Reviewed: Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, Paulson DF, et al. 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 2001;58:47–52.

Summary: In a pilot study, 25 men (average age 64 years) with prostate cancer and awaiting prostatectomy (removal of the prostate gland), were instructed to add 30 g (approximately 3 rounded tablespoons) of ground flaxseed (Linum usitatissimum L., Linaceae) to their daily diet. Additionally, they were given instructions for a low-fat diet (20 percent of kilocalories or less). Subjects were instructed to tally the number of fat grams they consumed each day; however, these did not include fat from high omega-3 fatty acid sources such as flax or fish. Blood was drawn at baseline and one to three days before surgery to measure prostate-specific antigen (PSA), testosterone, free androgen index, and total serum cholesterol. Following surgery, the tumors of these diet/flaxseed treated men were compared with historic controls (men with prostate tumor removal who did not alter their diet) matched by age, race, biopsy Gleason sum*, and PSA at the time of diagnosis. Tumor tissue samples were used to determine the degree of either apoptosis (using a TUNEL score**) or proliferation of the cancer (using a MIB-1 index**).

The average duration of the diet and flaxseed supplementation was 34 days (range of 21 to 77 days). Compared to baseline, there were significant (all p < 0.05) decreases in total testosterone (422 + 122 ng/dL to 360 + 128 ng/dl), free androgen index (36.3 percent + 18.9 percent to 29.3 percent + 16.8 percent), and total serum cholesterol (201 + 39 mg/dL to 174 + 42 mg/dL). Overall, there were no significant effects on PSA levels. However, using Gleason sums as a differentiating point, it was found that in men with less histopathologically aggressive disease, the low-fat diet and flaxseed supplementation led to slight but non-significant decrease in PSA levels compared to historic controls. PSA continued to rise in men with more aggressive disease. The apoptotic scores (TUNEL scores) were significantly different between the two groups (p = 0.01) with a higher score for those in the diet/flaxseed group. The proliferation index (MIB-1 index) was significantly lower for those in the diet/flaxseed group (p = 0.05). Decrease in proliferation and higher rates of apoptosis were significantly associated with the number of days on the diet and flaxseed supplement (p = 0.049 and p = 0.017, respectively).

Comments/Opinions: Less an herbal medicine study and more nutritional in scope, this pilot study completed by researchers at Duke University provides further evidence that dietary factors may play a role in the progression and possibly prevention of prostate cancer. Some epidemiological studies have linked prostate cancer risk to increased consumption of foods high in saturated fats (primarily from meat and dairy sources)¹ while some,^2,3 but not all,⁴ preliminary clinical trials have found this link.

Typically, as saturated fat is reduced in the diet, most people are likely to increase fruits and vegetables, which are higher in fiber and other nutrients linked to prostate cancer prevention. Among these are lycopene, a carotenoid abundant in tomatoes.⁵ Cruciferous vegetables, which are high in substances such as indole-3-carbinol, glucaric acid (calcium D-glucarate), sulforaphane, and the carotenoids lutein and zeaxatnhin, have been linked with prostate cancer prevention in a preliminary study.⁶ Other foods linked to decreased risk of prostate cancer in preliminary research include fish⁷ and soymilk.⁸

Flaxseed is a source of dietary fiber that is especially rich in dietary lignans⁹ (the authors of this study suggest it has "75 to 800 times more than any other food"). One study found that 50 to 60 g per day of fiber from mixed sources decreased PSA levels in 14 healthy men.¹⁰ Lignans (typically classified as phytoestrogens) have been found to influence both estrogen and androgen metabolism.¹¹ A study with premenopausal women suggests that flaxseed supplementation (10 g/day for 8 weeks) may influence estrogen metabolism in a way that may decrease risk of breast cancer.¹² Another study found that lignan levels were higher in the prostatic fluid of men at low risk of prostate cancer compared to those at increased risk.¹³

The authors of this study also point to the high omega-3 fatty acid content of flaxseed as another potential chemoprotective factor. However, this remains somewhat controversial — alpha-linolenic acid (ALA), the most predominant omega-3 fatty acid in flaxseed, has been linked to increased risk of prostate cancer in some,^14,15 but not all⁴ studies. Although meat is a common source of ALA, the two studies above still found a correlation between prostate cancer and ALA after an adjustment was made for meat intake. While this might not be a concern for ground flaxseed supplements, it does suggest that men should carefully weigh the risk versus benefits of using flaxseed oil.

Men wishing to add flaxseed supplements to their diet should remember that the ground seed has a propensity for rancidity. The product used in this study (provided by ENRECO, Inc., of Manitowoc, Wisconsin; trade name is not given) had added stabilizers, emulsifiers (for ease of mixing), a small amount of oat flour (to reduce the slightly bitter aftertaste of flaxseed), and was vacuum-packed. This delivery form made it easier to sprinkle into cereal or mix with juice, yogurt, or applesauce.

Practice Implications: Although these data must be viewed as preliminary, the results of this pilot study suggest that a flaxseed-supplemented, low-fat diet may affect prostate cancer biology, most likely through a hormonal mechanism. This study sets the stage for larger clinical trials that should investigate the role of this intervention as either (or both) a preventive or complementary therapy for prostate cancer. Future trials should also add groups taking only flaxseed without a low-fat diet and a control group using only a low-fat diet for comparison. Clinicians wishing to recommend this regimen for their patients should consider the potential risks of drops in serum testosterone levels over a long period of time (e.g., decreased muscle mass, lowered libido, depression) as well as the difficulty of compliance with the diet used in this study.

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Reference:

15. Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 1993;85:1571-9.

Clinical Updates are reproduced from HerbalGram, the Journal of the American Botanical Council (ABC) (www.herbalgram.org). ABC, based in Austin, Texas, is an independent, member-based, nonprofit, herbal medicine education and research organization serving the public, researchers, and the herbal community since 1988.