Plasma Phospholipid Fatty Acid Research Articles

Abstract MP38: Plasma Lipophilic Index and Risk of Coronary Heart Disease in Postmenopausal Women

Introduction: Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index (LI, defined as the sum of the products between FA percentage and melting points (°C) of each FA, divided by the total percentage of FAs) is a novel index that captures the overall FA profile and reflects lipoprotein fluidity. Limited studies have evaluated the relationship between plasma LI and CHD risk, and none has assessed this association among postmenopausal women. Hypothesis: Higher plasma LI is associated with increased CHD risk among postmenopausal women. Methods: In a nested case-control study in Women’s Health Initiative Observational Study, we measured levels of plasma phospholipid FAs, expressed as molar percentage (mol%), in 1214 matched CHD cases (including myocardial infarction and coronary death) and controls. Multivariate conditional logistic regression was used to calculate ORs for CHD risk between each quartiles (based on controls) of LI after adjusting for confounders. Results: The mean age of the women was 67.8±6.8 years, average BMI was 27.6±6.0, 89.5% were White, 6.6% were current smokers, 41.2% were hypertensive, and 15.2% had dyslipidemia. The median plasma LI among cases and controls were 22.5 and 22.1, respectively. Palmitic acid (16:0) and stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), and docosahexaenoic acid (22:6) were the most common saturated, monounsaturated, n-6 and n-3 polyunsaturated FAs, respectively. The association between quartiles of LI and CHD risk are shown in Table below. After multivariate adjustment in the parsimonious model, plasma LI was significantly associated with an increased risk of CHD: OR=1.61 (95% CI 1.25-2.07, P for trend<0.01) comparing extreme quartiles. This association was attenuated to 1.57 (1.22 - 2.03, P for trend<0.01) in the fully adjusted model. Conclusion: Our study indicated that higher plasma LI, which represents lower FA fluidity, was associated with higher risk of CHD among postmenopausal women.

Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis.

BackgroundAcculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults.Methods and FindingsParticipants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake.ConclusionAbsence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease.

Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children

BackgroundThere is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children.ObjectiveThe objective was to evaluate the suitability of a food frequency questionnaire (FFQ) to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).DesignCross-sectional data for the present study were derived from the prospective cohort ‘Environmental Triggers of Type 1 Diabetes Study’. Infants were recruited from the Norwegian general population during 2001–2007. One hundred and ten (age 3–10 years) children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution.ResultsSignificant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29), total fat dairy products (r=0.39), and cheese products (r=0.36). EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively) and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA). To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker.ConclusionsThe present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a high-fat content and cod liver/fish oil supplements.

Plasma phospholipid arachidonic acid and lignoceric acid are associated with the risk of cardioembolic stroke

Cardioembolic (CE) stroke is the most severe subtype of ischemic stroke with high recurrence and mortality. However, there is still little information on the association of plasma fatty acid (FA) with CE stroke. The objective of this study was to test the hypothesis whether the composition of plasma phospholipid FA is associated with the risk of CE stroke. The study subjects were collected from the Korea University Stroke Registry. Twenty-one subjects were selected as CE stroke group, and 39 age- and sex-matched subjects with non-CE stroke were selected as controls. Sociodemographic factors, clinical measurements, and plasma phospholipid FA compositions were compared between the groups. Logistic regression was used to obtain estimates of the associations between the relevant FAs and CE stroke. The result showed that the CE stroke group had higher levels of free FA and lower levels of triglycerides before and after adjustment (all P < .05). In the regression analysis, elaidic acid (18:1Tn9) and arachidonic acid (20:4n6) were positively related, but lignoceric acid (24:0) was negatively related to CE stroke in all constructed models (all P < .05). In conclusion, plasma phospholipid FA composition was associated with CE stroke risk in Korean population, with higher proportions of elaidic acid and arachidonic acid and lower proportion of lignoceric acid in CE stroke.

Plasma levels of marine n-3 polyunsaturated fatty acids and renal allograft survival.

Marine n-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on inflammation, fibrosis, endothelial function, lipid profile and blood pressure that may prevent graft loss. In this observational cohort study in Norwegian renal transplant recipients (n = 1990), transplanted between 1999 and 2011, associations between plasma marine n-3 PUFA levels and graft loss were assessed by multivariable Cox proportional hazard regression analysis. Plasma phospholipid fatty acid composition was determined by gas chromatography and individual fatty acids recorded as weight percentage (wt%) of total fatty acids in a stable phase 10 weeks after transplantation. During a median follow-up time of 6.8 years, 569 (28.6%) renal allografts were lost, either due to patient death (n = 340, 59.8% of graft loss) or graft loss in surviving patients (n = 229, 40.2%). Plasma marine n-3 PUFA levels ranged from 1.35 to 23.87 wt%, with a median level of 7.95 wt% (interquartile range 6.20-10.03 wt%). When adjusting for established graft loss risk factors, there was a 11% reduced risk of graft loss for every 1.0 wt% increase in marine n-3 PUFA level [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.84-0.93], and a 10% reduced risk of graft loss in surviving patients (adjusted HR 0.90; 95% CI 0.84-0.97). High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival.

Interaction between Marine-Derived n-3 Long Chain Polyunsaturated Fatty Acids and Uric Acid on Glucose Metabolism and Risk of Type 2 Diabetes Mellitus: A Case-Control Study.

The present case-control study explored the interaction between marine-derived n-3 long chain polyunsaturated fatty acids (n-3 LC PUFAs) and uric acid (UA) on glucose metabolism and risk of type 2 diabetes mellitus (T2DM). Two hundred and eleven healthy subjects in control group and 268 T2DM subjects in case group were included. Plasma phospholipid (PL) fatty acids and biochemical parameters were detected by standard methods. Plasma PL C22:6n-3 was significantly lower in case group than in control group, and was negatively correlated with fasting glucose (r = −0.177, p < 0.001). Higher plasma PL C22:6n-3 was associated with lower risk of T2DM, and the OR was 0.32 (95% confidence interval (CI), 0.12 to 0.80; p = 0.016) for per unit increase of C22:6n-3. UA was significantly lower in case group than in control group. UA was positively correlated with fasting glucose in healthy subjects, but this correlation became negative in T2DM subjects. A significant interaction was observed between C22:6n-3 and UA on fasting glucose (p for interaction = 0.005): the lowering effect of C22:6n-3 was only significant in subjects with a lower level of UA. In conclusion, C22:6n-3 interacts with UA to modulate glucose metabolism.

Abnormalities in Plasma Phospholipid Fatty Acid Profiles of Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. In the present study, we aimed to profile the possible changes in plasma phospholipid fatty acid composition of HCC patients, and to identify the fatty acid biomarkers that could distinguish HCC patients from healthy controls. A total of 37 plasma samples from healthy controls and HCC patients were collected and their phospholipid fatty acid profiles were characterized by gas chromatography-mass spectrometry followed by multivariate statistical analysis. Twenty-five fatty acids were identified and quantified, their proportions varied greatly between two groups, suggesting each group has its own fatty acid pattern. Orthogonal partial least squares discriminant analysis in terms of fatty acid profiles showed that HCC patients could be clearly distinguished from healthy controls. More importantly, linoleic acid (18:2n-6), oleic acid (18:1n-9), arachidonic acid (20:4n-6) and palmitic acid (16:0) were identified as the potential fatty acid biomarkers of HCC patients. Additionally, to further identify the major cause of the abnormality of plasma fatty acid profile, fatty acid distributions of cancerous tissue and its surrounding tissue from 42 HCC patients were also examined. Due to have similar variation trend of major fatty acid biomarkers, linoleic acid (18:2n-6), oleic acid (18:1n-9), abnormalities in plasma phospholipid fatty acid profiles of HCC patients may be mainly attributed to the alternation of intrinsic fatty acid metabolism caused by cancer per se, but not to the differences in dietary factors.

High-Oleic Ready-to-Use Therapeutic Food Maintains Docosahexaenoic Acid Status in Severe Malnutrition.

Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. It contains large amounts of linoleic acid and little α-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high-oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status. We conducted a prospective, randomized, double-blind clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid fatty acid status was measured on enrollment and after 4 weeks and compared between the 2 intervention groups. Among the 141 children enrolled, 48 of 71 receiving HO-RUTF and 50 of 70 receiving RUTF recovered. Plasma phospholipid samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and -25% in the HO-RUTF and RUTF groups, respectively (P = 0.04). For EPA, the change in content was 63% and -24% in the HO-RUTF and RUTF groups, respectively (P < 0.001). For arachidonic acid, the change in content was -3% and 13% in the HO-RUTF and RUTF groups, respectively (P < 0.009). The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation because they suggest that HO-RUTF support improved polyunsaturated fatty acid status, necessary for neural development and recovery.

Efficacy of docosahexaenoic acid-enriched formula to enhance maternal and fetal blood docosahexaenoic acid levels: Randomized double-blinded placebo-controlled trial of pregnant women with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) compromises the level of docosahexaenoic acid (DHA) in phospholipids of maternal and fetal red blood cells and fetal plasma. This is of some concern because of the importance of DHA for fetal neuro-visual development. We have investigated whether this abnormality could be rectified by supplementation with DHA-enriched formula. Women with GDM (n=138) recruited from Newham University Hospital, London received two capsules of DHA-enriched formula (active-group) or high oleic acid sunflower seed oil (placebo-group) from diagnosis until delivery. Maternal (baseline and delivery) and fetal (cord blood) red blood cell and plasma phospholipid fatty acid composition, and neonatal anthropometry were assessed. One hundred and fourteen women (58 active, 56 placebo) completed the trial. The active-group compared with the placebo-group had significantly enhanced level of DHA in plasma phosphatidylcholine (4.5% vs 3.8%, P=0.011), red blood cell phosphatidylcholine (2.7% vs 2.2%, P=0.022) and phosphatidylethoanolamine (9.5% vs 7.6%, P=0.002). There was no difference in cord plasma and red blood cell phospholipid DHA between the two groups. The neonates of the two groups of women had comparable anthropometric measurements at birth. Daily supplementation of 600mg DHA enhances maternal but not fetal DHA status in pregnancy complicated by GDM. The inefficacy of the supplement to improve fetal status suggests that the transfer of DHA across the placenta maybe impaired in women with the condition. Regardless of the mechanisms responsible for the impairment of the transfer, the finding has implications for the management of neonates of women with GDM because they are born with a reduced level of DHA and the condition is thought to be associated with a risk of neuro-developmental deficits. We suggest that babies of women with GDM, particularly those not suckling, similar to the babies born prematurely require formula milk fortified with a higher level of DHA.

Changes in Plasma Phospholipid Fatty Acid Patterns and their Impact on Plasma Triglyceride Levels Following Fish Oil Supplementation

The objective of the present study was to test for associations between changes in fatty acids (FAs) and changes in plasma triglyceride (TG) levels after an n-3 FA supplementation and to test whether SNPs from the FADS gene cluster were associ- ated with plasma FA levels or with specific FA patterns. A total of 210 subjects completed a 2-wk run-in period followed by 6-wk supplementation with 5g/d of fish oil. FA profiles of plasma phospholipids (PPLs) were obtained and 19 SNPs from the FADS gene cluster were genotyped. Principal component analysis was conducted and scores were calculated. There was an increase in EPA, DPA and DHA levels in PPLs as well as a decrease in ALA and all n-6 FA levels after the supplementa- tion. Factor analysis suggested 4 post-n-3 FA supplementation patterns. Changes in AA, ALA, DGLA, as well as changes in total n-3 and omega-6 FAs in absolute quantities of FAs were all associated with a change in TG levels whereas the cor- relation remained significant only for AA and DGLA when FAs were expressed as percentage of total FAs. Several SNPs from the FADS gene cluster were associated with post-supplementation FA levels. These results suggest that FAs alone or regrouped in factors could play a role in modulating plasma TG levels after fish oil supplementation. SNPs from the FADS gene cluster interact with both FAs and/or factors to modulate TG levels.

Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study

Polyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake. We aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk. Osteoporotic fractures were determined from medical records over 5-9 y of follow-up in men and women aged 66-96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression. In men, the highest tertile of PUFAs, n-3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n-6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98). Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n-3 fatty acid consumption may differ by sex.

Effects of Plasma Phospholipid Fatty Acid Composition and PPAR‐alpha L162V Polymorphism on C‐reactive Protein Levels in Response to an n‐3 Fatty Acid Supplementation

Background Fish-oil derived fatty acids (FAs) of the n-3 family including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce inflammation through several underlying mechanisms including altered phospholipids FA composition. The L162V polymorphism of the PPAR-α gene is associated with a deteriorated metabolic profile and with obesity indices in numerous studies. Objective: To study whether the PPAR-α L162V polymorphism and changes in plasma phospholipid FA composition influence plasma C-reactive protein (CRP) levels in healthy adults following the n-3 FA supplementation. Method: 189 subjects were supplemented daily with 3g of n-3 FAs (1.9-2.2g EPA and 1.1g DHA) during six weeks. Changes in CRP levels are defined by Δ CRP and changes in plasma phospholipids n-3 (EPA+DHA) by Δ n-3. Results: In univariate analyses, Δ n-3 was negatively correlated with Δ CRP (r=-0.17 p=0.02). After stratification for sex, correlations were stronger in men (r=-0.24 p=0.02) and no longer significant in women (r=-0.11 p=0.31). In multiple linear regression analyses including age, sex, BMI, and hormonal contraceptives as independent variables, Δ n-3 (3.65% p= 0.01) and PPAR-α L162V (2.10% p= 0.04) were the strongest correlates of Δ CRP. Conclusions These results suggest that the incorporation of n-3 FAs in plasma phospholipids and PPAR-α L162V polymorphism may contribute to changes in plasma CRP levels in response to an n-3 FA supplementation. Funding provided by CIHR Operating Grant.

Plasma Nutrient Biomarkers are Associated with Waist‐to‐Height Ratio in Youth with Type 1 Diabetes: SEARCH for Diabetes in Youth Nutrition Ancillary Study

BackgroundPlasma nutrient biomarkers may be associated with waist‐to‐height ratio (WHtR) in youth with type 1 diabetes (T1D).Design1,416 youth aged 3‐20 years at diagnosis were included at baseline and 1,178 youth had a follow‐up visit after 23 (range 16‐40) months. Data on plasma phospholipid fatty acids, desaturase activities and vitamins were obtained at baseline. Multiple linear regression was used with adjustment for demographic and diabetes‐related confounders. Findings were stratified by weight status when significant (P&lt;0.05) effect modification was observed.ResultsIn cross‐sectional analysis, palmitic acid (P=0.001), dihomo‐γ‐linolenic acid (DGLA, P=0.003) and Δ6‐desaturase (D6D, P=0.0004) were positively; oleic acid (P=0.014), linoleic acid (LA, P=0.002) and vitamin D (VD, P&lt;0.0001) were negatively associated with WHtR. In normal weight youth, VD (P=0.003) was negatively associated with WHtR. In obese youth, DGLA (P&lt;0.0001) and D6D (P&lt;0.0001) were positively; Δ9‐desaturase‐18 activity (P=0.011) and VD (P&lt;0.0001) were negatively associated with WHtR. In longitudinal analysis, baseline LA (P=0.017), n‐6/n‐3 fatty acid ratio (P=0.017), VD (P=0.003) and vitamin E (P=0.0001) were negatively associated with WHtR at follow‐up only in obese youth.ConclusionsPlasma nutrient biomarkers are associated with WHtR in T1D youth, most commonly among those who are obese.

N‐6 Fatty Acids Instead of n‐3 and Saturated Fatty Acids Correlate with Body Fat Distribution From Subcutaneous Adipose Tissue to Visceral Adipose Tissue in Healthy and Overweight Subjects

ObjectiveOur aim was to investigate the association between the plasma phospholipid (PPL) fatty acid profile and fat distribution in both healthy and overweight subjects.MethodsTotally 108 of 1066 Chinese adults stratified by gender and body mass index (BMI) were enrolled. The subjects received lifestyle questionnaire survey, physical examination and magnetic resonance imaging (MRI) scan. The PPL fatty acid profile was determined by gas chromatography. The fat distribution including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue (IMAT) and skeletal muscle (SM) was measured by MRI.ResultsPPL n‐3 PUFA levels were inversely associated with SAT in healthy but not overweight subjects. However, no correlation between PPL n‐3 PUFA levels and VAT was observed. PPL n‐6 PUFA levels were directly correlated with SAT and VAT in healthy subjects, while PPL SFA levels were positively associated with SAT and VAT in overweight subjects. Multiple regression analysis revealed PPL n‐6 PUFA were positively correlated with SAT instead of VAT in healthy subjects, but positively associated with VAT instead of SAT in overweight subjects after adjustment for age, sex, BMI, smoking, drinking and education level. PPL n‐3 PUFA did not significantly correlate with both SAT and VAT after adjustments. Logistic regression results showed that PPL n‐6 PUFA levels could be used to estimate the obese state.ConclusionsPPL phospholipid n‐6 PUFA instead of n‐3 PUFA and SFA as important predictors positively correlate with fat distribution from SAT to VAT. Consequently, PPL n‐6 PUFA levels could be used to estimate the obese state.

Plasma Nutrient Biomarkers Are Associated with Waist-to-Height Ratio in Youth with Type 1 Diabetes1–4

Plasma fatty acids (FAs) and micronutrients have been associated with central obesity in adults; however, previous studies of these associations in adults have yielded mixed results. In addition, no comparable research has been conducted among youth with type 1 diabetes (T1D). We investigated the cross-sectional and longitudinal associations between plasma nutrient biomarkers and waist-to-height ratio (WHtR) in youth with T1D. These analyses included 1324 youth aged 3-20 y at T1D diagnosis with a baseline visit in the SEARCH (Search for Diabetes in Youth) Study and a subset of 1178 of these youth with a follow-up visit an average of 23 mo (range: 16-40 mo) after their baseline visit. Plasma phospholipid FAs and vitamins were measured, and estimated desaturase activities were calculated at baseline. Anthropometric measurements and diabetes-related assessments were collected at each visit. Multiple linear regression was used to examine the association between plasma nutrient biomarkers and WHtR. In cross-sectional analysis, plasma palmitic acid (P = 0.004), dihomo-γ-linolenic acid (DGLA; P = 0.017) and Δ6 desaturase (D6D; P = 0.006) were positively correlated with WHtR after adjustment of confounders. Oleic acid (OA; P = 0.002), linoleic acid (LA; P = 0.015), Δ9 desaturase 18 (D9D-18; P = 0.027), and vitamin D (P < 0.0001) were negatively correlated with WHtR after adjustment. Weight status was an effect modifier (P < 0.05). In normal-weight youth, vitamin D (P = 0.003) was negatively associated with WHtR. In obese youth, stearic acid (P = 0.037), DGLA (P < 0.0001), and D6D (P < 0.0001) were positively associated and OA (P = 0.0008), D9D-18 (P = 0.0006), and vitamin D (P < 0.0001) were negatively associated with WHtR. In longitudinal analysis, baseline linoleic acid (P = 0.018), n-6:n-3 (ω-3:ω-6) FA ratio (P = 0.029), vitamin D (P = 0.003), and vitamin E (P < 0.0001) were negatively correlated with WHtR at follow-up only in obese participants. In T1D youth, plasma FAs and vitamins are associated with WHtR and are modified by weight status. These associations are particularly marked in obese youth.

Dietary and biomarker estimates of fatty acids and risk of colorectal cancer.

The associations between intake of or circulating fatty acids and risk of colorectal cancer (CRC) are unclear. We examined prospectively the associations between dietary or biomarker fatty acids and CRC. For 41,514 men and women, aged 40-69 years, baseline (1990-94) dietary intakes of fatty acids were estimated using a food frequency questionnaire and plasma phospholipid (PPL) fatty acids were measured for 4,205 participants including 395 CRC cases, according to a case-cohort design. Hazard ratios were computed using Cox regression adjusting for education, alcohol intake, smoking status, physical activity and total energy intake; and stratified for gender, ethnicity and family history of cancer, with age as the time scale. We assessed the heterogeneity of associations with colon and rectal cancers. PPL saturated fatty acids (SFAs) were positively associated with CRC risk, while total n-3 polyunsaturated fatty acids (PUFA) and long chain marine n-3 PUFAs showed inverse associations, significant only for 22:5 n-3. No significant associations were observed for dietary fatty acid intakes but positive associations with CRC of borderline significance were seen for both dietary and PPL linoleic acid. Positive associations with dietary palmitic acid (16:0), MUFAs and n-6 PUFAs were seen for rectal but not colon cancers. PPL 22:6 n-3 was inversely associated with rectal cancer. Limiting intakes of SFAs and MUFAs could be assisted by following existing guidelines to limit red and processed meats which are important sources in the Australian diet. Our observations regarding linoleic acid should be examined further.

Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study

Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes. We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs. In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively. At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes. In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.

The Pharmacokinetic Profile of a New Gastroresistant Capsule Preparation of Eicosapentaenoic Acid as the Free Fatty Acid.

Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for patients with inflammatory bowel diseases (IBD). In this study we analyzed the pharmacokinetic profile of eicosapentaenoic acid (EPA), as the free fatty acid (FFA), in an enteric-coated preparation, in 10 ulcerative colitis (UC) and 10 Crohn's disease (CD) patients and 15 healthy volunteers (HV). Subjects received 2 g daily of EPA-FFA for 8 weeks. Plasma phospholipid and red blood cell (RBC) membrane fatty acid content were measured by gas chromatography-mass spectrometry. There was a rapid incorporation of EPA into plasma phospholipids by 2 weeks and a slower, but highly consistent, incorporation into RBC membranes (4% total fatty acid content; coefficient of variation 10–16%). There was a concomitant reduction in relative n-6 PUFA content. Elongation and desaturation of EPA into docosahexaenoic acid (DHA) via docosapentaenoic acid (DPA) were apparent and DHA content also increased in membranes. EPA-FFA is well tolerated and no difference in the pharmacokinetic profile of n-3 PUFA incorporation was detected between IBD patients and HV. Our data support the concept that EPA can be considered the “universal donor” with respect to key n-3 PUFAs and that this enteric-coated formulation allows long term treatment with a high level of compliance.

Relative validation of the dietary intake of fatty acids among adults in the Swedish National Dietary Survey using plasma phospholipid fatty acid composition.

The aims of a national dietary study are several-fold. One purpose is to monitor the intake of foods and nutrients in the population and to compare intakes with dietary recommendations. It is, however, difficult to measure dietary fat intake and plasma biomarker fatty acid (FA) composition may be used as an objective measure of dietary fat intake. Thus, the relative ability of a diet record to capture habitual fat intake was validated against biomarker FA. Dietary fat intake was measured in a novel self-assisted web-based 4-d food record - the 'Riksmaten' method. Spearman rank correlations between dietary FA, certain food groups (fish-shellfish, dairy products, meat and sausages, and spreads) and the fat content of these food groups and biomarker FA were explored. Participants were 150 women and 129 men, aged 18-80 years, who took part in the Swedish National Dietary Survey, Riksmaten adults 2010-11. Blood samples were collected on average 20 d after the diet record and FA composition was measured in plasma phospholipids by GLC. Total n-3 FA (r 0·31), EPA (r 0·34) and DHA (r 0·42) were correlated between plasma and diet (all P≤0·001). Adjustment for covariates attenuated the relationships. Linoleic acid was only marginally correlated (r 0·15; P=0·06) in women. Plasma pentadecaenoic acid and heptadecaenoic acid were correlated with dairy product intake as previously reported. In conclusion, the Riksmaten method appears valid for the purpose of collecting data on dietary fat composition, at least in a healthy adult population.

A genome-wide association study of saturated, mono- and polyunsaturated red blood cell fatty acids in the Framingham Heart Offspring Study

Most genome-wide association studies have explored relationships between genetic variants and plasma phospholipid fatty acid proportions, but few have examined apparent genetic influences on the membrane fatty acid profile of red blood cells (RBC). Using RBC fatty acid data from the Framingham Offspring Study, we analyzed over 2.5 million single nucleotide polymorphisms (SNPs) for association with 14 RBC fatty acids identifying 191 different SNPs associated with at least 1 fatty acid. Significant associations (p<1×10−8) were located within five distinct 1MB regions. Of particular interest were novel associations between (1) arachidonic acid and PCOLCE2 (regulates apoA-I maturation and modulates apoA-I levels), and (2) oleic and linoleic acid and LPCAT3 (mediates the transfer of fatty acids between glycerolipids). We also replicated previously identified strong associations between SNPs in the FADS (chromosome 11) and ELOVL (chromosome 6) regions. Multiple SNPs explained 8–14% of the variation in 3 high abundance (>11%) fatty acids, but only 1–3% in 4 low abundance (<3%) fatty acids, with the notable exception of dihomo-gamma linolenic acid with 53% of variance explained by SNPs. Further studies are needed to determine the extent to which variations in these genes influence tissue fatty acid content and pathways modulated by fatty acids.