A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer

Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; P_trend = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (P_trend = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men.     

Cognitive decline and fatty acid composition of erythrocyte membranes--The EVA Study

BACKGROUND: Dietary factors might modify cognitive decline that results from aging. Fatty acids, which are limiting factors in brain development, are prime candidates. OBJECTIVE: We studied the relation between erythrocyte membrane fatty acid composition and cognitive decline in free-living volunteers. DESIGN: In 1995, erythrocyte membrane fatty acid composition was measured in 246 men and women (aged 63-74 y) from the Etude du Vieillissement Artériel (EVA) cohort. During a 4-y follow-up, cognitive abilities were assessed longitudinally with the Mini-Mental State Examination. Moderate cognitive decline was defined as a > or = 2-point decrease over the 4 y. The predictive value of fatty acid proportions on cognitive decline was assessed with a multivariate logistic model that included age, sex, education level, and initial Mini-Mental State Examination score as covariates. RESULTS: Higher proportions of both stearic acid (saturated, 18:0) and total n-6 polyunsaturated fatty acids were associated with greater risk of cognitive decline; the odds ratios were 1.91 (95% CI: 1.16, 3.15) and 1.59 (95% CI: 1.04, 2.44), respectively, for 1-SD differences in fatty acid proportions. Conversely, a higher proportion of total n-3 fatty acids was associated with a lower risk of cognitive decline; the odds ratio was 0.59 (95% CI: 0.38, 0.93). CONCLUSIONS: The inverse association between cognitive decline and the ratio of n-3 to n-6 fatty acids in erythrocyte membranes agrees with results obtained in some studies that assessed fatty acid intake by using dietary questionnaires. These results require confirmation but provide new rationale for studying how these modifiable risk factors might be implicated in the cognitive aging process.     

A valid food frequency questionnaire for measuring dietary fish intake

There is considerable interest in the potentially protective effects of high fish consumption on many chronic diseases. Many epidemiological studies use food frequency questionnaires (FFQ) to quantify usual dietary fish intake, so it is important to validate this assessment against objective markers. The objective of this study was to determine the relationship between plasma percentage fatty acids and dietary fish intake as assessed by a FFQ. A semiquantitative FFQ was completed by 174 adults from the community (aged 26-49 years) who also had venous blood analysed for plasma percentage fatty acids. Following linear regression modelling, total non-fried fish intake was a significant predictor of n-3 (regression coefficient, B = 0.94; 95% CI = 0.60-1.28), docosahexaenoic acid (DHA; B = 0.73; 95% CI = 0.47-0.99) and the ratio of n-6: n-3 fatty acids (B = -1.0; 95% CI = - 1.35- -0.65). Steamed, grilled or baked fish was a small but significant predictor of eicosapentaenoic acid (EPA) levels (B = 0.13; 95% CI = 0.05-0.21) while total fish intake was a predictor of n-6 fatty acids (B = -0.88; 95% CI = -1.41- -0.36). This semiquantitative FFQ could be useful for ranking subjects according to their likely plasma n-3, DHA, and n-6 fatty acid intake and the ratio of n-6: n-3 fatty acids, when the available resources may simply not permit biological markers to be used.     

Intake of Omega-3 and Omega-6 Fatty Acids and Risk of Basal and Squamous Cell Carcinomas of the Skin: A Longitudinal Community-Based Study in Australian Adults

Intake of omega-3 and omega-6 fatty acids may modify the risk of basal and squamous cell carcinoma of the skin (BCC and SCC), but population-based evidence is limited and inconsistent. We examined prospectively associations between intake of omega-3 and omega-6 fatty acids estimated from food frequency questionnaires and BCC and SCC incidence among 1322 randomly selected adults in Nambour, Australia. Relative risks (RR) and 95% confidence intervals (CI) were estimated based on histologically confirmed tumors diagnosed between 1997 and 2007. Incidence of BCC was lowest in the middle third of both total omega-6 intake (RR_mv.adj = 0.74, 95% CI = 0.56–0.97) and linoleic acid intake (RR_mv.adj = 0.75, 95% CI = 0.57–0.99) compared with the lowest third of intake. Evidence for associations with SCC was weak, though persons with arachidonic acid intake in the middle third had a marginally increased risk of SCC (RR_mv.adj = 1.42, 95% CI = 1.00–2.02). Consumption of omega-3 fatty acids was not associated with subsequent skin cancer risk. Suggestion that intake of arachidonic acid may be associated with increased SCC incidence and total omega-6 with reduced BCC from our study is still highly uncertain and may be due to chance. These data do not support an association between these fatty acids and risk of BCC or SCC.     

Dietary intakes of arachidonic acid and alpha-linolenic acid are associated with reduced risk of hip fracture in older adults

PUFA are hypothesized to influence bone health, but longitudinal studies on hip fracture risk are lacking. We examined associations between intakes of PUFA and fish, and hip fracture risk among older adults (n = 904) in the Framingham Osteoporosis Study. Participants (mean age ~75 y at baseline) were followed for incident hip fracture from the time they completed the baseline exam (1988-1989) until December 31, 2005. HR and 95% CI were estimated for energy-adjusted dietary fatty acid exposure variables [(n-3) fatty acids: α-linolenic acid (ALA), EPA, DHA, EPA+DHA; (n-6) fatty acids: linoleic acid, arachidonic acid (AA); and the (n-6):(n-3) ratio] and fish intake categories, adjusting for potential confounders and covariates. Protective associations were observed between intakes of ALA (P-trend = 0.02) and hip fracture risk in a combined sample of women and men and between intakes of AA (P-trend = 0.05) and hip fracture risk in men only. Participants in the highest quartile of ALA intake had a 54% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.46; 95% CI = 0.26-0.83). Men in the highest quartile of AA intake had an 80% lower risk of hip fracture than those in the lowest quartile (Q4 vs. Q1: HR = 0.20; 95% CI = 0.04-0.96). No significant associations were observed among intakes of EPA, DHA, EPA+DHA, or fish. These findings suggest dietary ALA may reduce hip fracture risk in women and men and dietary AA may reduce hip fracture risk in men.     

Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women

Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.     

n-3 Polyunsaturated fatty acids,fatal ischemic heart disease,and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study

BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults. OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event. RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.     

Dietary intake of α-linolenic acid and low ratio of n-6:n-3 PUFA are associated with decreased exhaled NO and improved asthma control

As recently described, adherence to the Mediterranean diet is associated with improved asthma control. However, evidence of how specific nutrients such as fatty acids and antioxidants may affect this relationship remains largely unknown. We aimed to examine the association between dietary intake of fatty acids and antioxidants and asthma control. A cross-sectional study was developed in 174 asthmatics, mean age of 40 (SD 15) years. Dietary intake was obtained by a FFQ, and nutritional content was calculated using Food Processor Plus? software (ESHA Research, Inc., Salem, OR, USA). Good asthma control was defined by the combination of forced expiratory volume during the first second, exhaled NO (eNO) and Asthma Control Questionnaire (ACQ) score (control: forced expiratory volume in the first second ≥80 %; eNO ≤35 ppb; ACQ <1·0, scale 0-6 score). Multiple linear and logistic regression models were performed to analyse the associations between nutrients and asthma outcomes, adjusting for confounders. A high n-6:n-3 PUFA ratio predicted high eNO, whereas high intakes of n-3 PUFA, a-linolenic acid (ALA) and SFA were associated with low eNO. Odds for controlled asthma improved along with an increased intake of n-3 PUFA (OR 0·14, 95% CI 0·04, 0·45; P for trend=0·001), SFA (OR 0·36, 95% CI 0·13, 0·97; P for trend=0·047) and ALA (OR 0·18, 95% CI 0·06, 0·58; P for trend=0·005). A high n-6:n-3 PUFA ratio increased the odds for uncontrolled asthma (OR 3·69, 95% CI 1·37, 9·94; P for trend=0·009), after adjusting for energy intake, sex, age, education and use of inhaled corticosteroids. Higher intakes of n-3 PUFA, ALA and SFA were associated with good asthma control, while the risk for uncontrolled asthma increased with a higher n-6:n-3 PUFA ratio. The present results introduce a protective effect of ALA in asthma control, independent of marine n-3 fatty acids, and provide a rationale to dietary intervention studies in asthma.     

Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross-sectional study in Japan

PURPOSE: To investigate the associations of fatty acid intake with seasonal allergic rhinoconjunctivitis. METHODS: The study subjects consisted of 1012 women aged 22 to 57 years (mean age +/- SD: 36.5+/-7.7 years), who had graduated from the Aichi Prefectural Junior College of Nursing, Nagoya, Japan. They completed a self-administered questionnaire on symptoms of the disease in August 1998. Symptoms of seasonal allergic rhinoconjunctivitis in spring were determined by response to the questionnaire, and fatty acid intake was estimated using a food frequency questionnaire. Odds ratios (ORs) were computed using unconditional logistic models to assess the strength of associations between the symptoms and fatty acid intake. RESULTS: An increasing trend in the ORs was observed with increasing dietary intake of n-6 polyunsaturated fatty acids. After adjustment for potential confounders, the ORs for the second, third, and highest quartiles of intake relative to the lowest were 1.28 [95% confidence interval (CI), 0.78-2.10], 1.55 (0.96-2.50), and 1.74 (1.09-2.77), respectively (trend p = 0.015). Consumption of saturated, monounsaturated, and n-3 polyunsaturated fatty acids was not significantly related to the symptoms. CONCLUSIONS: Dietary intake of n-6 polyunsaturated fatty acids was positively associated with seasonal allergic rhinoconjunctivitis in spring.     

Diet during pregnancy and risk of preeclampsia or gestational hypertension

PURPOSE: We sought to examine associations of first-trimester intake of calcium, n-3 and n-6 fatty acids, trans fatty acids, magnesium, folate, and vitamins C, D, and E with preeclampsia (PE) and gestational hypertension (GH). METHODS: We studied associations of diet with PE or GH among 1718 women in the prospective cohort study Project Viva, using logistic regression and adjusting for maternal age, prepregnancy body mass index, first trimester systolic blood pressure, race/ethnicity, education, and parity. We assessed first-trimester diet using a validated semiquantitative food frequency questionnaire. RESULTS: A total of 59 (3%) women developed PE, and 119 developed (7%) GH. We found a somewhat-lower risk of PE associated with higher intake of the elongated n-3 fatty acids docosahexaenoic and eicosapentaenoic acids (odds ratio [OR] 0.84, 95% confidence interval [95% CI]: 0.69-1.03 per 100 mg/day), fish (OR 0.91, 95% CI 0.75-1.09 per serving/day), and the ratio of docosahexaenoic + eicosapentaenoic to arachadonic acid (OR 0.82, 95% CI 0.66-1.01). We did not observe a lower risk of GH or PE with a greater intake of calcium; vitamin C, D, or E; milk; magnesium; folate; or with lower intake of n-6 or trans fatty acids. CONCLUSIONS: Our results support a potential benefit for elongated n-3 fatty acids in preventing preeclampsia.     

Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women

BACKGROUND: Dry eye syndrome (DES) is a prevalent condition, but information on risk or protective factors is lacking. OBJECTIVE: We aimed to determine the association between the dietary intake and ratio of n-3 and n-6 fatty acids (FAs) and DES occurrence. DESIGN: Of the 39876 female health professionals in the Women's Health Study (WHS), 32470 women aged 45-84 y who provided information on diet and DES were cross-sectionally studied. We assessed FA intakes by using a validated food-frequency questionnaire and assessed DES by using self-reports of clinically diagnosed cases. Of the sample, 1546 (4.7%) subjects reported DES. We used logistic regression models to estimate the odds ratios (ORs) and 95% CIs to describe the relation of FA intake with DES. RESULTS: After adjustment for demographic factors, hormone therapy, and total fat intake, the OR for the highest versus the lowest quintile of n-3 FAs was 0.83 (95% CI: 0.70, 0.98; P for trend = 0.05). A higher ratio of n-6 to n-3 FA consumption was associated with a significantly increased risk of DES (OR: 2.51; 95% CI: 1.13, 5.58) for >15:1 versus <4:1 (P for trend = 0.01). In addition, tuna consumption [1 serving was 113 g (4 oz)] was inversely associated with DES (OR: 0.81; 95% CI: 0.66, 0.99 for 2-4 servings/wk; OR: 0.32; 95% CI: 0.13, 0.79 for 5-6 servings/wk versus < or =1 serving/wk; P for trend = 0.005). CONCLUSIONS: These results suggest that a higher dietary intake of n-3 FAs is associated with a decreased incidence of DES in women. These findings are consistent with anecdotal clinical observations and postulated biological mechanisms.     

Allergic sensitisation and allergic rhinitis are associated with n-3 polyunsaturated fatty acids in the diet and in red blood cell membranes

OBJECTIVE: Due to inconsistent results based on dietary intake data, unsaturated fatty acids in red blood cell (RBC) membranes and diet were used to investigate their association with allergic sensitisation and allergic rhinitis. DESIGN: Cross-sectional, population-based study. SETTING: Bavarian Nutrition Survey II (2002-03), Germany. SUBJECTS: A total of 568 adult participants, 325 women and 243 men. METHODS: By means of logistic regression models, the relation of fatty acids to (i) allergic sensitisation as defined by means of specific serum immunoglobulin E analysis (CAPSX1 class > or = 2), and (ii) self-reported allergic rhinitis was examined. RESULTS: A high cell membrane level of eicosapentaenoic acid (EPA, 20:5 n-3) was inversely associated with allergic sensitisation, the adjusted odds ratio (OR) and 95% confidence interval (95% CI) were 0.52 (0.30-0.90) for the highest (vs lowest) quartile. A similar effect was observed for allergic rhinitis with an OR (95% CI) of 0.50 (0.24-1.03; P = 0.027 for trend). A higher dietary intake of alpha-linolenic acid (ALA, 18:3 n-3) was associated with a decreased risk of allergic sensitisation and allergic rhinitis with ORs (95% CIs) of 0.51 (0.28-0.93) and 0.43 (0.20-0.93), respectively, in the highest quartiles. No other dietary or cell membrane unsaturated fatty acid was significantly associated with the outcome variables, nor was the n-6/n-3 ratio. The strongest effects were observed among subjects under the age of 40 y. CONCLUSIONS: In this cross-sectional study among adults, a high content of n-3 fatty acids in RBC membranes (EPA) or in the diet (ALA) is associated with a decreased risk of allergic sensitisation and allergic rhinitis.     

Adipose tissue fatty acids and risk of myocardial infarction--a case-control study

OBJECTIVES: To study the association between content in adipose tissue of very long-chain n-3 fatty acids, trans fatty acids, linoleic acid and alpha-linolenic acid and risk of a first myocardial infarction. DESIGN AND SUBJECTS: A case-control design among 100 patients and 98 population controls both men and postmenopausal women, age 45-75 y. Adipose tissue fatty acids were determined by gas-liquid chromatography. Intake data were obtained through interview using a validated food frequency questionnaire. RESULTS: Dietary intake and adipose tissue content of the fatty acids studied correlated significantly. Adipose tissue contents of eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3) and docosahexaenoic acid (22:6n-3) were significantly lower while those of trans fatty acids, linoleic and alpha-linolenic acid were significantly higher in patients than in controls. Age and sex adjusted odds ratios (OR) were significantly reduced with increasing quintiles of very long-chain n-3 fatty acids, thus the OR in the fifth compared to the first quintile was 0.23 (95% CI 0.08-0.70). After further adjustment for waist-to-hip ratio, smoking, family history of CHD and content of trans fatty acids, the OR in the highest quintile was 0.17 (95% CI 0.04-0.76) and the P for trend 0. 016. Age and sex adjusted OR was increased in the fifth compared to the first quintile of trans fatty acids (OR 2.81, 95% CI 1.16-6.84), linoleic acid (OR 2.10, 95% CI 0.87-5.07) and alpha-linolenic acid (OR 1.96, 95% CI 0.83-4.61), and P for trend was 0.002, 0.005 and 0. 020, respectively. The trends remained significant after adjustment for waist-to-hip ratio, smoking, and family history of coronary heart disease. Trans fatty acids, linoleic acid and alpha-linolenic acid in adipose tissue were strongly correlated, indicating a common source, most likely margarine. When each of these fatty acid species were adjusted for the two others the trends were no longer significant. CONCLUSION: Intake of very long-chain n-3 fatty acids as reflected in adipose tissue content is inversely associated with risk of myocardial infarction. Trans fatty acids, linoleic and alpha-linolenic acid were intercorrelated and associated with increased risk. It is suggested that the increased risk may be connected to trans fatty acids or to some other factor associated with margarine consumption. European Journal of Clinical Nutrition 54, 618-625.     

Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk

BACKGROUND: The potential preventive role of polyunsaturated fatty acids (PUFAs) in Alzheimer disease has aroused increasing interest. Plasma n-3 PUFAs have been shown to be inversely related to the risk of dementia and to depression, which is frequently associated with dementia. OBJECTIVE: The objective was to ascertain whether plasma PUFAs predict the risk of incident dementia in a cohort of older persons, independently of their depressive status. DESIGN: Of 1214 nondemented participants in the Three-City Study from Bordeaux (France) who were followed up for 4 y, 65 developed dementia. The association between the proportion of plasma fatty acids at baseline and the risk of incident dementia was assessed by multivariate proportional hazard models, taking into account depressive status assessed on the basis of the Center for Epidemiologic Studies Depression scale. RESULTS: A higher plasma eicosapentaenoic acid (EPA) concentration was associated with a lower incidence of dementia [hazard ratio (HR) for 1 SD = 0.69; 95% CI: 0.48, 0.98], independently of depressive status and after adjustment for age, education, apolipoprotein E epsilon4 allele, diabetes, and baseline plasma vitamin E and triacylglycerol. The relations between docosahexaenoic acid (DHA), total n-3 PUFAs, and incident dementia did not remain significant in multivariate models. Higher ratios of arachidonic acid (AA) to DHA and of n-6 to n-3 fatty acids were related to an increased risk of dementia, particularly in depressive subjects (n = 90): ratio of AA to DHA (HR: 2.65; 95% CI: 1.07, 6.56) and ratio of n-6 to n-3 (HR: 1.61; 95% CI: 1.04, 2.47). CONCLUSIONS: A high plasma EPA concentration may decrease the risk of dementia, whereas high ratios of n-6 to n-3 fatty acids and of AA to DHA may increase the risk of dementia, especially in depressed older persons. The role of EPA in dementia warrants further research.     

Depression and cardiovascular mortality: a role for n-3 fatty acids?

BACKGROUND: Recent studies indicate that depression plays an important role in the occurrence of cardiovascular diseases (CVDs). The underlying mechanisms are not well understood. OBJECTIVE: We investigated whether dietary intake of the n-3 fatty acids (FAs) eicosapentaenic acid and docosahexaenoic acid could explain the relation between depressive symptoms and cardiovascular mortality. DESIGN: The Zutphen Elderly Study is a prospective cohort study conducted in the Netherlands. Depressive symptoms were measured in 1990 with the Zung Self-rating Depression Scale in 332 men aged 70-90 y and free from CVD and diabetes. Dietary factors were assessed with a cross-check dietary history method in 1990. Mortality data were collected between 1990 and 2000. Logistic and Cox regression analyses were performed, with adjustment for demographics and CVD risk factors. RESULTS: Compared with a low intake (x: 21 mg/d), a high intake (x: 407 mg/d) of n-3 FAs was associated with fewer depressive symptoms [odds ratio: 0.46; 95% CI: 0.22, 0.95; P for trend = 0.04] at baseline and no significant reduced risk of 10-y CVD mortality [hazard ratio (HR): 0.88; 95% CI: 0.51, 1.50]. The adjusted HR for an increase in depressive symptoms with 1 SD for CVD mortality was 1.28 (95% CI: 1.03, 1.57) and did not change after additional adjustment for the intake of n-3 FAs. CONCLUSION: An average intake of approximately 400 mg n-3 FA/d may reduce the risk of depression. Our results, however, do not support the hypothesis that the intake of n-3 FAs explains the relation between depression and CVD.     

Dietary intake of fatty acids, antioxidants and selected food groups and asthma in adults

OBJECTIVE: Within a prospective study, we explored the associations between dietary intake of fatty acids, antioxidants and relevant food sources of these nutrients on the clinical manifestation of asthma in adulthood. METHOD: A total of 105 newly physician-diagnosed cases of asthma from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort were identified during follow-up and matched with 420 controls. Baseline dietary intake was obtained by means of validated food frequency questionnaires. The association of dietary intake variables and asthma risk was explored by unconditional logistic regression models. RESULTS: A high intake of oleic acid (C18:1 n-9) was positively associated with asthma (P-value for trend 0.035), while no significant associations were found for the other dietary fatty acids. Most prominently, a high margarine intake increased the risk of onset of asthma in adulthood (adjusted odds ratio (OR) 3rd tertile: 1.73 (95% confidence interval (95% CI): 1.05-2.87), P for trend=0.050), the effect being stronger in men (2nd tertile: OR=1.66, 3rd tertile: OR=2.51) than in women (2nd tertile: OR=0.91; 3rd tertile: OR=1.47). The dietary intake of antioxidants and their main food sources had no effect on asthma risk. CONCLUSIONS: In summary, the present results provide evidence that even in adulthood a high margarine intake increases the risk of clinical onset of asthma. Whether oleic acid may serve as a proxy for margarine-derived trans-fatty acids (C18:1 t9) remains to be clarified.     

Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case–control study

Purpose

Animal and laboratory studies suggest that long-chain omega-3 (n-3) fatty acids, a type of polyunsaturated fat found in fatty fish, may protect against carcinogenesis, but human studies on dietary intake of polyunsaturated fats and fish with endometrial cancer risk show mixed results.

Methods

We evaluated the associations between endometrial cancer risk and intake of fatty acids and fish in a population-based sample of 556 incident cancer cases and 533 age-matched controls using multivariate unconditional logistic regression methods.

Results

Although total n-3 fatty acid intake was not associated with endometrial cancer risk, higher intakes of eicosapentaenoic (EPA 20:5) and docosahexaenoic (DHA 22:6) fatty acids were significantly associated with lower risks (OR = 0.57, 95 % CI: 0.39–0.84; OR = 0.64, 95 % CI: 0.44–0.94; respectively) comparing extreme quartiles. The ratio of n-3:n-6 fatty acids was inversely associated with risk only on a continuous scale (OR = 0.84, 95 % CI: 0.71–0.99), while total fish intake was not associated with risk. Fish oil supplement use was significantly associated with reduced risk of endometrial cancer: OR = 0.63 (95 % CI: 0.45–0.88).

Conclusions

Our results suggest that dietary intake of the long-chain polyunsaturated fatty acids EPA and DHA in foods and supplements may have protective associations against the development of endometrial cancer.     

Relationship between Dietary Fatty Acid Intake with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in People with HIV

We aimed to evaluate the relationship between food intake of lipids with nonalcoholic fatty liver disease (NAFLD) and/or liver fibrosis in people living with HIV/AIDS (PLWHA). In this cross-sectional study, transient elastography was used to detect the presence of NAFLD and/or liver fibrosis. The dietary intake of fats and fatty acids (FA) were assessed by two 24 h dietary recalls (24-HDR) (n = 451). Multivariate logistic regression models were performed. Participants with higher intake of total fat were associated with higher odds for NAFLD compared to those with lower consumption [adjusted odds ratio (aOR) = 1.91 (95% confidence interval (95% CI) 1.06–3.44)]. Furthermore, participants with intermediate intake of n6-PUFA (n6-poly-unsaturated FA) and lauric FA had lower odds for NAFLD, respectively aOR = 0.54 (95% CI 0.3–0.98) and aOR = 0.42 (95% CI 0.22–0.78). Additionally, a higher intake of myristoleic FA (fourth quartile) was a significant protective factor for NAFLD [aOR = 0.56 (95% CI 0.32–0.99)]. Participants with higher intake of lauric FA [0.38 (95% CI 0.18–0.80)], myristic FA [0.38 (0.17–0.89)], palmitoleic FA [0.40 (0.19–0.82)] and oleic FA [0.35 (0.16–0.79)] had positively less odds of having liver fibrosis. On the other hand, higher intake of n-6 PUFA was significantly associated with fibrosis [aOR = 2.45 (95% CI 1.12–5.32)]. Dietary assessment of total fat and FA should be incorporated into HIV care as a tool for preventing NAFLD and fibrosis in PLWHA.     

Adipose tissue n-6 fatty acids and acute myocardial infarction in a population consuming a diet high in polyunsaturated fatty acids

BACKGROUND: The Jewish population of Israel consumes a diet rich in n-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid. The consequences of this diet for ischemic heart disease (IHD) remain unclear. OBJECTIVE: We assessed the association of adipose tissue n-6 fatty acids, which are derived entirely from the diet, with acute myocardial infarction (AMI). DESIGN: A total of 180 cases and 492 IHD-free controls aged 25-64 were included in a population-based case-control study of Jerusalem residents hospitalized with a first AMI. Diet was assessed by the use of a food-frequency questionnaire and adipose tissue fatty acids by gas chromatography of biopsy samples taken from subcutaneous gluteal tissue. The data were analyzed by multivariate logistic regression. RESULTS: Dietary PUFAs (: 10.1% of energy) correlated (r = 0.43, P < 0.001) with adipose tissue linoleic acid, which constituted 25.6% of storage fatty acids. High intakes of linoleic acid were not associated with excess risk of AMI (age- and sex-adjusted odds ratio for the third versus the first tertile: 0.96; 95% CI: 0.62, 1.48; NS). In contrast, arachidonic acid, the long chain n-6 derivative of linoleic acid, was positively associated with AMI (age- and sex-adjusted odds ratio: 2.12; 95% CI: 1.33, 3.36; P = 0.004). With multivariate adjustment, there was no evidence for an adverse association of linoleic acid with AMI, whereas the risk associated with arachidonic acid persisted, albeit attenuated. CONCLUSIONS: A very high linoleic acid intake does not appear to confer increased risk of nonfatal AMI. Nonetheless, the increased risk associated with arachidonic acid, a finding that requires confirmation, tempers an inference that diets rich in n-6 fatty acids are safe vis-à-vis coronary health.     

n-6 Docosapentaenoic acid is not a predictor of low docosahexaenoic acid status in Canadian preschool children

BACKGROUND: The n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3) is important for neural and visual functional development. In animals, 22:6n-3 deficiency is accompanied by increased docosapentaenoic acid (DPA; 22:5n-6), which suggests that the ratio of 22:6n-3 to 22:5n-6 could be a useful biochemical marker of low n-3 fatty acid status. The n-3 fatty acid status of preschool children has not been described, and data are lacking on whether low 22:6n-3 is accompanied by high 22:5n-6 in humans. OBJECTIVE: We determined n-3 fatty acid status and investigated the relation between 22:6n-3 and 22:5n-6 in children. DESIGN: In Canadian children aged 18-60 mo (n = 84), the n-3 and n-6 fatty acid status of erythrocyte phosphatidylethanolamine was measured, and dietary fat intake was estimated by using a food-frequency questionnaire. RESULTS: The mean (+/- SEM) 22:6n-3 concentration in erythrocyte phosphatidylethanolamine among children was 3.06 +/- 0.13 g/100 g fatty acids (5th-95th percentiles: 1.43-5.79 g/100 g fatty acids). Concentrations of 22:5n-6 increased with increasing 22:6n-3 concentrations in erythrocyte phosphatidylethanolamine (P < 0.01). Mean intakes of linoleic acid (18:2n-6), linolenic acid (18:3n-3), and trans fatty acids were 3.6 +/- 0.2%, 0.7 +/- 0.5%, and 2.0 +/- 1.3%, respectively. Phosphatidylethanolamine 22:6n-3 and 22:5n-3 concentrations were inversely related to the intakes of 18:2n-6 and trans fatty acids, but not to those of total fat or n-3 fatty acids. CONCLUSIONS: The concentration of 22:5n-6 is not a useful biochemical marker of low n-3 fatty acid intake or status in the membrane phosphatidylethanolamine of preschool children. High intakes of 18:2n-6 and trans fatty acids could compromise the incorporation of 22:6n-3 into membrane phospholipids.