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Diet and the Risk of Prostate Cancer & Heart Disease
  "Dietary intake of n--3 and n--6 fatty acids and the risk of prostate cancer"
American Journal of Clinical Nutrition, Vol. 80, No. 1, 204-216, July 2004
Michael F Leitzmann, Meir J Stampfer, Dominique S Michaud, Katarina Augustsson, Graham C Colditz, Walter C Willett and Edward L Giovannucci
1 From the Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD (MFL and DSM); the Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston (MJS, WCW, and ELG); the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston (MJS, GCC, WCW, and ELG); and the Department of Medical Epidemiology, Karolinska Institutet, Stockholm (KA)
2 Supported by research grants CA055075 and HL035464 from the National Institutes of Health (to WCW) and Cancer Epidemiology Training Grant 5T32 CA09001-26 (to MFL) from the National Cancer Institute.
AUTHOR DISCUSSION: "...our results suggest that a high ALA intake is associated with an increased risk of advanced prostate cancer. In contrast, high EPA and DHA intakes may be associated with a decreased risk of total and advanced prostate cancer. Because the apparent adverse effect of ALA on risk of advanced prostate cancer may counter the reduction in cardiovascular disease that may be achieved through ALA use (73), further research in men is imperative to resolve the relation of ALA to prostate cancer and to determine the risk-benefit tradeoffs associated with dietary intake of ALA...
...Fatty acids may modulate prostate carcinogenesis through numerous processes, such as modification of membrane phospholipid composition, alteration of cell signaling and receptor activity, lipid peroxidation, cyclooxygenase inhibition, cytokine production, and interference with androgen activity. Experimental studies show that prostate tumor growth is inhibited by EPA and DHA. In contrast, ALA shows no protective effect on prostate tumor growth in animal models, and ALA can promote prostate cancer cell growth in vitro. Thus, laboratory studies of prostate carcinogenesis comparing the effects of ALA with those of EPA and DHA provide no evidence in support of a protective influence of ALA in its own right...
...In this large prospective study, we found that ALA from nonanimal sources and ALA from meat and dairy sources were associated or suggestively associated with an increased risk of advanced prostate cancer...
...In contrast, 3 case-control studies, all of which examined advanced prostate cancer outcomes separately, observed no association between ALA intake and prostate cancer...
...Fish-oil supplement use showed no relation with risk of prostate cancer. Compared with nonusers of fish-oil supplements, the multivariate RRs of total, organ-confined, and advanced prostate cancer for men at a dose of >=2.5 g supplemental fish oil/d were 0.89, 0.81, and 0.91, respectively...
...We were unable to identify individual foods responsible for an increased risk of advanced prostate cancer, although suggestive positive relations were observed for intakes of beef, pork, or lamb as a main dish and for mayonnaise or other creamy salad dressings. The most likely explanations for these findings are that most foods contribute only a fraction to overall ALA intake and that overall ALA intake rather than intake of any particular food item may be the main determinant of risk...
...The increased risk of advanced prostate cancer with ALA observed in the current study was within the range of adequate intake of 2.2 g/d, or 1% of energy, for adults recommended by the International Society for the Study of Fatty Acids and Lipids. The significance of a potentially adverse effect of ALA intake on prostate cancer risk is accentuated by a 40% increased availability of ALA as a proportion of total energy intake in recent decades in the United States...
...A high intake of EPA + DHA was associated or suggestively associated with a decreased risk of total and advanced prostate cancer. This finding is largely consistent with the findings of a recent analysis of fish consumption from our cohort, another prospective study, and 6 case-control studies that found decreased prostate cancer risk associated with high intakes of fish or marine n--3 fatty acids, all but one of which were statistically significant. However, the results of 9 prospective studies and 4 case-control studies argue against a relation between marine fatty acids or fish and prostate cancer; one cohort study reported a borderline statistically significant increased risk with greater fish intake. Our results for fish-oil supplement use were weaker than those for EPA + DHA from diet and supplements combined, which suggests that fish may contain additional protective agents not contained in fish-oil supplements, such as vitamin D and retinol..."
A Prospective Study of Intake of Fish and Marine Fatty Acids and Prostate Cancer
Cancer Epidemiology Biomarkers & Prevention Vol. 12, January 2003
Katarina Augustsson2, Dominique S. Michaud, Eric B. Rimm, Michael F. Leitzmann, Meir J. Stampfer, Walter C. Willett and Edward Giovannucci
Departments of Nutrition [K. A., D. S. M., E. B. R., M. F. L., M. J. S., W. C. W., E. G.] and Epidemiology [E. B. R., M. J. S., W. C. W., E. G.], Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital [E. B. R., M. J. S., W. C. W.], Boston, Massachusetts; Department of Medical Epidemiology, Karolinska Institutet, SE-171 77 Stockholm, Sweden [K. A.]; and Nutritional Epidemiology Branch, National Cancer Institute, Bethesda, Maryland [D. S. M., M. F. L.]
Experimental studies suggest that marine fatty acids have an antitumor effect on prostate tumor cells. The aim of this study was to investigate whether high consumption of fish and marine fatty acids reduces the risk of prostate cancer in humans. We followed 47,882 men participating in the Health Professionals Follow-up Study. Dietary intake was assessed in 1986, 1990, and 1994, using a validated food frequency questionnaire. During 12 years of follow-up, 2,482 cases of prostate cancer were diagnosed, of which 617 were diagnosed as advanced prostate cancer including 278 metastatic prostate cancers. Eating fish more than three times per week was associated with a reduced risk of prostate cancer, and the strongest association was for metastatic cancer (multivariate relative risk, 0.56; 95% confidence interval, 0.37--0.86, compared with infrequent consumption, i.e., less than twice per month). Intake of marine fatty acids from food showed a similar but weaker association. Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer. We found that men with high consumption of fish had a lower risk of prostate cancer, especially for metastatic cancer. Marine fatty acids may account for part of the effect, but other factors in fish may also play a role.
Consumption of (n-3) Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Activation in Women
The American Society for Nutritional Sciences J. Nutr. 134, July 2004
Esther Lopez-Garcia*,2, Matthias B. Schulze*, JoAnn E. Manson{dagger},{dagger}{dagger},{ddagger}{ddagger}, James B. Meigs**, Christine M. Albert{ddagger},{ddagger}{ddagger}, Nader Rifai§, Walter C. Willett*,{dagger} and Frank B. Hu*,{dagger},{dagger}{dagger}
Departments of Nutrition and {dagger} Epidemiology, Harvard School of Public Health; Department of Medicine, Harvard Medical School ** General Medicine Division and {ddagger} Cardiology Division, Massachusetts General Hospital and Harvard Medical School; {dagger}{dagger} The Channing Laboratory and {ddagger}{ddagger} Division of Preventive Medicine, Harvard Medical School; and § Department of Laboratory Medicine, Children's Hospital and Department of Pathology, Harvard Medical School
We evaluated the hypothesis that intake of (n-3) fatty acids is inversely associated with biomarkers of inflammation and endothelial activation. We conducted a cross-sectional study of 727 women from the Nurses' Health Study I cohort, aged 43--69 y, apparently healthy at time of a blood draw in 1990. Dietary intake was assessed by a validated FFQ in 1986 and 1990. C-reactive protein (CRP) levels were 29% lower among those in the highest quintile of total (n-3) fatty acids, compared with the lowest quintile; interleukin-6 (IL-6) levels were 23% lower, E-selectin levels 10% lower, soluble intracellular adhesion molecule (sICAM-1) levels 7% lower, and soluble vascular adhesion molecule (sVCAM-1) levels 8% lower. The intake of {alpha}-linolenic acid was inversely related to plasma concentrations of CRP (ß = --0.55, P = 0.02), Il-6 (ß = --0.36, P = 0.01), and E-selectin (ß = --0.24, P = 0.008) after controlling for age, BMI, physical activity, smoking status, alcohol consumption, and intake of linoleic acid (n-6) and saturated fat. Long-chain (n-3) fatty acids (eicosapentaenoic and docosahexaenoic) were inversely related to sICAM-1 (ß = --0.11, P = 0.03) and sVCAM-1 (ß = --0.17, P = 0.003). Total (n-3) fatty acids had an inverse relation with CRP (ß = --0.44, P = 0.007), IL-6 (ß = --0.26, P = 0.009), E-selectin (ß = --0.17, P = 0.004), sICAM-1 (ß = --0.07, P = 0.02), and sVCAM-1 (ß = --0.10, P = 0.004). These associations were not modified by intake of vitamin E, dietary fiber, trans fatty acids, or by the use of postmenopausal hormone therapy. In conclusion, this study suggests that dietary (n-3) fatty acids are associated with levels of these biomarkers reflecting lower levels of inflammation and endothelial activation, which might explain in part the effect of these fatty acids in preventing cardiovascular disease.
ABSTRACT from "Dietary intake of n--3 and n--6 fatty acids and the risk of prostate cancer"
Background: Laboratory studies have shown that n--3 fatty acids inhibit and n--6 fatty acids stimulate prostate tumor growth, but whether the dietary intake of these fatty acids affects prostate cancer risk in humans remains unclear.
Objective: We prospectively evaluated the association between intakes of {alpha}-linolenic (ALA; 18:3n--3), eicosapentaenoic (EPA; 20:5n--3), docosahexaenoic (DHA; 22:6n--3), linoleic (LA; 18:2n--6), and arachidonic (AA; 20:4n--6) acids and prostate cancer risk.
Design: A cohort of 47 866 US men aged 40--75 y with no cancer history in 1986 was followed for 14 y.
Results: During follow-up, 2965 new cases of total prostate cancer were ascertained, 448 of which were advanced prostate cancer. ALA intake was unrelated to the risk of total prostate cancer. In contrast, the multivariate relative risks (RRs) of advanced prostate cancer from comparisons of extreme quintiles of ALA from nonanimal sources and ALA from meat and dairy sources were 2.02 (95% CI: 1.35, 3.03) and 1.53 (0.88, 2.66), respectively. EPA and DHA intakes were related to lower prostate cancer risk. The multivariate RRs of total and advanced prostate cancer from comparisons of extreme quintiles of the combination of EPA and DHA were 0.89 (0.77, 1.04) and 0.74 (0.49, 1.08), respectively. LA and AA intakes were unrelated to the risk of prostate cancer. The multivariate RR of advanced prostate cancer from a comparison of extreme quintiles of the ratio of LA to ALA was 0.62 (0.45, 0.86).
Conclusions: Increased dietary intakes of ALA may increase the risk of advanced prostate cancer. In contrast, EPA and DHA intakes may reduce the risk of total and advanced prostate cancer.
Dietary fat has been one of the most frequently investigated modifiable risk factors for prostate cancer, yet findings from epidemiologic investigations of total fat intake are inconclusive. In recent years, interest has turned to the intake of specific fatty acids rather than to total fat intake, notably n--3 and n--6 fatty acids, and their ratios. {alpha}-Linolenic acid (ALA; 18:3n--3) is the principal dietary n--3 fatty acid in most Western diets; it is present in some vegetable oils and nuts, leafy vegetables, and animal fats. ALA can serve in a limited capacity as a precursor for eicosapentaenoic acid (EPA; 20:5n--3) and docosahexaenoic acid (DHA; 22:6n--3). The concentrations of EPA and DHA are high in fish oils and they consistently inhibit tumor cell growth in animal models and in cell lines from human prostate tumors. Linoleic acid (LA; 18:2n--6) is the most abundant n--6 fatty acid in the human diet, and it is found primarily in vegetable oils. Long-chain n--6 fatty acids enhance prostate tumor cell growth in human prostate tumor-derived cell lines.
Several biological mechanisms have been proposed to explain these observations. Among the most salient of these mechanisms is the inhibition of eicosanoid biosynthesis by arachidonic acid (AA; 20:4n--6), an n--6 fatty acid derived from LA by the action of cyclooxygenase-2. AA-derived eicosanoids, such as prostaglandin E2, strongly stimulate prostate tumor growth in animal models or prostate tumor-derived cell lines. In contrast, EPA and DHA inhibit cyclooxygenase-2 and the formation of prostaglandin E2 from AA. However, whether dietary n--3 and n--6 fatty acids and the ratio of these 2 classes of fatty acids affect the risk of prostate cancer in humans remains unclear.
In 1993, we reported on the association between dietary fat and risk of prostate cancer from a prospective study of male health professionals. The first study report was based on a single dietary assessment with follow-up from 1986 to 1990 and included 300 incident cases of prostate cancer. In that study, ALA was positively related to risk of advanced prostate cancer, whereas no association with prostate cancer was seen with n--3 fatty acids from fish and LA. More recently, with follow-up time through 1998 (2482 cases), we reported an inverse relation of fish and marine fatty acid intake with prostate cancer risk. The present analyses extend those findings to evaluate in detail the association between n--3 and n--6 fatty acids and prostate cancer based on repeated dietary assessments with follow-up from 1986 to 2000 and including 2965 incident cases of prostate cancer.
Study population
The Health Professionals Follow-Up Study was initiated in 1986 when 51529 US male health professionals aged 40--65 y responded to a mailed questionnaire concerning their medical history and known or suspected risk factors for cancer and other chronic diseases. Subsequently, follow-up questionnaires have been mailed every 2 y to the entire cohort to update information on potential risk factors and to identify newly diagnosed illnesses. The overall follow-up rate was 94%. We excluded at baseline men who had previously been diagnosed with cancer other than nonmelanoma skin cancer (1996 men excluded) and men who provided inadequate information on diet (1667 men excluded). After these exclusions, the analytic cohort consisted of 47 866 men, and they were followed to 2000. This study was approved by the Institutional Review Board on the Use of Human Subjects in Research of the Harvard School of Public Health.
Assessment of diet
Dietary intake was assessed in 1986, 1990, and 1994 by using a 131-item semiquantitative food-frequency questionnaire. To calculate intakes of nutrients and individual food items, a commonly used unit or portion size for each food (eg, one pat of margarine) was specified and the participants were asked to report how often, on average over the past year, they had consumed that amount. There were 9 possible response categories for each food item that ranged from never or less than once per month to >=6 times/d. The dietary questionnaire inquired specifically about the kind of fat usually used for frying, sautéing, and baking (vegetable oil, solid vegetable oil shortening, butter, margarine, lard, or none). In addition, we requested information on individual type and brand of cooking oil and margarine using one open-ended question each. We specifically queried about the frequency of intake of canned tuna, dark-meat fish (mackerel, salmon, sardines, bluefish, and swordfish), other fish (not specified), and shrimp, lobster, and scallops. We also inquired about the use of fish-oil supplements starting in 1988 (yes or no). Our assessment of fish-oil supplement use was expanded starting in 1990 (none, <2.5 g/d, 2.5--4.9 g/d, 5.0--9.9 g/d, and >=10 g/d). This information was used to update exposure to EPA during follow-up.
Nutrient intakes were calculated for each participant by multiplying the frequency of consumption for each item by the nutrient content of the specified portion size. Food-composition data were primarily based on values obtained from the US Department of Agriculture but were supplemented with information from the manufacturers. We considered total ALA, ALA from meat and dairy sources, and ALA from nonanimal sources separately.
The validity and reproducibility of the food-frequency questionnaire were assessed by comparing nutrient intakes from two 1-wk diet records with those of the food-frequency questionnaire among a random sample of 127 Boston area participants. The correlation between energy-adjusted intake of polyunsaturated fat measured by diet records and by food-frequency questionnaire was 0.37. The correlations between intakes of total polyunsaturated fat, LA, and EPA as a proportion of dietary fat and the proportion of fatty acids in adipose tissue samples were 0.50, 0.48, and 0.47, respectively (14).

Specific fatty acids and risks of breast and prostate cancer: dietary intake
Willett WC. Specific fatty acids and risks of breast and prostate cancer: dietary intake. Am J Clin Nutr 1997;66(suppl):1557S--63S
WC Willett
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Although international comparisons have suggested positive associations between consumption of total or saturated fat and risk of breast cancer, these relations have not been supported in large prospective studies in which confounding factors were minimized. There is no suggestion from international comparisons, case-control, or cohort studies that monounsaturated fat (the most abundant fat in the US diet) increases risk of breast cancer, and there is some evidence that higher intake, particularly in the form of olive oil, might actually reduce risk. The available epidemiologic evidence provides little support for any important relation between intake of either linoleic acid or extra- long-chain n-3 fatty acids from fish and risk of breast cancer. However, high consumption of linoleic acid is a relatively recent phenomenon in Western societies and continued evaluation of its relation with breast cancer risk is warranted because of animal data suggesting possible adverse effects. Ecologic, case-control, and cohort studies all support a positive relation between consumption of animal fat and risk of prostate cancer, but current evidence suggests that vegetable fat is not related to risk of this cancer. Although relevant data are limited, neither linoleic acid nor extra-long-chain n-3 fatty acid consumption appears to be related to risk of prostate cancer. Because of the strong evidence that some aspect of foods high in animal fat increases risk of prostate cancer, further studies of specific dietary fatty acids in relation to the occurrence of this malignancy are likely to be particularly valuable.
Omega-3 fatty acids: comparison of plant and seafood sources in human nutrition
J Am Diet Assoc. 1991 Mar;91(3):331-7
Nettleton JA.
Omega-3 Fatty acids (omega-3FAs) are found in seafoods, some plants, and some livestock rations. Fish oils are the only concentrated source of eicosapentaenoic acid (EPA; 20:5 omega-3) and docosahexaenoic acid (DHA; 22:6 omega-3). The major omega-3FA in plants is alpha-linolenic acid (LNA; 18:3 omega-3). LNA must be converted to EPA before it exerts biological effects similar to EPA, such as reduced platelet aggregation. Human beings convert LNA to EPA to a small extent only. LNA may be more readily oxidized than incorporated into tissues. The effects of consuming LNA-rich oils are more modest than the effects of EPA-rich oils. Evidence suggests that omega-3FAs are essential and highly desirable for brain and eye development and heart health. LNA is the only source of omega-3FAs for vegetarians. Because LNA and EPA are not biologically equivalent, food composition data or product claims mentioning total omega-3FA content must clarify the individual omega-3FAs present.
{alpha}-Linolenic Acid and Risk of Prostate Cancer: A Case-Control Study in Uruguay
Cancer Epidemiology Biomarkers & Prevention Vol. 9, 335-338, March 2000
Eduardo De Stéfani2, Hugo Deneo-Pellegrini, Paolo Boffetta, Alvaro Ronco and María Mendilaharsu
Registro Nacional de Cáncer, 11300 Montevideo, Uruguay [E. D. S., H. D-P., A. R., M. M.], and Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, 69372 Lyon, France [P. B.]
In the time period of 1994--1998, a case-control study on diet and prostate cancer was carried out in Uruguay to examine the risk associated with fat intake. Two hundred and seventeen (217) incident cases afflicted with advanced prostate cancer were frequency-matched with 431 controls on age, residence, and urban/rural status. The analysis was carried out using unconditional multiple logistic regression. {alpha}-Linolenic acid was associated with a strong positive association (fourth quartile of intake odds ratio, 3.91; 95% confidence interval, 1.50--10.1) after controlling for total calorie intake and for the other types of fat. The effect was similar when {alpha}-linolenic acid was analyzed by its sources of origin (odds ratio for vegetable linolenic acid, 2.03; 95% confidence interval, 1.01--4.07). Including this report, five of six studies that have examined the relationship between {alpha}-linolenic acid and prostate cancer yielded a positive association, which was significant in four studies. Thus, there appears to be evidence of a role of {alpha}-linolenic acid in prostate carcinogenesis.
The association of fatty acids with prostate cancer risk
Prostate. 2001 Jun 1;47(4):262-8.
Newcomer LM, King IB, Wicklund KG, Stanford JL.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
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.
Dietary fat intake and prostate cancer risk: a case-control study in Spain
Cancer Causes Control. 2000 Sep;11(8):677-8.
Ramon JM, Bou R, Romea S, Alkiza ME, Jacas M, Ribes J, Oromi J.
Preventive Medicine Department, Ciudad Sanitaria y Universitaria de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain.
OBJECTIVES: Epidemiological evidence suggests that dietary factors can play a role in the etiology of prostate cancer. Results from several case-control and cohort studies on nutrient intake and prostate cancer have been unclear. The authors examined the effect of lipid intake on the risk of prostate cancer. METHODS: In order to assess associations between lipid intake and prostate cancer risk, a case-control study was conducted between May 1994 and March 1998 in the Barcelona metropolitan area, Spain. Two hundred seventeen incident cases with histologically confirmed diagnosis of prostate cancer were matched to 434 hospital and community controls by age and residence. Information about food intake was gathered by a semiquantitative food-frequency questionnaire. Unconditional logistic regression was used for the analysis. RESULTS AND CONCLUSIONS: Animal fat intake was associated with prostate cancer with an estimated OR for highest quartile of 2.0 (95% CI 1.2-3.2). Vitamin C intake was inversely associated with prostate cancer (OR = 0.6; 95% CI 0.3-0.9). The prostate cancer risk increased in proportion to alpha-linolenic acid intake. In the analysis adjusting for energy and major covariables the estimated OR for upper quartile of alpha-linolenic acid was 3.1 (95% CI 1.1-3.8). In conclusion, the association between fat intake and prostate cancer may be correlated with alpha-linolenic acid, although the specific mechanism has to be determined.
Dietary fat and advanced prostate cancer
J Urol. 1998 Apr;159(4):1271-5
Bairati I, Meyer F, Fradet Y, Moore L.
Departement de Medecine Sociale et Preventive, Centre de Recherche en Cancerologie de l'Universite Laval, Quebec City, Quebec, Canada.
PURPOSE: We identify the dietary factors, particularly fat intake, associated with advanced prostate cancer. MATERIALS AND METHODS: We performed a case series analysis restricted to prostate cancer cases recruited in a hospital based, case control study evaluating the influence of diet on the development of prostate cancer. Patients eligible for study inclusion were 45 years old or older with prostate cancer who had been hospitalized for initial surgical treatment or radiotherapy between October 1990 and December 1992 at 1 of 8 hospitals in the Quebec City area. A diet history questionnaire was administered to 427 patients with prostate cancer of whom 384 (90%) had completed a reliable questionnaire, including 142 with advanced and 242 with local stages I and II disease. Logistic regression analysis was used to evaluate the associations between dietary intake and advanced prostate cancer. Odds ratios and trend odds ratios were adjusted for patient age, energy intake, method of cancer detection and cancer treatment. RESULTS: There was a moderate, not statistically significant relation to total fat (trend odds ratio 1.15, confidence interval [CI] 0.95 to 1.39). Cases in the highest quartile of saturated fat consumption had a statistically significant odds ratio of 2.15 (CI 1.14 to 4.04). In addition, the relation increased proportionally and significantly with saturated fat intake (trend odds ratio 1.24, CI 1.02 to 1.51). Inverse associations of borderline significance were observed between advanced cancer, and polyunsaturated fat (trend odds ratio 0.88, CI 0.73 to 1.07) and linoleic acid intake (trend odds ratio 0.86, CI 0.71 to 1.04). A positive trend was observed for total animal fat intake (trend odds ratio 1.20, CI 0.99 to 1.46), while a negative trend was noted for total vegetable fat intake (trend odds ratio 0.84, CI 0.70 to 1.01). CONCLUSIONS: This study suggests an association between saturated fat consumption and prostate cancer progression. If cohort studies performed on patients with local prostate cancer confirm these results, dietary fat intake modification may be a promising intervention to prevent prostate cancer progression.
Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features
Urology. 2001 Jul;58(1):47-52
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.
Fish Consumption and Risk of Stroke in Men
Ka He, MD, MPH; Eric B. Rimm, ScD; Anwar Merchant, DMD, ScD; Bernard A. Rosner, PhD; Meir J. Stampfer, MD, DrPH; Walter C. Willett, MD, DrPH; Alberto Ascherio, MD, DrPH
JAMA. 2002;288:3130-3136.
Context The effect of fish consumption or long-chain omega-3 polyunsaturated fatty acid (PUFA) intake on risk of stroke remains uncertain.
Objective To examine the relation of fish consumption and long-chain omega-3 PUFA intake and risk of stroke in men.
Design and Setting The Health Professional Follow-up Study, a US prospective cohort study with 12 years of follow-up.
Participants A total of 43 671 men aged 40 to 75 years who completed a detailed and validated semiquantitative food frequency questionnaire and who were free of cardiovascular disease at baseline in 1986.
Main Outcome Measure Relative risk (RR) of stroke by subtype based on cumulative average fish consumption or long-chain omega-3 PUFA intake, ascertained in 1986, 1990, and 1994.
Results We documented 608 strokes during the 12-year follow-up period, including 377 ischemic, 106 hemorrhagic, and 125 unclassified strokes. Compared with men who consumed fish less than once per month, the multivariate RR of ischemic stroke was significantly lower among those who ate fish 1 to 3 times per month (RR, 0.57; 95% confidence interval [CI], 0.35-0.95). However, a higher frequency of fish intake was not associated with further risk reduction; the RR was 0.54 (95% CI, 0.31-0.94) for men who consumed fish 5 or more times per week. This lack of linearity was confirmed by spline analyses. By dichotomized fish intake, the multivariate RR for men who consumed fish at least once per month compared with those who ate fish less than once per month was 0.56 (95% CI, 0.38-0.83) for ischemic stroke and 1.36 (95% CI, 0.48-3.82) for hemorrhagic stroke. The inverse association between fish intake and risk of ischemic stroke was not materially modified by use of aspirin. No significant associations were found between fish or long-chain omega-3 PUFA intake and risk of hemorrhagic stroke.
Conclusion Our findings suggest that eating fish once per month or more can reduce the risk of ischemic stroke in men.
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