Video

Antioxidants – Beyond The Hype

Introduction

The body’s trillion or so cells face formidable threats, from lack of food to infection with a virus. Another constant threat comes from nasty chemicals called free radicals. They are capable of damaging cells and genetic material. The body generates free radicals as the inevitable byproducts of turning food into energy. Others are in the food you eat and the air you breathe. Some are generated by sunlight’s action on the skin and eyes.

Free radicals come in many shapes, sizes, and chemical configurations. What they all share is a voracious appetite for electrons, stealing them from any nearby substances that will yield them. This electron theft can radically alter the “loser’s” structure or function. Free radical damage can change the instructions coded in a strand of DNA. It can make a circulating low-density lipoprotein (LDL, sometimes called bad cholesterol) molecule more likely to get trapped in an artery wall. Or it can alter a cell’s membrane, changing the flow of what enters the cell and what leaves it.

We aren’t defenseless against free radicals. The body, long used to this relentless attack, makes scads of molecules that quench free radicals as surely as water douses fire. We also extract free-radical fighters from food. These defenders are often lumped together as “antioxidants.” They work by generously giving electrons to free radicals without turning into electron-scavenging substances themselves.

There are hundreds, probably thousands, of different substances that can act as antioxidants. The most familiar ones are vitamin Cvitamin Ebeta-carotene, and other related carotenoids, along with the minerals selenium and manganese. They’re joined by glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, phytoestrogens, and many more.

But using the term “antioxidant” to refer to substances is misleading. It is really a chemical property, namely, the ability to act as an electron donor. Some substances that act as antioxidants in one situation may be prooxidants—electron grabbers—in a different chemical milieu. Another big misconception is that antioxidants are interchangeable. They aren’t. Each one has unique chemical behaviors and biological properties. They almost certainly evolved as parts of elaborate networks, with each different substance (or family of substances) playing slightly different roles. This means that no single substance can do the work of the whole crowd.

Health Benefits of Antioxidants: What’s the Buzz?

 Antioxidants came to public attention in the 1990s, when scientists began to understand that free radical damage was involved in the early stages of artery-clogging atherosclerosis and may contribute to cancer, vision loss, and a host of other chronic conditions. Some studies showed that people with low intakes of antioxidant-rich fruits and vegetables were at greater risk for developing these chronic conditions than were people who ate plenty of these fruits and vegetables. Clinical trials began testing the impact of single substances, especially beta-carotene and vitamin E, as weapons against heart disease, cancer, and the like.

Even before the results of these trials were in, the media, and the supplement and food industries began to hype the benefits of “antioxidants.” Frozen berries, green tea, and other foods labeled as being rich in antioxidants began popping up in stores. Supplement makers touted the disease-fighting properties of all sorts of antioxidants.

The trials were mixed, but most have not found the hoped-for benefits. Most research teams reported that vitamin E and other antioxidant supplements didn’t protect against heart disease or cancer (18) One study even showed that taking beta-carotene may actually increase the chances of developing lung cancer in smokers. On the other hand, some trials reported benefits; for example, after 18 years of follow-up, the Physicians’ Health Study found that taking beta-carotene was associated with a modest reduction in the rate of cognitive decline. (1)

These mostly disappointing results haven’t stopped food companies and supplement sellers from banking on antioxidants. Indeed, antioxidant supplements represent a $500 million dollar industry that continues to grow. Antioxidants are still added to breakfast cereals, sports bars, energy drinks, and other processed foods, and they are promoted as additives that can prevent heart disease, cancer, cataracts, memory loss, and a host of other conditions.

Often the claims have stretched and distorted the data: While it’s true that the package of antioxidants, minerals, fiber, and other substances found naturally in fruits, vegetables, and whole grains helps prevent a variety of chronic diseases, it is unlikely that high doses of antioxidants can accomplish the same feat.

Studies of Antioxidants and Disease Prevention: Little Supportive Evidence

Randomized, placebo-controlled trials—which, when performed well, provide the strongest evidence—offer little support that taking vitamin C, vitamin E, beta-carotene, or other single antioxidants provides substantial protection against heart disease, cancer, or other chronic conditions. The results of the largest such trials have been mostly negative.

Heart Disease and Antioxidants

Vitamin E, beta-carotene, and other so-called antioxidants aren’t the silver bullet against heart disease and stroke that researchers were hoping for. Although the final chapter has not been written on vitamin E.

In the Women’s Health Study, 39,876 initially healthy women took 600 IU of natural source vitamin E or a placebo every other day for 10 years. At the study’s end, the rates of major cardiovascular events and cancer were no lower among those taking vitamin E than they were among those taking the placebo. However, the trial did observe a significant 24 percent reduction in total cardiovascular mortality. Although this was not a primary endpoint for the trial, it nevertheless represents an extremely important outcome. (2)

Earlier large vitamin E trials, conducted among individuals with previously diagnosed coronary disease or at high risk for it, generally showed no benefit. In the Heart Outcomes Prevention Evaluation (HOPE) trial, the rates of major cardiovascular events were essentially the same in the vitamin E (21.5 percent) and placebo (20.6 percent) groups, although participants taking vitamin E had higher risks of heart failure and hospitalization for heart failure. (3) In the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) trial, the results were mixed but mostly showed no preventive effects after more than three years of treatment with vitamin E among 11,000 heart attack survivors.(4) However, some studies suggest potential benefits among certain subgroups. A recent trial of vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress. (5)

A 2014 study from the Journal of Respiratory Research found that different isoforms of vitamin E (called tocopherols) had opposing effects on lung function (20)

  • The study analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and measured serum levels of alpha and gamma tocopherol in 4,526 adults
  • Lung function was tested using spirometric parameters- Higher parameters are indicative of increased lung function, lower parameters are indicative of decreased lung function
  • The study found that higher serum levels of alpha tocopherol were associated with higher spirometric parameters and that high serum levels of gamma tocopherol were associated with lower spirometric parameters.
  • Though the study is observational in nature it confirmed the mechanistic pathway of alpha and gamma tocopherol in mice studies (21)

Beta-carotene, meanwhile, did not provide any protection against heart disease or stroke, as demonstrated by the Physicians’ Health Study. (6)

What about combinations? The findings are complicated and not entirely clear. In the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study, 13,017 French men and women took a single daily capsule that contained 120 milligrams of vitamin C, 30 milligrams of vitamin E, 6 milligrams of beta-carotene, 100 micrograms of selenium, and 20 milligrams of zinc, or a placebo, for seven and a half years. The vitamins had no effect on overall rates of cardiovascular disease. (7)

In the Women’s Antioxidant Cardiovascular Study, vitamin E, vitamin C, and/or beta-carotene had much the same effect as a placebo on myocardial infarction, stroke, coronary revascularization, or cardiovascular death, although there was a modest and significant benefit for vitamin E among women with existing cardiovascular disease. (8)

Cancer and Antioxidants

When it comes to cancer prevention, the picture remains inconclusive for some antioxidant supplements. Few trials have gone on long enough to provide an adequate test for cancer. In the long-term Physicians’ Health Study, cancer rates were similar among men taking beta-carotene and among those taking a placebo. (6) Other trials have also largely showed no effect, including HOPE. (3) The SU.VI.MAX trial (7) showed a reduction in cancer risk and all-cause mortality among men taking an antioxidant cocktail but no apparent effect in women, possibly because men tended to have low blood levels of beta-carotene and other vitamins at the beginning of the study. A randomized trial of selenium in people with skin cancer demonstrated significant reductions in cancer and cancer mortality at various sites, including colon, lung, and prostate. (9) The effects were strongest among those with low selenium levels at baseline.

Age-Related Eye Disease and Antioxidants

This is the one bright spot for antioxidant vitamins. A six-year trial, the Age-Related Eye Disease Study (AREDS), found that a combination of vitamin C, vitamin E, beta-carotene, and zinc offered some protection against the development of advanced age-related macular degeneration, but not cataract, in people who were at high risk of the disease. (10, 11) Lutein, a naturally occurring carotenoid found in green, leafy vegetables such as spinach and kale, may also protect vision. However, relatively short trials of lutein supplementation for age-related macular degeneration have yielded conflicting findings. (12, 13) A new trial of the AREDS supplement regimen plus lutein, zeaxanthin, and fish oil is underway. This trial could yield more definitive information about antioxidants and macular degeneration. (14)

Potential Hazards of Antioxidants

Cup of tea

If antioxidants were harmless, it wouldn’t much matter if you took them “just in case.” A few studies, though, have raised the possibility that taking antioxidant supplements, either single agents or combinations, could interfere with health. The first inkling came in a large trial of beta-carotene conducted among men in Finland who were heavy smokers, and therefore at high risk for developing lung cancer. The trial was stopped early when researchers saw a significant increase in lung cancer among those taking the supplement compared to those taking the placebo. (15) In another trial among heavy smokers and people exposed to asbestos, beta-carotene was combined with vitamin A. Again an increase in lung cancer was seen in the supplement group. (16) Not all trials of beta-carotene show this harmful effect, however. In the Physicians’ Health Study, which included few active smokers, no increase in lung cancer or any other adverse affect was seen even after 18 years of follow-up. (6)

Another possible red flag: In the SU.VI.MAX trial, rates of skin cancer were higher in women who were assigned to take vitamin C, vitamin E, beta-carotene, selenium, and zinc. (17)

The Bottom Line on Antioxidants and Disease Prevention

Free radicals contribute to chronic diseases from cancer to heart disease and Alzheimer’s disease to vision loss. This doesn’t automatically mean that substances with antioxidant properties will fix the problem, especially not when they are taken out of their natural context. The studies so far are inconclusive, but generally don’t provide strong evidence that antioxidant supplements have a substantial impact on disease. But keep in mind that most of the trials conducted up to now have had fundamental limitations due to their relatively short duration and having been conducted in persons with existing disease. That a benefit of beta-carotene on cognitive function was seen in the Physicians’ Health Follow-up Study only after 18 years of follow-up is sobering, since no other trial has continued for so long. At the same time, abundant evidence suggests that eating whole fruits, vegetables, and whole grains—all rich in networks of antioxidants and their helper molecules—provides protection against many of these scourges of aging.

References

1. Grodstein F, Kang JH, Glynn RJ, Cook NR, Gaziano JM. A randomized trial of beta-carotene supplementation and cognitive function in men: the Physicians’ Health Study II. Arch Intern Med. 2007; 167:2184–90.

2. Lee IM, Cook NR, Gaziano JM, 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.

3. Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005; 293:1338–47.

4. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999; 354:447–55.

5. Milman U, Blum S, Shapira C, et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype. A prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol.2007:ATVBAHA.107.153965.

6. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996; 334:1145–49.

7. Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004; 164:2335–42.

8. Cook NR, Albert CM, Gaziano JM, et al. 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. Arch Intern Med. 2007; 167:1610–18.

9. Duffield-Lillico AJ, Reid ME, Turnbull BW, 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. 2002; 11:630–39.

10. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001; 119:1417-36.

11. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta-carotene for age-related cataract and vision loss: AREDS report no. 9. Arch Ophthalmol. 2001; 119:1439-52.

12. Richer S, Stiles W, Statkute L, 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; 75:216-30.

13. Bartlett HE, Eperjesi F. Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease: a randomized controlled trial. Eur J Clin Nutr. 2007; 61:1121-27.

14. Age Related Eye Disease Study 2 (AREDS2). National Eye Institute.

15. Albanes D, Heinonen OP, Taylor PR, et al. Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst. 1996; 88:1560-70.

16. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996; 334:1150-55.

17. Hercberg S, Ezzedine K, Guinot C, et al. Antioxidant supplementation increases the risk of skin cancers in women but not in men. J Nutr. 2007; 137:2098-105.

18. Semba RD, Ferrucci L, Bartali B, Urpi-Sarda M, Zamora-Ross R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C.  Resveratol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med. 174(7):1077-84

19. Dysken MW, Sano M, Asthana S, et al. Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease: The TEAM-AD VA Cooperative Randomized Trial. JAMA. 2014;311(1):33-44. 

20. Marchese ME, Kumar R,Colangelo LA, Avila PC, Jacobs DR Jr, Gross M, Sood A, Lui K, Cook-Mills JM. The vitamin E isoforms α-tocopherol and γ-tocopherol have opposite associations with spirometricparameters: the CARDIA study. Respiratory Research 182(7):4395-405.

21. Berdnikovs S, Abdala-Valencia H, McCary C, Somand M, Cole R, Garcia A, Bryce P, Cook Mills JM. Isoforms of vitamin E have opposing immunoregulatory functions during inflammation by reducing leukocyte recruitment. J Immunol. 182(7):4395-405

Source: https://www.hsph.harvard.edu/nutritionsource/antioxidants/

Video

The Antioxidant Myth

Save money and get healthy by unleashing your own internal antioxidants

Antioxidant Hopes and Dreams

Marilyn Barbone/123RF
Source: Marilyn Barbone/123RF

Do you choose colorful vegetables, fruits and fruit juices in hopes that their antioxidants will destroy free radicals and fight inflammation?

Do you take expensive antioxidant supplements or plant extracts because they promise to help you ward off cancer and slow aging?

Antioxidant business is booming. What was already a 2.9 billion dollar industry in 2015 is expected to soar to 4.5 billion by 2022. This wild economic growth is fueled by the understandable human hope that we can improve our health simply by adding something magical to our diet. We humans desperately want to believe in the power of these potent little plant products, so we bite. Even if we’re not sure how well they work or what they actually do, why not take them? What do we have to lose?

The antioxidant sales pitch goes like this:

Free radicals damage our cells from the inside out through a process called “oxidation” (true). Left unchecked, oxidation wreaks havoc with cellular machinery, including DNA, increasing our risk for cancer, aging, and other chronic diseases (true). Therefore, we should take ANTI-oxidants, to neutralize these dangerous free radicals before they can do us harm…

Makes sense, so it’s an easy sell.

The Antioxidant Myth

Suzi Smith, used with permission
Source: Suzi Smith, used with permission

But the truth is that the antioxidant cure theory is just plain wrong. Here’s what the antioxidant commercials don’t tell you:

In short, there’s no scientific reason to believe that consuming non-essential antioxidants improves human health. The USDA went so far as to remove its antioxidant database for selected foods from its website due to:

“mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds, including polyphenols on human health…[antioxidant] values are routinely misused by food and dietary supplement manufacturing companies to promote their products and by consumers to guide their food and dietary supplement choices.”  

Yes, it is true that excess free radicals and oxidation can cause health problems over time. But consuming more antioxidants is NOT the answer. The answer is to understand what oxidation is and what causes it so you can fight it effectively with knowledge and common sense.article continues after advertisement

What is Oxidation?

Oxidation is a natural process occurring constantly within our cells as a by-product of chemical reactions needed to extract energy from food. Free radicals also form when we are exposed to sunlight’s radiation. Since some amount of oxidation is normal and natural, Mother Nature in her wisdom has armed our cells with their very own internal antioxidant called glutathione, ready, willing and able to mop up those pesky free radicals. Under normal circumstances, glutathione is sufficient to protect us from natural levels of oxidation, keeping oxidation and anti-oxidation forces in balance.

So why worry?

Refined Carbohydrates Increase Oxidation

We should worry because sugar and other refined carbohydrates are powerful promoters of free radical production and oxidation. These unnaturally concentrated sugars and starches overwhelm our cells’ chemical pathways, generating far more free radicals than glutathione can handle. [Processed foods may be the most important source of excess free radicals in our modern lives, but there are certainly others, including alcoholconsumption and cigarette smoking.] Refined carbohydrates throw us out of balance—they tilt our internal systems too far towards oxidation. As a result, it appears as if we need more antioxidant power than we already have.

Enter: antioxidant salespeople.

NOBODY is going to get rich telling you to STOP eating something. And nobody wants to be told they should stop eating something so delicious, convenient, inexpensive, and addictive as refined carbohydrates like sugar and flour. A much sweeter message to swallow is: keep eating sugar, take this magical plant product.article continues after advertisement

Turmeric Will Not Save You

Jigsawstocker/Freepik
Source: Jigsawstocker/Freepik

Curcumin (found in turmeric spice) is just one example of a plant extract that is making some people a lot of money; a 4-oz shot of turmeric at a Whole Foods juice bar will cost you $4.00! According to a detailed review of curcumin chemistry, even if you take very high doses, it simply doesn’t make it into your bloodstream.

Curcumin performs so abysmally in studies that the authors of the review concluded:

“To our knowledge, [curcumin] has never been shown to be conclusively effective in a randomized, placebo-controlled clinical trial for any indication. Curcumin is best typified, therefore, as a missile that continually blows up on the launch pad, never reaching the atmosphere or its intended target(s)…While these failures would normally end further research on its use as a therapeutic, they apparently have not deterred researchers interested in its development.” 

Is this innocent wishful thinking? Or is it something more complicated than that—perhaps the power of potential profit trumping logic and science? 

Pom Wonderful™—Crazy UNhealthy

Worse yet is Pom Wonderful. This pomegranate-squishing company wants you to believe that their very expensive, sexy bottle of colorful, all-natural juice is just bursting with “relentlessly ravenous, free-radical-annihilating antioxidants” that will help protect you from cancer and aging.article continues after advertisement

Yes, Pom Wonderful is loaded with antioxidants—ellagitannins and anthocyanins, to be exact. But what percentage of the miraculous antioxidants within Pom Wonderful can we absorb into our bodies? Only about 0.2% (or 2/1000th) of the anthocyanins are absorbed, and the ellagitannins are transformed into something else before we have a chance to even try to absorb them.  

So, what do you actually absorb from that 8-ounce curvaceous bottle of purple liquid? A whopping 32 grams of sugar—a powerful promoter of oxidation! You are in fact shelling out your hard-earned money to buy the OPPOSITE of what you were told you would get. Pom Wonderful does NOT fight free radicals—it literally causes more free radicals to form, increasingoxidative damage inside your body. Every time you drink it, you are accelerating aging and increasing your risk for cancer, diabetes, weight gain and dementia. And Pom Wonderful is just one example of this dangerous snake oil marketing strategy. Any antioxidant supplement, beverage, extract or food that contains sugar promotes oxidation.

Don’t Drink the Kool-Aid™

Get smart about your health. You don’t need an impostor of a wizard to sell you what you’ve had inside of you all along. Trust in the capacity of your own internal antioxidants. Give them a fighting chance by feeding them the foods they were designed to handle. Eat real whole foods, and avoid refined carbohydrates like sugar, flour, fruit juice and processed cereals as much as you possibly can. [For a more complete list click here]. Stop throwing your money away on impotent extracts—the science is quite clear that high-tech plant powders and sexy bottles of juice will not save you. You are going to have to save yourself the old-fashioned way—by eating right. You can do it!article continues after advertisement

UPDATE (3/11/18) [I added the below paragraphs in response to numerous comments and questions both below this article and on social media]:

Are All Antioxidants Difficult to Absorb?

No. Essential nutrients with antioxidant properties such as vitamin C, vitamin E and selenium are absorbed and utilized by the human body. The article above focuses on non-nutrient antioxidants. 

Do Antioxidant Supplements Have Any Benefits?

There are countless examples throughout history and within the scientific literature of human beings exploiting the naturally toxic and anti-nutritional properties of certain plant compounds to attempt to treat existing diseases such as arthritis, cancer, and such. This is essentially the practice of using plant compounds as drugs. Often these compounds are extracted/concentrated and/or manufactured into special designer formulas that don’t exist in nature, and are then used at high doses to try to target the problem at hand. When taken in this way, these chemicals can have benefits, but they can also have side effects in some individuals, just as any drug can. This *medicinal* use of plants is also very different than the *nutritional* use of plants–that is to say: eating whole plant foods or even taking simple plant extracts (such as curcumin) to try to improve your overall health and prevent disease in the first place. Many curcumin studies suggesting benefits in humans appear to have used specially-formulated curcumin supplements that have been altered in some special way to dramatically improve their absorption. It is also worth noting that compounds that are not absorbed at all still come into contact with cells within the digestive tract and may have real biological effects on gastrointestinal cells and the microbiome. 

Should I Stop Taking My Antioxidant Supplement?

If you are using a plant extract such as curcumin and it a) helps you feel better in ways you can identify and b) doesn’t give you side effects, I am not suggesting you need to stop taking it–that is up to you and your health advisers. My concern is that many people spend their hard-earned money on plant antioxidants simply because they believe they will reduce their risk of disease in the future by fighting free radicals/oxidation. As far as I can tell, there is no evidence to support that practice, and there are far more effective ways to improve your antioxidant balance. If you take an antioxidant supplement and it a) doesn’t give you side effects and b) doesn’t cost you more than you can afford, then probably no harm done. I just want you to have the information you need to make informed choices about your money and their health. 

Source: Article by Georgia Ede MD (https://www.psychologytoday.com/us/blog/diagnosis-diet/201712/the-antioxidant-myth)