Teased from fruits and vegetables, a network of antioxidants works better than the sum of its parts. Jack Challem reviews the research and explores potential combinations for condition-specific products.
If you take a page from nature, your eyes should be drawn not to whether one nutrient or another is a 'super' antioxidant. Rather, you should respect the remarkable diversity of antioxidants naturally found in vegetables, fruits and herbs—and then combine those that have exceptional properties.
Lester Packer, PhD, an antioxidant expert and professor emeritus at the University of California, Berkeley, coined the term 'antioxidant network' to convey the interactivity and interdependence of multiple antioxidants. For example, when an antioxidant, such as vitamin E, donates an electron to quench a hazardous free radical, it becomes a weak free radical itself. But vitamin E can be restored back to its full antioxidant strength when vitamin C donates an electron to it.1
Many other antioxidants recycle each other as well, and this characteristic may partly explain their natural synergism. In fact, studies by Al Tappel, PhD, of the University of California, Irvine, have clearly demonstrated this synergism: The combined antioxidant power of multiple antioxidants is far greater than the simple sum of their parts.2,3
When formulating functional foods or dietary supplements, it is necessary to evaluate the scientific evidence and benefits of individual antioxidants. However, a broader 'team' vision of antioxidants can lead to the development of useful consumer products. After reviewing some of both established and up-and-coming antioxidants, we will consider several possible combinations to address specific health concerns.
Vitamin E was first used in the 1940s to treat coronary artery disease. The 1996 Cambridge Heart Antioxidant Study (CHAOS), conducted by researchers at Cambridge University, UK, found that supplements of natural vitamin E (400IU to 800IU daily) reduced the risk of heart attacks by 77 percent in 2,002 patients.4 In addition, the natural d-alpha tocopherol (-yl) form of vitamin E has been shown to absorb twice as much as the synthetic form.5
Some recent studies have produced conflicting results about the heart benefits of vitamin E. However, Ishwarlal Jialal, MD, of the University of Texas Southwestern Medical Center in Dallas analysed the five largest clinical studies and found that four of them showed vitamin E to reduce the risk of heart attacks or related mortality, and the fifth study had serious design faults.6
Vitamin E has numerous other potential applications. It may reduce the risk of cataracts,7 and it also lowers levels of glucose, free radicals and clotting substances in people with diabetes, which may reduce complications of the disease.8 Still other research suggests that vitamin E may be the best supplement for overall reduction of cancer risk.9
Vitamin C supplements can significantly reduce blood pressure, which is important because hypertension increases the risk of other types of heart disease. In one study of 38 people, Joseph A. Vita, MD, of the Boston University School of Medicine, found that 500mg/day vitamin C lowered systolic blood pressure by an average of 10 percent after only one month.10 A similar clinical trial by Martin D. Fotherby, MD, of the Glenfield Hospital, Leicester, UK, found systolic blood pressure reductions of 2mm Hg in 40 elderly men and women after three months.11
Vitamin C also can improve endothelial dysfunction, which is a stiffening of blood vessels that reduces blood flow and increa-ses the risk of heart disease. British re-searchers recently reported that 1g of vitamin C improved blood flow as well as the flexibility of blood vessels.12
Alpha-lipoic acid is a vitamin-like antioxidant that is essential for the energy-producing Krebs cycle in cells. It is a precursor to glutathione, the body's principal endogenous antioxidant.13
Classified as a drug in Germany, where it is commonly used to treat diabetic neuropathy, alpha-lipoic acid is sold over the counter as a dietary supplement in the US.14 Clinical studies have found that it can improve insulin function, helping to improve glucose tolerance in people with diabetes.15,16 Some researchers have suggested that long-term use of alpha-lipoic acid may help prevent adult-onset diabetes.17
N-acetylcysteine (NAC), like alpha-lipoic acid, is a potential antioxidant and precursor to glutathione. However, NAC is also a powerful immune stimulant. For example, an Italian study of 262 elderly subjects found that 600mg NAC, taken twice daily, reduced flu symptoms by two-thirds.18 Large dosages of NAC—up to several grams daily—can extend the life expectancy of patients with AIDS,19 and some research suggests that it may also reduce the risk of cancer.20,21
Coenzyme Q10 (Co-Q10) plays a crucial role in the production of energy in cells, and it was the basis of the 1978 Nobel prize in chemistry, awarded to the late British researcher Peter D. Mitchell, PhD, of the University of Edinburgh, UK. Some cardiologists, such as Peter Langsjoen, MD, of Tyler, Texas, use Co-Q10 to treat cardiomyopathy and heart failure. One recent clinical study found that the hydrosoluble form of Co-Q10 resulted in significant decreases in blood pressure.22 Other medical journal reports indicate that it may have a role in preventing the recurrence of breast cancer.23,24
Beta-carotene is an antioxidant common in fruits and vegetables, and it may benefit people with asthma. Free radicals stimulate the activity of adhesion molecules, which help sustain inflammatory reactions such as those that characterize asthma. Ami Ben-Amotz, PhD, of Israel's National Institute of Oceanography, asked 38 asthmatics to exercise on a treadmill under laboratory conditions. At the start of the study, the subjects had a 15 per cent decrease in lung function after exercising. After taking 64mg of natural beta-carotene daily for a week, 20 (53 per cent) of the subjects had significant improvements in post-exercise breathing.25
Beta-carotene may also reduce the risk of developing prostate cancer in men who shun fruits and vegetables. Harvard University researchers found that men who ate few fruits and vegetables containing beta-carotene were 45 percent more likely to develop prostate cancer, compared with men who ate a lot of these foods. But when the produce-avoiding men took a 50mg beta-carotene supplement every other day, they had a 32 per cent lower risk of prostate cancer compared with the men who did not eat fruits and vegetables and did not take beta-carotene supplements.26
Lutein, found in kale, broccoli and spinach, can reduce the risk of macular degeneration, a leading cause of blindness in the elderly. This carotenoid, along with zeaxanthin, forms the macular pigment, a yellowish deposit in the center of the retina. Lutein (some of which the body converts to zeaxanthin) filters out harmful blue wavelengths of light and quenches free radicals.27
Macular degeneration is partly characterized by a thinning of the macular pigment, and studies have found that lutein-rich foods or lutein supplements (either as free lutein or lutein esters) can increase the thickness of the macular pigment.
In one study, pigment thickness increased by up to 39 per cent after subjects took 30mg of lutein esters for almost five months.28 In a small study, researchers found that patients with cataracts who took 15mg of lutein esters three times weekly had nearly normal visual acuity after approximately one year. Patients with macular degeneration also reported improvements in vision after approximately two years of supplementation.29
In addition, epidemiological studies and laboratory animal experiments suggest that lutein may have significant anti-cancer properties, particularly for ovarian and breast cancers.30,31
Lycopene, a red carotenoid found in tomatoes, can significantly reduce the risk of prostate cancer. Interest in lycopene developed after Edward Giovannucci, MD, of the Harvard School of Public Health, reported that regular intake of tomato sauces lowered the risk of prostate cancer by 45 per cent.32 More recently, in the Journal of the National Cancer Institute, Giovannucci cited 57 studies showing that high intake of either tomatoes or lycopene also reduced the risk of pancreatic, colorectal, breast and cervical cancers.33
Flavonoids, herbs and other supplements may be the largest untapped source of individual antioxidant compounds. More than 5,000 flavonoids have been identified in plants, not all of which are edible, however. Herbs contain hundreds of flavonoids and antioxidant polyphenols, and this diversity of antioxidants accounts for many of the health benefits attributed to botanicals. Among these supplements are bilberry for eye health,34-36 hawthorn for the heart,37 and silymarin for diabetes.38
In addition, selenium should be recognised for its role in the antioxidant enzyme glutathione peroxidase, a mineral that is useful in cancer prevention.39 Finally, non-antioxidant supplements—chromium picolinate, as but one example—should be considered for their complementary role in specific applications, such as in reducing blood sugar levels in people with diabetes.40
From Single Ingredients To Antioxidant Formulas
To make the best use of antioxidants in functional foods and supplements, consider leveraging the synergism of several antioxidants (as well as non-antioxidant ingredients) toward achieving specific health benefits. For example, different antioxidants reduce the risk of coronary artery disease, but probably through different mechanisms. Consider, as examples, the following four rudimentary formulations.
- Heart-protective formula: vitamin E, vitamin C, Co-Q10 and hawthorn.
- Cancer-prevention formula: vitamin E, vitamin C, NAC, Co-Q10, lutein, lycopene, beta-carotene, selenium.
- Eye-protection formula: vitamin E, vitamin C, beta-carotene, zinc, lutein and bilberry.
Antioxidant formulas may help prevent age-related macular degeneration (AMD), the leading cause of blindness among the elderly in the US. For six years, researchers studied more than 3,600 patients, ages 55 to 80, from 11 medical centres. Patients took either a multi-antioxidant containing 500mg/day vitamin C, 400IU/day vitamin E and 15mg/day beta-carotene; or 80mg/day zinc and 2mg/day copper; or both treatment protocols. Patients with the highest risk of advanced AMD experienced the greatest benefits. Antioxidants and zinc each reduced the risk of AMD, but their effect was greater in combination—the combination group reduced overall AMD risk by 28 per cent.41
- Diabetic-control formula: alpha-lipoic acid, vitamin E, silymarin and chromium picolinate.
Of course, food or supplements technologists spend much time investigating the compatibility of individual ingredients, as well as the effect of heating and other manufacturing processes on antioxidants. Under the best of circumstances, such formulas should be tested in both animal and clinical trials before being marketed. Meanwhile, your legal staff must investigate permissible labeling claims for the product.
Jack Challem, known as The Nutrition Reporter™, has written about natural products for 25 years. Visit him at www.nutritionreporter.com
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