Cognitive aging, childhood intelligence, and the use of food supplements: possible involvement of n-3 fatty acids

BACKGROUND: Food supplement use is widely promoted, but little is known about the cognitive effects of food supplements. OBJECTIVE: We examined the effects of food supplement use on cognitive aging. DESIGN: This was an observational study of subjects born in 1936 whose mental ability was tested in 1947 and who were followed up in 2000-2001, at which time cognition, diet, food supplement use, and risk factors for vascular disease were assessed. In a nested case-control study, fish-oil users were matched with nonusers, and cognitive function was related to erythrocyte n-3 fatty acid composition. RESULTS: Childhood intelligence quotient (IQ) did not differ significantly by category of food supplement use (ie, none, fish oil, vitamins, and other). At the age of 64 y, cognitive function was higher in food supplement users than in nonusers before adjustment for childhood IQ. After adjustment for childhood IQ, digit symbol (mental speed) test scores were higher in food supplement users. Fish-oil supplement users consumed more vitamin C and vegetable and cereal fiber than did non-supplement-users. In a nested case-control study, erythrocyte membrane n-3 content was higher in fish-oil supplement users than in nonusers, but cognitive function did not differ significantly between groups. Total erythrocyte n-3 fatty acids and the ratio of docosahexaenoic acid to arachidonic acid was associated with better cognitive function in late life before and after adjustment for childhood IQ. CONCLUSIONS: Food supplement use and erythrocyte n-3 content are associated with better cognitive aging. If associations with n-3 content are causal, optimization of n-3 and n-6 fatty acid intakes could improve retention of cognitive function in old age.     

Apolipoprotein E polymorphism modifies the alcohol-HDL association observed in the National Heart, Lung, and Blood Institute Family Heart Study

BACKGROUND: The apolipoprotein E gene (APOE) allele epsilon4 is associated with an increased risk of cardiovascular disease. The presence of the epsilon4 allele has been associated with lower concentrations of HDL cholesterol, but it is not known whether the epsilon4 allele modifies the association between alcohol consumption and HDL-cholesterol concentrations. OBJECTIVE: The objective of the study was to assess whether the epsilon4 allele modifies the association between alcohol consumption and HDL-cholesterol concentrations. DESIGN: In a cross-sectional design, we studied 670 men and women aged 26-78 y who participated in the National Heart, Lung, and Blood Institute Family Heart Study to assess whether the epsilon4 allele of the gene APOE modifies the association between alcohol consumption and HDL-cholesterol concentrations. Alcohol data were self-reported, and we used multivariate, generalized estimating equations to assess interactions. RESULTS: In a model with adjustment for age, sex, body mass index, smoking, exercise, waist-hip ratio, TV viewing, and study site, there was a significant effect of the interaction between the epsilon4 allele and alcohol consumption on HDL cholesterol (P=0.0001). In the absence of the epsilon4 allele, multivariate adjusted means of HDL were 1.24, 1.36, and 1.54 mmol/L among subjects who never drank and those who currently drink 0.1-12 and >12 g alcohol/d, respectively; in the presence of the epsilon4 allele, the corresponding values were 1.19, 1.27, and 1.25 mmol/L. CONCLUSION: Our data show a significant effect of the interaction between the epsilon4 allele and alcohol consumption on HDL. The increase in HDL associated with alcohol appears to be stronger in subjects without the epsilon4 allele than in those with the epsilon4 allele.     

n 3 fatty acid proportions in plasma and cognitive performance in older adults

BACKGROUND: Very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are suggested to be related to cognitive performance in older adults. However, limited data exist on the association between n-3 PUFAs and performance in specific cognitive domains. OBJECTIVE: We evaluated the association between plasma n-3 PUFA proportions and cognitive performance in 5 cognitive domains and determined whether plasma n-3 PUFA proportions predict cognitive change over 3 y. DESIGN: We used data from the FACIT trial, in which participants received folic acid or placebo capsules for 3 y. Fatty acid proportions in plasma cholesteryl esters at baseline were measured in 807 men and women aged 50-70 y. Cognitive performance for memory, sensorimotor speed, complex speed, information-processing speed, and word fluency was assessed at baseline and after 3 y. The cross-sectional analyses were based on all 807 participants; the longitudinal analyses were based only on 404 participants in the placebo group. RESULTS: Higher plasma n-3 PUFA proportions predicted less decline in sensorimotor speed (multiple linear regression coefficient, z score = 0.31; 95% CI: 0.06, 0.57) and complex speed (0.40; 95% CI: 0.10, 0.70) over 3 y. Plasma n-3 PUFA proportions did not predict 3-y changes in memory, information-processing speed, or word fluency. The cross-sectional analyses showed no association between plasma n-3 PUFA proportions and performance in any of the 5 cognitive domains. CONCLUSIONS: In this population, plasma n-3 PUFA proportions were associated with less decline in the speed-related cognitive domains over 3 y. These results need to be confirmed in randomized controlled trials.     

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.     

Genetic variants of the FADS gene cluster are associated with erythrocyte membrane LC PUFA levels in patients with mild cognitive impairment

Background

Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI).

Methods

The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes).

Results

Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck’s depression-inventory).

Discussion and conclusion

These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.

     

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。     

Apolipoprotein E genotypes and the incidence of Alzheimer's disease among persons aged 75 years and older: variation by use of antihypertensive medication?

The authors examined the impact of the apolipoprotein E (APOE)(*)epsilon4 allele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondemented Swedish subjects aged >/=75 years was followed for an average of 3 years (1990-1992); 164 dementia (122 Alzheimer's disease) cases were identified. Compared with (*)epsilon3/(*)epsilon3, the APOE(*)epsilon4 allele increased the risk of developing dementia (relative risk (RR) = 1.5, 95% confidence interval (CI): 1.1, 2.1) and Alzheimer's disease (RR = 1.7, 95% CI: 1.2, 2.5). Subjects using antihypertensive medication at baseline (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% CI: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) after adjustment for several variables, including APOE. The effect of antihypertensive medication use was more pronounced among (*)epsilon4 carriers. For those not using antihypertensive medication, the relative risks of dementia and Alzheimer's disease for carriers were 2.2 (95% CI: 1.4, 3.4) and 2.3 (95% CI: 1.4, 3.7), respectively. The corresponding relative risks for those using antihypertensive medication were 0.9 (95% CI: 0.5, 1.6) and 1.1 (95% CI: 0.6, 2.2). The APOE(*)epsilon4 allele is an important predictor of dementia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.     

APOE polymorphism and the hypertriglyceridemic effect of dietary sucrose

BACKGROUND: The E4 allele of the apolipoprotein gene (APOE) is associated with a greater serum cholesterol response to dietary changes in fat and cholesterol. However, less is known about the interaction between APOE polymorphism and other macronutrients in the diet. OBJECTIVE: We evaluated the interaction between APOE polymorphism and dietary fat and carbohydrate, particularly sucrose, in relation to serum lipid concentrations. DESIGN: A total of 284 men and 130 women with coronary artery disease (mean age: 61 y; range: 33-74 y) participated in the cross-sectional EUROASPIRE study. Serum lipids and fatty acids in cholesteryl esters (CEs) were measured and APOE genotypes were determined. Dietary intake was examined by using a 4-d food record. RESULTS: Patients were grouped by APOE genotype: E2 (E2/E2 and E2/E3; n = 21), E3 (E3/E3; n = 245), and E4 (E4/E2, E4/E3, and E4/E4; n = 148). Patients with the E2 allele had lower LDL-cholesterol concentrations and tended to have higher triacylglycerol concentrations than did patients with the E3 or E4 allele; concentrations were not significantly different between the last 2 groups. In regression analysis, significant predictors of serum triacylglycerol were the interaction between sucrose intake and the E2 allele, proportion of n-3 fatty acids in CEs, body mass index, and diabetes. A high sucrose intake was associated with high triacylglycerol concentrations only in patients with the E2 allele. Interaction between saturated fat intake and the E2 allele, proportion of linoleic acid in CEs, and fiber intake predicted serum cholesterol. CONCLUSION: Coronary artery disease patients with the E2 allele will likely have a greater triacylglycerol response to high dietary sucrose intakes than will patients with the E3 or E4 allele.     

Methodological problems in genetic association studies of longevity--the apolipoprotein E gene as an example

BACKGROUND: Cross-sectional genetic association studies are now widely employed to look for genes which confer longevity. Such studies are based on two assumptions; (a) initial relative allele frequencies in the different age cohorts are similar, and (b) the risk of mortality conferred by genotypes does not depend on year of birth. METHODS: We explored the validity of these assumptions and reviewed 15 cross-sectional studies of common apolipoprotein E (APOE) polymorphisms and longevity. RESULTS: Higher relative epsilon2 frequencies, and lower relative epsilon4 allele frequencies were observed in elderly versus younger populations. If assumptions (a) and (b) were correct the estimates for epsilon2 and epsilon4 alleles respectively versus epsilon3 alleles would be 1.34 (95% CI: 1.19, 1.35) and 0.54 (95% CI: 0.46, 0.63) in elderly versus younger individuals. However, there was an association between relative epsilon4 allele frequency in controls and APOE epsilon4 effect (beta = -0.45, 95% CI: -0.89, 0.00). In relation to assumption (a) there is substantial variation in relative APOE allele frequencies (4-21%), with considerable heterogeneity evident within geographically proximate populations, population admixture is likely to have resulted in changes in allele frequency over time, and assumption (b) APOE related causes of death are context specific and have changed considerably over the last 30 years. CONCLUSION: The validity of case-control type studies of the genetic basis of longevity based on the above assumptions is questionable, especially when considerable differences exist in allele frequency by population and when the genes in question interact with environmental factors, which vary by time and place.     

Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old

Background. Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties. Methods. We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer’s disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD. Results. During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia. Conclusions. Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.     

Maternal fish oil supplementation during lactation does not affect blood pressure, pulse wave velocity, or heart rate variability in 2.5-y-old children

Maternal (n-3) PUFA deficiency is associated with higher blood pressure (BP) later in life in rat offspring, and early intake of (n-3) PUFA in formula-fed infants was shown to modify later BP. BP, heart rate (HR), and heart rate variability (HRV) are affected by dietary (n-3) PUFA in adults. In this study, we investigated whether fish oil (FO) supplementation of lactating mothers could modify BP, pulse wave velocity (PWV), and HRV in their children after 2 y. Mothers with low fish intake were randomly assigned to FO or olive oil (OO) supplementation for the first 4 mo after delivery. A reference group of mothers with a high habitual fish intake (HFI) was also followed. At the follow-up study at 2.5 y of age, BP and PWV were measured, and electrocardiograms were recorded for 0.5 h. FO supplementation significantly increased RBC levels of long-chain (n-3) PUFA of the 4 mo-old children, but at 2.5 y, the FO and OO groups did not differ. BP, PWV, HR, and HRV also did not differ among the groups. However, for all 3 groups, the children's intake of (n-3) PUFA at 2.5 y was negatively correlated with mean arterial pressure after adjustment for outdoor temperature (r = -0.245, P = 0.04). In conclusion, maternal FO supplementation had no overall effect on BP, PWV, or HRV of the children, indicating that (n-3) PUFA intake of Danish mothers may be sufficient in this sense. However, children's dietary intake of (n-3) PUFA might have a beneficial effect on BP in childhood.     

Moderate increase in dietary sucrose does not influence fasting or postprandial serum lipids regardless of the presence of apolipoprotein E2 allele in healthy subjects

OBJECTIVE: To investigate whether a moderate increase in dietary sucrose intake induces different serum lipid responses in normolipidemic subjects with the epsilon 2 allele compared with subjects without the epsilon 2 allele. DESIGN: Controlled, parallel study. SUBJECTS: There were 15 subjects with the apolipoprotein E (APOE)3/2 genotype and 19 subjects with the APOE 3/3 or 3/4 genotype, whose mean+/-s.d. age was 48+/-14 and 35+/-10 years, respectively. All subjects had normal glucose metabolism. INTERVENTIONS: The subjects were instructed to increase their sucrose intake by 40 g/day for 8 weeks and to decrease the intake of saturated and unsaturated fat to maintain energy balance. Dietary adherence was monitored using food records and the actual increase in sucrose intake was 39.8+/-18.4 g/day. Sixteen subjects (nine with APOE 3/2 genotype, seven with APOE 3/3 or 3/4 genotypes) participated also in an 8 h oral fat tolerance test at the beginning and at the end of the intervention. RESULTS: Body weight remained stable during the intervention. Sucrose intake did not have a significant effect on fasting concentrations of serum total and lipoprotein lipids, plasma glucose, serum insulin, squalene and non-cholesterol sterols in either genotype group. Neither were there any changes in postprandial lipid or insulin responses. CONCLUSIONS: Moderate increase in sucrose intake does not affect fasting or postprandial serum lipid responses in healthy subjects with or without the epsilon 2 allele.     

Bread enriched with microencapsulated tuna oil increases plasma docosahexaenoic acid and total omega-3 fatty acids in humans

The aim of this study was to determine the acute and chronic effects of low doses of long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (<100 mg per day) on plasma LC n-3 PUFA levels using a novel delivery form; bread containing microencapsulated tuna oil (MTO). Six omnivores (three men and three women) participated in the acute study, which involved ingesting a prototype MTO bread containing approximately 80 mg of LC n-3 PUFA/four slices. Plasma triacylglycerol fatty acid compositions were measured after an overnight fast and postprandially at 2 and 4 h. In the chronic study, 10 vegetarian subjects (nine men and one woman) consumed MTO bread at six to eight slices/day (comprising 60 mg of LC n-3 PUFA) as the only dietary source of these PUFA for three weeks. Fasting plasma total and phospholipid fatty acid compositions were measured at baseline and endpoint. In the acute study, the proportions of 22:6 n-3 and total n-3 PUFA in plasma triacylglycerol were significantly increased (P < 0.05). In the chronic study, the proportions of 20:5 n-3, 22:5 n-3, 22:6 n-3, total n-3 PUFA in plasma, and 22:6 n-3 and total n-3 PUFA in plasma phospholipid fractions were significantly increased (P < 0.05) at the endpoint compared with the baseline. This study showed that a low dose of LC n-3 PUFA, consumed as MTO-enriched bread, was bioavailable, as measured by an increase in LC n-3 PUFA levels in the plasma of human subjects.     

Omega-3 Fatty Acid Intake during Pregnancy and Child Neuropsychological Development: A Multi-Centre Population-Based Birth Cohort Study in Spain

Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child’s neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children’s Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings.     

Current evidence for the clinical use of long-chain polyunsaturated N-3 fatty acids to prevent age-related cognitive decline and Alzheimer’s disease

An NIH State of the Science Conference panel concluded in 2010 that insufficient evidence is available to recommend the use of any primary prevention therapy for Alzheimer’s disease or cognitive decline with age. Despite the insufficient evidence, candidate therapies with varying levels of evidence for safety and efficacy are taken by the public and discussed in the media. One example is the long-chain n-3 (omega-3) polyunsaturated fatty acids (n-3 LC-PUFA), DHA and EPA, found in some fish and dietary supplements. With this report, we seek to provide a practical overview and rating of the level and type of available evidence that n-3 LC-PUFA supplements are safe and protective against cognitive aging and Alzheimer’s disease, with additional discussion of the evidence for effects on quality of life, vascular aging, and the rate of aging. We discuss available sources, dose, bioavailability, and variables that may impact the response to n-3 LC-PUFA treatment such as baseline n-3 LC-PUFA status, APOE ?4 genotype, depression, and background diet. Lastly, we list ongoing clinical trials and propose next research steps to validate these fatty acids for primary prevention of cognitive aging and dementia. Of particular relevance, epidemiology indicates a higher risk of cognitive decline in people in the lower quartile of n-3 LC-PUFA intake or blood levels but these populations have not been specifically targeted by RCTs.     

Erythrocyte fatty acid composition is associated with the risk of hypertension in middle-aged and older women

Experimental studies have suggested different effects of various fats on blood pressure. However, epidemiologic evidence of these relations remains limited and inconsistent. We therefore assessed the association of fatty acid (FA) composition in erythrocyte membranes with the risk of hypertension. We selected 516 cases of incident hypertension and 516 matched controls during 12.9 y of follow-up in the Women's Health Study. Erythrocyte FA was measured in baseline bloods using GC. After controlling matching factors and lifestyle factors, erythrocyte SFA showed a positive association, whereas total cis PUFA, cis (n-3) PUFA, and the ratio of PUFA:SFA (PS ratio) showed an inverse association with the risk of hypertension. The multivariable RR of hypertension across the increasing quartiles of erythrocyte FA subtypes were 1.00, 1.19, 1.44, and 1.76 for total SFA; 1.00, 0.84, 0.88, and 0.56 for total cis PUFA; 1.00, 0.87, 0.66, and 0.65 for cis (n-3) PUFA; and 1.00, 0.99, 0.70, and 0.51 for the PS ratio. After further adjusting for obesity-related metabolic factors, these associations were attenuated and remained significant only for the PS ratio. cis MUFA, cis (n-6) PUFA, and trans unsaturated FA in erythrocyte membranes were not associated with the risk of hypertension. Our study showed that FA composition in erythrocyte membranes is associated with the risk of hypertension in middle-aged and older women. However, after controlling for obesity-related metabolic factors, the associations remained significant only for the PS ratio.     

Dietary fish intake and plasma phospholipid n-3 polyunsaturated fatty acid concentrations in men and women in the European Prospective Investigation into Cancer-Norfolk United Kingdom cohort

BACKGROUND: The n-3 polyunsaturated fatty acids (n-3 PUFAs) docosahexaenoic acid and eicosapentaenoic acid, found in fish and fish-oil supplements and also formed by conversion of alpha-linolenic acid in soy and rapeseed (canola) oils, are thought to have cardioprotective effects. OBJECTIVE: Because the relative feasibility and measurement error of dietary methods varies, this study compared fish and fish-oil intakes obtained from 4 dietary methods with plasma n-3 PUFAs in men and women in a general population. DESIGN: The study participants were 4949 men and women aged 40-79 y from the European Prospective Investigation into Cancer-Norfolk United Kingdom cohort. Measurements of plasma phospholipid n-3 PUFA concentrations and fish intakes were made with the use of 4 dietary methods (food-frequency questionnaire, health and lifestyle questionnaire, 7-d diary, and first-day recall from the 7-d diary). RESULTS: Amounts of fish consumed and relations with plasma phospholipid n-3 PUFAs were not substantially different between the 4 dietary methods. Plasma n-3 PUFA concentrations were significantly higher in women than in men, were 20% higher in fish-oil consumers than in non-fish-oil consumers, and were twice as high in fatty fish consumers as in total fish consumers. Only approximately 25% of the variation in plasma n-3 PUFA was explained by fish and fish-oil consumption. CONCLUSIONS: This large study found no substantial differences between dietary methods and observed clear sex differences in plasma n-3 PUFAs. Because variation in n-3 PUFA was only partially determined by fish and fish-oil consumption, this could explain the inconsistent results of observational and intervention studies on coronary artery disease protection.     

Administration of low doses of fish oil derived N-3 fatty acids to elderly subjects

OBJECTIVES: To assess the incorporation of n-3 polyunsaturated fatty acids (PUFA) in plasma and erythrocyte lipids of elderly subjects after ingestion of very low doses of fish oil. The effects on alpha-tocopherol and retinol concentrations were also studied. SETTING: Municipal nursing home in Barcelona, Spain. SUBJECTS: Forty-five elderly subjects aged 60-92 y. DESIGN AND INTERVENTION: Subjects received a non-commercialized milk formula containing 1% fish oil for 15 months, which provided 0.40 g/d of n-3 PUFA. Fatty acid profiles and antioxidant concentrations were measured before and after the intervention period. RESULTS: Fish oil ingestion was associated with significant increases in total n-3 PUFA in plasma and erythrocytes by 32% and 18%, respectively. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid concentrations were higher after the ingestion period both in plasma and erythrocytes (P < 0.05), whereas linoleic and arachidonic acids remained unchanged. The n-6/n-3 ratio decreased by 21% in plasma and by 16% in erythrocytes (P < 0.05). Moreover, younger subjects showed a greater incorporation of EPA and DHA than older subjects. Plasma alpha-tocopherol and retinol concentrations did not vary significantly, whereas erythrocyte alpha-tocopherol was significantly higher after the intervention period. CONCLUSION: This study shows that low doses of n-3 PUFA supplemented with adequate amounts of alpha-tocopherol can be incorporated into blood lipids in elderly subjects without lowering their antioxidant concentrations.     

Long-chain polyunsaturated fatty acids at birth and cognitive function at 7 y of age

OBJECTIVE: During the central nervous system (CNS) growth spurt, rapid accretion of long chain polyunsaturated fatty acids (LCPUFA) takes place. This particularly concerns docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6), which are thought to play important roles in CNS development and function. The aim of this study was to investigate the relationship between cognitive performance at 7 y of age and LCPUFA levels in umbilical venous plasma phospholipids, representing the prenatal fatty acid availability, and in plasma phospholipids sampled at 7 y. DESIGN: As part of a follow-up study, the cognitive performance of 306 children, born at term, was assessed at 7 y of age with the Kaufman Assessment Battery for Children. Backward stepwise regression analysis was used to study the relationship between the outcomes and LCPUFA status. Social class, maternal intelligence and parenting skills were included as covariables, among others. RESULTS: Results show no significant association with either DHA or AA at birth and the cognitive performance at 7 y of age. The LCPUFA levels at 7 y were not associated with these outcomes either. Consistent with the literature, significant relationships were found between cognitive outcome measures and maternal education, maternal intelligence and the child's birthweight. CONCLUSIONS: In conclusion, our results do not provide evidence for a positive association between cognitive performance at 7 y and LCPUFA status at birth or at 7 y of age.     

Serum 25-hydroxyvitamin D concentrations are associated with erythrocyte levels of n-3 PUFA but not risk of CVD

Increasing evidence suggests that the status of vitamin D and n-3 PUFA is associated with the risk of CVD. Major dietary sources of vitamin D include fish and fish products, which are also rich in n-3 PUFA; however, the relationship between serum 25-hydroxyvitamin D levels and tissue contents of n-3 PUFA remains unknown. The present study investigates the hypothesis that serum 25-hydroxyvitamin D and erythrocyte n-3 PUFA levels are positively correlated in patients with CVD. We recruited sixty CVD cases and matched them with sixty healthy controls based on age, sex and season during which blood was drawn for the study. As serum 25-hydroxyvitamin D levels increased, erythrocyte levels of docosapentaenoic acid, DHA, omega-3 index and total n-3 PUFA increased significantly, while erythrocyte levels of stearic acid and total SFA decreased significantly, after adjusting for age, sex, BMI and smoking. Partial correlation analysis also showed that erythrocyte n-3 PUFA levels were positively correlated (r 0·215; P?=?0·021) and total SFA content was negatively correlated (r -?0·263; P?=?0·004) with serum 25-hydroxyvitamin D levels. However, multiple logistic regression analysis showed that serum 25-hydroxyvitamin D levels were not significantly associated with the risk of CVD, after adjusting or not adjusting for age, sex, BMI and smoking. In conclusion, the results of our case-control study suggest that serum 25-hydroxyvitamin D levels are positively related to erythrocyte n-3 PUFA levels, but are not associated with the risk of CVD in this population.