In The News August 2003

According to the National Institutes of Health, cancer costs the American public approximately $156.7 billion a year in direct medical costs, indirect morbidity costs and indirect mortality costs. Reducing incidents of cancer will not only save lives but significantly curtail our spiraling health care costs. Increasingly, scientific studies indicate that lycopene, a member of the carotenoid family, may reduce the incidence of prostate, lung and stomach cancers.

In an effort to make this research available to the public, attorneys at Emord & Associates filed a health claim petition with the FDA requesting that the FDA allow the use of various health claims for lycopene. The petition states, "The mechanism of lycopene's anticarcinogenic activity has demonstrated that lycopene reduces oxidative stress. Lycopene has the ability to quench singlet oxygen, trap peroxy radicals, inhibit the oxidation of DNA, inhibit lipid peroxidation and inhibit the oxidation of low-density lipoprotein. Lycopene has been shown to have the highest antioxidant activity of all the cartenoids.

Over seventy clinical trials have evaluated the effects of lycopene supplementation on the incidence of cancer. There is significant and strong scientific evidence that lycopene reduces the risk of certain forms of cancer; the evidence is strongest for reduction in the risk of prostate and lung cancers, but the evidence is suggestive for colon, stomach, cervix, breast, oral cavity, pancreas and esophagus cancers. The most supportive studies are the Harvard Physicians' Study and the Health Professional Follow-Up Study. Those studies measured the effect of a tomato product and lycopene intake on prostate cancer risk reduction and tracked blood levels of lycopene. The results of the Harvard Physicians' Study provide strong evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer since in this study blood levels of lycopene confirmed earlier associations of dietary intake of tomato products and lycopene with reduced prostate cancer risk."

If successful, this petition will allow any food product or nutritional supplement containing lycopene or tomatoes to make health benefit claims for these substances.

Omega-3-fatty acids reduce risk of AMD

Age-related macular degeneration (AMD), is a major cause of central vision loss in the elderly. Treatments are limited and hope lies in reducing the risk of the disease and preventing its development. A study reported at the Annual Meeting of the Association for Research in Vision and Ophthalmology, in Florida, May, 2003, provides new data supporting the effects of diet and nutrients, in lowering the risks of having a type of AMD that leads to blurred vision, and in severe cases, blindness. The study was carried out by Dr. JP SanGiovanni and colleagues from the National Eye Institute, in Bethesda MD. It showed a higher intake of omega n-3 polyunsaturated fatty acids and fish was associated with decreased risk of having neovascular AMD.

Approximately 1.7 million people over 64, suffer from the severe form of AMD, that leads to blindness. The macula is an area located in the center of the retina and is responsible for fine and detailed central vision.

The Age-related Eye Disease Study, reported at the meeting, was a case control retrospective study of 4,513 participants, aged 60 to 80 years. Subjects completed a self administered food questionnaire, and provided information on the frequency and portions of fish intake in the last year, as well as other health and lifestyle data. The types of fish considered, included fried fish or fish sandwiches, tuna salad or tuna casserole, oysters, other shell fish and broiled or baked fish. People without AMD served as control groups for each of the four different types of AMD tested.

The result showed that highest total fish consumption (compared to no intake), of more than two servings a week, of broiled or baked fish or of tuna, reduced the risk of having neovascular AMD, but not other types of AMD, by approximately 50%.

When assessing AMD risk in relation to intake of omega-3-fatty acids, that are high in marine products, the results showed that risk for neovascular AMD, but not other types of AMD, was significantly decreased, by approximately 60%, for people with the highest intake of total omega-3-fatty acids (highest quintiles versus lowest quintiles). A similar risk reduction (approximately 53%), was found with intake of docosahexaenoic (DHA), an omega-3-fatty acid, that is selectively taken up and retained in the photoreceptors of the eye.

The studies indicate an independent association between fish intake and omega-3-fatty acids intake and neovascular AMD, showing that high intake of fish, or omega-3-fatty acids, halves the risk of having the disease.

-Carmia Borek, Ph.D.

Neuroprotective effects of garlic

The praised health benefits of garlic include cardiovascular protection, stimulation of immunity and anticancer effects. Now, new experiments show that garlic, in the form of aged garlic extract (Kyolic), prevents the death of neurons, the hallmark of age-related dementias and Alzheimer's disease (AD). The studies, presented at the meeting of the Federation of the Societies for Experimental Biology, in San Diego, April 15, 2003, suggest that garlic has neuroprotective effects that may help prevent neurodegenrative conditions.

Alzheimer's disease is the most common form of progressive dementia. Its pathological markers in the brain, are deposits of amyloid-beta (A-beta) protein, a 39 to 43 amino acid peptide, evidence of oxidative damage and cell death. The death of neurons can occur following ischemia, when a deficiency in blood supply to the brain deprives cells of oxygen and glucose. Neuron death is triggered by oxidative stress, induced by A-beta, and by apoptosis, a genetically programmed cell suicide, where events, including oxidation, activate a series of enzymes called caspases, among them caspase 3. In a final blow to the cell caspase 3 cleaves critical cellular proteins and triggers its suicide.

At the meeting, studies from the Korea Food Research Institute showed that the water soluble organosulfur S-allyl cysteine (SAC), that is present in low amounts in fresh garlic, and enriched in aged garlic extract, prevents cell death following ischemia. Model cultures of human neurons (neuroblastoma) were fed SAC or served as control. Both cultures were then exposed to simulated ischemia, by oxygen and glucose deprivation (hypoxia and hypoglycemia), followed by re-oxygenation, a step that stimulates free radical damage. Results showed that SAC, a potent antioxidant, protected the cells and significantly increased neuronal survival, compared to controls. In a second set of experiments, gerbils were exposed to ischemia and reoxygenation, by tying and then releasing their carotid arteries. The animals were treated with SAC before ischemia and after reoxyenation (reperfusion). Seven days later, researchers found that SAC-treatment increased neuronal survival by 30%, compared to control, in the hippocampus, the area in the brain responsible for memory.

In addition, studies published in the May issue of Neuroscience Research show that S-allyl cysteine, in a concentration dependent manner, protects PC12 cells against A-beta induced oxidative death. Aged garlic extract is rich in antioxidants, as the aging and extraction process increases the levels of water soluble organosulfur antioxidants, such as S-allyl cysteine, and generates new compounds including allixin.

To be effective in protecting the health of brain cells and preventing decline in cognition, a nutrient must act on several fronts. The new studies show that garlic, in the form of the standardized aged garlic extract supplement (Kyolic), and its major water soluble component, S-allyl cysteine, exert a combination of antioxidativeand anti-amyloid beta, providing neuro-protection, that may help prevent the onset of neurodegenerative conditions, including Alzheimer's disease.

-Carmia Borek, Ph.D.

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Watermelon boosts plasma lycopene

Watermelon is one of the few foods rich in lycopene, a carotenoid with twice the antioxidant capacity as beta carotene, and the source of red in watermelon, tomatoes, pink grapefruit and guava; the redder the fruit, the higher its lycopene content. Epidemiological studies have shown that lycopene protects against cardiovascular disease and certain types of cancer, notably prostate cancer. The sources of lycopene, in most of these studies, were tomato products, which represent 80% of lycopene consumption in the U.S.

But watermelon, may soon get its deserved attention. A new study, from the U.S. Department of Agriculture, reported in the April issue of the Journal of Nutrition, found that drinking three cups of fresh-frozen watermelon juice a day, raises blood lycopene to the same levels as drinking one cup of canned tomato juice. Plant carotenoids are absorbed poorly, compared to carotenoid supplements. In the case of tomatoes, processing that includes heat, increases the absorption efficiency (bioavailabilty) of lycopene and beta carotene, by breaking the walls of the tomato cells and releasing the carotenoids. Watermelon carotenoids are similar to those in tomatoes, but since watermelon is not heat treated for consumption, the bioavailabilty of carotenoids, that determines their protective potential, has yet to be assessed.

The study set out to determine lycopene absorption efficiency into the blood, after consuming watermelon juice, as compared to tomato juice; it also investigated if doubling the consumption of watermelon juice lycopene would result in a doubling of blood lycopene. Plasma levels of other carotenoids present in watermelon and tomato juice, including beta carotene, phytoene and phytofluene were also examined.

In a 19-week study, 23 healthy volunteers, aged 36 to 69, consumed daily fresh-frozen watermelon juice that contained a total of 20.1 mg lycopene and 2.5 mg beta carotene. After three weeks; they had a washout period, that is, two to four weeks without lycopene-rich food; this was followed by a controlled diet (no juice) for three weeks, and then a washout period. The third three-week treatment was watermelon juice, containing twice the carotenoid amounts (40.2 mg lycopene and 5.0 mg beta-carotene) or canned tomato juice (18.4 mg lycopene and 0.6 mg beta-carotene).

The results showed higher plasma levels of the carotenoids, after periods of drinking juice, compared to control; plasma lycopene levels were similar following watermelon juice and tomato juice consumption, indicating that lycopene from fresh-frozen watermelon juice was as bioavailable as that from canned tomato juice, though more watermelon juice was needed to get the same results. The study also found that doubling watermelon juice lycopene did not double the blood levels of lycopene, possibly because the additional lycopene was absorbed into tissues, such as the prostate. Beta-carotene was more bioavailable from watermelon juice, while phytoene and phytofluene were better absorbed from tomato juice.

Watermelon juice is now a proven good source of bioavailable lycopene; if you prefer fresh fruit, two and a half cups of cut-up watermelon yield about 20 mg of lycopene. Fat aids lycopene absorption; having watermelon as dessert, following a meal, will do the trick.

-Carmia Borek, Ph.D.

Brain tumor rate on the rise

A worrying trend is evolving: the rate of brain tumor cases in the United States and Europe has increased by up to 40% in the past 20 years, according to data released at the 2nd International Conference in Neuro-Oncology in Italy this past March. Although the rate is increasing among people of all ages, males between the ages of 20 and 40 years old are the most affected. Furthermore, recent studies have shown that the rate is highest among white collar workers. Scientists are unsure of the reason for this increase in brain tumor incidence, although they speculate that modern technology may play a role. "The reason is still unknown, though environmental causes such as cellular phones, computers and exposure to electromagnetic fields cannot be ruled out," said Dr. Alba Brandes, an oncologist at the Azienda Ospedale-Università in Padova, Italy and chairperson of the conference.

-Dr. Marc Ellman

Folate and vitamin B6 may
reduce breast cancer

Consuming adequate amounts of folate and vitamin B6 may help women reduce their risk of developing breast cancer, new study findings suggest.1 High levels of folate may be especially important in counteracting the increased risk of breast cancer in women who consume alcohol regularly.

"The benefits of folic acid (the synthetic form of folate) in reducing birth defects and cardiovascular disease have been well established, however, its protective impact on breast cancer has been less clear," said Shumin Zhang, M.D. ScD of Brigham and Women's Hospital and the Harvard School of Public Health. "The findings from this large study suggest more precisely that by ensuring adequate levels of folate and vitamin B6-by consuming foods rich in these nutrients and taking vitamin supplements-a woman's risk of breast cancer may be reduced."

For their study, which was published in the March 5, 2003 issue of the Journal of the National Cancer Institute, Dr. Zhang and colleagues examined blood levels of folate, vitamin B6, vitamin B12 and homocysteine in 712 women who developed breast cancer. They compared their findings to blood levels of these elements in 712 similar women who did not develop breast cancer. All women were selected from a pool of more than 32,000 participants of the on-going Nurses' Health Study, a major research effort initiated in 1976 at Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

The researchers found that women with the highest levels of folate in their blood were 27% less likely to develop breast cancer as compared to women with the lowest levels. This association was even stronger for women who consumed moderate amounts of alcohol regularly, which is already known to increase the risk of developing breast cancer. Among the women in the study who consumed on average at least one alcoholic beverage (defined as 15 grams of alcohol) per day, those who had the highest levels of folate in their blood were 89% less likely to develop breast cancer as compared to women with the lowest folate levels who consumed alcohol regularly.

The risk of developing breast cancer for women with the highest levels of vitamin B6 in their blood was 30% less than the risk in women with the lowest levels of vitamin B6. A link between vitamin B12 levels and breast cancer risk was also discovered, but only in women who had not yet reached menopause. The researchers found that premenopausal women with the highest levels of vitamin B12 in their blood were 64% less likely to develop breast cancer than premenopausal women with the lowest levels of vitamin B12. However, this finding contradicts a study published in the March 1999 issue of Cancer Epidemiology Biomarkers & Prevention that found a link between breast cancer risk and low B12 levels mostly among postmenopausal women.2 The re-searchers therefore recommend that this finding be confirmed by additional studies. Finally, the investigators found no link between breast cancer risk and homocysteine levels in this study.

Folate and vitamin B6 are found naturally in foods such as oranges and green leafy vegetables. They are also found in many vitamin supplements. Wheat flour and breakfast cereals have been fortified with folic acid since 1998, when the U.S. Food and Drug Administration mandated it to increase levels of these elements in the American diet. Although the association between these nutrients and breast cancer risk is not fully understood, scientists hypothesize that their role in DNA synthesis and repair is most likely responsible.

"The findings from this study suggest that folate and vitamin B6 may have the potential to be chemopreventive against breast cancer and that ensuring adequate circulating levels of folate and vitamin B6 by consuming foods that are rich in these nutrients, such as oranges, orange juice, and fortified breakfast cereals or vitamin supplements, may contribute to a reduction in the risk of breast cancer," concluded the researchers in their report. "Adequate folate levels may be particularly important for women who are at higher risk of breast cancer because of higher alcohol consumption."

-Dr. Marc Ellman

1. Zhang, S.M. et al. Plasma folate, vitamin B6, vitamin B12, homocysteine and risk of breast cancer. J Natl Cancer Inst 2003 Mar 5;95(5):373-80.

2. Wu, K. et al. A prospective study on folate, B12 and pyridoxal 5'-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 1999 Mar 1;8(3):209-17.

Coenzyme Q10 deficiency linked
to cerebellar ataxia

Coenzyme Q10 (CoQ10) supplementation may help some people with cerebellar ataxia, a rare neurological disorder. The cerebellum is a part of the brain that is responsible for coordinated movement. If the cerebellum does not function properly, a person can acquire movement disorders known as cerebellar ataxia. These patients may develop such symptoms as difficulty with balance, coordination or speech, and may even develop seizures. Researchers at the Columbia University College of Physicians and Surgeons in New York City have discovered that some patients with cerebellar ataxia have low levels of CoQ10. They speculate that CoQ10 supplementation may make these patients better.

CoQ10, also known as ubiquinone, is involved in energy production in probably every cell in the human body. Research has shown that it is especially important for cardiovascular health, as the heart requires large amounts of energy to efficiently pump blood throughout your body. CoQ10 has also been shown to have antioxidant properties.

For their study, which was published in the April 8, 2003 issue of the medical journal Neurology,1 the researchers measured CoQ10 concentration in muscle biopsies from 135 patients with cerebellar ataxia. Thirteen of the patients demonstrated markedly decreased levels of CoQ10 in their skeletal muscle. All of these patients had childhood-onset ataxia and atrophy of their cerebellum on MRI scans. Five more patients with low CoQ10 levels were identified, but four were excluded from the study because they had adult-onset ataxia and one child was excluded because of a coexisting medical disorder.

The researchers stated that of the 135 patients studied, more may actually be suffering from CoQ10 deficiency than the ones they reported. This is due to their stringent laboratory cut-off values for defining CoQ10 deficiency. "Some ataxic patient with milder CoQ10 deficiency may also have primary CoQ10 deficiency," stated the study authors.

In 2001, the authors of the current study published a report of six patients with cerebellar ataxia and a severe deficiency of CoQ10 in the skeletal muscle.2 Therefore, they have now reported a total of 19 patients with cerebellar ataxia probably related to low CoQ10 levels. The most common feature among these 19 patients is seizures. Many also demonstrated delayed motor development and mental retardation.

All the patients in the current study were started on CoQ10 supplementation. The researchers, however, were unable to control the daily dosages received because of availability and financial constraints. Most patients demonstrated improvement of symptoms with CoQ10 supplementation. One patient, a nine-year-old female with cerebellar ataxia since age six, was suffering from seizures that were not well-controlled with valproic acid, a common anti-seizure medication. After receiving CoQ10 supplements, her seizures disappeared.

"Within one year, we have identified 13 new cases of cerebellar ataxia associated with CoQ10 deficiency, indicating that this syndrome may be a relatively common cause of cerebellar atrophy in children," concluded the researchers. "Diagnosis is important because there is some evidence that patients may benefit from early CoQ10 supplementation."

-Dr. Marc Ellman

1. Lamperti C. et al. Cerebellar ataxia and coenzyme Q10 deficiency. Neurology 2003 Apr 18; 60(7):1206-8.

2. Musumeci O. et al. Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 2001 Apr 10; 56(7):849-55.