Should You Take An Antioxidant (Supplement or Vitamin) To Prevent Or Treat Heart Disease?

The pseudoscientific sneakiness of snake oil salesmen, like Dr. Mercola creates a booming business for useless vitamins and supplements like Vitamins E and C and beta-carotene.

The following is an update of a post the skeptical cardiologist wrote 7 years ago. Although nothing has changed on this topic since then, I am reposting it for new readers and because I am in the process of revisiting whether any supplement should be taken to reduce cardiovascular disease or prolong health span.

Part of my motivation for diving into the supplement cesspool again was that the prominent longevity guru, Peter Attia, who I respect for a very science-based approach to cardiovascular disease, is taking around a dozen supplements.

When I looked at the science behind over-the-counter supplementary neutraceuticals, vitamins, and multivitamins 10 years ago, I concluded that there was no evidence to consume any of them.

My goal in this series will be to reassess benefits and risks of OTC products with an eye to finding any that are safe and useful for me and my patients.

I cross-posted on my substack website last year a great article by Dr. Gunter (not to be confused with the ubiquitous former cardiac surgeon and snake-oil salesman Charles Gundry) which summarizes why the FDA doesn't monitor these products and the dangers of consuming these products but I haven't heretofore revisited individual supplements/vitamins/neutraceuticals.

I'll begin this series with one area where it is very clear there is no benefit: antioxidants.

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Antioxidant-rich foods, vitamins and supplements are incessantly promoted to Americans as effective and safe means to stave off the chronic diseases of aging and even aging itself.

The simple concept that sells billions of dollars of these products seems logical and seems to be supported by science: damaging and disease-causing free radicals are neutralized by super hero antioxidants. All you have to do to benefit from these disease-fighting agents is identify foods with the highest level of antioxidants or take supplements with super antioxidant vitamins or chemicals.

To remain young and free of heart disease, cancer and dementia, the glowing marketing material for antioxidant products proclaims, eat this magical Italian fruit or drink this fruit juice or take this concentrated substance that we have carefully extracted from a super fruit. Unfortunately, the early hopes that antioxidant therapy would reduce heart disease,in particular, and other chronic diseases of aging in general have been dashed by excellent scientific studies performed in the 1990s.

For antioxidant vitamins, in particular, which continue to be heavily promoted for heart disease and cancer prevention, over the last 20 years a wealth of studies have accumulated which clearly demonstrate a lack of efficacy. Despite data clearly showing no benefit in well done randomized trials (and in some cases evidence for harm) sales of antioxidant vitamins C, E and beta-carotene continue to thrive. Why did scientists strongly believe in the idea that antioxidants in pure and concentrated form would prevent heart disease?

Antioxidants: Free Radical Scavengers

Laboratory and animal studies beginning in the 1950s suggested that excess free radicals generated by oxidative processes could be responsible for the chronic degenerative diseases of aging. Oxygen, which is essential to animal life, undergoes processing in cells which creates unstable free radicals.

Free radicals are short an electron and seek other molecules which can donate an electron and make them more stable. This process is termed oxidation. The molecules produced by oxidation play an important role in a a number of biological processes such as the killing of bacteria and in cell signaling

These same unstable molecules, however, have been implicated in a number of deleterious processes as they can participate in unwanted side reactions and create cell damage. Thus, too many free radicals have been implicated as potentially causal in diseases ranging from cancer to cardiovascular disease to dementia.

Antioxidants can reduce damage from free radical reactions because they can donate electrons to neutralize free radicals or their offspring without forming another free radical. This observation logically lead to the theory that large amounts of antioxidants taken as an oral supplement or within (either naturally or added artificially) food and beverages can prevent the free radical damage presumably causing chronic disease and aging.

Investigators early on identified three vitamins as the most important cellular antioxidants:

• Vitamin E or d-alpha tocopherol is a fat soluble vitamin.

• Vitamin C or ascorbic acid. is a water soluble vitamin, deficiency of which leads to scurvy

• Beta-carotene is a precursor to vitamin A (retinol)

Early Observational Studies Suggest Taking An Antioxidant Prevents Heart Disease

Based on laboratory, animal and human clinical trials many investigators by the early 1990s were convinced that oxidation of LDL cholesterol was the major cause of atherosclerosis and that antioxidant supplementation , in particular Vitamin E, could prevent the heart attacks and strokes caused by atherosclerosis. The introduction to the landmark Nurses Health Study summarizes the seemingly compelling evidence leading to these conclusions:

Rapidly growing evidence suggests that oxidation of low-density lipoprotein (LDL) plays an important part in atherosclerosis. As Steinberg et al. have found, oxidized LDL is taken up more readily than native LDL by macrophages to create foam cells. Also, oxidized LDL is chemotactic for circulating monocytes, and it inhibits the motility of tissue macrophages. It may also be cytotoxic to endothelial cells and may increase vasoconstriction in arteries. Oxidized LDL has been identified in atherosclerotic lesions,and elevated titers of circulating autoantibodies to epitopes of oxidized LDL are found in patients with atherosclerosis. Lipid peroxide concentrations have been found to be higher in patients with atherosclerosis. In addition, the susceptibility of LDL to oxidation was correlated with the severity of atherosclerosis. Vitamin E is a potent lipid-soluble antioxidant carried in LDL. It inhibits the proliferation of smooth-muscle cells in vitro, and when added to plasma, it increases the resistance of LDL to oxidation. LDL from volunteers given alpha-tocopherol supplements showed increased resistance to oxidation.

Starting in 1980 the Nurses Healthy Study began gathering information on diet and supplement use in 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer. Information on diet was assessed every two years and the participants were monitored for cardiovascular outcomes for 8 years. High consumers of Vitamin E compared to lower consumers had a 34% lower risk of major coronary disease. Those who took Vitamin E for more than 2 years had a 41% reduction in risk which was significant after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multivitamins).

After reading this study, I and many of my colleagues began recommending that our patients take Vitamin E. These observational trials, however, could only show an association between antioxidants and disease, they didn't prove causality.

Good Quality Randomized Trials Fail To Show Any Benefit of Antioxidants and Raise Concerns of Possible Danger

Given the strong evidence for antioxidants in reducing heart disease from the observational and laboratory studies the theory that antioxidant supplementation would reduce heart disease needed to be tested in randomized trials.

Fortunately, multiple well done randomized studies have tested whether supplementation with the major proposed antioxidants will reduce heart disease, cancer or mortality.

Sadly, the consensus assessment is that they are useless and in some cases antioxidant vitamin supplementation may increase risks.

The Physicians' Health Study II is a great example: Published in 2008, This study randomly assigned 14,641 physicians without heart disease to treatment with vitamin E 400 international units every other daily, vitamin C 500 mg daily, both, or neither; After eight years, treatment with vitamin E and Vitamin C either alone or in combination had no effect on major cardiovascular events or all-cause mortality.

Those participants taking Vitamin E had a significant 70% increased risk of hemorrhagic stroke compared to those taking placebo. After this trial was published I took all my patients off Vitamin E. Multiple good quality randomized controlled studies of Vitamin E, Vitamin C and beta-carotene in various combinations have also been done on patients who have established coronary heart disease and have shown no benefit in reducing cardiovascular events or mortality.

This 2003 Lancet meta-analysis nicely summarizes the data. These studies strongly called into question the theory that supplementation with antioxidants reduce chronic disease and by 2003 there was a broad consensus among serious scientists, cardiologists and nutritionists that Vitamin E and Vitamin C in various doses and in diverse populations had no benefit in reducing mortality, cardiovascular disease or cancer. In fact, Vitamin E may increase hemorrhagic stroke and high-dose vitamin E supplementation (≥400 international units/day) may be associated with an increase in all-cause mortality Studies with beta-carotene overall suggested an increase in overall mortality and one study has shown an increased risk of lung cancer in male smokers who received supplementation.

More recently, a 2012 BMJ meta-analysis concluded that there was no benefit for any vitamin or antioxidant supplement in reducing cardiovascular risk or mortality.

Despite Scientific Studies Showing No Benefit, Antioxidant Sales Continue To Grow

You might conclude that based on high quality studies showing no benefits and potential harm that sales of antioxidants would taper off. Unfortunately, the opposite has occurred.

Nutraceuticals World reported that sales of antioxidant supplements are growing steadily, reaching all time highs.

Combining top antioxidant ingredient sales such as green tea, dark chocolate, superfruit juice and dietary supplements, Euromonitor estimated the combined global sales in these categories totaled $34 billion in 2010. According to Euromonitor, the top antioxidant markets are Japan, the U.S. and China, with sales growing steadily in all five ranked product areas in the past five years. Growth from 2005 to 2010 was 43% in current terms. As a point of comparison, the global organic packaged food and beverage market was only $27 billion.

The Sneakiness of the Nutraceutical Snake Oil Salesmen

The quacks and charlatans that make their living selling useless vitamins, minerals, supplement and nutraceuticals are masters at creating the appearance of a scientific basis for buying their snake oil.

Their promotional material always features references to scientific studies. Almost invariably, these references do not prove any health benefit for the product being sold.

In cases like antioxidants where initial studies suggest a benefit and subsequent higher quality studies have shown no benefit, only the earlier studies will be quoted.

If relevant negatives studies for an antioxidant are referenced, the talented snake oil salesman will explain to his gullible audience that the lack of efficacy was because the wrong form of the antioxidant was utilized.

Fortunately, for you, the snake oil salesman has developed his own special formulation which is superior. Such formulations are typically described as containing additional ingredients that enhance efficacy. Often, the special formulation is described as somehow better at getting into the body or being absorbed.

None of these special formulations has any scientific support for treating or preventing any disease.

Dr. Mercola, A Master of Pseudoscientific Support For Selling Useless Vitamins

The most successful marketers of useless antioxidant supplements and vitamins convince their audience that they alone have the insight and wisdom to provide the consumer with the knowledge and products they need to be healthy.

To accomplish this, they must create mistrust of standard medical advice and prescription medications, often portraying doctors as ignorant of proper nutrition and hostile to allegedly superior "natural" or alternative cures.

Doctors, in this portrayal, are the enemy, pushing dangerous prescription medications along with unneeded procedures like coronary stents and bypass surgery because we are in the pay of the pharmaceutical and medical device industries.

Joseph Mercola,¹ an osteopath, has created an alternative medicine internet empire by convincing millions to follow his advice and buy his useless supplements. He is arguably the master of alternative medicine misinformation. (See this article to fully understand how dangerous Mercola's ideas are.)

Hoovers reports that Mercola makes 9.8 million dollars per year selling useless stuff and Alexa describes his website as the top "alternative medicine" website. Mercola sells so much snake oil it is mind-numbing.

Mercola (or more likely his marketing department) has an astonishingly long and detailed list of pseudoscientific reasons why you should buy only his own special formulation of Vitamin E

• His form is natural versus synthetic.

• Other natural forms of vitamin E come from soy which you should avoid because it is genetically engineered.

• You need all 8 forms of natural vitamin E and they must be balanced in the way that he deems most healthy. His form comes from sunflower seeds.

• Science has ignored the tocotrienol form of Vitamin E but has "started to wake up to the potential benefits."

• Tocotrienols potentially "help support normal cholesterol levels., protect against free radical damage and the normal effects of aging" and promote brain health."

• The average consumer reading this long and complicated discussion is likely to be impressed with the pseudoscientific language, the complicated chemical names, and the appeal to a more natural approach and has no way of knowing that it is all unsubstantiated marketing hype.

None of these seemingly science-based statements are supported by scientific references.

The average consumer is not likely to see buried in small print at the bottom of the page the truth:

*These statements have not been evaluated by the Food and Drug Administration.

These products are not intended to diagnose, treat, cure, or prevent any disease.

Don't Buy Antioxidant Supplements and Vitamins

What have we learned?

1. Although early research suggested a role for antioxidant vitamins in preventing heart disease when high quality randomized controlled rials were performed they showed no benefit and in some cases increased risk.

2. Despite this, antioxidant sales are booming.

3. Supplement marketers are brilliant at confusing consumers with pseudoscience and sell billions of dollars of useless product.

There is minimal regulation of the nutraceutical/supplement industry. The snake oil purveyors get away with their lies and escape (for the most party) FDA scrutiny by admitting that their products don't "treat, cure or prevent any disease." Rather than hiding this information, at a minimum, they should be forced to put it in large, bold letters at the beginning of every page on their website.

THESE PRODUCTS ARE NOT INTENDED TO TREAT, CURE OR PREVENT ANY DISEASE! Please don't buy them any more.

Uncleoxidantly Yours,

-ACP