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 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 isoflavones may protect against prostate cancer in Japanese men

We examined associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men. Two hundred patients and 200 age-matched controls (+/-5 y) were selected from 3 geographic areas of Japan. BMI, physical activity, occupation, family history of prostate cancer, and medical history were not associated with prostate cancer risk. Isoflavones and their aglycones (genistein and daidzein) were significantly associated with decreased risk. The odds ratio for the highest category (> or = 89.9 mg/d) compared with the lowest category (<30.5 mg/d) of isoflavone intake was 0.42 (95% CI = 0.24-0.72) and the linear trend was significant (P < 0.01). PUFA, (n-6) fatty acids, and magnesium were significantly associated with decreased risk but not after adjustment for isoflavone intake. Isoflavone intake was correlated with the intake of PUFA (r = 0.68, P < 0.001), (n-6) fatty acids (r = 0.69, P < 0.001), and magnesium (r = 0.56, P < 0.001), because soy products contain high levels of these nutrients. On the other hand, isoflavone significantly decreased the risk of prostate cancer regardless of adjustment by PUFA, (n-6) fatty acids or magnesium. In conclusion, our findings indicate that isoflavones might be an effective dietary protective factor against prostate cancer in Japanese 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.     

Dietary intakes of α-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men

Investigations suggest a protective role of n-3 polyunsaturated fatty acids (PUFA) but opposing roles of n-6 PUFA in inflammation, but the effects in vivo the human are not clear. We therefore tested the hypothesis that higher intakes of n-3 PUFA and n-6 PUFA are associated with lower levels of inflammation among a population consuming a diet high in PUFA. This study aimed to assess the association between PUFA intake and serum C-reactive protein (CRP) concentrations in a group of Japanese employees. The study subjects were 300 men and 211 women aged 21 to 67 years working in 2 municipal offices of Japan. We measured the serum high-sensitivity CRP concentrations by the latex agglutination nephelometry method and assessed dietary habits by a validated self-administered diet history questionnaire. We analyzed the data using multiple linear regression analysis with adjustment for potential confounding variables. Mean serum CRP concentrations tended to decrease as the intake of eicosapentaenoic acid, docosahexaenoic acid, or their combination increased in men and women, although none of these relationships was statistically significant. In men, there were statistically significant inverse relationships between dietary intake of n-3 or n-6 PUFA and serum CRP concentrations (P for trend = .03 and .008, respectively). Among specific PUFA, only α-linolenic acid and linoleic acid showed clear inverse relationships (P for trend = .001 and .003, respectively) in men. The results suggest that increased intake of not only α-linolenic acid (n-3 PUFA) but also linoleic acid (n-6 PUFA) has a beneficial effect on systemic inflammation in men.     

广州成人膳食n-6/n-3脂肪酸比值与心血管疾病危险因素的关系

目的分析广州40～65岁居民膳食n-6/n-3脂肪酸比值与心血管疾病危险因素的关系。方法 40～65岁广州市民1133人,采用定量食物频数问卷调查对象的每日摄入食物种类和数量,计算能量和营养素摄入量,检测其红细胞膜脂肪酸构成、血脂及颈动脉内中膜厚度(IMT),分析n-6/n-3比值大小高Q3,中Q2,低Q1与血压、血脂和IMT的关系。结果 995人资料完整纳入分析。对象日均膳食总能量摄入为9.10±2.09MJ、脂肪供能比为(34.3±7.9)%。膳食n-6/n-3脂肪酸比值为(29.74±22.71):1,红细胞膜n-6/n-3脂肪酸比值为(2.7±1.0):1,膳食SFA:MUFA:PUFA为1:1.5:1。膳食n-3脂肪酸摄入量与红细胞膜n-3构成比、膳食n-6/n-3比值与红细胞膜n-6/n-3比值均呈显著正相关关系。膳食n-6/n-3比值最高组Q3(>31.16)对象的收缩压、TC和IMT水平显著高于最低组Q1(<17.40);红细胞膜n-6/n-3比值最高组Q3(>3.04)和中间组Q2(2.18～3.03)对象的收缩压、舒张压、TC、LDL-C及IMT水平均显著高于最低组Q1(≤2.17)。结论广州市40～65岁居民膳食n-6/n-3脂肪酸比值约为30:1;该比值小于17.40:1时,有较低的血压,总胆固醇及IMT水平。     

n-6 fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials

Randomised controlled trials (RCT) of mixed n-6 and n-3 PUFA diets, and meta-analyses of their CHD outcomes, have been considered decisive evidence in specifically advising consumption of 'at least 5-10 % of energy as n-6 PUFA'. Here we (1) performed an extensive literature search and extracted detailed dietary and outcome data enabling a critical examination of all RCT that increased PUFA and reported relevant CHD outcomes; (2) determined if dietary interventions increased n-6 PUFA with specificity, or increased both n-3 and n-6 PUFA (i.e. mixed n-3/n-6 PUFA diets); (3) compared mixed n-3/n-6 PUFA to n-6 specific PUFA diets on relevant CHD outcomes in meta-analyses; (4) evaluated the potential confounding role of trans-fatty acids (TFA). n-3 PUFA intakes were increased substantially in four of eight datasets, and the n-6 PUFA linoleic acid was raised with specificity in four datasets. n-3 and n-6 PUFA replaced a combination of TFA and SFA in all eight datasets. For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22 % (risk ratio (RR) 0.78; 95 % CI 0.65, 0.93) compared to an increased risk of 13 % for n-6 specific PUFA diets (RR 1.13; 95 % CI 0.84, 1.53). Risk of non-fatal MI+CHD death was significantly higher in n-6 specific PUFA diets compared to mixed n-3/n-6 PUFA diets (P = 0.02). RCT that substituted n-6 PUFA for TFA and SFA without simultaneously increasing n-3 PUFA produced an increase in risk of death that approached statistical significance (RR 1.16; 95 % CI 0.95, 1.42). Advice to specifically increase n-6 PUFA intake, based on mixed n-3/n-6 RCT data, is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.     

(n-6) PUFA increase and dairy foods decrease prostate cancer risk in heavy smokers

Previous studies offer suggestive, but not definitive, evidence that total fat or specific fats may increase prostate cancer risk. This study investigates associations of dietary fat, meat, and dairy foods with prostate cancer risk among 12,025 men in the Carotene and Retinol Efficacy Trial (CARET). After 11 y of follow-up, 890 incident prostate cancers were reported and confirmed. Diet was assessed by a biannual FFQ. Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HR) of intake of fat and fat-related foods (meat and dairy) with prostate cancer incidence. Multiplicative interaction terms tested whether associations differed by family history, race, or smoking. Overall, fat was not associated with total, nonaggressive or aggressive prostate cancer. In subgroup analyses the HR for men with a family history of prostate cancer were 2.47 (95%CI = 0.96-6.37) and 2.61 (95% CI = 1.01-6.72) for total polyunsaturated fat (PUFA) and (n-6) PUFA for the 4th vs. 1st quartiles of intake, respectively. Red meat was not associated with total or aggressive prostate cancer. However, higher dairy intake had a statistically significant reduced risk of aggressive prostate cancer than lower dairy intake (HR = 0.59, 95% CI = 0.40-0.85). Dairy foods also protected current, but not former, smokers against aggressive cancer (HR = 0.42, 95% CI = 0.25-0.70). Our findings suggest that associations of dietary fat with prostate cancer risk may vary by type of fat or fat-containing food, and that risk may vary by host factors, including family history and smoking.     

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.     

Intake of n-6 and n-3 fatty acids and fish and risk of community-acquired pneumonia in US men

BACKGROUND: Essential fatty acids modulate inflammation and glucose metabolism and may alter infection risk. OBJECTIVE: We examined the association between intakes of n-6 and n-3 fatty acids and fish and the risk of community-acquired pneumonia. DESIGN: We prospectively evaluated 38,378 male US health professionals aged 44-79 y at the outset. We updated medical and lifestyle information biennially through questionnaires and diet every 4 y with the use of a validated food-frequency questionnaire. We excluded men who reported pneumonia, myocardial infarction, stroke, other heart disease, arterial surgery, cancer, or asthma before 1990 or those with incomplete dietary data. Community-acquired pneumonia was determined by blinded medical record review of chest radiographs. RESULTS: During 10 y of follow-up, there were 441 new cases of nonfatal community-acquired pneumonia. Pneumonia risk was lower in men in the highest energy-adjusted quintiles of intake than in men in the lowest quintiles of intake of linoleic acid [multivariate relative risk (RR): 0.70; 95% CI: 0.51, 0.96; P for trend = 0.01] and alpha-linolenic acid (multivariate RR: 0.68; 95% CI: 0.50, 0.93; P for trend = 0.01). Pneumonia risk decreased 4% for every 1-g/d increase in linoleic acid intake (multivariate RR: 0.96; 95% CI: 0.93, 0.99). Pneumonia risk was reduced by 31% for every 1-g/d increase in alpha-linolenic acid intake (multivariate RR: 0.69; 95% CI: 0.51, 0.93). Intakes of eicosapentaenoic acid and docosahexaenoic acid were not significantly related to pneumonia risk. CONCLUSION: Higher intakes of alpha-linolenic and linoleic acids and possibly of fish may reduce the risk of pneumonia.     

n-3 fatty acids and periodontitis in US adults

Background

Periodontitis is a common, chronic inflammatory disease. Although n-3 fatty acids have anti-inflammatory properties, it is unclear whether n-3 fatty acids can treat or prevent periodontitis.

Method

We studied 9,182 adults aged 20 years and older who participated in the National Health and Nutrition Examination Survey between 1999 and 2004. Periodontitis was assessed by dental exam and was defined as >4 mm pocket depth and >3 mm attachment loss in any one tooth. Intake of n-3 fatty acids was assessed by 24-hour dietary recall. We used multivariable logistic regression to estimate the associations between periodontitis and intakes of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linolenic acid (LNA).

Results

The weighted prevalence and 95% confidence interval (CI) of periodontitis was 8.2% (95% CI 7.0 to 9.4). Compared with the lowest tertiles, the adjusted odds ratios for periodontitis associated with the highest tertiles of dietary n-3 intake were 0.78 (95% CI 0.61 to 1.00; P=0.009) for DHA, 0.85 (95% CI 0.67 to 1.08; P=0.10) for EPA, and 0.86 (95% CI 0.60 to 1.23; P=0.28) for LNA. The associations were little changed by multivariable adjustment or exclusion of individuals reporting use of dietary supplements containing DHA, EPA, or LNA.

Conclusions

In this nationally representative sample, higher dietary intakes of DHA and, to a lesser degree, EPA, were associated with lower prevalence of periodontitis. Interventional studies are needed to confirm the potential protective effects of n-3 fatty acids on periodontitis.     

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.     

Fat intake and risk of squamous cell carcinoma of the skin

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.     

Association between Dietary Fatty Acid Patterns and Colorectal Cancer Risk: A Large-Scale Case-Control Study in China

Associations of dietary fatty acids with the risk of colorectal cancer (CRC) remain controversial. The objective of this study was to examine whether dietary-derived fatty acid patterns were related to CRC risk among Chinese people. A total of 2806 CRC patients and 2806 frequency-matched controls were interviewed in this case-control study between July 2010 and May 2021. A food frequency questionnaire was used to gather information on dietary intake. Four fatty acid patterns were identified using factor analysis. The even-long-chain fatty acid pattern had no statistically significant association with CRC risk (adjusted Odds ratio (aOR), 1.16; 95% confidence interval (CI), 0.97–1.39; p_trend = 0.129). However, significant inverse associations were found between the medium-chain and long-chain saturated fatty acid (SFA) pattern (aOR, 0.34; 95%CI, 0.27–0.42), the highly unsaturated fatty acid pattern (aOR, 0.73; 95%CI, 0.60–0.88), the odd-chain fatty acid pattern (aOR, 0.69; 95%CI, 0.57–0.83), and CRC risk. The interaction between fatty acid patterns and sex was observed, and the association between the highly unsaturated fatty acid pattern and CRC risk differed by subsite. In conclusion, increasing the intakes of foods rich in medium-chain SFAs, highly unsaturated fatty acids, and odd-chain fatty acids may be related to a lower risk of CRC.     

Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats

Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P < .01). The effects of the 3 diets were also examined by analyzing the fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.     

Correlation of erythrocyte fatty acid composition and dietary intakes with markers of atherosclerosis in patients with myocardial infarction

The purpose of this study was to examine the hypothesis that erythrocytes that are low in n-3 fatty acids and high in trans-fatty acids and nutrient intakes are associated with the risk of atherosclerosis. Fifty patients with acute nonfatal myocardial infarction were recruited to measure their dietary intake, erythrocyte fatty acid composition, intima medial thickness (IMT), and the Gensini score, which are markers of atherosclerosis. Trans-oleic acid of erythrocytes was positively (P = .05) correlated with the carotid IMT. After adjusting for age, sex, and energy intake, the IMT was negatively associated with the intake of protein, fat, phosphate, zinc, vitamin B₁, vitamin B₂, vitamin B₆, niacin, linoleic acid, linolenic acid, total fatty acids, total n-3 fatty acids, and total n-6 fatty acids. The Gensini score was also negatively associated with the intake of protein, fat, phosphate, sodium, zinc, vitamin E, vitamin B₁, vitamin B₂, vitamin B₆, niacin, linolenic acid, total fatty acids, and total n-3 fatty acids. In conclusion, lower levels of trans-oleic acid (elaidic acid) in erythrocytes and higher intakes of vitamins, minerals, and n-3 fatty acids were associated with the decreased risk of atherosclerosis. However, these findings need further investigation in randomized controlled clinical trials before public health recommendations for atherosclerosis prevention can be made.     

不同n-3/n-6多不饱和脂肪酸构成比膳食对大鼠一磷酸腺苷活化蛋白激酶表达的影响

目的研究不同n-3/n-6配比脂肪酸对大鼠磷酸腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)蛋白及活性表达的影响。方法58只SD大鼠适应性喂养7d后,尾静脉取血。根据血清总胆固醇水平随机分为:空白(基础饲料);高脂(高脂饲料);高脂1:1(高脂饲料+n-3/n-6=1:1配方油);高脂1:5(高脂饲料+n3/n6=1:5配方油);低脂1:1(脱脂基础饲料+n-3/n-6=1:1配方油);低脂1:5(脱脂基础饲料+n3/n6=1:5配方油)6组,喂养45d,观察大鼠摄食与体重增长。于实验前1d,15d,30d,45d分别各取血测血清总胆固醇水平,于D45处死动物。Western blotting分别分析肝和下丘脑组织中AMPK-α总蛋白及其活性表达。结果添加PUFA的4个比例组血清TC、体重与高脂组相比,显著降低,且低脂2个比例组和高脂1:1组均与高脂1:5组相比有显著差异。添加PUFA的4个比例组均与高脂组相比,大鼠下丘脑AMPK-α总蛋白表达水平明显降低,肝AMPK-α蛋白表达水平均比高脂组明显升高。结论PUFA改善血脂可能是通过增加肝AMPK表达,抑制下丘脑AMPK表达,增加肝脂肪酸氧化和抑制食欲,影响血脂代谢。     

A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA^1:1), or low n-3/n-6 PUFA ratio (1∶4, PUFA^1:4). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA^1:1 diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA^1:1 compared with SFA; however, PUFA^1:4 diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA^1:1 diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines.     

Lack of effect of dietary n-6:n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK

Summary Background Indian Asians living in Western Countries have an over 50 % increased risk of coronary heart disease (CHD) relative to their Caucasians counterparts. The atherogenic lipoprotein phenotype (ALP), which is more prevalent in this ethnic group, may in part explain the increased risk. A low dietary long chain n-3 fatty acid (LC n-3 PUFA) intake and a high dietary n-6 PUFA intake and n-6:n-3 PUFA ratio in Indian Asians have been proposed as contributors to the increased ALP incidence and CHD risk in this subgroup. Aim To examine the impact of dietary n-6:n-3 PUFA ratio on membrane fatty acid composition, blood lipid levels and markers of insulin sensitivity in Indian Asians living in the UK. Methods Twentynine males were assigned to either a moderate or high n-6:n-3 PUFA (9 or 16) diet for 6 weeks. Fasting blood samples were collected at baseline and 6 weeks for analysis of triglycerides, total-, LDL- and HDL-cholesterol, non-esterified fatty acids, glucose, insulin, markers of insulin sensitivity and C-reactive protein. Results Group mean saturated fatty acid, MUFA, n-6 PUFA and n-3 PUFA on the moderate and high n-6:n-3 PUFA diets were 26 g/d, 43 g/d, 15 g/d, 2 g/d and 25 g/d, 25 g/d, 28 g/d, 2 g/d respectively. A significantly lower total membrane n-3 PUFA and a trend towards lower EPA and DHA levels were observed following the high n-6:n-3 PUFA diet. However no significant effect of treatment on plasma lipids was evident. There was a trend towards a loss of insulin sensitivity on the high n-6:n- 3 PUFA diet, with the increase in fasting insulin (P = 0.04) and HOMA IR [(insulin x glucose)/ 22.5] (P = 0.02) reaching significance. Conclusion The results of the current study suggest that, within the context of a western diet, it is unlikely that dietary n-6:n-3 PUFA ratio has any major impact on the levels of LC n-3 PUFA in membrane phospholipids or have any major clinically relevant impact on insulin sensitivity and its associated dyslipidaemia. Source of support: This project was funded by the Food Standards Agency (FSA), UK.