The New England Journal of Medicine (NEJM) recently reported that cabergoline (Dostinex®), a drug commonly used as an adjuvant therapy for men with prostate cancer, may cause heart valve damage.*

Unfortunately, this report could cause oncologists to advise their patients to discontinue this helpful medication. Before prostate cancer specialists limit their patients’ treatment options, it is important that both they and their patients be aware that the drug doses associated with heart valve damage in the NEJM study were literally thousands of times higher than the cumulative lifetime dose typically taken by men with prostate cancer.

The drugs in question in the study—pergolide (Permax®) and cabergoline (Dostinex®)—are categorized as dopamine agonists, a class of drugs that increase production of the brain neurotransmitter dopamine while decreasing production of the pituitary hormone prolactin. Reducing prolactin can help avert the breast enlargement and tenderness that may occur as a side effect of various hormonal treatments for prostate cancer.

The NEJM study found that when patients with Parkinson’s disease received massive doses of cabergoline, they displayed signs of heart valve damage.* According to the study authors, these patients were exposed to a mean cumulative dose of cabergoline of 4015 mg.

Prostate cancer patients typically use vastly lower amounts of cabergoline than the dosage associated with heart valve damage in the NEJM study. A typical dose regimen for lowering prolactin in prostate cancer patients is 0.25 mg taken three times weekly, to a maximum of 0.5 mg three times weekly of cabergoline. Using even the latter dose (1.5 mg weekly), achieving the mean cumulative dose of 4015 mg associated with moderate to severe (grade 3-4) valve abnormalities cited in the NEJM study would take a prostate cancer patient more than 51 years! Even the lowest cumulative dose reported by the authors with this degree of valvular abnormality would take 10.3 years to occur at the 1.5 mg weekly dose of cabergoline. In fact, most prostate cancer patients take the maximum dose of 1.5 mg weekly for periods ranging from months to a few years. If we assume a five-year duration of therapy, this would equate with a cumulative dose of 390 mg, less than one tenth of the mean cumulative dose reported in the NEJM article.

For physicians to stop prescribing dopamine agonist drugs in their prostate cancer patients who are being treated for overproduction of prolactin would appear to reflect an overreaction and misreading of the NEJM study results. This is even more the case if patients receiving dopamine agonist drugs are monitored using a standard echocardiogram on an annual basis to document any cardiac valve abnormalities. In my practice, I have yet to see a prostate cancer patient with clinically significant valvular disease who has been on cabergoline as part of an anti-cancer treatment or to help reduce breast tenderness. In the few patients I have seen with trace to mild (grade 1-2) heart valve abnormalities per echocardiogram, a review of echocardiograms done prior to the initiation of cabergoline showed the same valvular findings.

The NEJM study results underscore that physicians must be mindful not to discard helpful therapies in the treatment of prostate cancer without a detailed review of the issues and context involved.

—Stephen B. Strum MD, FACP

Medical Oncologist Specializing in Prostate Cancer Ashland, Oregon

Green tea extract lowers blood sugar and decreases blood lipid levels in diabetic rats, report scientists in India.* Excess blood sugar contributes directly to many of the damaging effects of diabetes, while elevated lipids are linked to increased risk of heart disease.

Rats with experimentally induced diabetes were treated with green tea extract; a control group did not receive the extract. After one month, the control rats were heavier and had higher levels of blood glucose and artery-clogging blood lipids—such as low-density lipoprotein (LDL) and triglycerides—than did the rats given green tea. The supplemented animals also had increases in beneficial high-density lipoprotein (HDL) and decreased levels of total cholesterol and blood sugar.

“Green tea can reduce the risk of cardiovascular disease in diabetes, with a significant improvement in lipid metabolism,” the investigators concluded.

—Dale Kiefer

Pomegranate fruit extract significantly reduces the number and size of lung cancer tumors in mice, report scientists at the University of Wisconsin.*

The researchers gave one group of mice pomegranate fruit extract in their drinking water; a second group did not receive the extract. Both groups were then exposed to one or two known lung carcinogens. The number of tumors that developed in pomegranate-fed mice was reduced by up to 61% compared to control mice. The scientists also confirmed that various signaling chemicals ordinarily found among cancerous tumors were greatly inhibited in the pomegranate-treated mice.

Noting that the treated mice were given a “human-achievable dose” of pomegranate fruit extract, the scientists concluded that the extract markedly inhibits lung tumor development and “merits investigation as a chemopreventive agent for human lung cancer.”

—Dale Kiefer

Japanese researchers say mice supplemented with the potent natural antioxidant astaxanthin appeared to burn fatty acids for fuel more efficiently, were able to exercise far longer, and had greatly decreased fat accumulation compared to mice that did not receive the compound.1

Previous research has shown that astaxanthin reduces oxidative damage from strenuous exercise in the skeletal and heart muscles of supplemented mice.2 Research also suggests that astaxanthin may improve human cardiovascular health and prevent cancer, among other potential benefits.3,4

Produced by certain marine algae, astaxanthin is a more potent antioxidant than other carotenes such as beta carotene.

—Dale Kiefer

Increasing vitamin D intake may reduce the risk of developing multiple sclerosis (MS), according to a recent Harvard study.* In a study of 257 US military personnel with MS and 51 healthy control subjects, white adults in the highest quintile of serum vitamin D levels had a 62% lower risk of developing MS than those in the lowest quintile. Among white/non-Hispanics, the risk of MS dropped 41% for every 50-nmol/L increase of 25-hydroxyvitamin D in the blood. No association between serum levels of 25-hydroxyvitamin D and MS risk was noted for African-Americans or Hispanics, who had lower levels of this form of vitamin D in their blood compared to whites.

The researchers called for further investigation into vitamin D’s protective role against multiple sclerosis.

—Dale Kiefer

Creatine increases life span and enhances cognitive function in mice, according to a recent report from German scientists.1

Used clinically to enhance endurance and improve muscle strength,2,3 creatine and its ability to increase energy utilization and reduce oxidative damage in the nervous system has recently drawn attention from scientists seeking cures for Huntington’s disease, muscular dystrophy, and Alzheimer’s disease.4-6

Due to its “marked neuroprotective effect” in rodent models of these and other diseases, as well as similar processes underlying aging and neurological disorders, the German researchers wondered whether creatine might also offer anti-aging benefits.1 They found that mice fed creatine lived an average of 9% longer than control subjects, performed better in neurobehavioral tests, and exhibited less accumulation of lipofuscin, a lipid pigment associated with aging.1,7

“[Creatine] may be a promising food supplement to promote healthy human aging,” the scientists concluded.1

—Dale Kiefer

British researchers have demonstrated that low doses of docosahexaenoic acid (DHA), an omega-3 fatty acid found in algae and fish oil, modestly reduce blood pressure.* Previous studies have associated intake of omega-3 fatty acids with a decreased risk of death from heart attack.

In a randomized, double-blind, placebo-controlled trial of 38 healthy men and women aged 40-65, the subjects received either 0.7 grams of DHA or placebo daily for three months. After a four-month washout period, the treatments were switched. When subjects took DHA, their diastolic blood pressure fell by 3.3 mm Hg and their heart rate dropped by 2.1 beats per minute.

“The results indicate that a moderate increase in the daily intake of DHA . . . lowers diastolic blood pressure,” the researchers concluded.

—Dale Kiefer

Patients with stable atherothrombosis are at an alarmingly high risk of death or cardiovascular disease, according to the first study to document the effects of atherothrombosis in outpatients.1,2 Atherothrombosis, which occurs when a blood clot (thrombus) forms on a ruptured plaque (atheroma) in a blood vessel wall, is the common link among heart attack, stroke, and peripheral arterial disease.

Data from 68,000 outpatients in 44 countries showed that despite appearing and feeling healthy in many cases, patients with established disease had roughly a one-in-seven chance of death, suffering a heart attack or stroke, or being hospitalized due to cardiovascular disease within one year. Patients with peripheral arterial disease (clogged arteries in the legs or abdomen) were at even greater risk, with a 22% one-year risk of suffering a major cardiovascular event. Those with atherothrombotic disease in three or more locations had a 28% risk of major adverse cardiovascular events.

—Dale Kiefer

A compound in blueberries protected laboratory animals from colon cancer, according to presenters at a national meeting of the American Chemical Society.* Known as pterostilbene, the compound is an antioxidant similar to resveratrol that could be developed into a preventive nutritional supplement.

After rats were given a known carcinogen to induce colon cancer, half were supplemented with pterostilbene. After eight weeks, the supplemented animals had 57% fewer pre-cancerous colon lesions than the control rats, as well as reduced colon cell proliferation and expression of genes involved in inflammation, which is a risk factor for the disease.

This study, the first to demonstrate pterostilbene’s ability to combat colon cancer, “underscores the need to include more berries in the diet, especially blueberries,” the researchers concluded.

—Dayna Dye

A traditional Mediterranean diet may protect children from developing allergic rhinitis (hay fever) and asthma, according to a recent report.*

Scientists evaluated 690 children, aged 7-18, residing on the island of Crete. The subjects’ parents provided information on the children’s diets and allergy and respiratory symptoms. Adherence to a Mediterranean diet was determined by the intake of 12 foods, including fruits, vegetables, whole grains, legumes, nuts, and olive oil.

Greater adherence to the Mediterranean diet protected against allergic rhinitis and was modestly protective against asthma and skin allergy. Grapes high in antioxidants and resveratrol were

especially protective against allergic rhinitis and wheezing, while oranges, apples, and tomatoes were also protective. Eating nuts (which are high in magnesium and vitamin E) at least three times per week halved the risk of wheezing.

—Dayna Dye

Women who consume high levels of lignans may have a reduced risk of breast cancer, according to a recent report.* Found in foods such as flaxseed, legumes, seeds, fruits, vegetables, and whole grains, plant lignans are a type of phytoestrogen.

In a study of 58,049 postmenopausal women in France, scientists analyzed the subjects’ intake of lignans. Those whose intake was in the top 25% of participants had a 17% lower risk of developing breast cancer than those whose intake was in the lowest quartile. The protective effect was limited to cancers that were estrogen- or progesterone-receptor-positive.

According to the study authors, “In view of the epidemiologic results of this study, the recommendation that women should consume diets that consist largely of fruits, vegetables, and cereals—all foods rich in lignans—should continue.”

—Dayna Dye

A widely available herbal extract known as forskolin may help reduce painful bladder infections and enhance the efficacy of anti-biotic treatment, according to Duke University scientists.1,2

Bladder infections (90% of which are caused by E. coli bacteria) are common in women and often recur despite antibiotic treatment. While antibiotics typically kill most bacteria in the bladder, a small number may survive by hiding in cells lining the bladder, where antibiotics cannot reach them. After antibiotic treatment, these bacteria may re-emerge and begin multiplying again, leading to another bladder infection.

In mice, administering forskolin via injection or intravenously flushed out hidden E. coli bacteria into the urine, where they would be susceptible to antibiotic treatment. “This type of treatment strategy may prove to be beneficial for patients with recurrent urinary tract infections,” the Duke researchers concluded.

—Dayna Dye

Improving Americans’ dietary ratio of omega-6 to omega-3 fatty acids could decrease their risk of depression and inflammatory diseases, according to a new report.*

Americans consume about 20 times more omega-6 fatty acids than omega-3 fatty acids, far in excess of an optimal ratio of 4:1 or even 2:1. Omega-6 fatty acids are found in eggs, poultry, and grains, while omega-3s are supplied by cold-water fish, flaxseed, and walnuts.

The blood of 43 middle-aged to elderly men and women was analyzed for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), two cytokines that enhance inflammation. Those who consumed the most omega-6 fatty acids and reported more symptoms of depression had much higher levels of IL-6 and TNF-alpha.

The scientists suggested that low intake of omega-3s are associated with chronic inflamation.

—Dayna Dye

Women who regularly used low to moderate doses of aspirin (1-14 325-mg tablets per week) had a lower risk than non-users of dying from any cause, especially cardiovascular disease, during a 24-year period.*

Scientists evaluated data from 79,439 women enrolled in the Nurses’ Health Study, who were free of cardiovascular disease and cancer at the study’s onset. The women were queried every two years from 1980 to 2004 concerning aspirin use. Current aspirin users had a 25% lower risk of dying from any cause, a 38% lower risk of cardiovascular disease death, and a 12% lower risk of dying of cancer than those that had never been regular users.

According to the authors, “aspirin therapy may influence cardiovascular disease and cancer through its effect on common pathogenic pathways such as inflammation, insulin resistance, oxidative stress, and cyclooxygenase (COX) enzyme activity.”

—Dayna Dye

Supplying multivitamin supplements to pregnant women in Tanzania lowered their risk of giving birth to low-weight and small-for-gestational-age infants, according to a new report in the New England Journal of Medicine.*

The researchers gave a daily multivitamin containing vitamin B-complex, vitamin C, and vitamin E, or a placebo, to 84,468 HIV-negative women at 12-27 weeks of gestation until six weeks following delivery. All participants received folic acid and iron supplements. The supplements reduced the risk of low birth weight (less than 5.5 pounds) by 18% and the risk of delivering an infant that was small for gestational age (less than the tenth percentile) by almost 25% compared to placebo. Women who supplemented with the multivitamin were also less likely to develop anemia.

“In light of these findings, we recommend that multivitamins be considered for all pregnant women in developing countries,” the scientists concluded.

—Dayna Dye

A combination of antioxidant vitamins and magnesium may help prevent noise-induced hearing loss, according to scientists at the University of Michigan.

The researchers treated guinea pigs with vitamins A, C, and E, vitamins A, C, and E plus magnesium, magnesium only, or a placebo, one hour before and five days after five hours of exposure to 120-decibel noise (comparable to a jet engine at take-off). Although neither the antioxidants nor magnesium alone protected hearing function, animals that received both antioxidants and magnesium experienced significantly less hearing loss and sensory cell death than the other groups.

These findings may be useful in developing a protective nutritional therapy for people in occupations involving significant exposure to noise, as well as those suffering Alzheimer’s and Parkinson’s diseases, stroke-like ischemia, and other conditions that involve neural degeneration.

—Elizabeth Wagner, ND

Migraine sufferers may be able to reduce the frequency and severity of their headaches by supplementing with lipoic acid, a nutrient known to enhance energy metabolism.* Previous studies have shown that other “mitochondrial energizers” such as vitamin B2 (riboflavin) and coenzyme Q10 help prevent migraine.

Belgian scientists recruited 44 migraine sufferers averaging 38 years of age, 26 of whom received 600 mg of lipoic acid daily for three months while the remaining 18 subjects received placebo. The frequency of headaches was modestly reduced in the lipoic acid group compared to the placebo group. Intra-group analysis showed that the lipoic acid group had markedly reduced frequency and severity of headaches, as well as fewer headache days.

While further studies are needed, these preliminary findings suggest lipoic acid may offer benefits for migraine prevention.

—Elizabeth Wagner, ND

Supplementing with L-carnitine or acetyl-L-carnitine may help improve male infertility, according to a recent research review.* Male infertility affects an estimated 40% of infertile married couples.

Scientists in Beijing, China, evaluated data from nine randomized trials that examined the efficacy of the two forms of carnitine on several measures of male fertility. Supplementing with carnitineproduced significant improvements in pregnancy rate, total sperm motility, and forward sperm motility, though no significant effects on sperm concentration were seen.

The scientists believe that supplementing with L-carnitine and/or acetyl-L-carnitine may help improve sperm kinetic features and improve pregnancy rate in patients affected by male infertility.

—Elizabeth Wagner, ND

An international group of scientists is recruiting 1,000 men to participate in a two-year study to determine whether combining high-dose vitamin D with conventional chemotherapy improves treatment outcomes for patients with advanced prostate cancer.

The researchers hope a pill containing a high dose of calcitriol, a biologically active form of vitamin D, will work with the chemotherapy drug Taxotere® (docetaxel) to improve survival rates among patients with advanced prostate cancer. Such patients who have stopped responding to traditional hormone therapy currently have few options. For more information, please contact Nicole Adams, public relations officer for the BC Cancer Agency, at 604-877-6272.

—Robert Gaston