Mackerel is recommended for breast cancer in moderation
Like herring, mackerel is a good source of vitamin D, coenzyme Q10, selenium and omega-3 polyunsaturated fatty acids. Generally speaking, the benefits of consuming fatty fish are thought to outweigh the potentially detrimental effects of the toxins from pollution and other sources that tend to accumulate in their adipose tissue. Consumption of fatty fish or fish oil has been found to reduce the risk of coronary heart disease. Consumption of dried mackerel was shown in one study to improve the learning ability of laboratory mice, apparently by increasing the level of the marine omega-3 fatty acid docosahexaenoic acid in their brains. Eating fatty fish such as mackerel has been found to be associated with reduced risks of leukemia, multiple myeloma, and non-Hodgkin lymphoma, as well as renal cell, endometrial and prostate cancer.Breast cancer-related effects of eating mackerel
Like other fatty fish, mackeral contains marine fatty acids, in which there has been considerable interest. It is felt that these fatty acids probably have anticarcinogenic effects against breast cancer, especially since they have been shown to inhibit proliferation of breast cancer cells in the laboratory. One study found that docosahexaenoic acid enhances the cytotoxic effect of taxanes used in chemotherapy and reduces Her-2/neu oncogene expression in human breast cancer cells. Another study found that docosahexaenoic acid increased survial times for almost half of a group of stage IV breast cancer patients on FEC (5FU, epirubicin and cyclophosphamide), an anthracycline-based chemotherapy regimen. Fish protein hydrolysates also have been shown to have antiproliferative activity against human breast cancer cell lines in vitro. Not all epidemiological studies have found convincing evidence of a negative association between marine fatty acid intake or fatty fish consumption and the risk of breast cancer. One study concluded that higher intakes of fish were actually associated with higher incidence rates of ER+ breast cancer for postmenopausal women. However, several studies have found that higher omega-3/omega-6 polyunsaturated fatty acid ratios are associated with reduced risk of breast cancer and consuming mackerel would tend to improve the ratio for most women.
Additional comments
Mackerel consumption should be reduced or eliminated by pregnant and nursing mothers since toxins from pollution and other sources might reduce birth weight and are secreted in breast milk. While mackerel is not generally considered a high mercury level fish, king mackerel from the Gulf of Mexico have been found to have high levels of mercury.
We recommend against consuming all but modest amounts of smoked mackerel, dried mackerel, salted dried mackerel, or mackerel pâté since such preserved fish foods have been associated with increased risks of gastric, colorectal and other cancers.
Pan frying mackerel has been shown to release carcinogenic heterocyclic amines in concentrations high enough to affect human health.
Selected studies
Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort Cancer Epidemiology, Biomarkers & Prevention, July 2010The present prospective study was designed to investigate the influence of nonvitamin, nonmineral supplements on risk of breast cancer. The use of such specialty supplements has greatly increased over recent decades. Some of these supplements may have anti-inflammatory or anticancer activities. In addition, supplements taken to relieve symptoms of menopause have been associated with reduced risk of breast cancer in two case-control studies. However, until now there have been no prospective studies of the association between the long-term use of such supplements and risk of breast cancer. The study included 35,016 postmenopausal members of the VITamins And Lifestyle (VITAL) Cohort residing in western Washington State and aged 50 to 76. The women, who did not have a history of breast cancer, completed a 24-page baseline questionnaire about their use of non-vitamin, non-mineral supplements during the period 2000 to 2002. Questions were designed to assess the recency (current versus past), frequency (days per week), and duration (number of years) of specialty supplement use. The Surveillance, Epidemiology and End Results (SEER) registry was used to find new breast cancer diagnoses among the women. Cox proportional hazards models were used to calculate multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (CIs). During the period 2000 to 2007, 880 of the study participants were diagnosed with invasive breast cancer. Current use of fish oil was found to be associated with reduced risk of breast cancer (HR = 0.68; 95% CI = 0.50-0.92). Ten-year average use was suggestive of reduced risk (P trend = 0.09). When analyzed according to histological subtype, the results held for ductal but not lobular tumors. The remaining specialty supplements were not found to be associated with breast cancer risk. In particular, use of supplements sometimes taken for menopausal symptoms (black cohosh, dong quai, soy, or St. John's wort) was not found to be associated with breast cancer risk. The authors conclude that fish oil may be inversely associated with breast cancer risk.
Omega-3 fatty acids strongly induce apoptosis in human breast cancer cells in vitro and in vivo via formation of reactive oxygen species and caspase 8 activation American Association for Cancer Research (AACR) Meeting, April 2010
The current study was designed to investigate the anticancer effect of two important omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid, while focusing on the possible role of fatty acid-induced oxidative stress and apoptosis as mechanisms for chemopreventive actions. In vitro cell culture of MCF-7 human breast cancer cells and an in vivo athymic nude mice both were used to study the effect of omega-3 fatty acids on cancer cell proliferation and investigate the mechanism of the cell death. Cell studies demonstrated that docosahexaenoic acid and eicosapentaenoic acid both strongly reduced the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and that these fatty acids also promoted apoptosis. Accumulation of reactive oxygen species and activation of caspase 8 were found to be important to the induction of apoptotic cell death. The simultaneous presence of antioxidants or a selective inhibition or knockdown of caspase 8 each were found to greatly interfere with the cytotoxic effect of docosahexaenoic acid. In the mouse experiments, it was found that feeding the animals with a 5% fish oil diet for six weeks significantly reduced the growth of implanted MCF-7 human breast cancer cells. The fish oil diet resulted in an inhibition of cancer cell proliferation and promotion of cell death. Using 3-nitrotyrosine as a parameter, it was confirmed that the fish oil diet significantly increased oxidative stress in tumor cells in the mice. Analysis of fatty acid content in mouse plasma and tissues demonstrated that the 5% fish oil diet significantly increased docosahexaenoic acid and eicosapentaenoic acid levels in both normal (329% increase) and cancerous mammary tissues (300%). The authors comment that omega-3 fatty acids strongly inhibited human breast cancer proliferation in vitro and in vivo through formation of reactive oxygen species and induction of apoptosis by caspase 8 activation.
Elucidation of dietary omega-6/omega-3 ratio effects on chemopreventive activity using mammographic density as a surrogate marker in rats American Association for Cancer Research (AACR) Meeting, April 2010
The present study was designed to determine the optimal dietary omega-6 to omega-3 (n-6/n-3) fatty acid ratio for breast cancer prevention in an animal model. Although consumption of omega-3 fatty acids has been reported to be beneficial in preventing breast cancer, the optimal n-6/n-3 ratio has not been established. Both n-6 and n-3 fatty acids are essential for normal development and biological functioning. However, both also have metabolizing enzymes in common and have the potential to antagonize each other’s metabolism thereby. In the study, experiments were performed to determine the ratio or ratios of dietary n-6/n-3 that are optimal for chemoprevention while at the same time avoiding adverse effects on normal development. Mammographic density was used as a surrogate marker for breast cancer risk. Groups of nine 32-day old female Sprague Dawley rats were randomly assigned to one of seven dietary regimens with n-6/n-3 ratios as follows: 25:1, 10:1, 5:1, 1:1, 1:5, 1:10, and 1:25. The overall proportion of calories from fat was fixed at 30% across all seven diets. Rat mammary gland density was measured using digital analyses of abdominal-inguinal mammary gland whole mounts stained with alum carmine. Density was estimated using either area or integrated optical density and reported as percentage of the mammary gland fat pad occupied by mammary epithelium. Density was found to be unaffected in the high n-6 group of the study; in other words, a high omega-6 diet did not induce any increase in density. However, mammary gland density was found to be significantly reduced in the high omega-3 group (16%, p<0.03). The authors comment that they are in the process of determining (1) whether reduced mammary gland density is accounted for by effects on the cell cycle or by induction of a pro-apoptotic environment; (2) the extent to which these effects are influenced by altered signaling via activated protein kinase B (Akt); and (3) the mechanism of action by which the n-6/n-3 ratio alters eicosanoid-mediated bioactivity.
Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial British Journal of Cancer, November 2009
The present report describes the results of an open-label single-arm Phase II trial designed to evaluate the safety and efficacy of the addition of 1.8 g docosahexaenoic acid each day to an anthracycline-based chemotherapy regimen in Stage IV breast cancer patients. The patients selected had rapidly progressing internal organ metastases. Breast cancer has reached a deadly period when such visceral metastases develop and anti-cancer treatments normally have the goal of relieving symptoms and postponing death without additional toxicity. It has been shown that cancer cells can be made more sensitive to chemotherapy than non-cancer cells when membrane lipids are enriched with docosahexaenoic acid (DHA), marine oxidative-stress-inducing lipid. In the study, safety and efficacy (measured by response rate) were the primary end points; time to progression and overall survival were the secondary end points. The study included 25 breast cancer patients with rapidly progressing visceral metastases who were given 1.8 g DHA daily, in addition to FEC, an anthracycline-based chemotherapy regimen. The objective response rate was 44%. With an average follow-up time of 31 months (range 2 to 96 months), the median time to progression was six months. Median overall survival was 22 months. Median survival reached 34 months in the 12 patients with the highest plasma DHA. The most common grade 3 or 4 toxicity observed was neutropaenia (low white blood cell count), which was observed in 80% of the study group and a known chemotherapy side effect. The authors conclude that DHA administered during chemotherapy had no adverse side effects and improved the outcome of chemotherapy when highly incorporated.
Marine n-3 polyunsaturated fatty acids in adipose tissue and breast cancer risk: a case–cohort study from Denmark Cancer Causes and Control, November 2009
This prospective study was designed to investigate the association between marine omega-3 (n-3) polyunsaturated fatty acids in fat tissue (a biomarker for long-term intake of seafood) and risk of breast cancer. The study included a cohort of healthy Danish women who donated adipose tissue biopsies to a biobank during the 1990s in an effort to investigate the role of diet in the development of cancer and other chronic diseases. Subsequent cases of breast cancer were identified through Danish national registries; 463 new cases of breast cancer were identified during the follow-up period. After adjusting for potential confounders, no significant associations were found between the concentration of marine n-3 polyunsaturated fatty acids in adipose tissue and risk of breast cancer. Compared to the lowest fifth, the highest quintile was found to have a hazard ratio (HR) equal to 0.96 (95% confidence interval (CI) = 0.64–1.43) for total marine n-3 polyunsaturated fatty acids, 0.84 (95% CI = 0.58–1.23) for eicosapentaenoic acid, and 1.08 (95% CI = 0.73–1.58) for docosahexaenoic acid. The authors conclude that the study found no associations between the content of total or individual marine n-3 polyunsaturated fatty acids in adipose tissue and development of breast cancer.
A comparison of the effects of soya isoflavonoids and fish oil on cell proliferation, apoptosis and the expression of oestrogen receptors α and β in the mammary gland and colon of the rat British Journal of Nutrition, December 2008
The current study investigated the impact of soybean-derived isoflavonoids and omega-3 fatty acids from fish oil on apoptosis, proliferation and estrogen receptor (ER) expression in the colon and mammary glands of laboratory rats. Female rats were fed diets high in omega-3 fatty acids (80 g/kg diet) or soy protein (765 mg/kg diet isoflavones) for two weeks, then sacrificed in advance of removal of their colons and mammary glands. Cell proliferation and apoptosis were assessed and ERα and ERβ expression were measured in colon tissue and mammary glands. Fish oil was found to significantly increase apoptosis and decrease mitosis in both types of tissue. These effects were associated with a decrease in the expression of both ERα and ERβ. Soy was found to have no effect on apoptosis in either tissue, but did reduce mitosis in the colon while increasing it in the mammary gland. The changes in proliferation were associated with contrasting changes in ER expression: fish oil significantly decreased both ERα and ERβ, whereas soy increased ERα and decreased ERβ. The authors conclude that the results may provide a mechanism by which omega-3 acids could reduce cancer risk. The interpretation of the results in relation to soy consumption and breast cancer risk requires further investigation.
Linking Exposure to Polychlorinated Biphenyls With Fatty Fish Consumption and Reduced Fetal Growth Among Danish Pregnant Women: A Cause for Concern? American Journal of Epidemiology, August 2008
The present study examined the association between intake of fatty fish, plasma concentrations of polychlorinated biphenyls (PCBs), and fetal growth. One hundred nulliparous women aged 25 to 35 years during 1996–2002 with normal prepregnancy body mass index were selected from the Danish National Birth Cohort and divided into groups according to their intake of fatty fish: low (0 meals/month, n = 34), medium (1–3 meals/month, n = 33), and high (4 meals/month, n = 33)). Women with a high intake of fatty fish were found to have 50% higher plasma PCB concentrations than women with low consumption. Maternal plasma PCB concentrations were found to be inversely associated with both birth weight and placental weight. The adjusted average difference between the 75th and 25th PCB percentiles was –155 grams for birth weight and –81 grams for placental weight. The authors conclude that dietary recommendations that often encourage weekly consumption of fatty fish should be reconsidered for women of childbearing age.
Dietary Fat and Risk of Postmenopausal Breast Cancer in a 20-year Follow-up American Journal of Epidemiology, September 2006
This prospective study evaluated the relationship between dietary fat and the incidence of postmenopausal breast cancer in a cohort of 80,375 U.S. women followed for 20 years from 1980 to 2000. Fat intake was assessed by repeated questionnaires. There were 3,537 new breast cancer cases during the study period. No association was found between energy from total dietary fat intake and risk of breast cancer. Furthermore, no specific type of fat was associated with an increased (or decreased) risk of breast cancer. The study found no differences in breast cancer risk by estrogen receptor (ER) or progesterone receptor status. Pre-menopausal fat intake also was not related to risk of postmenopausal breast cancer.
Exogenous supplementation with [omega]-3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n-3) synergistically enhances taxane cytotoxicity and downregulates Her-2/neu (c-erbB-2) oncogene expression in human breast cancer cells European Journal of Cancer Prevention, June 2005
The current study was designed to assess the in vitro relationship between supplementation with docosahexaenoic acid and breast cancer chemosensitivity to taxanes. Omega-3 polyunsaturated fatty acid docosahexaenoic acid and other ω-3 and ω-6 polyunsaturated fatty acids are of interest as anticancer agents because they have been found to exert proapoptic effects on human breast cancer cells without affecting normal cells. The highly metastatic human breast cancer cell line MDA-MB-231 was exposed sequentially to docosahexaenoic acid followed by paclitaxel (Taxol) or docetaxel (Taxotere) and cell viability was measured. Docosahexaenoic acid by itself showed cytotoxic effects. Possible synergistic interactions between docosahexaenoic acid and taxanes were then assessed. Strong synergistic cytotoxic action was found between docosahexaenoic acid and both taxanes in MDA-MB-231 cells and the enhanced cytotoxic activity was found to behave in a dose-dependent manner (up to 13- and 5-fold increase in Taxol and Taxotere efficacy, respectively). Importantly, sequential exposure to docosahexaenoic acid followed by taxanes also was found to produce strong synergism in Her-2/neu (c-erbB-2)-overexpressing and taxanes-resistant SK-Br3 and BT-474 breast cancer cells. Moreover, exogenous supplementation with docosahexaenoic acid was found to significantly attenuate the expression of Her-2/neu-codified p185Her-2/neu oncoprotein (up to a 78% reduction in BT-474 cells). The authors conclude that omega-3 polyunsaturated fatty acids can be used as modulators of tumor cell chemosensitivity and that the omega-3 polyunsaturated fatty acid docosahexaenoic acid downregulates Her-2/neu oncogene expression in human breast cancer cells.
Fish Intake Is Positively Associated with Breast Cancer Incidence Rate Journal of Nutrition, November 2003
The current prospective study evaluated the association between total fish intake (as well as the fat content and preparation method of the fish) and the risk of breast cancer among postmenopausal women. The study also investigated the effect of fish intake with regard to estrogen receptor (ER) expression of breast cancer. 23,693 postmenopausal women from the Diet, Cancer and Health study were included; 424 women were diagnosed with breast cancer during the follow-up period. The overall incidence rate ratio (IRR) and 95% confidence interval (CI) per each additional 25 g of average daily intake of fish were found to be 1.13 (CI, 1.03–1.23). For fatty fish the IRR was 1.11 (CI, 0.91–1.34), for lean fish the IRR was 1.13 (CI, 0.99–1.29). When fish intake was divided by preparation method, the IRR was found to be 1.09 (CI, 0.95–1.25) for fried fish, 1.09 (CI, 0.85–1.42) for boiled fish, and 1.12 (CI, 0.93–1.34) for processed fish. The IRR for each additional 25 g of average daily intake of fish for estrogen receptor–positive (ER+) breast cancer was 1.14 (CI, 1.03–1.26) whereas it was 1.00 (CI, 0.81–1.24) for estrogen receptor–negative (ER-) breast cancer. The authors conclude that higher intakes of fish were significantly associated with higher incidence rates of ER+ breast cancer.
Dietary (n-3)/(n-6) Fatty Acid Ratio: Possible Relationship to Premenopausal but Not Postmenopausal Breast Cancer Risk in U.S. Women Journal of Nutrition, May 2003
The current case-control study investigated the association between intake of omega-3 and other fatty acids and the omega-3/omega-6 polyunsaturated fatty acid ratio and breast cancer risk. Combining the data from two related Connecticut case-control studies resulted in a study group consisting of 1119 women (565 cases and 554 controls). A food-frequency questionnaire was used to gather information on dietary intake. No significant trends for any macronutrient or fatty acid were observed in the overall study population when comparing the highest to the lowest quartile of intake. However, for the premenopausal women considered alone, consumption of the highest compared with the lowest quartile of the omega-3/omega-6 ratio was associated with a nonsignificant lower risk of breast cancer [odds ratio = 0.59, 95% confidence interval 0.29-1.19, P for trend = 0.09]. The authors conclude that these results are consistent with the hypothesis that a higher omega-3/omega-6 ratio may reduce the risk of breast cancer, especially in premenopausal women.
Fish consumption and colorectal cancer: a case-reference study in Japan European Journal of Cancer Prevention, April 2003
The current epidemiological study was designed to clarify the relationship between fish consumption and the likelihood of developing colorectal cancer. Studies have suggested that fish oil supplementation can suppress the proliferation of colorectal mucosa and thereby help prevent the development of colorectal cancer. However, evidence concerning fish consumption and colorectal cancer risk is limited and inconsistent. The authors conducted a large case-control population study with 928 cases of colon cancer, 622 cases of rectal cancer and 46,886 cancer-free outpatient controls aged 40 to 79 years. Frequent raw or cooked fish intake was found to be associated with decreased risk of colon cancer (odds ratio (OR) 0.68 with 95% confidence interval (CI) 0.47-0.99), especially for males over 60 years old, smokers, and frequent meat eaters. A marginal decrease in risk (OR 0.58, CI: 0.31-1.07) also was found for female rectal cancer, especially in the subgroup that performed regular physical exercise. However, frequent dried or salted fish intake was found to be associated with increased colorectal cancer risk in females younger than 60 years old and alcohol drinkers. The authors conclude that frequent raw or cooked fish intake may decrease the risk of colorectal cancer while dried or salted fish intake may increase it.
