Linda Ohr

Linda Milo Ohr

Health reports on the television news, healthy eating sections in newspapers and magazines, nutritional supplement advertisements, and endless health information and resources on the Internet. It’s no wonder that today’s consumer is more educated about healthy components in foods, such as antioxidants.

“Generally speaking, consumers think that antioxidants are a good thing,” said Jeffrey Blumberg, Professor, Friedman School of Nutrition Science and Policy, and Director, Antioxidants Research Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston. “They are aware that they should be eating antioxidant-rich fruits and vegetables. They can tell you green tea is rich in antioxidants. I am confident in saying that the number of consumers recognizing antioxidants like vitamin C, vitamin E, and lycopene are substantially greater than 5 or 10 years ago.”

This is indeed true. According to a 1998 H.J. Heinz Co. survey, only 6.5% of consumers said they had heard of lycopene. However, 2003 survey results showed that 37.3% of people asked had heard of the antioxidant.

According to Blumberg, consumers seek antioxidants for benefits related to cancer, heart disease, and eye disease. This is due in part to reports citing protective effects of antioxidants in regard to specific health conditions, such as vitamin E to cancer, lycopene to prostate cancer, and lutein to macular degeneration. Whether it is a single antioxidant or a combination of antioxidants, several studies have been released this past year that highlight potential benefits in the areas of eye health, skin health, cancer, and heart disease.

Lutein
Age-related macular degeneration (AMD) is a growing concern for the aging Baby Boomers and is one of the areas antioxidant research has heavily focused on. AMD is the leading cause of irreversible vision loss in people beyond age 65 in the United States, according to the Alliance for Aging Research. As many as 13 million people in the U.S. age 40 and older have signs of macular degeneration, and more than 1.2 million have the later, vision-threatening stages of the disease.

AMD occurs when the cells in the macula, the center of the retina, break down, causing loss of sight in the central part of the field of vision. It is believed that lutein, a yellow-colored pigment that accumulates in the macula region, and another carotenoid, zeaxanthin, may protect against AMD by protecting the macula from the damaging photo-oxidative effects of blue light.

A recent study at the North Chicago VA Medical Center showed that lutein supplementation may be an effective approach in improving symptoms of AMD, going beyond the initial belief that lutein was purely a preventive measure (Richer et al., 2004). The Lutein Antioxidant Supplementation Trial (LAST study) recorded improvement in several key visual functions among patients with AMD. In the study, 90 AMD patients were supplemented daily with an OcuPower supplement capsule containing either 10 mg of crystalline FloraGLO® lutein (Kemin Foods, Des Moines, Iowa), 10 mg lutein plus a mixed antioxidant formula, or placebo for 12 months.

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Patients ingesting the lutein supplement experienced significant improvements in several objective measurements of visual function, including glare recovery, contrast sensitivity, and visual acuity compared to those ingesting the placebo. Patients also experienced a 50% increase in macular pigment density relative to those on placebo.

“Our findings show that AMD symptoms may be reversed through purified lutein supplementation or a supplement mix of lutein and other antioxidants such as vitamin A, vitamin C, vitamin E, and beta carotene,” said Stuart Richer, lead investigator. “By no means a cure for AMD, the study does show improvement among several disease symptoms in AMD patients.”

Another small clinical trial showed that lutein supplements appeared to increase macular pigment in people at earlier stages of AMD (Koh et al., 2004). Researchers from the Dept. of Optometry and Neuroscience at the University of Manchester in the UK evaluated the effects of a lutein ester supplement over a period of 18–20 weeks in seven patients with early stages of the disease (age-related maculopathy, ARM) and six age-matched controls. The subjects were given a daily dose of 20 mg of Xangold natural lutein esters (Cognis, Cincinnati, Ohio).

Macular pigment density and levels of lutein in blood plasma were measured at regular intervals throughout the study. Both increased significantly, and to the same extent in the controls and in the ARM patients, providing evidence that the macula can accumulate lutein, not only in healthy eyes but also in those with the early stages of AMD. According to the researchers, the findings suggested that a much larger group of at-risk individuals than previously thought may gain some benefit from taking lutein supplements.

Although lutein is mostly associated with eye health, research discussed at this year’s IFT FOOD EXPO® indicated that the antioxidant may play a role in skin health as well. Kemin Foods presented several research reports that supported lutein’s skin benefits. The most recent work was a study presented at the 62nd Annual Meeting of the Society of Investigative Dermatology by Richard Granstein of Weill Medical College/Cornell University. Researchers examined the effects of orally ingested lutein on some of the effects of ultraviolet light on the skin. Mice were fed diets containing 0, 0.04, or 0.4% of a dietary form of FloraGLO lutein for up to 35 days. The researchers concluded that lutein accumulated in the skin following dietary supplementation, lutein decreased reactive oxygen species generation following UV radiation, and dietary lutein reduced UV-induced inflammation in the mice.

Lycopene
Over the past years, evidence has emerged indicating that the consumption of lycopene, an antioxidant that gives tomatoes their red color, may help reduce the risk of prostate and cervical cancer. The National Cancer Institute lists lycopene as a compound that “has shown some evidence that it may be able to prevent cancer.” Population studies show that people who eat large amounts of foods with lycopene, such as cooked tomatoes, have a reduced risk of prostate, lung, and colon cancer. According to NCI, a preliminary investigation of 21 men with prostate cancer found that lycopene supplements appeared to reduce the uncontrolled growth of prostate cancer cells (proliferation) and restored normal cell turnover (apoptosis and differentiation). In animal studies, lycopene prevented lung, colon, and breast cancers and had similar effects on cancer cells in culture.

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Lycopene has also been linked to potentially reducing the risk of heart disease. For example, researchers showed that women with the highest levels of lycopene in their blood had a 34% reduced risk of heart disease compared to those with lower levels of the nutrient (Sesso et al., 2004).

Led by Howard Sesso of the Harvard School of Public Health, researchers used data from the ongoing, randomized, double-blind Women’s Health Study. The 40,000 women included in the trial were free from cardiovascular disease at the start of the study.

After nearly five years of followup, the researchers recorded 483 cases of the disease. Subjects in the study were divided into four groups, in order of increasing plasma lycopene levels. The 34% reduction was found in the women in the top two quarters—those with plasma lycopene levels higher than the study population average. In addition, after excluding women with angina, those with plasma lycopene values in the top three quarters had a 50% reduced risk of cardiovascular disease. Women in the second quarter were still 22% less likely to develop the disease than women in the first quarter, who had the lowest plasma lycopene values.

Vitamin E
Vitamin E has been largely associated with potentially reducing the risk of cancer. In fact, three large-scale clinical trials are currently investigating the effect of vitamin E and other antioxidants on cancer. The Women’s Health Study is currently evaluating the effect of vitamin E in the primary prevention of cancer among U.S. female health professionals age 45 and older. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking place in the U.S., Puerto Rico, and Canada to find out if taking selenium and/or vitamin E supplements can prevent prostate cancer in men age 50 and older. The Physicians’ Health Study II (PHS II), a followup to an earlier clinical trial by the same name, is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total cancer incidence; the study is expected to end in August 2007.

Vitamin E has recently been shown to be helpful for the aging population. One study linked vitamin E and vitamin C supplements to a reduced incidence of Alzheimer’s disease, while another liked vitamin E to a reduced occurrence of colds.

Zandi et al. (2004) examined data from the Cache County Study, a large, population-based investigation of the prevalence and incidence of Alzheimer’s disease and other dementias. About 4,700 residents age 65 or older were assessed from 1996 to 1997 and again from 1998 to 2000. The study participants were asked at their first contact about vitamin usage. The researchers then compared the subsequent risk of developing Alzheimer’s disease over the study interval among supplement users vs nonusers.

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The researchers reported a trend toward reduced Alzheimer’s disease with a combination of vitamin E and C supplements, even after controlling for age, sex, education, and general health.

“Use of vitamin E and C (ascorbic acid) supplements in combination reduced Alzheimer’s disease prevalence by about 78% and incidence by about 64%,” the authors wrote.

“Further study with randomized prevention trials is needed before drawing firm conclusions about the protective effects of these antioxidants,” said lead author Peter P. Zandi, Johns Hopkins Bloomberg School of Public Health. “Such trials should consider testing a regimen of vitamin E and C in combination. If effective, the use of these antioxidant vitamins may offer an attractive strategy for the prevention of Alzheimer’s disease.”

A separate study showed that vitamin E could potentially protect the elderly from getting colds (Meydani et al., 2004). The researchers found that nursing home residents supplemented with the vitamin were 20% less likely to get a cold and also had fewer colds over the study period than a placebo group.

In addition, significantly fewer vitamin E participants acquired one or more respiratory tract infections—the primary outcome measured in the study—although the supplements did not have an impact on the incidence or duration of such infections and there was no effect on lower respiratory tract infections.

Vitamin C
Block et al. (2004) showed that vitamin C appeared to reduce levels of C-reactive protein (CRP), a marker of inflammation and possibly a predictor of heart disease. Participants who took 500 mg of vitamin C supplements per day saw a 24% drop in plasma CRP levels after two months. According to the authors, recent research suggests that CRP may be a better predictor of heart disease than cholesterol levels.

“C-reactive protein is a marker of inflammation, and there is a growing body of evidence that chronic inflammation is linked to an increased risk of heart disease, diabetes and even Alzheimer’s disease,” said Gladys Block, Professor of Epidemiology and Public Health Nutrition at the University of California, Berkeley, and lead author of the study. “If our finding of vitamin C’s ability to lower CRP is confirmed through other trials, vitamin C could become an important public health intervention,” she added.

Inflammation occurs as part of the body’s defense against infection or injury. The body triggers the production of inflammatory cytokines, such as interleukin-6, that then triggers the production of CRP by the liver.

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Resveratrol
Resveratrol is the antioxidant in red wine that is believed to be responsible for the low incidence of cardiovascular disease in wine-drinking European countries. According to NCI, resveratrol has been shown to reduce tumor incidence in animals by affecting one or more stages of cancer development. It has been shown to inhibit growth of many types of cancer cells in culture. Evidence also exists that it can reduce inflammation. It also reduces activation of NF kappa B, a protein produced by the body’s immune system when it is under attack. This protein affects cancer cell growth and metastasis.

The cell and animal studies on red wine have examined effects in several cancers, including leukemia, skin, breast, and prostate cancers. NCI stated that recent evidence from animal studies suggests that this anti-inflammatory compound may be an effective chemopreventive agent in three stages of the cancer process: initiation, promotion, and progression. However, studies of the association between red wine consumption and cancer in humans are in their initial stages.

Beta-Carotene
Beta-carotene, which is found in plants, is a precursor of vitamin A. The body converts it into vitamin A. According to NCI, epidemiologic studies have linked high intake of foods rich in beta-carotene and high serum levels of the micronutrient to a reduced risk of cancer.

Scientists from DSM Nutritional Products recently revealed new findings on a possible mechanism for beta-carotene’s action against skin damage from exposure to sunlight (Wertz et al., 2004). They have found that it can counter a specific type of reactive oxygen species, singlet oxygen (1O2), induced by the UV radiation from sunlight.

In a study using human skin cells, the researchers found that beta-carotene suppressed UVA-induction of the matrix metalloprotease enzymes MMP-1, MMP-3, and MMP-10, which are key to degradation of the extracellular matrix during premature skin aging.

The action involved 1O2 quenching in the cells by beta-carotene but not the provitamin A function of the carotenoid. In addition, the scientists showed that UVA rapidly destroys beta-carotene in the cells, indicating that the carotenoid has to be replenished after sunlight exposure. DSM said that the beta-carotene had to be taken orally as a supplement to exert its photo-protective effects in skin.

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Green Tea Antioxidant
Epigalloctechin-3 gallate (EGCG) is an antioxidant present in green tea that has been shown to possibly fight cancer. Researchers at the Mayo Clinic showed that EGCG interrupted the communication signals needed by cancer cells to survive, prompting them to die in 8 of 10 patient samples tested in their laboratory (Lee et al., 2004).

The cells came from patients with B-cell chronic lymphocytic leukemia (CLL), most often diagnosed in patients in their mid-to-late 60s and currently without cure. “We’re continuing to look for therapeutic agents that are nontoxic to the patient but kill cancer cells, and this finding with EGCG is an excellent start,” said Neil Kay of the Mayo Clinic.

The research suggested that EGCG works by inhibiting a pathway in the leukemia cells related to angiogenesis, the process that maintains nourishing blood flow to a biological structure, in this case a cancer cell.

“With these findings we may be able to pursue the idea of culling out early-stage patients who have historically not been treated and perhaps use an EGCG-based treatment,” said author Yean K. Lee. “That’s our next step with our research.”

A research team at Kyushu University in Japan reported that EGCG inhibits tumor cell growth by binding to a receptor on cells called the 67-kDa laminin receptor (Tachibana et al., 2004). According to the authors, a variety of tumors produce abnormally high levels of 67 LR, and the receptor is thought to be involved in the spread of cancers through the body. The team showed that the growth of human lung cancer cells that have the receptor slows significantly when they are exposed to EGCG at the concentrations reached in the body after drinking just two or three cups of green tea.

Antioxidant Synergy
While much research focuses on single antioxidants, work is also being done on the benefits of combinations of antioxidants. For example, researchers at the U.S. Dept. of Agriculture’s Agricultural Research Service showed that there may be more than lutein to benefit eye health (Bliss, 2003). In a study on almost 500 women, those with the highest intakes of vitamins C and E, riboflavin, folate, beta-carotene, and lutein/zeaxanthin had a lower prevalence of cataracts than did those with the lowest intakes of the nutrients.

Another study analyzed the dietary habits of 414 women with breast cancer and 429 healthy subjects to evaluate the influence of carotenoids and essential fatty acids on breast cancer risk (Nkondjock and Ghadirian, 2004). In postmenopausal women, the combined high intake of carotenoids and omega-3 fats (found in fish) was associated with a 48% lower risk of breast cancer.

Researchers at the Antioxidants Research Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging conduct studies aimed at fostering a better understanding of the impact of dietary antioxidants on free radical reactions and changes in oxidative stress status during aging. “What we are really pursuing is the antioxidant synergy story,” said Blumberg. “We are trying to show that dietary antioxidants in fact work together as a category of nutrients. Although we call them all antioxidants, they are in fact qualitatively and quantitatively different in their ability to quench free radical reactions. They form a very dynamic network.”

Scientists at the laboratory are currently studying how the mixture of antioxidants in whole foods or extracts of whole foods work together. They are looking for synergistic effects among individual antioxidants. For example, some of their work has looked at the flavonoids in dark chocolate and their effect on endothelial function, and the protective effect of polyphenolics in oat bran on human low-density lipoprotein from oxidation. “Pursuing the antioxidant synergy story and understanding their dynamic relationship may help us understand and better design studies looking for health benefits,” said Blumberg.

by LINDA MILO OHR
Contributing Editor, Chicago, Ill.
[email protected]

About the Author

Linda Milo Ohr, Contributing Editor, Nutraceuticals column
[email protected]
Linda Ohr

References

Bliss, R.M. 2003. Scientists link nutrition and eye health. Agric. Res., Vol. 51, No. 8.

Block, G., Jensen, C., Dietrich, M., Norkus, E.P., Hudes, M., and Packer, L. 2004. Plasma C-reactive protein concentrations in active and passive smokers: Influence of antioxidant supplementation. J. Am. Coll. Nutr. 23(2): 141-147.

Koh, H., Murray, I.J., Nolan, D., Carden, D., Feather, J., and Beatty, S. 2004. Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: A pilot study. Experimental Eye Res. 79: 21-27.

Lee, Y.K., Bone, N.D., Strege, A.K., Jelinek, D.F., and Kay, N.E. 2004. VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG) in B cell chronic lymphocytic leukemia. Blood 104: 788-794.

Meydani, S.N., Leka, L.S., Fine, B.C., Dallal, G.E., Keusch, G.T., Singh, M.F., and Hamer, D.H. 2004. Vitamin E and respiratory tract infections in elderly nursing home residents: A randomized controlled trial. J. Am. Med. Assn. 292: 828-836.

Nkondjock, A. and Ghadirian, P. 2004. Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal, Canada. Am. J. Clin. Nutr. 79: 857-864.

Richer, S., Stiles, W., Statkute, L., Pulido, J., Frankowski, J., Rudy, D., Pei, K., Tsipursky, M., and Nyland, J. 2004. 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 75 (4): 216-230.

Sesso, H.D., Buring, J.E., Norkus, E.P., and Gaziano, J.M. 2004. Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women. Am. J. Clin. Nutr. 79: 47-53.

Tachibana, H., Koga, K., Fujimura, Y., and Yamada, K. 2004. A receptor for green tea polyphenol EGCG. Nature Struct. Molec. Biol. 11: 380-381.

Wertz, K., Seifert, N., Buchwald Hunziker, P., Riss, G., Wyss, A., Lankin, C., and Goralczyk, R. 2004. ß-carotene inhibits UVA-induced matrix metalloprotease 1 and 10 expression in keratinocytes by a singlet oxygen-dependent mechanism. Free Radical Biol. Med. 37: 654-670.

Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V., Gustafson, D., Tschanz, J.T., Norton, M.C., Welsh-Bohmer, K.A., and Breitner, J.C.S. 2004. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County study. Arch Neurol. 61: 82-88.