (DHA can be made from EPA) that are essential for brain and nerve health. The deficit of these two fatty acids increases the likelihood of uncontrolled inflammatory processes in the body, as an imbalance of beneficial dietary fats like EPA, DHA and GLA that can reduce the fatty acids needed to make prostaglandins responsible for maintaining a healthy inflammatory response. The fact that EPA is needed for healthy membranes throughout the body and DHA is an important constituent of the brain itself also testify to the importance of these fatty acids for healthy brain structures and functions, including memory.

• Natural antioxidant vitamins Beta-Carotene, C, and E are protective of brain tissues and are available in antioxidant formulas and multiple vitamins..

• Alpha GPC is a form of choline that is bioavailable to the brain; an acetylcholine precursor, it supports memory and cognitive acuity.

• DMAE is a naturally occurring amino metabolite known primarily as a precursor to choline and acetylcholine, chemicals in the brain responsible for nerve transmissions and cognitive function; DMAE has been used most predominantly to improve memory and focus while stimulating neural activity.

• NADH is a metabolite of niacin (vitamin B3) that is directly involved in neurotransmitter production to support mental alertness.

• Ginkgo biloba extract is thought to improve memory and quality of life, and is available in various strengths.

• Acetyl-L-Carnitine is a form of an important amino acid, which in short-term studies has improved memory in older adults.

• Vitamin B1 deficiencies have been associated with confusion and memory loss in seniors deficient in that nutrient.

• High strength fish oils and Krill oil supply the omega-3 fatty acids DHA and EPA that are important brain and nerve components often deficient in the general population.

• Genistein, a phytoestrogen found in Soy Protein Isolates and Soy Isoflavones, has been shown to act as an antioxidant to preserve brain cell integrity.

• Ashwagandha has been shown to be protective of brain cells in non-clinical laboratory experiments.

Nutrition, Eye Health & Diseases of Aging Eyes

Glaucoma is pressure in the eyes and can be from different causes such as narrow/inflamed tear duct drainage or a type of high blood pressure type problem. Since synthetic prostaglandin eye drops (travatan, etc) are sometimes used to maintain normal pressure, it implies that natural prostaglandins (GLA, fish oil) might prevent certain forms of glaucoma. Cataracts and macular degeneration are caused by oxidative damage. http://www.ncbi.nlm.nih.gov/pubmed/17478338?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum Lutein is the key but not sole antioxidant. It does take about 5 grams of fat to absorb 10 milligrams of lutein (usually found in a complex also containing zeaxanthin), so lutein only absorbs well if taken with a meal. Eye formulas are also very good to supply multiple antioxidants and eye nutrients. These should also be taken with meals. Lutein is also the yellow pigment in egg whites, dark green leafy vegetables, yellow corn, orange peppers and squash. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9828775

Glutamine, MSG & excitotoxins, and protective nutrients

Clinicians giving several grams a day of pure L-Glutamine do not report excitotoxic reactions. The main one is for the synthetic chemical MSG. Sometimes people react to fermented foods, which indicates a problem in containment and nutritional status. Vitamin C removes glutamate from the neurons, which are additionally protected by antioxidants (tocotrienols, tocopherols, et al) and by magnesium. Branched-chain amino acids help to compartmentalize glutamates. Glutamine is fine with other aminos; the main competition is between the arginine pathway aminos (arginine, ornithine, and lysine); with another noted competition to get through the Blood Brain Barrier between the Large Neutral Amino Acids: aromatic aminos (tyrosine, phenylalanine, and tryptophan) and the BCAAs (leucine, isoleucine, and valine).

Studies fail, not vitamins

Single antioxidants have far less power than mixtures of synergistic dietary nutrients, and both dietary and supplemental antioxidants should be considered to determine total antioxidant status before undertaking a well-designed clinical trial. Even the ability of most animals to synthesize their own vitamin C, which is not possible in humans, guinea pigs and some fruit-eating bats, affects one’s antioxidant status. The failure of most nutrient/supplement trails to consider these additional and critical variables casts most such studies in doubt, and is undoubtedly responsible for the conflicting and confusing results of so-called “gold standard” studies that are tarnished by the common failure to consider both nutrient sources and how nutrients interact. But that’s what happens when drug researchers attempt to study nutrients in the usual manner that they successfully use for pharmaceutical drugs. They simply do not understand or consider the additional variables, do not measure them or screen for them as variables, and thus fail to reach valid conclusions. Of course, the media parrots their triumphant press releases that nutrients are both dangerous and worthless. It makes me wonder why I bother to eat…

Science Sins and Media Mistakes

Science Sins and Media Mistakes What You Should Know About Dietary Supplement News Reporting By Neil E. Levin, CCN, DANLA Are male smokers taking beta-carotene really at increased risk of cancer? Are high dosages of Vitamin E really hazardous to your health? Is ephedra, an herb with demonstrated weight loss benefits, really a “killer” that merits its banned status by the U.S. Food and Drug Administration? Natural health remedies have a long history of promoting health and wellness, dating back thousands of years. But sloppy science and sensationalist health reporting by the news media make this increasingly hard to believe. And misleading and contradictory information about the safety of nutritional supplements may cause consumers to make poor health choices – or to avoid making any choices at all. The result: Many miss out on the myriad health benefits supplementation can bring about. Understanding the common sins of commission and omission on the part of science and the press arms the public with the ability to make better decisions – if not to apply a liberal grain of sea salt to what they’re reading and seeing. Beta Carotene: Myth vs. Fact There have been several instances where the reputation of a dietary supplement or herb has been tarnished due to poor science combined with the media’s inertia. The association of cancer risk with the use of the anti-oxidant beta-carotene is a prime example. In 1994, an antioxidant study being conducted in Finland was halted as a result of a report noting an increase in cancer rates among male smokers taking beta-carotene. Headlines roared: Beta-carotene connected with cancer risk. Doctors told patients to avoid this nutrient and sales dropped. Yet ten years later, the data was re-analyzed, this time taking into the account the smoker’s total antioxidant intake – not just beta-carotene. The results were clear: a combination of antioxidants – including beta-carotene – actually lowered lung cancer risk in male smokers. Supplementing beta-carotene to people with low antioxidant status was simply a matter of too little, too late. The antioxidant itself was not to blame; the lack of other antioxidants was. Science Sin: Poor science did not originally eliminate additional dietary antioxidants as variables or look at how antioxidants interact and support each other. Adding one antioxidant does not make up for the lack of others. Nutrients are not drugs, and supplementing a single nutrient is actually a model of a drug study, not a nutrient study. Media Mistake: Failing to fact check. In the original report, the researchers stated that the slightly increased risk was possibly due to chance and that there was no known mechanism as to how this could happen. Yet the news media and others, including a National Institute of Health (NIH) scientific panel, stubbornly continue to refer to beta-carotene as potentially harmful even though credible scientists actually revised those findings years ago and high blood levels of beta-carotene are shown to be consistently protective to populations at risk for cancer. Sloppy Science and Vitamin E One of the strongest examples of sloppy science is the controversy over Vitamin E. In 2004, warnings were issued by authors of a study published in Annals of Internal Medicine about taking 400 IU or more of Vitamin E per day. This warning was based on a “meta-analysis” report that was generated by statisticians who mathematically integrated the results collected from 19 individual studies, selected partly on the basis of at least ten deaths occurring - from any cause - in the course of each study. Sales of this essential vitamin dropped dramatically. This was a major national news event. But when leading antioxidant researchers re-reviewed the same individual datasets more carefully for the American Journal of Clinical Nutrition, they found that daily doses of Vitamin E up to 2,000 IU were actually safe in the same study populations. It seems that the Annals report did not properly segregate doses and forms, such as taking into account other supplements taken. Nor did it find a dose-dependent relationship between vitamin E and death risk, which is a normal toxicological rationale for determining risk. Apparently, it was simply sloppy work that was not able to be replicated using more accurate statistical models that properly accounted for more variables. Similarly, the Institute of Medicine sets the safe upper level of Vitamin E at 1,500 IU per day. And a recent SENECA study of 90,000 nurses showed a 30% to 40% lower incidence of heart disease among those who take in the highest amounts of Vitamin E from diet and supplements, indicating that the Annals report may have scared a lot of people from taking a life-saving essential vitamin. Science Sin: Mistaking unverified statistics for proven science. The straight mathematical integration of data from different selected scientific studies – and the interpretation of the results – were left largely to statisticians whose methods were heavily criticized in comments by other researchers published by the same journal. Consequently, apples were compared to oranges and the reputation of Vitamin E among consumers continues to feel the squeeze. The researchers have never adequately addressed the criticism or the reanalysis that produced vastly different results. Media Mistake: Making a mountain out of a molehill. The outcome of the original study was interpreted by the press to be more meaningful than it really was, as if one study negated all others, and no follow-up was done to report the reanalysis or to mention the myriad of studies showing the proven protective effects of vitamin E. To this day, journalists continue to cite the flawed report – even though Vitamin E has been proven safe and beneficial. Ephedra’s Bad Rap But it’s Ephedra – an herb most commonly used to assist with gentle weight loss and easing breathing difficulties – that will go down in history as the most pilloried dietary supplement ever. The FDA banned Ephedra in 2004 based on a series of unproven Adverse Event Reports (AERs.) AERs are by definition preliminary, unscreened and unverified reports of possible associations of a substance with a side effect. In banning Ephedra, the FDA said that evidence proving that the product has caused actual harm to someone is not required; all that is required is scientific evidence that supports the existence of some theoretical risk. Ironically, after closer examination of the claims, the FDA eliminated virtually all of the Ephedra AERs from consideration. It also admitted that a total ban on the herb would possibly prevent only one estimated death per year out of 3 billion doses taken by 20 million consumers. In comparison, about 100 out of 11 million people with true food allergies die each year. Yet tree nuts, fish and dairy (the most common food allergens) are still legal. Science Sin: Considering AERs to behard evidence. AERs are unverified and thus cannot be considered scientific evidence as proof of toxicity. Government and medical authorities falsely and cynically assumed that most dietary supplement AERs are true, while drugs that have received far more numerous AERs outlining severe side effects (including death) continue to be widely prescribed. More than 100 years of scientific studies were arbitrarily ignored by the FDA in ruling that ephedra had no benefits and no safe level of use; and the agency likewise ignored its own scientific panels that found no smoking gun. Supplements containing large doses of caffeine and other stimulants were lumped in as “ephedra-related” AERs because they also happened to contain ephedra; or more likely, synthetic ephedra alkaloids. Ironically, ephedrine alkaloids are still universally available as OTC drugs for allergies in doses considered too dangerous to sell in a dietary supplement label. However, they are usually sold behind the counter at pharmacies because of the risk of people making crystal meth from these drugs. Ironically, the ephedra herb is too dilute to economically make meth from. I assume that ephedra was axed as an innocent bystander in the drug war to avoid it competing with products which had to be locked up behind the counter. The coincidental timing of the supplement ban and access to the competing drug is very suspicious. Media Mistake: Not getting the whole story; scaring people unnecessarily. Journalists did not bother to research the whole story when it when it came to reporting on this controversial herb. The media made the all-too common assumption that press releases issued by researchers or governmental offices are true. With a little digging, the “real” story might have been reported. But the media was largely content to focus on the sensational “killer herb” rather than to investigate the facts and find out the truth. When controversy arises around dietary supplement or herb, an unproven AER is often at its root. AERs are intended to be an early warning system to allow experts to try to look for and hopefully isolate a dose-related cause and effect. But most, if not all, AERs involving dietary supplements actually involve a combination of substances and issues that include the supplement as well as prescription drugs or other substances along with pre-existing conditions. And many “adverse effects” attributed to supplements are known side effects of prescription drugs. It’s dubious that either science or the media will admit fault or repent. But with a little effort, consumers can get the most accurate and up-to-date information to ensure they can make informed and beneficial decisions when it comes to their most important asset: our families’ health.

Detoxification

Detoxification By Neil E. Levin, CCN, DANLA The EPA tracks about 650 toxic chemicals used in 23,600 facilities in the US. The agency reports that about half of the 4.24 billion pounds of these toxic chemicals are annually released into the air, ground or water. These include chemicals from the mining, smelting and power generation industries, paper production, electronic equipment manufacturing, plastics, pesticides, etc. While the highest release of chemicals is associated with mining and power production, other industries release problematic chemicals into the environment on a daily basis, all over our country. Certain groups are most at risk (e.g., children, pregnant and nursing women, the elderly). I would also add that people with multiple chemical exposures or even a single toxic level of exposure can develop a hyper-sensitivity to chemicals that can be debilitating. This condition is often called multiple chemical sensitivity. Of course, there is an increase in exposures as our exposure to so many chemicals uses up key nutrients and can overload the body’s ability to detoxify these toxic “insults” to the liver and other body systems. As our need for key nutrients and optimal detoxification processes grows during repeated, chronic exposures, our bodies may fail to keep pace and the levels of toxins can accumulate in our body. The results can be subtle (acne, headaches, persistent “colds”) or extreme (hair or tooth loss, chronic fatigue, pain). We see inflammatory-related conditions increasing, such as liver problems, cardiovascular issues, joint degradation and brain degeneration. While it is true that these conditions are associated with aging, it is also true that aging relates to the body’s inability to properly remove toxins and distribute nutrients to all of its tissues. Inflammatory chemicals can be either the original chemical or a biochemical metabolite that is produced in the body as a temporary step in neutralizing and removing the chemical. If inadequate nutrient stores do not allow the detoxification to complete - and often heroic levels of nutrients far above the RDI’s are required in these situations – then the body still will have a burden of toxic, inflammatory chemicals to contend with. The old adage is to reduce the exposure and increase the nutrients in order to allow the body to clear these toxins in its usual manner. Everything that lowers exposure, even removing shoes when entering a house or using appropriate filters for air ducts, may be helpful in reducing airborne toxins. But it is also important to reduce exposures through varied sources such as medications, non-organic food and the environment as best we can. Antioxidants, including sulfur-containing substances, are the key to detoxification. Methylation, sulfation and antioxidant reduction are some detoxification techniques used by the liver, especially. The liver utilizes these methods to render toxins inert enough to allow removal through the bile or the urine. Methylation can be enhanced by methyl donor nutrients, such as choline, TMG, DMG and SAMe. Sulfation is done with MSM, sulfur from plants (garlic, onions, broccoli, kale) or sulfur-containing proteins (methionine, cysteine, glutathione). Antioxidants include Vitamin C, alpha lipoic acid, etc. Any sources of these nutrients would be beneficial to aiding the body’s natural detoxification systems. One problem is that people often fear to use adequate, high levels of these nutrients, such as taking Vitamin C up to bowel tolerance levels. Some natural substances that enhance/support detoxification include Zinc, Selenium, Copper, Manganese, Sodium Alginate, Chlorella, Bladderwrack, MSM, Beet Root, Red Clover, Dandelion Root, Oregon Grape Root, and Milk Thistle Extract. Another new product is a broccoli seed concentrate called “sgs™”, which is backed by numerous clinical studies at Johns Hopkins regarding its ability to enhance natural detoxification. Adequate fiber is also important in moving the waste quickly through the colon to help remove toxins while avoiding exposure to toxins from the waste or from inappropriate microbes that fester in an unhealthy colon. Probiotics are important, especially bifidobacteria (Bifidus). Drinking adequate amounts of clean, filtered water is another must. Eating organic whenever possible is important, avoiding non-organic fruits and vegetables prone to heavy chemical exposure. Detoxification is a normal bodily function, so claiming that a dietary supplement can support this function would be a legitimate “structure-function statement” authorized by federal law if the clinical documentation is available. Neil E. Levin, CCN, DANLA is a nationally certified clinical nutritionist with a Diplomate in Advanced Nutritional Laboratory Assessment. He is a professional member of the International & American Associations of Clinical Nutritionists. Neil is the nutrition education manager and a product formulator for NOW Foods, a natural food and dietary supplement manufacturer in Bloomingdale, Illinois. Neil is a member of the Scientific Council of the national Clinical Nutrition Certification Board and serves on the board of directors of the Mid-American Health Organization (MAHO), the Midwest regional affiliate of the National Products Association (formerly NNFA). Neil is routinely interviewed for articles in trade magazines serving the natural products industry and has published articles in magazines and newspapers, contributed to scientific journals and has been a guest on numerous radio shows. He has been interviewed for television news reports many times over a 33-year career. You can read some of Neil’s recent articles at his non-commercial website: http://www.honestnutrition.com/

Cardiovascular Health

Cardiovascular Health By Neil E. Levin, CCN, DANLA For a healthy cardiovascular system it is important to get plenty of nutrients over the whole range. B-Vitamins, for example, help to produce energy and to control metabolic processing, including the one that results in excessive levels of the inflammatory compound homocysteine. Homocysteine is a greater risk factor for cardiovascular risk than total cholesterol level. Antioxidants support each other, and clinical research indicates that total antioxidant status is more important than a single level of a single antioxidant nutrient. Antioxidants protect cholesterol from oxidizing, and also protect arterial surfaces from being damaged, leading to plaque formation and cholesterol “patches”. Minerals are also useful for cholesterol metabolism - especially chromium - also calcium, copper, and possibly magnesium and selenium. With the recent stories about obese children – some with Type-2 “adult-onset” diabetes - and with kids getting heart attacks in their teens, there is a growing awareness that cardiovascular health issues are not limited to middle aged men. Recent reports also point to the increased risk for women after menopause or who are on hormone replacement drugs, hammering the point home that age and gender are no longer rigid dividers of people into cardiovascular risk groups. That’s not to say that everyone is aware of these cardiovascular risk factors, but the risk categories in terms of age have certainly broadened dramatically in recent years. We have seen an increasing number of college-aged young men be afflicted by cardiac events at sports or training events, with some dying. Still, the risks do not seem as immediate to young adults with their heightened sense of immortality, especially young men. By the time men hit their 40s, there is an increased awareness of cardiac risks that keeps increasing throughout their lives. The young are mostly oblivious to health risks unless some event creates the beginnings of awareness that they may be at risk, such as a close relative suffering a cardiac event at an early age or a health scare. Unfortunately, these events seem to be increasing. Genetics, sedentary lifestyles, poor diet and obesity all make people susceptible to vascular problems. The emergence of hemorrhoids or any hint of varicose veins should be obvious indications of cardiovascular weakness at any age. Obesity and lack of stamina are also good indicators. Family health history is another consideration that should affect awareness. Circulation depends on body movement/exercise and requires an unobstructed blood flow through flexible blood vessels that have structural integrity. Collagen, elastin and supporting nutrients (proline, lysine, Vitamin C, Pycnogenol®, rutin) help to strengthen these tissues, while certain herbs (cayenne, garlic, horse chestnut, prickly ash extract, hawthorn extract) help to improve blood flow. Smoking and stress narrow the blood vessels, increasing the risk of forming clots or obstructions. Certain amino acids in the diet (arginine, citrulline) support NO (nitric oxide) formation that dilates blood vessels to reduce blood pressure and enhance blood flow to the peripheries. The presence of these components and modulators in the diet help to maintain cardiovascular health and vascular integrity. People should be eating a variety of fruits and vegetables, along with whole grains, in order to provide nutrients essential to the integrity of blood vessels. Products in the Cholesterol/Cardiovascular Support category include plant sterols (containing beta sistosterol), ascorbyl palmitate, Vitamin E, chromium, garlic, guar gum, Guggul extract, tocotrienols, policosanol, B1, B6, folate, B12, iodine, magnesium, selenium, potassium, garlic, carnitine, ginger, cayenne, hawthorn extract, CoQ10, alpha lipoic acid, TMG, Red Yeast Rice Extract, prickly ash extract, horse chestnut extract, butcher’s broom extract, grape seed extract rutin, nattokinase (fibrin enzyme for supporting the body’s control of clotting), fish oil, lecithin, Pycnogenol®, as well as hawthorn leaf and flower extract. Remember, you must take care of your heart and cardiovascular system if you expect them to take care of you for a lifetime! Neil E. Levin, CCN, DANLA is a nationally certified clinical nutritionist with a Diplomate in Advanced Nutritional Laboratory Assessment. He is a professional member of the International & American Associations of Clinical Nutritionists. Neil is the nutrition education manager and a product formulator. Neil is a member of the Scientific Council of the national Clinical Nutrition Certification Board and serves on the board of directors of the Mid-American Health Organization (MAHO), the Midwest regional affiliate of the National Products Association (formerly NNFA). Neil is routinely interviewed for articles in trade magazines serving the natural products industry and has published articles in magazines and newspapers, contributed to scientific journals and has been a guest on numerous radio shows. He has been interviewed for television news reports many times over a 36-year period. You can read some of Neil’s recent articles at his non-commercial website: http://www.honestnutrition.com/

Natural Health: Ten Predictions for the Year 2008

Natural Health: Ten Predictions for the Year 2008 By Neil E. Levin, CCN, DANLA 12/10/2007 The New Year will bring more proof of antioxidant benefits for human health. Recent research shows that antioxidants help to maintain healthy brain functions during aging, protect brain and nerve cells, and prevent hormones and cholesterol fractions from oxidizing to become more harmful forms. Look for an expanded understanding of the benefits of these synergistic nutrients in 2008. 2008 will provide more proof of omega-3 fatty acids’ benefits. For example, DHA helps to maintain healthy balances of cholesterol fractions and protects the brain and nerves. EPA helps normalize cell membranes and cellular health. These essential fats are typically very low in the American diet, so dramatic results could occur in clinical trials providing these nutrients to participants. There will be more safety scares regarding popular prescription and Over-The-Counter drugs, creating new safety warnings and label cautions. Since the most popular medications are typically blocking or inhibiting natural body functions (calcium channel blockers, cholesterol production inhibitors, serotonin re-uptake inhibitors, stomach acid production inhibitors, etc.) rather than dealing holistically with the causes of problems that create body imbalances (lack of optimal levels of nutrients, environmental chemicals and metals, chronic stress - lack of deep sleep, low fiber - high carbohydrate diets, etc.), major side effects from such drugs are inevitable. Side effects from pain medications will become more evident, increasing the number of people looking for safer alternatives. Herbs and spices are the major natural alternatives with some scientific evidence of efficacy. The market for organic and local foods will continue to grow at amazing levels. This will put pressure on the regulatory, farm and grocery industries to manage these products and segregate them to maintain their integrity. That contrasts with the increased reliance on genetically engineered corn to produce ethanol that raises food costs and increases the use of farm chemicals. And there is much evidence that non-genetically engineered foods are both environmentally and nutritionally superior to their modified cousins, while natural farming techniques are proving superior to chemical and genetically engineered farming in terms of managing fuel and seed costs, water use, improving both crop yields and selling prices, etc. Millions of farmers around the world have already weaned themselves from the chemical-genetic “green revolution” to use appropriate local farming techniques and have actually been more successful as a direct result of truly “green” practices. America has begun to awaken to the benefits of local and organic foods in terms of freshness, reducing the use of fossil fuels for transportation and demonstrable benefits to local economies. Watch for these trends to accelerate in 2008. Blood pressure and blood sugar concerns will continue to grow, along with a medical backlash attacking natural strategies to manage these concerns. However, science will also continue to amass evidencing the positive health benefits of natural products to help people maintain already healthy blood levels, in contrast with the poor symptom management that is a characteristic of pharmaceutical or surgical interventions used to “correct” chronic biological imbalances. These issues dovetail with current obesity and cardiovascular concerns and are part of the same syndrome related to chronic stress and poor diets. Positive reports of the benefits of higher levels of vitamin D will continue to proliferate, though with some bias against the synthesized vegetarian/vegan form of vitamin D2 versus D3 from fish oil or sheep lanolin. Health authorities will be pressured to raise both the recommended Daily Value and the Upper Limit of vitamin D to five times the current levels. Research will continue to accumulate regarding the health benefits of whole grains and whole foods, as will reports of people allergic or sensitive to gluten, corn, and other grains. More mainstream processed groceries will have whole food options in 2008. This is a good trend, though with cautions for the sensitive minority. There will be continuing claims that “dietary supplements” are illegally contaminated with steroids or other pharmaceutical drugs. These claims will typically be self-serving and defensive, made primarily by athletes accused of cheating by using banned substances. Beyond the obvious fact that legitimate supplement manufacturers do not have illegal substances on hand and that GMP (Good Manufacturing Practices certification) quality manufacturing protocols would avoid inadvertent contamination, these accusations are a barometer of how “unregulated” the mainstream media and the public thinks dietary supplements are. While there are plenty of regulations written specifically to regulate supplements, and even the FDA claims that it has adequate regulatory authority, somehow certain medical authorities and journalists like to pretend otherwise; perhaps to have a handy punching bag to deflect attention from the well-documented hundreds of thousands of deaths caused annually from pharmaceuticals and medical errors. In any case, expect more of this blame game in 2008. With a presidential election campaign under full swing, no meaningful legislation regarding health care or Medicare will be passed in 2008. There will be a narrow window of opportunity for such measures in 2009 with a new Congress and Administration. Natural health advocates will continue to press for meaningful use of nutrition to combat the major causes of disease and illness in America, with probably little impact against the lobbying might of the medical and pharmaceutical interests. The wild card is if, by some miracle, the insurance industry finally notices that their costs could be contained by the use of targeted nutrition such as the use of calcium and vitamin D to prevent osteoporosis, antioxidants to prevent age-related macular degeneration and oxidative-related glaucoma that affect vision and impact seniors’ independence, omega-3 fats to prevent coronary heart disease, the use of fiber to manage healthy cholesterol levels, etc. That could swing the pendulum towards the use of natural products to control healthcare costs. But I’m not betting on it happening in 2008, though I hope that they wise up soon enough to manage the recently overactive increases in medical costs. There will be additional, unjustified health scares about essential nutrients in 2008. Especially beware of “meta-analyses” that mix unrelated studies and magnify the number of variables using often-flawed statistical models. Some probable targets: · Kava (a few unrelated, anecdotal reports of liver problems) · Folic acid (a few reports of higher cancer levels despite a lot of cellular data indicating the opposite, creating a backlash against re-fortification of refined foods) · Vitamin E (continued championing/publicity of questionable meta-analyses over more rigorous blood-level studies will continue the inexplicable controversy over the safety of this essential nutrient that most Americans are reportedly deficient in.) · Beta-Carotene (again, blood level studies and total antioxidant studies repeatedly show its safety, but studies measuring only administration of certain doses to sick populations that may be deficient in antioxidants create a conflicting picture.) · DHEA (this adrenal hormone has been vilified as a “steroid”, but is no more so than vitamin D. No less an authority than physician and US Senator Tom Coburn has sent a letter to his colleagues informing them that he has reviewed the issues and urging them to avoid a ban of this natural product, which is useful in anti-aging strategies but not for bodybuilders. Efforts by leading senators (including presidential candidates Clinton and McCain) to ban DHEA are ongoing.

Are antioxidants worthless against heart disease?

Are antioxidants worthless against heart disease? By Neil E. Levin, CCN, DANLA 8/15/07 In a published report, A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women (Results From the Women’s Antioxidant Cardiovascular Study), researchers concluded that, “There were no overall effects of ascorbic acid (vitamin C), vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.” (1) This is simply untrue. In order to reach that conclusion, the researchers had to count non-compliant subjects as taking vitamin E, even when it was obvious that they weren’t following the study protocol. Is that intellectually honest? I would have given the opposite conclusion. When subjects assigned to take vitamin E actually took their vitamin E, the results were significant and proved that the vitamin had benefits: “Censoring participants on noncompliance led to a significant 13% reduction in the primary end point…Reductions in secondary study end points were also stronger, with a 22% reduction in MI … a 27% reduction in stroke … and a 9% reduction in CVD mortality … There was a 23% reduction in the combination of MI, stroke, or CVD death…Among those with prior CVD, the active vitamin E group experienced fewer major CVD events …” [-11%] "A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior cardiovascular disease (RR, 0.89; 95% CI, 0.79 - 1.00 [P = .04]; P value for interaction = .07). There were no significant interactions between agents for the primary end point, but those randomized to both active vitamins C and E experienced fewer strokes (P value for interaction = .03)." Why did the researchers gloss over these admitted benefits (that those assigned to take vitamin E who actually did take it had "significant" benefitsand those with prior CVD who took the relatively low levels of C plus E experience fewer strokes)? This was wholly ignored in the study's conclusion, as well as the subsequent press release and extensive news coverage. I have found and published (2) criticisms of this particular failing (reaching improper conclusions not truly supported by the data) before: (3-10) REFERENCES: 1. Cook N, et al. A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women. ARCH INTERN MED. VOL 167 (NO. 15), AUG 13/27, 2007 2. Levin N. Land of Confusion: How Poor Science and Misleading Media Coverage Create Public Confusion About How Dietary Supplements Affect Health. J App Nutr, Vol 55, No. 1, 2005 8-15 3. Edgar R. Miller, III, MD, PhD; et al. High-dose vitamin E supplementation may increase all-cause mortality, a dose response meta-analysis of randomized trials. Annals of Internal Medicine: Online: Nov. 10, 2004: Print: 4 January 2005 | Volume 142 Issue 1 4. A study conducted by USA Today found that more than half of the experts hired to advise the government on the safety and effectiveness of medicine had a direct financial interest in the drug or topic they were asked to evaluate. An analysis of financial conflicts of interest at 159 FDA advisory committee meetings from January 1, 1998, through June 30, 2000, found that at 92% of the meetings, at least one member had a financial conflict of interest, while at 55% of meetings, half or more of the FDA advisers had conflicts of interest. These conflicts included helping a pharmaceutical company develop a medicine, then serving on an FDA advisory committee that judges the drug. 5. Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338–47. PMID: 15769967 6. Blumenthal M, Farnsworth NR. Echinacea angustifolia rhinovirus infections [letter]. N Engl J Med. Nov.3, 2005;353(18):1971–1972. 7. 21 C.F.R. Pt. 119, Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk (Published February 11, 2004) (Effective April 12, 2004) available at http://www.fda.gov/ohrms/dockets/98fr/1995n-0304-nfr0001.pdf 8. Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, Calabrese C. Efficacy and safety of Echinacea in treating upper respiratory tract infections in children: A randomized controlled trial. J Amer Med Assn Dec 3, 2003;290(21):2824–30. 9. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 2004 Sep;229(8):698–704. Review. PMID: 15337824 10. Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer. JAMA. Vol. 293 No. 11, Vol. 293 No. 11, March 16, 2005

Selenium and Antioxidant Safety

My letter criticizing their editorial in Annals of Internal Medicine was accepted and published online by that journal: http://www.annals.org/cgi/eletters/0000605-200708210-00177v1#21702 It is unfortunate that synergistic nutrients are tested individually, like drugs. This is a pharmaceutical practice, not human nutrition, and shouldn’t imply that comprehensive mixtures of nutrients (like a multivitamin) would have the same effects. I dispute that “randomized, controlled clinical trials have shown that ß-carotene and vitamin E supplements, which were widely believed to be safe, increase mortality and morbidity”. The choices, increasing variables, and manipulation by statistical models in meta-analyses are often questionable. In this report, prediabetic symptoms were not even considered as a variable. Buijsse noted that high carotenoid intake, confirmed by measures of blood levels, was associated with lower mortality rates among the elderly over a ten-year period, countering the claim that ß-carotene dangers are proven. The Miller meta-analysis, cited as proof of vitamin E’s dangers, was heavily criticized in published responses, and its conclusions were NOT replicated when the same data was re-analyzed (Hathcock). It should therefore not be cited as proof of the vitamin’s danger. Another meta-analysis cited (Bjelakovic) reported that antioxidant vitamins may increase death rates. But the authors did not determine a dose-dependent or cause-and-effect relationship between antioxidants and deaths (from all causes) of study participants. The researchers pooled 68 published trials, excluding 405 published studies with no deaths reported. Too wide a range of potencies (Vitamin A 1333 IU - 200,000 IU, vitamin E 10 IU to 1000 IU), and durations (28 days to 12 years) were lumped together. The statement, “No dietary supplement, including selenium, has proven useful so far for the prevention of cardiovascular disease or cancer in the general U.S. population,” is questionable. The Alpha-Tocopherol, Beta- Carotene Cancer Prevention (ATBC) Study published by the National Cancer Institute demonstrated a 32% reduction in prostate cancer incidence in response to daily alpha-tocopherol supplementation. The Women’s Health Study (JAMA) reported a significant 24% reduction in cardiovascular death with supplemental vitamin E. The NIH reports, “Taking a daily supplement containing 200 μg of selenium … significantly reduced the occurrence and death from total cancers. The incidence of prostate cancer, colorectal cancer, and lung cancer was notably lower in the group given selenium supplements.” Yet you suggest lowering consumption below the Daily Value (70 μg) used in multivitamins and far below the current upper limit. On the contrary, the Lewin Group reports that the use of antioxidants could save the vision and independence of many senior citizens, saving billions of dollars in healthcare costs. REFERENCES: Bjelakovic G, et.al. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA 2007. 297(8):842-857 Buijsse B, et al. Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: The Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA). Am J Clin Nutr 2005;82:879–886. DaVanzo JE, et al. An Evidence-Based Study of the Role of Dietary Supplements in Helping Seniors Maintain their Independence. The Lewin Group Inc. January 20, 2006 Hathcock JN, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005 Apr;81(4):736-45. Review. PMID: 15817846 Weinstein SJ, et al. Serum α -Tocopherol and γ-Tocopherol in Relation to Prostate Cancer Risk in a Prospective Study. J. Natl. Cancer Inst. 2005 97: 396-399; doi:10.1093/jnci/dji045

Antioxidant Confusion

Antioxidant Confusion By Neil E. Levin, CCN, DANLA Board certified clinical nutritionist with diplomate in advanced nutritional laboratory assessment March 2, 2007 A meta-analysis published in the medical journal JAMA this week reported that antioxidant vitamins do not extend life and may even increase death rates slightly. 1 These conclusions make no sense, based on the scientific record. A meta-analysis relies on a statistical model of existing science, and this model has severe limitations. Even the authors admit some of the basic problems inherent in this type of analysis. More importantly, the authors could not find a dose-dependent or cause-and-effect relationship between antioxidants and deaths (from all causes) of study participants. In other words, they couldn’t show that antioxidants actually caused any deaths or that there was risk at a particular dosage. Yet this questionable speculation received widespread publicity from the sensation-hungry media during “Sweeps Month”, dutifully spreading the lie that antioxidants are now worthless and dangerous. The researchers pooled 68 previously published trials but arbitrarily excluded all published studies that had no deaths reported from any cause. Indeed, 405 otherwise eligible studies were excluded solely for this reason, which if included would likely have dramatically changed the results and conclusion. The researchers did not disclose why they decided to exclude these. This is equivalent to playing a card game after removing all but 7 cards from the deck. (That wouldn’t be a fair game, would it?) They largely ignored the original outcome measures of the studies, many of which had shown positive results for antioxidants, to look only for deaths from any cause in a tiny segment of all published research. This arbitrary decision echoes a frequently cited complaint by scientists commenting to the journal Annals of Internal Medicine when the infamous Miller meta-analysis of vitamin E was released a few years ago, which led to a dramatic slowdown of vitamin E sales. 2 It is interesting that the Miller study’s negative conclusions about vitamin E safety have since been thoroughly debunked by a more rigorous analysis published in the American Journal of Clinical Nutrition by leading antioxidant experts. 3 It is even more interesting that the flawed Miller review was cited as a reference by the JAMA authors but the second, more thorough analysis of the same data by real nutrition experts was not. The lesson learned is that a flawed meta-analysis of nutrients by statisticians and physicians may not hold up to a more competent review done by actual experts in the field of nutrient interactions, though the initial report may have scared people and changed their behavior. Critical comments and corrections typically go ignored, uncited and unreported, in contrast with the sensational initial report. 4 I question both the selection of studies reviewed and the references cited in this meta-analysis. Obviously, excluding six times as many potentially eligible studies as were actually chosen solely because of a requirement that someone in the study population had to die unfairly magnifies negative results by dramatically reducing the pool of studies with potentially positive results and healthier populations. This negative shift is a result of limiting the combined patient population to those studies with at least one dying patient. This population shifts to those individuals who are more likely to be deficient in a variety of antioxidant substances and who are unlikely to respond to limited amounts of one or few supplemental antioxidants. The lack of additional supporting antioxidants may even sometimes increase the oxidative stress on the body. A review of antioxidant science noted, “These negative results…should not be taken as evidence that the free radical theory of aging is flawed. In fact, they prove merely that a complex organism like a human or rodent is unlikely to respond predictably to crude manipulations such as supplementation with one or a small number of compounds.” 1, 5, 6 This mirrors the JAMA authors’ admissions that “antioxidant supplements may show interdependency and may have effects only if given in combination,” and that their findings “should not be translated to potential effects of fruits or vegetables,” which are sources of numerous and varied antioxidant substances. 1 Previous studies have shown the folly of such a protocol. Some years ago an antioxidant study in Finland was halted early because of a widely reported increase in cancer rates among male smokers taking beta-carotene. 7 Headlines associated this supplement with cancer risk. Despite objections that the study was flawed, beta-carotene use dropped. A later analysis published in July 2004 took another look at that same Finnish smokers' study data, but now taking into account total antioxidant intake, which (should have) cleared away the scientific controversy. 8 A composite antioxidant index was generated for each of the 27,000 men over 14 years. The calculated amounts of carotenoids, flavonoids, Vitamin E, selenium and Vitamin C were compared to actual lung cancer rates, with a clear result: an increased intake of a combination of antioxidants lowered lung cancer risk in male smokers. Another large study has noted that high carotenoid intake, as confirmed by measures of blood levels, was associated with lower mortality rates among the elderly over a ten year period. 9 The dietary level of antioxidants is an independent predictor of plasma beta-carotene, especially in moderate alcohol drinkers. A more recent study reports, “This may explain, at least in part, the inverse relationship observed between plasma beta-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of beta-carotene supplements alone in reducing such risk.” 10 In other words, we shouldn’t expect one or two supplemented antioxidants to compensate for a deficiency of total antioxidants in the diet. In fact, many of the protocols for supplementation in the included studies may have actually been of too low potency to achieve noticeable health benefits by remedying latent nutrient deficiencies in fragile patient populations. In other words: many of the interventions were too little, too late. Don’t blame the vitamins. The JAMA report admits that the study populations, the variety of antioxidants used, their potencies and the protocols for taking them were extremely variable, complicating their data with many uncompensated variables. Yet the authors actually claim that, “This increases the trustworthiness of our findings.” I don’t think so! One trial included gave only a single serving of antioxidants and then monitored participants for 3 months. Others used doses of as little as 10 IU of vitamin E (a low amount that is below the Daily Value) and 20 mcg of selenium 1 (an amount far below the 70 mcg DV and not anywhere near the 200+ mcg/day associated with lower cancer rates). 11, 12 I am not alone in these criticisms. Alexander Schauss, PhD, FACN has written, “The range of doses in the different trials they selected for the meta-analysis is dramatic. For example, vitamin A ranged from 1333 IU to 200,000 IU, and vitamin E from 10 IU to 1000 IU. The duration of the studies range from 28 days to 12 years. Nevertheless they were all lumped together.” An Associated Press article quoted other experts criticizing this meta-analysis: ‘Meir Stampfer, professor of nutrition and epidemiology at the Harvard School of Public Health, said the new analysis hasn't discouraged him from taking his vitamins. Stampfer said the studies were too diverse to pool together because they looked at various combinations and doses of antioxidants tested in different groups of people. The trials ranged from a three-month study of 109 elderly nursing home residents to a 12-year study of 22,071 male doctors. "This study does not advance our understanding, and could easily lead to misinterpretation of the data," said Stampfer, who was not connected to the new report.’ The AP report also quoted Donald Berry, chairman of the department of biostatistics at the University of Texas’ M.D. Anderson Cancer Center, stating that this expert also disagreed with the researchers' finding of an increased risk of dying. "There are so many choices you can make when you're doing these analyses," he said. A study of approximately 90,000 nurses suggested that the incidence of heart disease was 30% to 40% lower among nurses with the highest intake of vitamin E from diet and supplements. Researchers found that the apparent benefit was mainly associated with intake of vitamin E from dietary supplements. High vitamin E intake from food was not associated with significant cardiac risk reduction. 13 Levels of Vitamin E above 100 IU daily are associated with decreased risk of coronary heart disease and certain types of cancer, as well as enhancement of immune function. These increased vitamin E intakes are considerably above levels obtainable from diet alone. 14, 15, 16 In a report on the Women’s Health Study published in JAMA, subjects supplementing with vitamin E were reported to have a significant 24% reduction in cardiovascular deaths. 17 Have these previously published benefits of antioxidants miraculously vanished simply because some doctors manipulated a statistical model to elicit unreliable data with no solid basis? Many of the studies included were of patients with specific, serious medical conditions, including one of elderly nursing home patients measuring incidences of bacterial infections (contrasting with a 2004 study published in JAMA noted that, “we observed a protective effect of vitamin E supplementation on upper respiratory tract infections, particularly the common cold, that merits further investigation.” 18), patients with tumors removed from their colon/rectum (antioxidants are associated with apoptosis, a desirable change that leads to death of cancer cells 19, 20), patients with age-related macular degeneration (a condition associated with a deficiency of various antioxidants 21-24), patients with coronary heart disease (a condition related to oxidative damage 14-16), dialysis patients with a history of cardiovascular disease (a condition related to oxidative damage that is reduced by supplemental vitamin E 17), cataract patients (another condition related to oxidative damage 25), male cigarette smokers/present and former cigarette smokers/asbestos workers (all related to low levels of total antioxidants and high toxic load), as well as patients with alcoholic hepatitis, cirrhosis, lupus, heart failure, ALS, etc. This meta-analysis will not stand the test of time because of its many variables, flaws and the arbitrary structuring of its statistical model. When better studies exist, often supported by blood assays, that show higher serum antioxidant levels reduce actual death rates in large populations, then no arbitrary statistical model should be able to negate that robust science with a merely theoretical danger based on such preliminary, questionable criteria. All studies cited here were published in peer-reviewed scientific journals, but that does not make them all of equal quality. Remember my story of the meta-analysis on vitamin E that was refuted by a better meta-analysis, yet both were peer-reviewed? A meta-analysis has more validity if fewer variables are included and if the selection of studies included is not biased by a presumed conclusion. Were hundreds of studies without dying participants ineligible for this particular meta-analysis review simply because of a selection bias, with an intent to demonstrate the dangers of supplementation? These scientists should know better. I see their report as an ill-disguised partisan attack by medical special interests on dietary supplements, a smokescreen for those that don’t look at the quality and quantity of well-designed studies that do show the benefits of vitamins to protect health and prevent deaths. The Lewin Group has presented evidence that the use of antioxidants could save the vision and independence of many senior citizens, while saving the public billions of dollars in healthcare costs. 26 The Institute of Medicine, part of the National Institutes of Health, after reviewing hundreds of well-designed studies, has set safe upper limits for several antioxidants at levels far above the Daily Values. 27 Antioxidants are safe, and proven so in better studies than this one. REFERENCES: 1. Bjelakovic G, et.al. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA 2007. 297(8):842-857 2. Miller ER 3rd, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. Summary for patients in: Ann Intern Med. 2005 Jan 4;142(1):I40. PMID: 15537682 3. Hathcock JN, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005 Apr;81(4):736-45. Review. PMID: 15817846 4. Levin, N. Land of Confusion: How Poor Science and Misleading Media Coverage Create Public Confusion About How Dietary Supplements Affect Health. J App Nutr, Vol 55, No. 1, 2005 8-15 5. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998 Apr;78(2):547-81. Review. PMID: 9562038 6. BLOCK, G. Are clinical trials really the answer? Am. J. Clin. Nutr. 62, Suppl.: 15175-15205, 1995 7. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994 Apr 14;330(15):1029-35. http://content.nejm.org/cgi/content/full/330/15/1029?ijkey=bd47b716724d0dad4cad0fb19337308753658337 8. Wright ME, et al. Development of a Comprehensive Dietary Antioxidant Index and Application to Lung Cancer Risk in a Cohort of Male Smokers. July 2004 American Journal of Epidemiology http://aje.oupjournals.org/cgi/content/abstract/160/1/68?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&andorexacttitle=and&andorexacttitleabs=and&fulltext=beta+carotene&andorexactfulltext=and&searchid=1100534768534_1530&stored_search=&FIRSTINDEX=0&sortspec=relevance&fdate=7/1/2004&tdate=7/31/2004&journalcode=amjepid 9. Buijsse B, et al. Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: The Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA). Am J Clin Nutr 2005;82:879–886. 10. Brighenti F. The total antioxidant capacity of the diet is an independent predictor of plasma beta-carotene. European Journal of Clinical Nutrition (2007) 61, 69–76. 11. Clark LC, Marshall JR. Randomized, controlled chemoprevention trials in populations at very high risk for prostate cancer: elevated prostate-specific antigen and high-grade prostatic intraepithelial neoplasia, Urology 57 (2001), pp. 185–187. 12. Duffield-Lillico, AJ, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial, Cancer Epidemiol. Biomarkers Prev. 11 (2002), pp. 630–639. 13. Stampfer MJ, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444-9 14. Bauernfeind, J. Tocopherols in Foods. In: Vitamin E: A Comprehensive Treatise. Marcel Dekker, Inc., New York and Basel, pp. 99-167, 1980. 15. Horwitt, M.K. The Promotion of Vitamin E. J. Nutr. 116:1371-1377, 1986. 16. Weber, P., Bendich, A. and Machlin, L.J. Vitamin E and Human Health: Rationale for Determining Recommended Intake Levels. Nutrition 13:450-460, 1997. 17. I-Min Lee, MBBS, ScD; 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 18. Meydani SN, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):828-36. Erratum in: JAMA. 2004 Sep 15;292(11):1305. PMID: 15315997 19. Narayanan BA. Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets. Curr Cancer Drug Targets. 2006 Dec;6(8):711-27. Review. PMID: 17168675 20. Valko M, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84. Epub 2006 Aug 4. Review. PMID: 16978905 21. Chiu CJ, Taylor A. Nutritional antioxidants and age-related cataract and maculopathy. Exp Eye Res. 2007 Feb;84(2):229-45. Epub 2006 Jul 31. Review. PMID: 16879819 22. Moriarty-Craige SE, et al. Antioxidant supplements prevent oxidation of cysteine/cystine redox in patients with age-related macular degeneration. Am J Ophthalmol. 2005 Dec;140(6):1020-6. PMID: 16376645 23. Richer S, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr;75(4):216-30. PMID: 15117055 24. Koh HH, et al. Macular Pigment Optical Density in Early, Age-Related Maculopathy (ARM); Comparisons With Normals and Effects of a Lutein Supplement. Invest Ophthalmol Vis Sci 2002; 43:2562 25. Meyer CH, Sekundo W. Nutritional supplementation to prevent cataract formation. Dev Ophthalmol. 2005;38:103-19. Review. PMID: 15604620 26. DaVanzo JE, et al. An Evidence-Based Study of the Role of Dietary Supplements in Helping Seniors Maintain their Independence. The Lewin Group Inc. January 20, 2006 27. National Institutes of Health, Institute of Medicine, Office of Dietary Supplements. Vitamin E Fact Sheet