1: Urology 2001 Jul;58(1):47-52 
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. 
Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, Paulson DF, Walther PJ, Gannon M, Vollmer RT. Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina, USA Objectives. Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia.Methods. Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1).Results. The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 
0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively).Conclusions. These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy. 
PMID: 11445478 [PubMed - in process] 
2: Lancet 2001 Jun 2;357(9270):1764-6 
Fatty fish consumption and risk of prostate cancer. Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Consumption of fatty fish might reduce the risk of prostate cancer, although epidemiological studies of fish consumption are rare. We studied the association between fish consumption and prostate cancer in a population-based prospective cohort of 6272 Swedish men. During 30 years of follow-up, men who ate no fish had a two-fold to three-fold higher frequency of prostate cancer than those who ate moderate or high amounts did. Our results suggest that fish consumption could be associated with decreased risk of prostate cancer. Publication Types: 
Letter 
PMID: 11403817 [PubMed - indexed for MEDLINE]
3: Prostate 2001 Jun 1;47(4):262-8 
The association of fatty acids with prostate cancer risk. Newcomer LM, King IB, Wicklund KG, Stanford JL. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. BACKGROUND: Animal studies indicate that omega-6 fatty acids promote and omega-3 fatty acids inhibit tumor development. This pilot study was designed to evaluate whether these fatty acids are associated with human prostate cancer. METHODS: Levels of erythrocyte membrane omega-3 and omega-6 fatty acids were determined for 67 incident prostate cancer cases and 156 population-based controls. RESULTS: Prostate cancer risk was increased in the highest compared to the lowest quartile of alpha-linolenic acid (OR = 2.6, 95% CI = 1.1-5.8, trend P = 0.01). Positive associations were also observed with higher levels of linoleic acid (OR = 2.1, 95% CI = 0.9-4.8) and total omega-6 fatty acids (OR = 2.3, 95% CI = 1.0-5.4). CONCLUSIONS: Results are consistent with other studies showing that linoleic and total omega-6 fatty acids increase risk of prostate cancer. Contrary to animal studies, alpha-linolenic acid was also positively associated with risk. Further research will be required to clarify the role of these fatty acids in human prostate cancer. Copyright 2001 Wiley-Liss, Inc. PMID: 11398173 [PubMed - in process] 
4: Cancer Chemother Pharmacol 2001;47(1):34-40 Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin. 
Yam D, Peled A, Shinitzky M. 
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. 
PURPOSE: The anticancer activity of omega-3 polyunsaturated fatty acids 
(omega-3 PUFA) has been shown in a large number of studies. This study was undertaken to analyze the combined effect of omega-3 PUFA and antioxidative vitamins on the level of spontaneous metastatic dissemination. The supportive effect of this dietary combination on chemotherapy with cisplatin (CP) was determined in parallel. METHODS: C57BL/6J mice bearing the Lewis lung carcinoma 3LL were fed ad libitum one of three isocaloric diets containing 5% soybean oil supplemented with 40 mg/kg alpha-tocopherol acetate (SO diet), or 4% fish oil plus 1% corn oil, and basal amounts of vitamin E (FO diet) or FO diet supplemented with vitamins E and C (FO+E+C diet). These diets were tested in combination with the conventional cytotoxic agent CP in a series of regimens. Tumor growth, feed consumption, body weight, lung metastasis and lung histology were followed. RESULTS: Both the FO dietary groups showed significantly lower tumor development than the SO group in all examined parameters, indicating that omega-3 PUFA have anticancer activity. However, the FO diet, in comparison with the FO+E+C diet induced a significantly slower rate of tumor growth, and lower metastatic load, as reflected in lung weight. The decrease in the anticancer activity of FO by the addition of vitamins E and C suggests that in situ oxidation of omega-3 PUFA underlies their anticancer action. It is thus proposed that oxidized omega-3 PUFA accumulates in the membranes and the cytosol of tumor cells, reducing their vitality and eventually leading to their death. No signs of anorexia or cachexia were observed in either FO group, in contrast to the SO group. CP treatment with the SO diet had no apparent therapeutic effect, while with the FO diets it reduced the metastatic load. The best regimen of this combined treatment was FO diet followed by CP treatment with FO diet supplemented with vitamins E and C after resection of the primary growth. This regimen could be translated to a combined therapy for human cancer. CONCLUSIONS: Diets enriched with omega-3 PUFA may have beneficial anticancer effects in particular when containing only basal amounts of antioxidants such as vitamin E or C. Furthermore, the addition of drugs which promote oxidation of omega-3 PUFA, such as ferrous salts (e.g. as prescribed for the treatment of anemia), may further increase these effects. However, the supportive effect of omega-3 PUFA in chemotherapy (e.g. with CP) increases when vitamins E and C are also included. 
PMID: 11221959 [PubMed - indexed for MEDLINE]
5: World J Surg 2000 Dec;24(12):1477-85 
Advances in perioperative nutrition: cancer. Heslin MJ, Brennan MF. Department of Surgery, University of Alabama at Birmingham, 35294, USA. marty.heslin@ccc.uab.edu 
The role of perioperative nutritional support in the management of cancer patients remains controversial. The benefit of supplemental calories is not the only current issue: in fact, the route of delivery, composition of basic nutrients (carbohydrate, protein, fat), and the role of supplemental additives (arginine, glutamine, omega-3 fatty acids, nucleotides) in improving immune status and ultimate outcome have been the focus of much discussion. Emerging data suggest that the use of supplemental agents is associated with improvement in immune status in these patients, although there is little clear evidence that this improves outcome. Ongoing studies are aimed at defining the group of patients who would most benefit from nutritional interventions during the perioperative period. 
Publication Types:
Review
Review, tutorial 
PMID: 11193711 [PubMed - indexed for MEDLINE]
6: JAMA 2001 Jan 17;285(3):304-12 
Intake of fish and omega-3 fatty acids and risk of stroke in women. Iso H, Rexrode KM, Stampfer MJ, Manson JE, Colditz GA, Speizer FE, Hennekens CH, Willett WC. 
Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave, Third Floor, Boston, MA 02215, USA. CONTEXT: Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes. OBJECTIVE: To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake. RESULTS: After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke. CONCLUSIONS: Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke. PMID: 11176840 [PubMed - indexed for MEDLINE] 
7: Breast Cancer 1997 Mar 25;4(1):7-16 Dietary Fat, Fatty Acids and Breast Cancer. Rose DP. American Health Foundation, Valhalla, NY 10595, USA. Results from some, but not all, epidemiological studies, and experimental investigations using animal models indicate that the level of fat in the diet, and more importantly the nature of the constituent fatty acids, influence both breast cancer risk and the progression of the established disease. High-fat diets rich in polyunsaturated omega-6 fatty acids stimulate mammary carcinogenesis and tumor progression; the long-chain omega-3 fatty acids present at high concentration in some fish oils exert inhibitory effects. Prominent among the biochemical mechanisms involved is the regulation of eicosanoid biosynthesis from dietary linoleic acid; both prostaglandins resulting from cyclooxygenase activity, and the leukotrienes and hydroxy-fatty acids produced under the influence of the lipoxygenases are involved in mammary carcinogenesis, tumor cell growth and apoptosis, angiogenesis, invasion and metastasis. A shift towards the typical high-fat Western diet, rich in omega-6 and poor in omega-3 fatty acids, may be a major factor in the increasing breast cancer incidence and mortality rates in Japanese women. Moreover, the results of the preclinical studies, together with supporting epidemiological data, suggest that a nutritional intervention comprising dietary omega-3 fatty acid supplementation and, in populations consuming a high fat diet a reduction in total fat and omega-6 fatty acid intake, may have a place not only in breast caner prevention, but as an adjunct to the surgical treatment of the breast cancer patient. 
PMID: 11091570 [PubMed - as supplied by publisher]
8: Curr Gastroenterol Rep 1999 Aug;1(4):341-53 
Nutritional strategies in the prevention of colorectal cancer. Mason JB, Kim Yi. 
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 0211, USA. A variety of dietary factors have been implicated as agents that can modulate the development of malignancies of the gastrointestinal tract, particularly colorectal cancer. The effects of fat, red meat, fruits, vegetables, and alcohol on colorectal carcinogenesis have been examined extensively and appear to play substantial roles. Although fiber may play a protective role, recent studies raise the question of whether the protection is conveyed by other components in fiber-laden foods. Folate, selenium, calcium, and omega-3 fatty acids have emerged as factors more recently but may be equally important agents in nutritional chemoprevention, whereas the role of antioxidant vitamins is less certain. Until more firm data are available, the dietary recommendations provided by the American Cancer Society and the National Cancer Institute are appropriate for use in counseling patients on this issue. Publication Types: 
Review
Review, tutorial 
PMID: 10980971 [PubMed - indexed for MEDLINE]
9: J Nutr Health Aging 2000;4(3):172-5 
The effects of lipids on the immune response of patients with cancer. Gogos CA, Skoutelis A, Kalfarentzos F. 
Patras University Medical School, Dpt of Medicine, Rion - Patras 26500, Patras, Greece. gogos@hellasnet.gr 
The role of diet and certain nutritional factors in the etiology or promotion of various malignant diseases has widely been studied. A link between dietary fat and cancer has long been proposed through various human epidemiologic and experimental data. High fat diets are associated with a high incidence and accelerated development of certain tumors, while there is evidence that dietary 
w-3 fatty acids have beneficial effects in cancer growth and metastasis. The relation between the different lipid formulations and cancer appears to be mainly related to the influence of specific fatty acids on the synthesis of the immunosuppressive prostaglandin E2. Omega-3 polyunsaturated fatty acids seem to have an anti-tumor effect through their immunomodulating, anti-inflammatory action and direct inhibition of tumor cell proliferation via alteration in prostaglandin E2 production. 
Publication Types:
Review
Review, tutorial 
PMID: 10936906 [PubMed - indexed for MEDLINE]
10: J Surg Res 2000 Aug;92(2):201-5 
omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells. 
Kontogiannea M, Gupta A, Ntanios F, Graham T, Jones P, Meterissian S. Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, Canada. 
BACKGROUND: Diets rich in omega-3 fatty acids have been shown to 
decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied. MATERIALS AND METHODS: CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used. Cells were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid modifications confirmed with gas chromatography. Both human umbilical vein and hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion assays were performed in a standard fashion using (51)Cr-labeled cells to tumor necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial adhesion on the surface of control and fatty acid-modified cells. RESULTS: Gas chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057 nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/- 0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl-Lewis(x) expression with omega-3 treatment. CONCLUSIONS: These data indicate that omega-3 fatty acids may also be protective against the formation of hepatic metastases. The mechanism for this may be decreased endothelial cell adhesion which in turn may be due to decreased expression of the endothelial receptor sialyl-Lewis(x). Copyright 2000 Academic Press. 
PMID: 10896822 [PubMed - indexed for MEDLINE]
11: Nutr Cancer 2000;36(2):155-62 
Fat intake and risk of squamous cell carcinoma of the skin. Hakim IA, Harris RB, Ritenbaugh C. 
Arizona Cancer Center, College of Medicine, University of Arizona, Tucson 85724, USA. ihakim@azcc.arizona.edu The varied effects of different classes of dietary fatty acids on carcinogenesis suggest that fatty acid composition is an important determining factor in tumor development. In the present study, we investigated the association between dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the skin (SCC). Data were taken from a population-based case-control study of skin SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95% confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74 (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies are clearly needed to elucidate the function of dietary fatty acids so that recommendations can be made to alter the human diet for cancer prevention, particularly in light of the increasing incidence of SCC of the skin. PMID: 10890025 [PubMed - indexed for MEDLINE] 
12: Anticancer Res 1999 Nov-Dec;19(6C):5583-6 Increased survival in brain metastatic patients treated with stereotactic radiotherapy, omega three fatty acids and bioflavonoids. Gramaglia A, Loi GF, Mongioj V, Baronzio GF. National Cancer Institute, Milan, Italy. Stereotactic radiotherapy represents a method to effectively treat brain metastases with high precision and with high doses. Few acute toxicities are associated with stereotactic radiotherapy, however delayed reactions may occur and after six months, 20% of patients can develop radionecrosis. To avoid this adverse effect, in patients with metastases localized in critical brain areas, a supplementation of Omega three fatty acids and bioflavonoids has been used. At the end of 1997, we initiated a series of retrospective studies to test the efficacy of stereotactic radiotherapy on 405 patients, and the prognostic importance on survival of various variables among which this type of supplementation. From the comparison of various survival curves with the Cox multivariate analysis, it emerged that the patients using this supplementation had a decreased risk ratio and an improvement in survival time. A decreased number of radionecrosis was noted. We suggest their use as radioprotectors. 
PMID: 10697622 [PubMed - indexed for MEDLINE]
13: Int J Vitam Nutr Res 1999 Nov;69(6):385-95 
Serum concentrations of carotenoids, alpha-tocopherol, fatty acids, and lipid peroxides among Japanese in Japan, and Japanese and Caucasians in the US. 
Ito Y, Shimizu H, Yoshimura T, Ross RK, Kabuto M, Takatsuka N, Tokui N, Suzuki K, Shinohara R. 
Department of Public Health, Fujita Health University School of Health Sciences, Ioyoake, Japan. 
Serum concentrations of carotenoids, alpha-tocopherol, fatty acids, and thiobarbituric acid-reactive substances (TBARS) were measured in 217 Japanese residents of Japan, and in 99 Japanese and 100 Caucasian residents of the US, aged from 50 y to 74 y. In females, serum values of carotenoids such as beta-carotene (BC) and zeaxanthin & lutein (ZL) were highest among Japanese in Japan, followed by Japanese in the US and Caucasians in the US. In males, these values, except for serum BC values, were also highest among Japanese in Japan. Moreover, serum values of n-3 polyunsaturated fatty acids (n-3PUFAs) such as eicosapentaenoic acid and docosahexaenoic acid were significantly higher among Japanese in Japan than among Japanese and Caucasians in the US in both sexes. In contrast, serum values of n-6 polyunsaturated fatty acids such as linoleic acid and arachidonic acid were lowest among Japanese in Japan. For women, serum levels of n-9 unsaturated fatty acids were lowest among Japanese living in Japan. Serum TBARS values were highest among Japanese in Japan, followed by Japanese in the US and Caucasians in the US. A significant positive correlation was observed between serum values of TBARS and n-3 PUFAs among Japanese both in Japan and in the US. Serum TBARS values showed a significant inverse relationship with the serum values of BC and ZL among Japanese in Japan and with those of BC among Japanese in the US. These relationships were not always observed among Caucasians in the US. The results of this study suggest that the high TBARS values among Japanese in Japan may depend in part on lipid peroxidation induced in vitro by n-3PUFAs, while high reduction of lipid peroxidation could be expected among Japanese in Japan with high antioxidants such as BC and ZL. In conclusion, serum levels of nonprovitamin A carotenoids such as ZL may be a useful intake marker of vegetables. Dietary intakes of dark green vegetables and fish rich in n-3PUFAs might be more important in the prevention of some sites of cancer and of ischemic heart disease. 
PMID: 10642896 [PubMed - indexed for MEDLINE]
14: Carcinogenesis 1999 Dec;20(12):2209-18 
Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Bartsch H, Nair J, Owen RW. 
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. h.bartsch@dkfz-heidelberg.de 
The hypothesis that a high-fat diet promotes the development of postmenopausal breast cancer is supported by international data showing a strong correlation between fat intake and breast cancer rates and a modest positive association with high-fat diet in case-control studies. Dietary fat intake was found to be unrelated to the risk of breast cancer in cohort studies. In view of these conflicting findings it has been difficult to make nutritional recommendations for the prevention of breast cancer. Studies in animal models and recent observations in humans, however, have provided evidence that a high intake of omega-polyunsaturated fatty acids (PUFAs), stimulates several stages in the development of mammary and colon cancer, from an increase in oxidative DNA damage to effects on cell proliferation, free estrogen levels to hormonal catabolism. In contrast, fish oil-derived omega-3 fatty acids seem to prevent cancer by influencing the activity of enzymes and proteins related to intracellular signalling and, ultimately, cell proliferation. In this commentary, current evidence from experimental and human studies is summarized that implicates a high intake of omega-6 PUFAs in cancer of the breast, colon and, possibly, prostate and which indicates that omega-3 PUFAs and monounsaturated fatty acids such as oleic acid (omega-9) are protective. Plausible mechanisms for modulation of steps in the multistage carcinogenesis process by fats are discussed. Properly designed epidemiological studies are now needed, that integrate relevant biomarkers to unravel the contributions of different types of fat, their interactions with hormonal catabolism, protective nutritional factors and human cancer risk. 
Publication Types:
Review
Review, tutorial 
PMID: 10590211 [PubMed - indexed for MEDLINE]
15: Eur J Cancer Prev 1999 Jul;8(3):213-21 
Possible beneficial effect of fish and fish n-3 polyunsaturated fatty acids in breast and colorectal cancer. 
de Deckere EA. 
Unilever Nutrition Centre, Unilever Research Vlaardingen, The Netherlands. 
Breast and colorectal cancer are main causes of death in industrialized countries. In these cancers dietary factors appear to play beneficial or adverse roles. One of the possible beneficial factors may be fish intake or the n-3 polyunsaturated fatty acids from fish, as found in epidemiological and clinical studies. In population studies, high intake of fish during many years is associated with reduced risks of breast and colorectal cancer. Prospective and case-control studies either do not show an association between fish intake and cancer risks or show reduced risks at high fish intakes. In these studies, fish consumption may have been too low or may not reflect fish consumption over a longer period. In population, case-control, and prospective studies, fish and fish n-3 polyunsaturated fatty acids were not found to increase cancer risks. Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk. In several studies in which the effect of fish consumption on cancer risk was investigated, meat and meat products were positively related to cancer risk, suggesting that cancer risks might be reduced more effectively when meat and meat products in meals are replaced by fish. In conclusion, the existing knowledge suggests that an increase in the consumption of fish and fish n-3 polyunsaturated fatty acids in industrialized countries may contribute to lower breast and colorectal cancer risks. Publication Types: 
Review
Review literature 
PMID: 10443950 [PubMed - indexed for MEDLINE]
16: Proc Nutr Soc 1998 Nov;57(4):543-50 
The effects of dietary lipids on gene expression and apoptosis. Fernandes G, Troyer DA, Jolly CA. 
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7874, USA. fernandes@uthscsa.edu The beneficial effects of dietary FO with respect to autoimmune disease, CVD and some types of cancer are well established. Studies conducted over the last 10-15 years have established the potent effects of FO on gene expression in the previously mentioned diseases. The effects of dietary FO appear to be selective in nature, with the expression of individual genes simultaneously being increased, decreased or completely unaffected. In order to elucidate the molecular mechanism(s) involved, recent studies have focused on analysing the effects of the long-chain polyunsaturated n-3 fatty acids EPA and DHA which are highly enriched in FO and thought to be the primary mediators of its biological activity. Indeed, it has been found that EPA and DHA appear to both directly and indirectly modulate gene expression in vivo, depending on the gene examined. The direct effects of EPA and DHA are most probably mediated by their ability to bind to positive and/or negative regulatory transcription factors, while the indirect effects appear to be mediated through alterations in the generation of intracellular lipid second messengers (e.g. diacylglycerol and ceramide). Future studies need to be focused on further elucidation of the inter- and intracellular signalling events mediated by dietary n-3 fatty acids. Understanding the molecular mechanism(s) modified by dietary FO will ultimately lead to improved dietary strategies to aid in the prevention of autoimmune disease, CVD and/or certain types of cancer. Publication Types: Review 
Review, tutorial 
PMID: 10096114 [PubMed - indexed for MEDLINE]
17: Clin Tech Small Anim Pract 1998 Nov;13(4):224-31 
Interventional nutrition for the cancer patient. Ogilvie GK. College of Veterinary Medicine and Biomedical Sciences, Department of Clinical Sciences, Veterinary Teaching Hospital, Colorado State University, Ft. Collins 80523, USA. 
Dogs and cats with cancer have significant alterations in carbohydrate, protein, and fat metabolism, which can result in cancer cachexia and subsequently can decrease quality of life, reduce response to therapy, and shorten survival time. Nutritional modulation may be beneficial in the treatment of cancer patients to reverse these metabolic alterations. There is evidence that foods relatively low in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat (especially fats of the omega-3 fatty acid series) are beneficial for pets with cancer. In addition, certain supplemental nutrients may have potential to reduce the risk of developing cancer, or the growth and metastases of established malignant disease. Nutritional intervention can be a powerful tool for controlling malignant disease and for reducing toxicity associated with chemotherapy and radiation therapy. Publication Types: 
Review
Review, tutorial 
PMID: 9842115 [PubMed - indexed for MEDLINE]
18: Proc Soc Exp Biol Med 1997 Nov;216(2):224-33 
Dietary fatty acids and prevention of hormone-responsive cancer. Rose DP. 
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, New York 10595, USA. 
The results from some, but not all, epidemiological studies indicate that the level of dietary fat intake and the nature of the constituent fatty acids influence both breast and prostate cancer risk, and disease progression. These observations derive support from the use of animal models, which demonstrate that polyunsaturated omega-6 fatty acids stimulate mammary carcinogenesis and tumor growth and metastasis, whereas long-chain omega-3 fatty acids exhibit inhibitory effects. While studies of prostate cancer are less advanced, the available data are in agreement with those designed to evaluate the associations between breast cancer and dietary fatty acids. In both cases, a multiplicity of biological actions of eicosanoids derived from tumor cell arachidonate metabolism appear to elicit responses, both in the tumor itself and in the host cells that subscribe to its microenvironment. This review concludes that clinical intervention trials designed to reduce total fat intake and increase the ratio of omega-3 to omega-6 fatty acids in the diet should be targeted at groups at a relatively high risk for breast or prostate cancer, and also at postsurgically treated cancer patients with the objective of preventing disease recurrence. Publication Types: Review 
Review, tutorial 
PMID: 9349691 [PubMed - indexed for MEDLINE]
19: JAMA 1998 Jan 7;279(1):23-8 
Comment in:
 JAMA. 1998 Jan 7;279(1):65-6 
Fish consumption and risk of sudden cardiac death. Albert CM, Hennekens CH, O'Donnell CJ, Ajani UA, Carey VJ, Willett WC, Ruskin JN, Manson JE. Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA. 
CONTEXT: Dietary fish intake has been associated with a reduced risk of 
fatal cardiac end points, but not with nonfatal end points. Dietary fish intake may have a selective benefit on fatal arrhythmias and therefore sudden cardiac death. OBJECTIVE: To investigate prospectively the association between fish consumption and the risk of sudden cardiac death. DESIGN: Prospective cohort study. SETTING: The US Physicians' Health Study. PATIENTS: A total of 20 551 US male physicians 40 to 84 years of age and free of myocardial infarction, cerebrovascular disease, and cancer at baseline who completed an abbreviated, semiquantitative food frequency questionnaire on fish consumption and were then followed up to 11 years. MAIN OUTCOME MEASURE: Incidence of sudden cardiac death (death within 1 hour of symptom onset) as ascertained by hospital records and reports of next of kin. RESULTS: There were 133 sudden deaths over the course of the study. After controlling for age, randomized aspirin and beta carotene assignment, and coronary risk factors, dietary fish intake was associated with a reduced risk of sudden death, with an apparent threshold effect at a consumption level of 1 fish meal per week (P for trend=.03). For men who consumed fish at least once per week, the multivariate relative risk of sudden death was 0.48 (95% confidence interval, 0.24-0.96; P=.04) compared with men who consumed fish less than monthly. Estimated dietary n-3 fatty acid intake from seafood also was associated with a reduced risk of sudden death but without a significant trend across increasing categories of intake. Neither dietary fish consumption nor n-3 fatty acid intake was associated with a reduced risk of total myocardial infarction, nonsudden cardiac death, or total cardiovascular mortality. However, fish consumption was associated with a significantly reduced risk of total mortality. CONCLUSION: These prospective data suggest that consumption of fish at least once per week may reduce the risk of sudden cardiac death in men. 
PMID: 9424039 [PubMed - indexed for MEDLINE]
20: Support Care Cancer 1997 Sep;5(5):381-6
Immuno-nutrition: designer diets in cancer. 
Imoberdorf R. 
Klinik B fur Innere Medizin, Kantonsspital, St. Gallen, Switzerland. Weight loss, associated with advanced stage of neoplastic disease, is negatively correlated with survival in cancer patients. Alterations in substrate metabolism contribute to the impaired nutritional status. Energy expenditure, assessed by indirect calorimetry, seems to be very variable. Hypermetabolism may occur frequently, but the increase in energy expenditure rarely exceeds 10-15%. Another hallmark of cancer is depression of both cellular and humoral immune functions. Glutamine, the most abundant amino acid in the body, is an important substrate for rapidly proliferating cells and tissues. Arginine has been shown to stimulate the immune system, to enhance wound healing and to decrease the rate of tumour growth. Dietary supplementation with omega-3 fatty acids shifts the production of prostaglandins from the dienoic to the trienoic variety, which is much less immunosuppressive. Finally, administration of oligonucleotides improved survival to a challenge with Candida albicans. The needs for nutritional support in cancer patients should be considered from at least two perspectives: curative versus palliative treatment. Several prospective, randomized, double-blind studies in cancer patients undergoing major upper gastrointestinal surgery demonstrated significant improvements in postoperative immunological responses, a reduction in the frequency of infections and wound complications and in the length of hospital stay in the group receiving a diet enriched with arginine, RNA and omega-3 fatty acids. However, the impact on mortality remains to be established. In palliative situations, no clinical data documenting beneficial effects of long-term nutritional support with designer diets have been published, probably as a consequence of persisting concern about promoting tumour growth. Moreover, because of the heterogeneity of this patient population such studies are difficult to perform. Finally, nutritional intervention for patients with terminal cancer remains highly controversial. The basis for improvements in nutritional support is a better understanding of the metabolism of cancer patients, especially in patients with advanced disease. Publication Types: Review 
Review, tutorial 
PMID: 9322350 [PubMed - indexed for MEDLINE]
21: S Afr Med J 1997 Feb;87(2):152-8 
Dietary factors associated with a low risk of colon cancer in coloured west coast fishermen. 
Schloss I, Kidd MS, Tichelaar HY, Young GO, O'Keefe SJ. Gastro-intestinal Clinic, University of Cape Town. OBJECTIVE: To examine the relative roles of dietary fibre, anti-oxidant vitamins and fish oils in the relatively low incidence of colon cancer in coloured West Coast fishermen. DESIGN: Dietary intake survey, based on food frequency questionnaire and household surveys. Blood sampling for vitamin and fatty acid concentrations. SETTING: Isolated West Coast fishing villages (sample population) and urban Cape Town inhabitants (controls). PARTICIPANTS: 101 male and female West Coast fishermen over the age of 40 years, and 99 age- and sex-matched urban whites. OUTCOME MEASURES: Dietary analysis by 'Foodfinder' technique, and nutrient blood levels. Statistical analysis using SASR program version 6. RESULTS: An analysis of the number of recorded cases of colorectal cancer over a period of 5 years leading up to the study confirmed a lower rate of colorectal cancer in the West Coast fishermen than in the Cape Town population: fishermen 6 cases/120000, urban whites 677/2 million. A significantly higher proportion of fishermen were smokers, had hypertension and gave a history of previous tuberculosis infections. Vitamin supplementation was noted in one-third of whites but in no fishermen. The results of the dietary analysis (mean (SD)) demonstrated that fishermen consumed less fibre (9.9 (4.7) g/d v. 17.4 (7.2) g/d; P < 
0.01) and less fruit and vegetables (190 g/d v. 365 g/d; P < 0.001), with a lower intake of vitamin C, thiamin, riboflavin, vitamin B6 and folate. Sodium intake was higher in fishermen, whereas intakes of potassium, magnesium, calcium, iron, zinc and copper were lower. In addition, the daily intake of omega-3 fatty acids (fish oils), docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) in the West Coast population was considerably higher (0.71 (0.51) g/d v. 0.14 (0.09) g/d; P < 0.0001 and 0.37 (0.3) g/d v. 0.05 (0.05) g/d; P < 0.0001, respectively) than in the urban population owing to their higher intake of fish (110 g v. 30 g/d; P < 0.001). Plasma fatty acids correlated positively with these dietary intake figures, showing fishermen to have higher levels of circulating omega-3 fatty acids, C20:5 (3.9 (1.8)% v. 0.66 (0.29)%; P < 0.001) and C22:6 (5.6 (1.8) v. 2.9 (0.08)%; P < 0.001) and lower levels of omega-6 fatty acids, C18:2 and C20:3 (29.7 (4.7)% v. 33.5 (5.6)%; P < 0.05 and 0.85 (0.48)% v. 1.5 (0.47)%; P < 0.001, respectively) compared with the urban group. CONCLUSION: The low incidence of colorectal carcinoma in West Coast fishermen might be explained by the protective effects of fish (omega-3) oils, but not by other "protective' dietary items such as fibre, anti-oxidant vitamins or calcium. The high incidence of hypertension may be related to a higher sodium intake, accompanying high consumption of salted fish, or to the higher prevalence of tobacco smoking. PMID: 9107220 [PubMed - indexed for MEDLINE] 
22: Cancer Epidemiol Biomarkers Prev 1996 Nov;5(11):889-95 Comment in: 
  Cancer Epidemiol Biomarkers Prev. 1996 Nov;5(11):859-600 Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma. 
Godley PA, Campbell MK, Gallagher P, Martinson FE, Mohler JL, Sandler RS. 
Department of Internal Medicine, University of North Carolina at Chapel Hill 27599, USA. 
Animal studies have suggested that omega-6 fatty acids found in vegetable oils may promote prostate cancer. Our goal was to use erythrocyte membrane and adipose tissue fatty acid composition as biomarkers to investigate whether essential fatty acids modulated prostate cancer risk. An outpatient clinic-based study of 89 cases and 38 controls was conducted in North Carolina between July 1989 and December 1991. Cases were recruited from a university-based urology outpatient clinic. Eligible cases were more than 45 years of age and had histological confirmation of a prostate cancer diagnosis within 1 year of entry into the study. Controls were histologically confirmed free of prostate cancer. Erythrocyte membranes from venous blood and adipose tissue fatty acids from s.c. fat samples were analyzed in batches using capillary gas chromatography. Unconditional logistic regression analysis was used to calculate odds ratios for the association of each fatty acid with prostate cancer while controlling for potential confounders. Linoleic acid consumption was positively associated with prostate cancer risk. The odds ratios comparing the first and fourth quartiles of linoleic acid consumption were 3.54 (95% confidence interval, 1.0-12.53) with P trend < 0.04 for erythrocyte membranes, and 2.47 (95% confidence interval, 
0.66-9.26) with P trend < 0.08 for adipose tissue. These data suggest that linoleic acid consumption may increase prostate cancer risk, which is consistent with results from animal experiments. Linoleic acid is found in vegetable oils used in cooking and in cereals, snack foods, and baked goods. Our data failed to demonstrate consistently a protective effect of marine omega-3 fatty acids on prostate cancer. PMID: 8922296 [PubMed - indexed for MEDLINE] 
23: Nutrition 1996 Jan;12(1 Suppl):S39-42 Dietary omega-3 polyunsaturated fats and breast cancer. Cave WT Jr. Endocrine Unit, University of Rochester School of Medicine, New York, USA. 
Although early experimental investigations concluded that quantitative increases in dietary fat promote mammary tumor growth, recent studies have indicated that not all fatty acid families equally express this tumor-promoting capability. This article provides an overview of some of the experimental evidence demonstrating that the omega-6 polyunsaturated fats have significantly different mammary tumor-promoting capabilities from those of the omega-3 polyunsaturated fats. Collectively, these data indicate that whereas increasing dietary levels of omega-6 polyunsaturated fatty acids enhances tumor development, equivalent increases in dietary levels of omega-3 polyunsaturated fatty acids delay or reduce tumor development. Some of the theoretical mechanisms proposed for these contrasting results and their supporting experimental data are discussed. 
Publication Types:
Review
Review, tutorial 
PMID: 8850219 [PubMed - indexed for MEDLINE]
24: Prostaglandins Leukot Essent Fatty Acids 1995 Oct;53(4):273-7 
Erratum in: 
  Prostaglandins Leukot Essent Fatty Acids 2001 Jan;64(1):74. Evnard AR [corrected to Eynard AR] 
Effects of dietary n-3, n-6 and n-9 polyunsaturated fatty acids on benzo(a)pyrene-induced forestomach tumorigenesis in C57BL6J mice. Silva RA, Munoz SE, Guzman CA, Eynard AR. Catedra de Histologia, Instituto de Biologia Celular (FCM), Universidad Nacional de Cordoba-CONICET, Argentina. 
The modulating effect of dietary polyunsaturated fatty acids (PUFAs) on benzo(a)pyrene-induced forestomach tumorigenesis was assayed in mice fed with corn oil (CO), olein (O), Zizyphus mistol seed oil (MO), cod liver oil (CLO), and mixed fat (Stock diet). The fatty acid composition of liver lipids correlated well with the fatty acid composition of each diet. Only mice fed the O diet showed biochemical and clinical evidences of essential fatty acid deficiency (EFAD). Only 3 animals developed well-differentiated invading squamous cell carcinomas in the O group. The papilloma incidence was reduced in MO and CLO with respect to the O group. Forestomach papillomatosis was increased in mice fed an n-9 enriched diet in comparison to stock and CO groups. In comparison with stock mice, the frequency of multiple epidermoidal hyperplasia (MEH) was significantly decreased in the CLO group. Animals fed n-3 enriched diets (MO and CLO) showed significant antipromoting effect. These findings indicate that dietary fat can modulate tumorigenesis initiated in mouse forestomach by benzo(a)pyrene. In addition, the lack of action of an n-6 fatty acid-enriched diet in our experimental model suggests that the effect of PUFAs on tumorigenesis has target-tissue specificity. Mistol seed oil might be of potential value as a natural vegetable antipromoter nutrient. 
PMID: 8577781 [PubMed - indexed for MEDLINE]
25: Clin Immunol Immunopathol 1994 Aug;72(2):193-7 
Dietary lipids and risk of autoimmune disease. Fernandes G. Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7874. 
In summary, it is well established that moderate calorie restriction or reduction in overall high calorie food intake prevents or forestalls the development of age-associated disease incidence such as breast cancer and renal disease in rodents. A similar approach could also readily be applied in humans for preventing the risk and rise of life-shortening diseases. Many age-associated diseases, particularly autoimmune diseases with viral etiology, appear to be exacerbated in the presence of adverse lipid intake such as an increased level of vegetable oils or trans-fatty acids from the usage of hydrogenated dietary oils. At present, nearly 35-40% of the total calories are from dietary fats and/or of lipid origin. Although usage of saturated fat, which increases cardiovascular disease, has been reduced to a large extent in the United States, consumption of both monounsaturated and polyunsaturated fats of omega-6 origin has either increased or simply been substituted in place of saturated fats. Further, for the past 50 years, a significant reduction in highly polyunsaturated fat consumption such as marine oil has also occurred specifically in the United States. The reduction in omega-3 lipids of marine or vegetable source occurs primarily because of short shelf life due to rancidity. However, the increased consumption of omega-6 or a vegetable source of oils and decreased omega-3 intake may increase in vivo the production of free radicals and higher proinflammatory cytokines. Our ongoing studies reveal that proinflammatory vegetable oil could increase autoimmune disease by increasing the free radical formation by decreasing the antioxidant enzyme mRNA levels, thereby further decreasing immune function, particularly the production of anti-inflammatory cytokines such as IL-2 and TGF beta mRNA levels. In contrast, omega-3 lipid intake in the presence of an antioxidant supplement appears to exert protection against autoimmunity by enhancing antioxidant enzymes and TGF beta mRNA levels and by preventing the rise in oncogene expression. However, detailed studies are required to establish the protective and deleterious role of different commonly consumed lipids or dietary oils by the general population, particularly during middle and aging years. Further, we also propose that combining nonsteroidal drug therapy along with moderate calorie reduction in the presence of more protective omega-3 dietary lipids of either marine or vegetable source and decreasing the levels of mono- and polyunsaturated lipids may provide additional protection against the age-associated rise in malignancy and autoimmune disorders. 
Publication Types:
Review
Review, tutorial 
PMID: 8050192 [PubMed - indexed for MEDLINE]
26: Arch Surg 1993 Nov;128(11):1242-5 
Immunoenhancement via enteral nutrition. Alexander JW. Department of Surgery, College of Medicine, University of Cincinnati, Ohio. 
Arginine, glutamine, the long chain polyunsaturated omega-3 and omega-6 fatty acids, and, to a lesser extent, ribonucleic acid and the vitamins E, C, and A have pharmacologic effects when given in amounts in excess of what is needed to prevent nutritional deficiency. These effects are exerted primarily via the immune system, and immunoenhancing diets that embody the recently developed principles of nutritional pharmacology have been shown to reduce infectious complications by approximately 75% in surgical patients and hospital stay by more than 20% in surgical patients and patients in the intensive care unit in three independent, prospective, randomized studies, two of which were double-blinded. These findings suggest that specialized diets can be designed that will be of benefit to patients with cancer, atherosclerosis, intestinal diseases, autoimmune diseases, infections, and trauma. However, the interaction of these nutrients in pharmacologic amounts with standard pharmacologic drugs is largely unknown, as are the effects of long-term administration of specialized diets to treat these conditions. Publication Types: Review 
Review, tutorial 
PMID: 7694565 [PubMed - indexed for MEDLINE]
27: Ann Epidemiol 1993 May;3(3):235-8 
Diet and melanoma. An exploratory case-control study. Bain C, Green A, Siskind V, Alexander J, Harvey P. Department of Social and Preventive Medicine, University of Queensland Medical School, Australia. This population-based case-control study contrasted nutrient intakes of 41 women with cutaneous malignant melanoma to those of 297 women sampled from the same community (Brisbane, Australia). Diet was assessed by a comprehensive food frequency questionnaire. The strong inverse relation we observed between high intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient weight to prior findings for this persisting causal hypothesis to be abandoned. A relatively strong association with alcohol was observed: Women drinking 20 g or more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are inconsistent. With regard to potential protective factors, our data fit with prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in risk seen for those eating the most fish (> or = 15 g daily versus < 5 g) suggests the effects of marine oils and omega-3 fatty acids may deserve specific attention. PMID: 8275194 [PubMed - indexed for MEDLINE] 
28: Crit Care Nurs Clin North Am 1993 Mar;5(1):107-20 The immunologic role of the gastrointestinal tract. Phillips MC, Olson LR. During the past few decades, researchers have shed new light on the role of nutritional support in the immunocompromised critically ill patient. "Nutritional pharmacology" has become the catch phrase of the 1990s due to the impact of selected nutrients on host immune defenses. When feasible, enteral nutrition is preferred to parenteral nutrition to preserve the integrity of the gut mucosal barrier, especially when administered jejunally in the early stages of hypermetabolism. Glutamine and fiber provide necessary fuels for the gastrointestinal tract, whereas arginine and omega-3 fatty acids exert beneficial effects on certain cells of the immune system. Daly et al demonstrated that "enteral nutrition with supplemental arginine, RNA nucleotides and omega-3 fatty acids (Impact, Sandoz Nutrition, Minneapolis, MN) compared with a standard enteral diet, significantly improved immune, metabolic and clinical outcomes (22% mean reduction in length of stay) in UGI cancer patients undergoing surgery." Although more research is needed in the area of nutritional pharmacology, newly available nutrient-specific enteral products (Table 1) provide promise for altering the clinical outcome of immunocompromised patients. 
PMID: 8447988 [PubMed - indexed for MEDLINE]
29: Photochem Photobiol 1992 Aug;56(2):195-9 
Influence of dietary omega-6, -3 fatty acid sources on the initiation and promotion stages of photocarcinogenesis. Black HS, Thornby JI, Gerguis J, Lenger W. Veterans Affairs Medical Center, Houston, TX. To determine the segment along the carcinogenic continuum at which dietary lipid exerts its principal effect, six groups of 35 Skh-HR-1 hairless mice were placed on defined isocaloric diets containing either 0.75%, 12% corn oil or 12% menhaden oil as sources of omega-6 or omega-3 fatty acids, respectively. All animals received an 11 week course of UV-radiation from fluorescent sunlamps. Upon termination of UV, diets of some groups were crossed-over to either low fat, high fat, omega-6 or omega-3 fatty acid sources. The first tumor appeared at week 14. Life-table analysis of the tumor incidence curves and Wilcoxon tests of tumor multiplicity provided evidence that high corn oil diets significantly (P less than 0.01) enhance carcinogenic expression; that tumor enhancement by the omega-6 fatty acid source occurs during the post-initiation, or promotion, stage; that replacement with a low corn oil diet after UV-initiation will negate the exacerbating effect of high corn oil; and that an omega-3 fatty acid source inhibits UV-carcinogenesis even at high dietary levels, although not during the post-initiation stage. 
PMID: 1502263 [PubMed - indexed for MEDLINE]
30: Cancer Res 1991 Jan 15;51(2):487-91 
Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis. Reddy BS, Burill C, Rigotty J. 
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, New York 10595. 
The effect of dietary menhaden oil containing omega-3 fatty acids and corn oil rich in omega-6 fatty acids fed during the initiation and/or postinitiation stages of colon carcinogenesis was investigated in male F344 rats. At 5 weeks of age, all animals were divided into seven groups (39 rats/group) and fed the semipurified diets containing 5% corn oil (LCO), 23.5% corn oil (HCO), or 18.5% menhaden oil plus 5% corn oil (HFO). At 7 weeks of age, all animals except the vehicle (normal saline)-treated groups were given two weekly s.c. injection of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight, once weekly. Three days after the second injection of AOM, groups of animals fed LCO, LCO, HCO, HCO, HCO, HFO, or HFO diets were transferred, respectively, to LCO, HCO, LCO, HCO, HFO, HCO, or HFO and continued on these diets until termination of the experiment. All animals were necropsied 42 weeks after carcinogen treatment. Body weights of animals fed various experimental diets during the initiation and postinitiation periods were comparable. As expected, the HCO diet fed during the postinitiation period significantly increased the AOM-induced incidence and multiplicity of colon adenocarcinomas, whereas the HCO diet fed during the initiation phase of carcinogenesis had no effect. Colon tumor incidence and multiplicity were significantly reduced in groups fed the HFO diet at either initiation and/or postinitiation phases of carcinogenesis as compared with those fed the HCO diet. Whereas the precise mechanisms producing the difference between the high menhaden oil (HFO) diet as compared with high corn oil (HCO) diet remain to be elucidated, it is likely that the effect during the initiation and postinitiation phases may be due to alteration in carcinogen metabolism and to modulation of prostaglandin synthesis, respectively. PMID: 1821094 [PubMed - indexed for MEDLINE] 
31: Environ Health Perspect 1990 Jun;86:233-8 Food systems: the relationship between health and food science/technology. 
Levine AS, Labuza TP. 
Neuroendocrine Research Laboratory, VA Medical Center, Minneapolis, MN 
55417. 
Changes in our understanding of diet and health drive changes in the way foods are processed. Conversely, what is available on the shelf will have an impact on the choices consumers make, thereby affecting their health. Historical examples of industrial manipulation of the diet include fortification and enrichment of cereal grains with vitamins; increased production of unsaturated vegetable oils and margarine as substitutions for hydrogenated fat, lard, and butter; lowered cholesterol content foods; reduced sugar content foods; lower sodium foods; decreased portion sizes or caloric density in prepackaged foods for use in weight loss or maintenance; and increased calcium levels to prevent osteoporosis. However, degenerative diseases such as cancer, atherosclerosis, bone disease, arthritis, and dementia will continue to be prevalent in the future. Whether or not the food systems available on the shelf can influence all of these disease states is not clear; however, studies have indicated that nutritional factors do contribute to the development of some of these diseases. Patterns in food consumption have changed and will continue to change as recommendations such as decreased consumption of saturated fats, salt, and cholesterol continue to be made. Increased ingestion of fish and/or fish oil is one recommendation that has been suggested because of the effect of omega-3 fatty acids on platelet aggregability and circulating levels of lipids. Wildly speculating from preliminary studies, fish oil has also been recommended for disease states including arthritis, cancer, and diseases of the immune system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 2401259 [PubMed - indexed for MEDLINE] 
32: Crit Care Med 1990 Feb;18(2 Suppl):S145-8 Dietary immunomodulation: beneficial effects on oncogenesis and tumor growth. 
Lowell JA, Parnes HL, Blackburn GL. 
Nutrition Support Service, New England Deaconess Hospital, Boston, MA 
02215. 
Our understanding of the interrelationship between nutrition, immunology, oncogenesis, and tumor growth is steadily increasing. Well known are the detrimental effects of malnutrition on host defenses. New work has shown that the addition of omega-3 polyunsaturated fatty acids or the amino acid arginine to the diet may significantly enhance immune function. These dietary manipulations have been shown to inhibit tumorigenesis and cancer spread in animal models, and form the basis for exciting new work in the prevention and treatment of cancer in humans. Publication Types: 
Review
Review, academic 
PMID: 2404668 [PubMed - indexed for MEDLINE]