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October 2003

Family History Remains the Strongest Risk Factor for Prostate Cancer

Men with a brother or father with prostate cancer may be more than twice as likely to develop the disease than men with no family history, according to a major review of the medical literature published in the April 15, 2003 issue of the American Cancer Society’s medical journal Cancer.* This finding confirms the importance of regular and early screening for prostate cancer in men with a family history of the disease.

Prostate cancer is the second largest killer of men in the United States. According to the American Cancer Society, more than 200,000 new cases of prostate cancer will be diagnosed this year and nearly 30,000 men will die from it.

The prostate is a gland which surrounds the bladder and urethra (the canal that brings urine from the bladder out of the tip of the penis). It is found only in men, as it secretes fluid into the urethra that forms part of the semen when a man ejaculates.

The first research study evaluating the risk of developing prostate cancer for people who have relatives with the disease was published in 1956. Since then, many scientists have reported family history as a risk factor for developing the disease.

In an effort to summarize the previous findings, researchers at Maastricht University in the Netherlands and at the New York University School of Medicine in New York reviewed all of the relevant published studies on this issue – thirty-three studies in total.

“Epidemiologic studies to date have revealed no other risk factor that is as consistently and strongly associated with the development of prostate carcinoma as a positive family history,” reported the researchers.

They found that the risk of developing prostate cancer was 2.53 times greater for those with first-degree relatives (father or brother) with the disease than men with no family history of the disease. Men with an affected brother had an even higher risk than men with an affected father (3.37 times versus 2.17 times).

Risk also increased as the total number of affected family members increased and as their ages decreased. Although the risk was not as strong for men with a second-degree relative with prostate cancer as those with a first-degree relative, they were still 1.68 times more likely to be diagnosed with the disease than those with no family history.

These findings were consistent for studies from different years, geographic locations and the ethnicity of the participants. While the researchers feel that their findings suggest a genetic component to prostate cancer, they state that familial clustering of the disease may also be due to “common exposures of relatives to environmental carcinogens.”

The investigators concluded their research article with a discussion of screening for prostate cancer with prostate-specific antigen (PSA) testing. They stated that opponents of screening with PSA tests feel that these tests lead to the detection of too many insignificant cancers. However, proponents of PSA screening argue that, since its initiation, there has been a trend toward catching the disease at an earlier stage. This could lead to better survival rates.

“Men with a positive family history of disease constitute an easily identifiable high-risk group that could benefit from PSA screening at an earlier age and at shorter intervals compared with the general male population,” concluded the researchers.

— Marc Ellman, M.D.


*Zeegers MPA, et al. Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma. Cancer 2003 Apr 15;97(8):1894-1903.

Orange Juice and Vitamin C Reduce Inflammatory Markers

Orange juice is an excellent source of vitamin C, an essential nutrient that improves human health and decreases the risk of chronic disease. Unlike most other mammals, humans cannot synthesize vitamin C and must obtain it from the diet. Vitamin C is needed for development and for maintaining cell structure and metabolism, including the maintenance of healthy blood vessels. Vitamin C is also a powerful antioxidant that protects cellular molecules against disease-causing oxidant damage.

Orange juice is traditionally pasteurized by heat treatment at 95 degrees Centigrade for 15 seconds or at 90 degrees C. for one minute. Since vitamin C is vulnerable to heat and air, an alternate non-thermal process for producing a stable product with vitamin C bioavailability, from freshly squeezed orange juice, would be important.

A new study from the USDA Center on Aging at Tufts University in Boston, MA, and institutes in Madrid, Spain, reports that the consumption of orange juice, processed by a non-thermal high pressure (HP) procedure, increased vitamin C levels in the blood by 86% in men and by 79% in women and decreased the inflammatory markers C-reactive protein (CRP) and PGE-2, and the oxidant stress marker 8-epiPGF(2 alpha).*

Subjects enrolled in the study (six men and six women, ages 20 to 32) drank 500 ml of HP orange juice daily, for 14 days, corresponding to 250 mg/day of vitamin C. On day one volunteers drank the juice in one dose, on day two and until the end of the study, they drank 250 ml in the morning and 250 ml in the afternoon. Blood was collected for analysis every hour, for six hours, on day one and on days seven and 14.

Initial vitamin C levels (baseline) were slightly higher in men than in women. In both men and women plasma vitamin C rose to the highest level only three hours after drinking the juice and remained elevated on days seven and 14. Levels of 8-epiPGF(2 alpha) were similar in men and women at baseline and decreased in both by day 14. The decrease correlated with the increase in vitamin C, showing an inverse relationship between the two. In both men and women plasma PGE-2 and CRP concentrations decreased by day 14 compared to baseline.

Plasma CRP is a sensitive marker for cardiovascular disease in both men and women; PGE-2, one of the major prostaglandins produced during inflammation, is positively linked to the severity of stroke, where inflammation plays a key role in post-stroke brain damage and a patient’s prognosis. The eicosanoid 8 epiPGF-2 is produced by random oxidation of phopholipids by oxygen radicals; it is a blood vessel constrictor and has toxic effects on the lungs and kidneys.

This study showed, for the first time, that drinking two glasses of HP orange juice (500ml) significantly increased plasma vitamin C and reduced oxidative stress and inflammatory status, emphasizing the vitamin’s health-promoting effects and its disease risk-reducing potential.

— Carmia Borek, Ph.D.


*Sanchez-Moreno C, et al. High-pressurized orange juice consumption affects plasma vitamin C antioxidative status and inflammatory markers in healthy humans. J Nutr 2003 Jul;133(7): 2204-2209.

Soy Shown to Have Vascular Benefits

Soy is rich in protein and in the isoflavones genistein and daidzein, which are structurally similar to estrogens. The isoflavones bind to the estrogen receptor in vessel walls and produce an estrogen-like effect.

A joint study, reported from the University of California, Davis, showed that a diet rich in soy proteins with isoflavones resulted in vascular benefits in healthy postmenopausal women. Soy consumption increased blood levels of isoflavones and enhanced arterial vasodilation, an important factor in improving blood flow and preventing thrombosis.*

In a randomized, double blind, crossover study, 28 healthy postmenopausal women consumed 25 grams of one of three protein supplements; ultimately all subjects underwent all three regimens. The supplements were: Soy protein with 107.67 mg naturally occurring isoflavones (55 mg genistein) (Soy+); ethanol-washed soy protein with trace amounts (1.87 mg) of isoflavones (Soy-); and milk protein with 0 mg isoflavones. Participants consumed each product for six weeks, followed by a four week washout, free of any of the products. All kept their normal diet but abstained from alcohol, additional soy products and phytoestrogen-rich supplements and foods (tea, chocolate, flaxseed).

During clinic visits, at weeks 0, 6, 16 and 26, blood samples were collected for analysis and artery diameter and blood flow were measured, using ultrasound scans of the brachial (arm) artery. Plasma concentrations of inflammatory markers and substances that regulate vasodilation, such as nitric oxide and endothelin, were measured, as were plasma lipids and oxidative products.

The study found that the diet rich in soy protein with isoflavones (Soy+) resulted in a significant increase in plasma isoflavones and a decrease in peak blood flow velocity (PFV) in the brachial artery, indicating a vasodilation response to the soy. PFV was 37% lower after consuming the Soy+ product, compared to milk protein; the Soy- diet resulted in an intermediate value for PFV, not significantly different from that seen after milk consumption. There was no significant improvement in the antioxidant capacity of the plasma, nor in inflammatory markers and LDL cholesterol in the Soy+ compared to the other groups, which suggested to the authors that fruits and vegetable antioxidants, in the diet, may have masked any antioxidant effects of the soy isoflavones.

The authors conclude that daily consumption of 25 grams of soy protein with 107 mg isoflavones, which includes 55 mg genistein, benefits vascular health, independently of the antioxidant action and lipid-lowering effects of soy. As endothelium-dependent vasodilation declines with age and in menopause, this study offers healthy postmenopausal women a possible alternative that mimics the vascular effects of HRT.

— Carmia Borek, Ph.D.


*Steinberg FM, et al. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. Am J Clin Nutr 2003 July;78(1): 123-130.

Vegetarians: At Risk for Vitamin B12 Deficiency

A vegetarian diet can potentially ward off cardiovascular disease, as it provides high antioxidant intake and is associated with a favorable blood lipid profile. While some investigators find vegetarianism protects against coronary disease, others do not agree and point out that plant-based diets may have harmful effects by depriving the body of essential micronutrients.

A recent clinical study showed that vegetarians, especially vegans, have a deficiency in vitamin B12 (cobalamin), and an increased level of homocysteine, a high risk factor for cardiovascular disease.*

Vitamin B12 is essential for metabolism, for forming red blood cells and for maintaining a healthy nervous system. B12 is needed for DNA synthesis during cell division, which is especially important in bone marrow, where red cells are formed.

Prolonged vitamin B12 deficiency, due to low intake or poor intestinal absorption, causes a slow depletion in tissues. The depletion process may take years and results in a loss of red blood cells, anemia and irreversible neurological damage. Vitamin B12 deficiency symptoms include fatigue, depression, weakness and poor memory.

The only reliable unfortified natural sources of vitamin B12 in the human diet are meat, dairy products and eggs. People who restrict their diet to plant-based foods are at risk of becoming vitamin B12 deficient.

The new study recruited 174 healthy vegetarian subjects. These included 66 lactoovovegetarians (LOV), who exclude meat, poultry and fish from their diet and lactovegetarians (LV), who further exclude eggs, as well as 29 vegans, whose diet excludes all animal-based foods. Control subjects were omnivors (79 subjects), who ate both animal and plant foods. In the study, 17 of the vegans and 12 of the LV-LOV subjects supplemented their diet with B vitamins.

The subjects were monitored for a year, after which their blood was analyzed for vitamins B12, B6 and folic acid, three nutrients that play an important role in reducing blood homocysteine. Two substances that are sensitive markers for B12 deficiency, methylmalonic acid and holotranscobalamin, were also measured. The results showed that vegetarians had different degrees of vitamin B12 deficiency, which were related to the degree of animal product restriction in the diet. Vegans had the lowest levels of B12 and the highest levels of homocysteine, as compared to the LV, LOV and omnivors. Those who took vitamins had similar levels of B12 as the omnivors. A form of anemia and relative folate shortage were linked to vitamin B12 deficiency. Homocysteine rises with advancing age, whereas vitamin B12 declines, which further increases the risk of cardiovascular disease risk, in older vegans.

The study concluded that “more emphasis should be placed on effective vitamin B12 supplementation and monitoring of vitamin B12 status, in persons who have chosen lifelong adherence to a vegetarian diet.”

— Carmia Borek, Ph.D.


* Herrmann W, et al. Vitamin B12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clinical Nur 2003 Jul;78(1): 131-136.