The authors comment that these results support the hypothesis that the lower risk of kidney cancer is possibly due to the increased intake of fish oil rich in the two marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as vitamin D. They discuss the evidence for the biological plausibility of this hypothesis. The authors also point out that an explanation for the null results from earlier studies of the influence of fish consumption of cancer may have been the failure to distinguish fatty from not-fatty fish intake. As regards vitamin D, they discuss studies that found a connection between kidney cancer and vitamin D deficiency as measured by serum marker levels. This epidemiologic study, according to the authors, is the first to address this dietary association.
Wolk, A et al. Long-term Fatty Fish Consumption and Renal Cell Carcinoma Incidence in Women. Journal of the American Medical Association, 2006, Vol. 296, No. 11, pp. 1371-6 Fish oils in cancer prevention
STOCKHOLM, SWEDEN. Several test tube (in vitro) and animal experiments have clearly shown that the long-chain omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main components of fish oil, help inhibit the promotion and progression of cancer. Their beneficial effect is particularly pronounced in hormone-dependent cancers such as breast and prostate cancer. Some, but not all, epidemiologic studies have also found a beneficial effect.
Researchers at Sweden’s famous Karolinska Institutet have just published a comprehensive review of the current knowledge regarding the role of PUFAs in carcinogenesis. They conclude that omega-3 PUFAs are protective against cancer progression, while omega-6 PUFAs, notably arachidonic acid and its derivatives, help promote the growth of cancer. They believe the n-3 PUFAs exert their beneficial effects in several different ways:
- They suppress the synthesis of pro-inflammatory eicosanoids from arachidonic acid and thus produce an overall anti-inflammatory effect.
- They positively affect gene expression or the activities of signal transduction molecules involved in the control of cell growth, differentiation apoptosis, angiogenesis and metastasis.
- They suppress excessive production of nitrogen oxide (NO) during chronic inflammation and thereby help prevent DNA damage and impaired DNA repair.
- They decrease estrogen production and thus reduce the estrogen-stimulated growth of hormone- dependent cancer cells.
- Fish oils improve insulin sensitivity and cell membrane fluidity and may help prevent metastasis through these effects.
Free radicals and reactive oxygen species produced in cells may attack PUFAs resulting in the formation of more free radicals, specifically hydroperoxides. The hydroperoxides, in turn, may damage DNA ultimately leading to cancer. These effects have indeed been observed in some in vitro experiments, but not in actual human beings. Many studies have shown that fish oils actually retard aging and suppress so- called free radical diseases such as atherosclerosis and cancer. Other studies have shown that a daily EPA + DHA intake in excess of 2.3 grams decreases the production of superoxide, a potent cancer promoter. At least one in vitro and one animal experiment have observed that EPA + DHA kill human breast cancer cells via the formation of hydroperoxides, but that this effect is strongly inhibited by vitamin E. Thus, at this point, it is not entirely clear whether EPA + DHA exert part of their beneficial effect through an increase or a decrease in the production of free radicals and reactive oxygen species. The researchers recommend more work in this area, but emphasize that the major benefits of fish oils probably are associated with their ability to inhibit the synthesis of arachidonic acid-derived, pro-inflammatory eicosanoids. The Swedish researchers also confirm that fatty, cold-water fish are the best sources of EPA and DHA and that the conversion rate of alpha-linolenic acid (flaxseed oil) to EPA is very low, even in healthy humans – probably in the order of 2-5%.
Larsson, SC, et al. Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. American Journal of Clinical Nutrition, Vol. 79, June 2004, pp. 935-45
Fish consumption reduces lung cancer risk
NAGOYA, JAPAN. Lung cancer is the leading cause of cancer deaths in Japan even though the incidence and mortality is still less than two-thirds of that found in the USA and the UK. Japanese researchers have just completed a study aimed at determining the association between lung cancer and diet. Their study involved 748 men and 297 women aged 40 to 79 years who had been diagnosed with lung cancer and 2964 male and 1189 female cancer-free controls.
The researchers found that both men and women who ate cooked or raw fish five times a week or more had half the incidence of lung adenocarcinoma when compared to participants who ate cooked or raw fish less than once a week. Women who consumed tofu (soybean curds) five times a week or more were found to have half the risk of adenocarcinomas, as compared to women who consumed tofu less than once a week. Frequent consumption of carrots was found to be beneficial for women, but detrimental for men especially smokers. Green vegetables were found to be highly beneficial for men, but not statistically so for women. There was also some evidence that increased coffee consumption is associated with an increased risk of squamous cell and small cell lung carcinomas in men. Increased consumption of dried or salted fish was not beneficial for men or women. The researchers speculate that this is because the processing destroys the healthy omega-3 oils (eicosapentaenoic acid and docosahexaenoic acid) present in raw and cooked fish.
Takezaki, T., et al. Dietary factors and lung cancer risk in Japanese with special reference to fish consumption and adenocarcinomas. British Journal of Cancer, Vol. 84, No. 9, May 4, 2001, pp. 1199- 1206
Fish oils and the immune system
OXFORD, UNITED KINGDOM. Animal studies have shown that an increase in fat intake can decrease the number of natural killer (NK) cells found in the blood and spleen. NK cells are an integral part of the natural immune response to virus infections and certain types of cancer. Researchers at Oxford University now report that fish oil significantly decreases NK cell activity in healthy human subjects.
Docosahexaenoic acid halts melanoma
VALHALLA, NEW YORK. The incidence of cutaneous malignant melanoma is growing rapidly among persons with fair skin. It is estimated that one in 75 Americans will develop melanoma within their lifetime. Melanoma has a pronounced tendency to spread to other organs (metastasis) and the 5-year survival rate for metastatic melanoma is less than 10%. There is growing evidence that diet can influence the risk of developing melanoma. It is now believed that a high intake of omega-6 fatty acids stimulates the growth of melanoma and other cancers whereas omega-3 fatty acids suppress the growth of cancer cells.
Researchers at the New York Medical College and the American Health Foundation have just released the results of a laboratory experiment which clearly shows that docosahexaenoic acid (DHA), a main component of fish oil, is highly effective in inhibiting the growth of human melanoma cells. The researchers treated 12 different human metastatic melanoma cell cultures (in vitro) with DHA and found that more than 50% of them stopped growing. They urge further testing of their findings in full-scale clinical trials involving patients with melanoma. They conclude that “if DHA is capable of suppressing cell and tumor growth and metastatic potential in in vivo models of melanoma, a clinical trial of DHA would be warranted as an adjuvant to current surgical and chemotherapeutic interventions”.
Albino, Anthony P., et al. Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid: association with decreased pRb phosphorylation. Cancer Research, Vol. 60, August 1, 2000, pp. 4139- 45
Fish oils combat weight loss in cancer patients
EDINBURGH, UNITED KINGDOM. Cachexia (abnormal weight loss) is a major problem in many types of cancer especially cancer of the pancreas. Preliminary research has shown that supplementing the diet with fish oils, about 2.2 grams of EPA (eicosapentaenoic acid) and 1.4 grams of DHA (docosahexaenoic acid) daily, will stabilize weight in patients with inoperable pancreatic cancer. Now researchers at the Royal Infirmary of Edinburgh report that patients with pancreatic cancer can actually gain weight by consuming a nutritional supplement fortified with fish oils. The experiment involved 20 patients with inoperable pancreatic cancer (aged 18 to 80 years). The participants were asked to ingest two cans of fish oil-enriched nutritional supplement per day in addition to their normal food intake. The nutritional supplement provided 310 kcal per can and contained 16.1 g protein, 49.7 g carbohydrate, 6.5 g fat, 1.09 g EPA, 0.46 g DHA, and 28 essential vitamins and minerals.
After three weeks the patients had gained an average (median) of 1 kg in weight and at seven weeks an average of 2 kg. A significant improvement in performance status and appetite was also noted after three weeks on the supplement. Other research has shown that EPA inhibits the growth of pancreatic cancer cells in vitro. It is therefore of interest to note that the average survival time among the patients was over eight months. This compares very favourably with the normal survival time of 4.1 months and is at least as good as the survival time that can be obtained with aggressive chemotherapy.
The researchers conclude that a fish oil-enriched nutritional supplement has the potential to be a safe and effective means of preventing weight loss in cancer patients and may even increase survival time in patients with cancer of the pancreas. NOTE: This study was partially funded by Abbott Laboratories, the maker of the nutritional supplement.
Barber, M.D., et al. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. British Journal of Cancer, Vol. 81, No. 1, September 1999, pp. 80-86
Fish oils improve survival of cancer patients
PATRAS, GREECE. Chemotherapy and other conventional medical treatments have proven ineffective in improving quality of life and survival of patients with end stage cancer. Now Greek medical researchers report that fish oil supplementation markedly increases the survival time for cancer patients with generalized malignancy. Their study involved 60 patients with generalized solid tumors. The patients were divided into two groups with one group receiving 18 grams/day of fish oil (six capsules of MAXEPA three times daily containing 170 mg eicosapentaenoic acid [EPA] and 115 mg docosahexaenoic acid [DHA] per capsule) and the other group receiving a placebo. The fish oil group also received 200 mg of vitamin E daily to compensate for the oxidative effect of the fish oil. Each group included 15 well-nourished and 15 malnourished patients. None of the well-nourished patients suffered from cancer cachexia (abnormally low weight and general weakness). The researchers measured the level of T cells, natural killer cells, and the synthesis of interleukin and tumor necrosis factor before the start of the supplementation and on day 40 of the trial. The study followed all patients until they died. Malnourished patients were found to have a considerably impaired immune function and a decreased production of tumor necrosis factor; both parameters were restored through fish oil supplementation. Malnourished patients overall had a much shorter survival time than well-nourished ones (mean of 213 days versus 481 days). Both malnourished and well-nourished patients who received fish oil and vitamin E survived significantly longer than did patients on placebo. The researchers speculate that fish oils exert their beneficial effect by decreasing the body’s production of prostaglandin E2 which is believed to play an important role in the initiation and progression of cancer. They conclude that supplementation with dietary omega-3 polyunsaturated fatty acids, specifically fish oils with an antioxidant such as vitamin E may offer significant palliative support to cancer patients with end stage metastatic disease.
Gogos, Charalambos A., et al. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy. Cancer, Vol. 82, January 15, 1998, pp. 395-402
Fat consumption and cancer
LONDON, UNITED KINGDOM. Several major epidemiologic studies have found a clear association between a high dietary fat intake and the risk of developing breast and colon cancer. The correlation is particularly strong in the case of animal fats. One study found that a high fish or fish oil consumption is protective against later stage colon cancer in men, but has no effect on mortality from breast cancer. British medical researchers now report that fish and fish oils not only protect against colon cancer in men, but also against colon and breast cancer in women. This protective effect, however, is only apparent in countries where the intake of animal fats is high. In other words, a high intake of fish or fish oils counteracts the detrimental effects of a high animal fat consumption.
The study compared cancer mortality rates in 24 European countries, Canada and the USA with fish consumption and the intake of animal fats. In countries where the animal fat intake was high the researchers found a clear inverse correlation between the ratio of fish fat to animal fat and the risk of developing breast cancer in women and colon cancer in both men and women. A similar correlation was found between cancer risk and the ratio of fish fat to total fat intake.
The researchers conclude that a 15% decrease in animal fat intake combined with a 3-fold increase in fish oil intake could possibly reduce male colon cancer risk by as much as 30% in countries with a high animal fat intake. A 3-fold increase in fish oil intake could be achieved by eating fish three times a week or by taking two standard fish oil capsules daily.
Caygill, C.P.J., et al. Fat, fish, fish oil and cancer. British Journal of Cancer, Vol. 74, No. 1, July 1996, pp. 159-64
Colon cancer progression associated with fatty acid status
BADALONA, SPAIN. Several epidemiological studies have shown that high fat diets are associated with an increased risk of colon cancer. Other studies have shown that diets rich in fish and fish oils are protective against colon cancer. Spanish medical researchers have just released the results of a major study aimed at determining if and how polyunsaturated fatty acids play a role in the progression of adenomas (benign polyps) to full-blown colon cancer. The study involved 27 patients with sporadic benign polyps of the rectum or colon, 22 patients with cancer of the colon or rectum, and 12 subjects with a normal colon. The researchers measured the fatty acid profile of blood plasma and biopsy samples of the lining of the colon from both diseased and normal areas. They found no differences between polyp patients and patients with a normal colon as far as plasma profile and normal colon lining profile was concerned. However, there was a significant difference between the fatty acid profile of normal colon tissue and diseased colon tissue in adenoma patients. Diseased lining tissue was found to have higher levels of linoleic acid, dihomogammalinolenic acid, and eicosapentaenoic acid (EPA) and lower levels of alpha-linolenic and arachidonic acids. There was also a very significant stepwise reduction in EPA content of diseased colon lining from the benign polyp stage to the most severe colon cancer stage.
The researchers conclude that there are significant changes in the levels of n-3 and n-6 fatty acids early on in the sequence leading from benign polyps to colon cancer and speculate that these changes might participate in the progression to colon cancer. They recommend further work to investigate the benefits of long-term dietary manipulation in view of the finding that low-dose fish oil supplementation normalizes the cell proliferation pattern in patients with sporadic polyps.
Fernandez-Banares, F., et al. Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence. Gut, Vol. 38, 1996, pp. 254-59
Fish oils help patients with pancreatic cancer
EDINBURGH, UNITED KINGDOM. Cachexia (abnormally low weight, weakness, and general bodily decline) is common in patients suffering from pancreatic cancer. Cachexia makes patients more prone to infections, can shorten their survival, and reduce their mobility.
Researchers at the Royal Infirmary of Edinburgh have released the results of a study which clearly shows that fish oil supplementation can halt and even reverse cachexia in patients with pancreatic cancer. The study involved 18 patients with inoperable pancreatic cancer (9 had stage IV tumors). The patients were started out on 2 grams/day of fish oils (containing 360 mg of eicosapentaenoic acid and 240 mg of docosahexaenoic acid). The dose was subsequently increased by 2 grams/day every week until the patients’ body tolerance was reached. The average final intake was 12 grams/day. Prior to entering the trial the average (mean) weight loss among the patients was 2.9 kg (6.3 lbs) per month. After 3 months of fish oil supplementation an average weight gain of 0.3 kg/month was observed among the patients. Overall, 11 patients (61%) gained weight, 3 became weight-stable, and 4 continued to lose weight, but at a significantly reduced rate. The concentration of eicosapentaenoic acid in plasma phospholipids increased from 0 to 5.3% of total fatty acids after 1 month of supplementation while the concentration of docosahexaenoic acid increased to 6.6% from a base level of 3.5%. The researchers conclude that fish oil supplementation arrests weight loss in cancer patients with cachexia.
Wigmore, Stephen J., et al. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition (suppl), Vol. 12, No. 1, 1996, pp. S27-S30
Fish consumption and colon cancer
LONDON, UNITED KINGDOM. British researchers have published a major epidemiologic study dealing with the association between fish consumption and the incidence of breast and colon cancer, The researchers gathered data concerning the consumption of fish in 25 European countries for the periods 1961-63, 1974-76 and 1984-86. They also determined the standardized mortality rates for breast and colon cancer for the period 1983-87 for the same 25 countries. A statistical evaluation of the data showed a strong inverse correlation between recent fish consumption and colon cancer in men. The correlation was somewhat weaker for fish consumption 10 years earlier and non-existent for consumption 23 years earlier. A similar pattern was found for women, but the correlations were not statistically significant. The researchers found no correlation between breast cancer mortality and fish consumption at any time. They conclude that the consumption of fish and fish oils helps protect against colon cancer in its later stages, but does not affect the initiation stage. They believe fish oils exert their protective effect by inhibiting the formation of prostaglandin PGE2 which has been associated with the development and progression of colon cancer.
Caygill, C.P.J. and Hill, M.J. Fish, n-3 fatty acids and human colorectal and breast cancer mortality. European Journal of Cancer Prevention, Vol. 4, 1995, pp. 329-32
Fish oil supplementation helps prevent colon cancer
ROME, ITALY. The presence of benign polyps (adenomas) is a significant risk factor for full-blown colon or rectal cancer. Animal studies have shown that the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit the development of colon cancer and epidemiological studies have shown that fish consumption is inversely proportional with the incidence of colon cancer. Encouraged by these findings, researchers at the Catholic University of Rome set out to determine if fish oil supplementation would inhibit the development of benign polyps, the precursors of colon cancer.
Their study involved 34 men and 26 women who had just undergone surgery to remove benign polyps from their colon. The patients were divided into 4 groups. Group 1 was supplemented with 1.4 grams of EPA and 1.1 grams of DHA per day, group 2 with 2.7 grams of EPA and 2.4 grams of DHA, group 3 with 4.1 grams of EPA and 3.6 grams of DHA while group 4 received placebo capsules containing mainly olive oil. Biopsy samples from the lower part of the colon lining and blood samples were taken and analyzed at the start of the trial and 30 days later at the end of the supplementation period. Overall, patients in the fish oil groups experienced a significant decline in the number of abnormal cells in their colon lining as compared to members of the placebo group. Further analysis showed that the reduction in the number of abnormal cells was limited to patients who had a large number of abnormal cells at the beginning of the trial. The researchers also noted a very significant increase in EPA and DHA levels and a significant drop in arachidonic acid level in the biopsy samples from the fish oil supplemented patients.