Flaxseed and Prostate Cancer

Recently, interest has been considerable in diets that influence cellular growth of the prostate, especially diets low in fat and rich in phytoestrogens. Varying levels of phytoestrogens (eg, isoflavonoids, flavonoids, and lignans) are found in plant foods, such as soybeans, some vegetables, and flaxseed. These are hypothesized to influence the prostate by three mechanisms: estrogenic or antiestrogenic effects, antioxidant effects, and/or inhibiting effects on growth signal factors, such as insulin-like growth factor-1.¹

Flaxseed has gained attention as a “functional food” because of its unique nutrient profile. Greek and Roman writings reference the healing properties of flax as far back as 650 BC. In fact Charlemagne, the 8th century emperor, considered flax so important for health that he passed regulations related to a requirement for flax consumption. Typically flaxseed consists of approximately 40% fat, 28% dietary fiber, 21% protein, 4% ash, and 6% carbohydrates such as sugars, lignans, and hemicellulose.

Flaxseed has a unique and healthy fatty acid profile with very low saturated fat (approximately 9%) and moderate amounts of monounsaturated fat (approximately 18%). Of the nutritionally beneficial polyunsaturated fats, about 16% belong to the omega-6 family as linoleic acid (LA) and 57% is the omega-3 fatty acid, alpha-linolenic acid (ALA).

Flaxseed also contains several bioactive compounds such as phenolic acids, anthocyanin pigments, several flavonols and flavones, and phytic acid – all known to be significant antioxidants. Extensive scientific research over the past few decades has revealed an array of nutritional benefits of flaxseed – and new research points to positive effects in prostate cancer.

Prostate cancer – the most common in men

Cancer is a group of diseases characterized by the uncontrolled growth (proliferation) and spread (metastasis) of abnormal cells that develops along a complex path involving many small, gradual changes in the behavior of normal cells. Prostate cancer, like breast cancer, is hormone-sensitive and in the early stages of development, tumor growth is influenced by the sex hormone testosterone and its active metabolite, dihydrotestosterone.²

Prostate cancer is the most commonly diagnosed cancer in American men other than skin cancer. An estimated 186,320 men were diagnosed with the disease in 2008 according to the American Cancer Society. Prostate cancer is the second leading cause of cancer death in American men, behind lung cancer. The American Cancer Society estimated that 28,660 men in the U.S. would die of prostate cancer in 2008. Prostate cancer accounts for about 10% of cancer-related deaths in men. The exact cause of prostate cancer is not known.

Impressive clinical results with flaxseed

Feeding 30 grams of milled flaxseed to 161 prostate cancer patients for an average of 30 days before prostatectomy resulted in a significant lowering of cancer cell proliferation rates1. The trial was multisite, randomized and controlled and also included a low-fat diet alone (20% energy) or with flaxseed. Median Ki-67-positive cells were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) versus 3.23 (control) and 2.56 (low-fat diet). The down-regulation of Ki-67, the surrogate for cell proliferation, in the flaxseed-treated arms suggests an anticarcinogenic effect on prostate cancer cells in the body.

In 2007, Synder et al. reported that flaxseed may slow the growth of prostate tumors³. The study again involved 161 men with prostate cancer scheduled for prostatectomy. The trial included diets with 30 grams per day of flaxseed a day, low-fat diet alone (20% energy), or low-fat plus flaxseed. Cancer cell proliferation rates were 1.71 (flaxseed-supplemented diet) and 1.58 (flaxseed-supplemented, low-fat diet) versus 2.38 (control) and 2.93 (low-fat diet).

These scores indicated that cancer cells in the two flaxseed groups grew roughly 30% to 40% slower than the placebo or dietary fat groups. The researchers concluded “It’s reasonable to suspect that reducing cell proliferation -- the rate at which cancer cells divide -- is a good thing and likely to be associated with relief of symptoms and better survival”. Further, the flaxseed treatment did not cause side effects such as nausea or vomiting.

In earlier work by Demark-Wahnefried et al.⁴, 25 prostate-cancer patients awaiting prostatectomy were placed on a low-fat (20% of energy or less) diet supplemented with 30 grams per day ground flaxseed for the 21 to 77 days (average = 34 days) before surgery. At baseline and follow-up levels of prostate-specific antigen (PSA), testosterone, free androgen index, and total serum cholesterol were measured, and tumor proliferation and apoptosis were compared with historical data from controls. Total cholesterol was significantly lowered, as were total testosterone and free androgen index. Levels of PSA were unaffected. As compared with historical controls, both proliferation rate and apoptosis were favorably affected by the flaxseed intervention.

The findings suggest that ground flaxseed may affect prostate cancer biology. Flaxseed lignans appear to be partly responsible for this effect as they have been shown to significantly inhibit the growth of three human prostate cancer cell lines in vitro⁵. Flaxseed is rich in omega-3 fatty acids, which are believed to influence cell signaling and the production of cell membranes and to reduce cell proliferation.

In the study of 2007 by Synder and co-workers described above³, men receiving flaxseed had higher levels of the long chain omega-3 eicosapentaenoic acid (EPA) derived from ALA in erythrocytes and prostatic tissue as well as higher n-3/n-6 ratios in prostatic tissue. The authors concluded that conversion of ALA to EPA occurs with flaxseed and may support its use in the treatment of prostate cancer. Epidemiologic studies support an inverse association between ALA⁶ and EPA⁷ intake and prostate cancer risk. Omega-3 fatty acids have been shown to lower prostatic cell tumor growth rates, serum PSA levels and cancer cell proliferation and to increase apoptosis relative to n-6 fatty acids⁸.

The cumulative evidence suggests that flaxseed (a) is a good, low-cost source of nutrients, omega-3 ALA and fiber, (b) is well-accepted and safe to use, and (c) warrants further testing as a preventive or complementary therapy for prostate cancer.

References

1. Demark-Wahnefried, W.; T.J. Polascik; S.L. George; et al. 2008. Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery. Cancer Epidemiol. Biomarkers Prev. 17:3577-3587.

2. Denis L, Morton MS, Griffiths K. 1999. Diet and its preventive role in prostatic disease. Eur. Urol; 35: 377-387.

3. Snyder DC, BR Switzer, V Hars, RT Vollmer, JF Madden, SL George, MT Ruffin, W Demark-Wahnefried. 2007. Flaxseed supplementation and/or dietary fat restriction alters fatty acid profiles in the diet, erythrocytes, and prostatic tissue in men with prostate cancer. J Am Diet Assoc 107(Suppl 1):A38.

4. Demark-Wahnefried W, Price DT, Polascik TJ, et al. 2001. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: Exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology; 58: 47-52.

5. Lin X, Switzer BR, Demark-Wahnefried W. 2001. Effect of mammalian lignans on the growth of prostate cancer cell lines. Anticancer Res; 21: 3995-4000.

6. Schuurman AG, van den Brandt PA, Dorant E, et al. 1999. Association of energy and fat intake with prostate carcinoma risk: Results from the Netherlands Cohort Study. Cancer; 86: 1019-1027.

7. Augustsson K, Michaud DS, Rimm EB, et al. A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiol Biomarkers Prev 2003;12:64–7.

8. Kobayashi N, Barnard RJ, Henning SM, 2006. Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2. Clin. Cancer Res. 12(15):4662-70.