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Omega-3 Fatty Acids Stabilize Atherosclerotic Plaques

September 2004

LE Magazine September 2004
Omega-3 Fatty Acids Stabilize Atherosclerotic Plaques

Heart disease can be seen as the symptom of lipid-containing plaques in the walls of the coronary arteries, carotid arteries, aorta, and peripheral arteries. In at least one-half of all first heart attacks, however, the plaques are hemodynamically insignificant—that is, they do not block arteries or cause chest pain. These plaques become clinically significant when they release fragments that lodge in smaller blood vessels, causing occlusion and depriving the neighboring tissues of blood and oxygen. By either direct pathological examination or with the assistance of magnetic resonance imaging, arterial plaques can now be assessed and classified as either stable or unstable.

With this in mind, researchers at the University of Southampton (UK) designed a prospective, randomized, double-blind clinical trial to determine the effect of dietary omega-3 fatty acids in 162 patients scheduled to undergo carotid endarterectomy for advanced atherosclerosis.* The patients were given capsules containing omega-3 fatty acids in amounts known to be cardioprotective, capsules containing omega-6 fatty acids, or capsules containing a mixture of oils comparable to a typical Western diet. At the time of surgery, arterial sections were obtained and classified by a cardiopathologist as stable or unstable based on plaque morphology and degree of macrophage infliltration.

Compared with participants who received omega-6 fatty acids or a blend of Westernized diet oils, those receiving omega-3 fatty acids had a greater than 50% increase in stable versus unstable plaques. The investigators hypothesized that arterial plaques are dynamic structures and responsive to dietary modification.

Increasing dietary omega-3 fatty acids by consuming fish or supplements is cardioprotective, reduces atherosclerosis, prevents sudden deaths caused by unstable plaques, and decreases the likelihood of future heart attacks. Scientists believe this protection is conferred by the anti-inflammatory properties of omega-3 fatty acids.

—Dean S. Cunningham, MD, PhD


* Thies F, Garry JM, Yaqoob P, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 2003 Feb 8;361(9356):477-85.

Anti-Prostate Cancer Vaccine Shows Promise

At the June 2004 annual meeting of the American Society of Clinical Oncology, Johann Vieweg, MD, associate professor of urology and immunology at Duke University Medical Center, presented exciting findings on an immunotherapeutic vaccine he is testing against prostate cancer.

Unlike traditional vaccines that when administered protect the recipient from acquiring a disease, immunotherapeutic vaccines facilitate the destruction of an existing disease. Dr. Vieweg’s vaccine provokes an immune attack against cells that overexpress telomerase, a polypeptide that is silent in normal human cells but abundantly expressed in more than 85% of all tumor cells, including those of the prostate, breast, lung, colon, and kidney. Telomerase is known to protect tumor cells from undergoing preprogrammed cell death, yet because of these differences in expression, telomerase can serve as an immunological target, thereby making tumor cells vulnerable while preserving the integrity of normal cells.

Of the 20 men with prostate cancer who are enrolled in Dr. Vieweg’s study, 19 were able to successfully generate their own specific immune T cells with cytotoxic activity against telomerase-associated tumor cells and without appreciable side effects. As a result, the typical 2.9-month doubling time for prostate-specific antigen (PSA) in the blood increased to 100 months. PSA doubling time is a convenient measure of a prostate cancer patient’s response to treatment—the longer the doubling time, the better the response.

Furthermore, 9 of 10 subjects who initially had detectable levels of circulating prostate cancer were found to have a significant reduction or complete absence of these cells following vaccination. In the study’s next phase, the subjects will receive booster vaccinations to prolong their immunity and presumptive protection from prostate cancer.

Unfortunately, while the few men participating in the study have benefited, many other eligible men will not. The telomerase vaccine is in Phase I/II clinical trials as a product in development for Geron Corporation, and it may well be years before this promising vaccine is made available to the public.

—Dean S. Cunningham, MD, PhD

Short-Term Statin Use Depletes CoQ10 Levels

In a new study on statin use published in the Archives of Neurology, researchers at Columbia University in New York report that even a short course of statin therapy dramatically reduces levels of coenzyme Q10 (CoQ10).* This finding, the researchers noted, could explain the troubling side effects of statin therapy, which include exercise intolerance, muscle pain, and other indicators of muscle dysfunction.

A widely prescribed class of drugs that reduce harmful cholesterol levels, the statins include Pravachol® (pravastatin), Zocor® (simvastatin), and Lipitor® (atorva-statin), which was used in the Columbia study. CoQ10 is a natural antioxidant and cofactor that is crucial to cellular energy metabolism. The body’s natural production of CoQ10 declines with age and drops precipitously with statin use.

In the Columbia study, a majority of patients’ CoQ10 levels dropped by as much as 49% after just two weeks of therapy. The study authors recommended CoQ10 supplementation as a preventive measure for patients taking Lipitor® or other statins.

High low-density lipoprotein (LDL) is implicated in atherosclerosis, which may lead to heart disease and stroke. Reducing cholesterol is a recommended health goal for most adults. While attention to diet helps, not all cholesterol comes from fatty foods; cholesterol is also manufactured within the body. Statins are effective because they interfere with one stage of a biochemical pathway that leads to the production of cholesterol. Because CoQ10 is created downstream by the same pathway, statins block its synthesis as well, making CoQ10 supplementation crucial for those taking statins.

—Dale Kiefer


* Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004 Jun; 61(6):889-92.

Sex Hormones Implicated in Prostate Enlargement

The enlargement of the prostate gland that occurs with aging, known as benign prostatic hyperplasia (BPH), makes its appearance in most men while they are in their thirties. By the age of 80, approximately 85% of men have BPH. Up to one-third of men between 40 and 79 years of age have severe symptoms of BPH, including difficulty initiating urination, a weak urine stream, or awakening from sleep to urinate more than two or three times each night.

With more and more men are opting for testosterone supplementation to enhance their overall health, it is important to ascertain whether such therapy will correspondingly increase the risk of BPH. To date, the epidemiological evidence has not implicated serum testosterone levels in adversely affecting prostate health, nor have men who have received hormone replacement therapy been shown to have a higher rate of either prostate cancer or BPH.

Researchers at Gazi University in Ankara, Turkey, sought to determine the association, if any, between the serum concentration of sex hormones and severe symptoms of BPH.* The study enrolled 61 men who were scheduled for radical surgery as a treatment for BPH, along with 45 asymptomatic matched control subjects. Although the degree of hyperplasia increased with age, the only significant relationship between hyperplasia and hormone levels involved estradiol. Estradiol levels were significantly higher in men with greater than 50 grams of hyperplastic tissue. The fluctuation of circulating hormones that occurred as a function of age was similar between the BPH group and control group. Specifically, free testosterone levels declined with age, while estradiol, prolactin, and gonadotropin levels increased.

The authors concluded that it is unlikely that serum concentrations of sex hormones are related to BPH, but rather it is the increasing ratio of estradiol to free testosterone that is important in the development of BPH.

—Dean S. Cunningham, MD, PhD


* Tan MO, Karabiyik I, Uygur MC, Diker Y, Erol D. Serum concentrations of sex hormones in men with severe lower urinary tract symptoms and benign prostatic hyperplasia. Int Urol Nephrol. 2003;35(3):357-63.