Mark A. Moyad

An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part I.

The correction of a subtle nutritional deficiency that may reduce the risk of a future chronic disease is indeed a challenge. However, some specific examples in the past, such as the addition of folic acid to prevent neural tube defects and calcium and vitamin D to prevent osteoporosis, should provide some encouragement that some conditions can be prevented with the appropriate addition of a deficient compound. One of the most intriguing current and future impacts on public health may come from a greater intake of omega-3 fatty acids such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The omega-3 fatty acids continue to accumulate research that suggests that may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In Part 1 of this manuscript the potential for these compounds to prevent certain cardiovascular conditions are discussed. In Part 2 the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurological diseases, osteoporosis, and other medical disciplines are also briefly covered. The future appears bright for these agents, but specifically which conditions, who qualifies, testing, frequency, adequate sources, future trials and numerous other questions need to be addressed and answered before the potential impact can catch up to the recent hype.

SELENIUM AND VITAMIN E SUPPLEMENTS FOR PROSTATE CANCER: EVIDENCE OR EMBELLISHMENT?

Selenium and vitamin E are probably 2 of the most popular dietary supplements considered for use in the reduction of prostate cancer risk. This enthusiasm is reflected in the initiation of the Selenium and Vitamin E Chemoprevention Trial (SELECT). Is there sufficient evidence to support the use of these supplements in a large-scale prospective trial for patients who want to reduce the risk of prostate cancer? Results from numerous laboratory and observational studies support the use of these supplements, and data from recent prospective trials also add partial support. However, a closer analysis of the data reveals some interesting and unique associations. Selenium supplements provided a benefit only for those individuals who had lower levels of baseline plasma selenium. Other subjects, with normal or higher levels, did not benefit and may have an increased risk for prostate cancer. The concept that supplements reduce prostate cancer risk only in those at a higher risk and/or those with lower plasma levels of these compounds is supported by trials examining beta-carotene supplements. Smokers may be the only individuals who benefit, as has also been shown with vitamin E supplementation. In 4 recent prospective studies, vitamin E was found to reduce the risk of prostate cancer in past/recent and current smokers and those with low levels of this vitamin. Vitamin E supplements in higher doses (> or =100 IU) were also associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers from a past prospective study. The dose of vitamin E in the SELECT trial (400 IU/day) is 8 times higher than what has been suggested to be effective (50 IU/day) by the largest randomized prospective trial in which the incidence rate of prostate cancer was used as an endpoint. Recent research also suggests that dietary vitamin E may be associated with a lower risk of prostate cancer than the vitamin E supplement. Additionally, recent results from all past cardiovascular prospective, randomized trials suggest that vitamin E shows little benefit for cardiovascular disease risk, especially at the dose being used in the SELECT trial. Other intriguing positive findings from past prospective studies of supplements suggest that aspirin and other nonsteroidal anti-inflammatory drugs have a role in reducing the risk of prostate cancer or other types of cancer (eg, colon cancer). It may be time to conduct a large costly trial to reconsider the use of selenium and vitamin E supplements for the reduction of prostate cancer risk. Some evidence for the use of these supplements exists, but serious embellishment of study findings may be leading to an inappropriate use of these supplements in a clinical setting.

Is obesity a risk factor for prostate cancer, and does it even matter? A hypothesis and different perspective

Measurement of obesity is not as simple as its definition. Currently, several methods of measuring obesity are used in clinical studies. Skinfold thickness, crude weight, lean body mass (LBM), body mass index (BMI), and waist-to-hip ratio (WHR) are some of the more popular methods, but each contains its inherent strengths and flaws. In general, the results of the largest studies on prostate cancer and obesity have not been conclusive. One of the largest studies found an inverse relation to prostate cancer in the youngest age groups. The age and duration of obesity or any rapid changes in weight gain, along with other unhealthy exposures, may have some relation to prostate cancer incidence and mortality. Early intrinsic or extrinsic exposure to estrogen or estrogenlike compounds may provide a protective effect. The timing and duration of a higher estrogen and/or lower testosterone exposure may have a beneficial or detrimental impact on the prognosis of an established prostate tumor. Negative exposures over time such as low levels of sex hormone-binding globulin (SHBG), a greater exposure to growth factors, elevated insulin levels, greater sympathetic activity, higher cholesterol levels, immune system dysfunction, inadequate diets, smoking status, and other factors may be associated with an increased risk of prostate cancer and other diseases. Obesity may also be associated with other cancers for similar and different reasons. For example, morbidity and mortality from postmenopausal breast cancer, colon, kidney, and other cancers are potentially associated with obesity. Other comorbidities such as cataracts, coronary heart disease, diabetes, erectile dysfunction, hypertension, and others are also associated with obesity. The 2 largest prospective studies on BMI and overall mortality have also demonstrated the substantial negative impact of excess weight on society. Prostate cancer risk and obesity need further research to establish if a true association exists, but at this time, does it really matter? Overall, the profound adverse effect of being obese on general health is dramatic, and this is what clinicians and patients need to remember.

Complementary/alternative therapies for reducing hot flashes in prostate cancer patients: reevaluating the existing indirect data from studies of breast cancer and postmenopausal women

Vasomotor hot flashes are a common problem in women who are postmenopausal or receiving antiestrogen treatment for breast cancer. Hot flashes are also a common problem after orchiectomy/luteinizing hormone-releasing hormone therapy, occurring generally in 50% to 66% of these men. Prescribed treatments for hot flashes for men on hormonal ablation treatment for prostate cancer are well documented. These conventional agents have shown good results, but their long-term efficacy, safety, and cost are still questioned. Therefore, the search for other viable agents, including nontraditional treatments, continues. Complementary/alternative treatments to alleviate hot flashes in women have generated an enormous amount of interest. However, these options have received little attention in men with hot flashes. Research with vitamin E, soy, black cohosh, red clover, and numerous other alternative treatments in women may provide some indirect but valuable insight on their potential effectiveness in men. Many of these alternatives have been a disappointment in recent randomized trials of women, and it is likely that there will be similar results with men. However, numerous supplements have yet to be tested in a clinical trial against a placebo, and clinicians should become aware of this ever-increasing list. Patients should be made aware of the primary importance of lifestyle interventions that could partially affect hot flashes and immediately affect overall health, especially during the period of androgen suppression, when it is not uncommon to observe accelerated weight changes and insulin insensitivity. Otherwise, recent research with older and newer conventional agents, such as antidepressants or estrogen/progesterone, should be emphasized at this time for moderate-to-severe hot flashes that profoundly affect daily activities and/or sleep. Antidepressant supplements (St. Johns wort) or acupuncture could also be an attractive option in future investigations. Low-dose estrogen seems particularly attractive, because it is inexpensive and may simultaneously reduce hot flashes and the risk of osteoporosis in men receiving long-term androgen suppression therapy; however, the potential for cardiovascular complications must be further investigated. Ultimately, adequate research (vs placebo) should determine the fate of the alternative supplements proposed for hot flash reduction.

Primary Causes of Death After Permanent Prostate Brachytherapy

PURPOSE To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. METHODS AND MATERIALS From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. RESULTS The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. CONCLUSIONS Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily resulted from an excess of cardiovascular deaths. Changes in lifestyle to improve cardiovascular health may improve overall survival in patients with clinically localized prostate cancer.

Osteoporosis: a rapid review of risk factors and screening methods.

Osteoporosis is a significant problem in women and it is beginning to become a recognized etiology of morbidity and mortality in men. However, before reviewing any potential therapies, it is imperative that clinicians first gain adequate knowledge on the risk factors for osteoporosis and fractures, and the various screening methods that are utilized in clinical practice. For example, advancing age, hormonal status, lifestyle, and overall diet are just a few of the potential risk factors. The majority of the risk factors in men seem to parallel those that have already been well known in women. Heel ultrasound (HUS), dual-energy X-ray absorptiometry (DEXA), and quantitative computerized tomography (QCT) are the most popular and effective methods utilized for osteoporosis screening. All of these imaging tests contain an inherent number of advantages and limitations. This brief review serves as a simplistic but important primer to a condition that is increasing in prevalence in a diverse area of medical fields.

Use of PC-SPES, a commercially available supplement for prostate cancer, in a patient with hormone-naive disease

OBJECTIVES PC-SPES, an over-the-counter supplement, is actually a combination of eight different herbs. It is being used by patients to treat cancer of the prostate at different stages of the disease and has been commercially available since November 1996. It has been observed to dramatically decrease prostate-specific antigen (PSA) values in several patients; however, its out-of-pocket cost (

Complementary therapies for reducing the risk of osteoporosis in patients receiving luteinizing hormone-releasing hormone treatment/orchiectomy for prostate cancer: a review and assessment of the need for more research.

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The placebo effect and randomized trials: analysis of conventional medicine

486/mo) and potential side effects must be weighed against its potential objective benefits. We reviewed its use in 1 patient. METHODS A patient with clinically localized prostate cancer (T1c) with a PSA of 8.8 ng/mL, who decided to delay any conventional treatment, began treatment with 9 PC-SPES capsules/day. RESULTS After 3 weeks, his PSA dropped to 1.4 ng/mL and after a total of 8 weeks, his PSA was less than 0.1 ng/mL (undetectable). He has continued on a maintenance dose of 6 capsules per day, decreasing to 4 capsules per day, with a continuing undetectable PSA. During this time the patient also experienced a number of strong estrogenic effects: loss of libido, erectile dysfunction, extreme breast enlargement and tenderness, reduction in overall body hair, pitting edema, and a significant drop in his lipoprotein (a) level (from 46 to 11 mg/dL). CONCLUSIONS PC-SPES may provide additive advantages (or disadvantages) over prescribed hormonal treatments but must be compared with other hormonal and nonhormonal treatments in clinical trials with hormone-sensitive and -insensitive patients with prostate cancer to determine its future use or nonuse.

An analytical comparison of the three most commonly used prostate-specific antigen assays: Tandem-R, Tandem-E, and IMx

Osteoporosis in women has received a substantial amount of attention, but its impact in men is also significant and noteworthy. Those men who benefit from treatment for prostate cancer with androgen deprivation therapy (ADT) may also be at a higher risk for osteoporosis. Pharmacologic approaches to reduce this risk have received some attention. For example, agents such as bisphosphonates, estrogen receptor-binding drugs (diethylstilbestrol, tamoxifen, and raloxifene), calcitonin, and fluoride are some of the more promising interventions that have been previously outlined. In addition, statin drugs, or hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have recently been hypothesized to lower osteoporosis risk. However, complementary therapies, which may also have an impact on reducing osteoporosis risk, have not received attention. Dietary and supplemental calcium and vitamin D have been shown, in some preliminary investigations, to maintain bone density in women and men. Numerous healthy and affordable dietary sources of this mineral and vitamin exist, and large intakes can be realistically achieved through proper education. Similarly, the supplemental dosages required to impact risk have been moderate, appear to be safe, are of low cost, and thus may provide an additional route for reducing risk, especially if these interventions are initiated at the start of medical treatment. More studies in men receiving ADT are needed because the existing work has mostly focused on men without castrate levels of male hormone. Additionally, many studies with conventional and nonconventional agents have only focused on individuals with baseline osteoporosis, rather than normal bone mineral densities or osteopenia. Other promising complementary therapies, such as weight-bearing exercise and abstaining from smoking, may also be of benefit. Newer estrogenic-type supplements (eg, ipriflavone) appear interesting and have some preliminary data, but more research is desperately required to determine their actual impact and potential for adverse effects (such as lymphocytopenia from a recent trial). Simple, inexpensive, and potentially effective dietary and supplemental approaches to reduce the risk of osteoporosis in men exist, and they should be discussed with patients. Whether these approaches effectively reduce the risk of osteoporosis in men receiving androgen ablation remains to be determined. The possibility is intriguing, and future research is needed. In the meantime, it is important to keep in mind that these complementary approaches are, at the very least, an integral part of the conventional options used today to the reduce the risk of osteoporosis in men and women.