Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study

This study investigated the correlation between the plasma phospholipid (PL) saturated fatty acid (SFA) concentration (as a surrogate marker of SFA intake) and plasma lipid and lipoprotein lipid concentrations in 139 healthy Australian men aged 20-55 years old with widely varying intakes of saturated fat (vegans, n=18; ovolacto vegetarians, n=43; moderate meat eaters, n=60; high meat eaters, n=18). Both the ovolacto vegetarian and vegan groups demonstrated significant decreases in plasma total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C) and triacylglycerol concentrations compared with both the high-meat-eater and moderate-meat-eater groups. Total SFA and individual SFA [palmitic acid (16:0), stearic acid (18:0) and arachidic acid (20:0)] in the plasma PL were significantly lower in both the ovolacto vegetarian and vegan groups than in both the high- and moderate-meat-eater groups, while myristic acid (14:0) was significantly lower in the vegans than in the high-meat-eaters. Bivariate analysis of the results showed that the plasma PL stearic acid concentration was strongly positively correlated with plasma TC (P<0.0001), LDL-C (P<0.0001) and triacylglycerol (P<0.0001), with r(2) values of 0.655, 0.518 and 0.43 respectively. In multiple linear regression, after controlling for potential confounding factors (such as exercise, dietary group, age, body mass index, plasma PL myristic acid, palmitic acid and arachidic acid, and dietary total fat, saturated fat, cholesterol, carbohydrate and fibre intake), the plasma PL stearic acid concentration was still strongly positively correlated with plasma TC (P<0.0001) and LDL-C (P=0.006) concentrations. Based on the present data, it would seem appropriate for the population to reduce their dietary total SFA intake rather than to replace other SFA with stearic acid.

Epidemiological studies on the effect of individual saturated fatty acids (SFAs) on cardiovascular disease, especially in developing countries with different dietary patterns, are scarce. To determine the risk of nonfatal acute myocardial infarction (MI) associated with consumption of individual SFAs and their food sources in Costa Rica. The cases (n=485) were survivors of a first acute MI and were matched by age, sex and area of residence to population controls (n=508). Data on anthropometrical measurements, lifestyle and diet were collected using interviewer-administered questionnaires. In analyses adjusted for confounders, consumption of total and individual SFAs was associated with an increased risk of MI. The odds ratio (OR) (95% confidence intervals) for 1% increase in energy from total saturated fat was 1.12 (1.03-1.21) while it was 1.51 (1.03-2.22) for lauric acid+myristic acid, 1.14 (1.01-1.30) for palmitic acid and 2.00 (1.34-3.00) for stearic acid. Although lauric and myristic acids were associated with increased risk of MI, they were consumed in small amounts and most of the saturated fat (87%) came from palmitic and stearic acids, which derived mainly from red meat and fried foods. Consumption of cheese (1-2 vs 0 servings/day) was associated with increased risk of MI (OR=3.07; 95% confidence interval: 1.74-5.39; P for trend <0.0001), while consumption of low-fat milk was not. Increased consumption of total and individual SFAs is associated with increased risk of MI. Lauric, myristic and stearic acids were more potent than palmitic acid.

Objectives To investigate the association between long term intake of individual saturated fatty acids (SFAs) and the risk of coronary heart disease, in two large cohort studies. Design Prospective, longitudinal...

Effects of dietary fiber content and different fiber-rich ingredients on endogenous loss of fat and fatty acids in growing pigs

Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up=15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 =0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 =0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 =0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 =0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 =1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD =0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD =1.04, 95%CI:0.95-1.15, Pheterogeneity =0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD =1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.

PurposeThe association between dietary saturated fatty acids (SFA) intake and type 2 diabetes (T2D) remains unclear. This study aimed at investigating the association between SFA intake and T2D risk based on (1) individual SFA (differing in carbon chain length), (2) food sources of SFA and (3) the substituting macronutrients.Methods37,421 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included in this study. Baseline dietary intake was assessed by a validated food frequency questionnaire. T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates.Results893 incident T2D cases were documented during 10.1-year follow-up. We observed no association between total SFA and T2D risk. Marginally inverse associations were found for lauric acid (HR per 1 SD of energy%, 95% CI 0.92, 0.85–0.99), myristic acid (0.89, 0.79–0.99), margaric acid (0.84, 0.73–0.97), odd-chain SFA (pentadecylic plus margaric acids; 0.88, 0.79–0.99), and cheese derived SFA (0.90, 0.83–0.98). Soft and liquid fats derived SFA was found related to higher T2D risk (1.08, 1.01–1.17). When substituting SFA by proteins, carbohydrates and polyunsaturated fatty acids, significantly higher risks of T2D were observed (HRs per 1 energy% ranging from 1.05 to 1.15).ConclusionIn this Dutch population, total SFA does not relate to T2D risk. Rather, the association may depend on the types and food sources of SFA. Cheese-derived SFA and individual SFA that are commonly found in cheese, were significantly related to lower T2D risks. We cannot exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by trans fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein.

Objectives. Type 2 diabetes and the consumption of saturated fatty acids (FAs) are on the rise among Alaska Inuits. This analysis, based on a cross-sectional study, explores the possible associations of saturated FA content in red blood cells (RBCs) and parameters of glucose metabolism in a sample of Alaska Natives.Study design and methods. The sample included 343 women and 282 men aged 35–74. Statistical analyses explored the associations of selected RBC (myristic, palmitic and stearic acids) FAs with fasting glucose (plasma), fasting insulin (plasma), 2h glucose (2-hour glucose tolerance test), 2h insulin and homeostasis model assessment (HOMA) index. The models included sex and glucose metabolism status as fixed factors and age, body mass index (BMI), waist circumference, physical activity (METS) and FA content in RBCs as covariates. Measures of insulin, glucose and HOMA index were used as dependent variables.Results. Myristic acid was positively associated with fasting insulin (β=0.47, p&0.001), 2h insulin (β=0.53, p=0.02) and HOMA index (β=0.455, p&0.001). Palmitic acid was associated with 2h glucose (β=2.3×10–2, p&0.001) and 2h insulin (β=5.6×10-2, p=0.002) and stearic acid was associated with fasting glucose (β=4.8×10-3, p=0.006).Conclusions. These results strongly support the hypothesis that saturated fatty acids are associated with insulin resistance and glucose intolerance and that saturated fatty acids are significant risk factors for type 2 diabetes.

Background/Aims: Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Methods: Differentiated preadipocytes were treated with either 250 µ<smlcap>M</smlcap> PA, SA, PMA, or OA for 48 h. Gene expression was analyzed using microarrays and real-time RT-PCR. Data were compared with those of a previous study reporting AT gene expression in humans following the consumption of SFA- or MUFA-enriched diets. Results: Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Conclusions: Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.

ABSTRACTBackgroundLittle is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population.ObjectiveThe aim of this study was to estimate changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes.MethodsPlasma phospholipid fatty acids were profiled at 3 time-points (1993–1997, 1998–2000, 2004–2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Linear regression models were used to estimate both 1) mean changes over time in 27 individual fatty acids and 8 prespecified fatty acid groups and 2) associations of changes in dietary and lifestyle factors with changes in the 8 fatty acid groups, mutually adjusted for dietary/lifestyle factors and other confounders. The prespecified fatty acid groups were odd-chain saturated fatty acids (SFAs), even-chain SFAs, very-long-chain SFAs, marine n–3 polyunsaturated fatty acids (PUFAs), plant n–3 PUFA, n–6 PUFAs, monounsaturated fatty acids (MUFAs), and trans-fatty acids (TFAs).ResultsAdjusted for confounders, fatty acid concentrations decreased for odd-chain SFAs (annual percentage difference in mol percentage: −0.63%), even-chain SFAs (−0.05%), n–6 PUFAs (−0.25%), and TFAs (−7.84%). In contrast, concentrations increased for marine n–3 PUFAs (1.28%) and MUFAs (0.45%), but there were no changes in very-long-chain SFAs or plant n–3 PUFA. Changes in fatty acid levels were associated with consumption of different food groups. For example, a mean 100 g/d increase in fatty fish intake was associated with a 19.3% greater annual increase in marine n–3 PUFAs.ConclusionsEven-chain SFAs and TFAs declined and marine n–3 PUFAs increased over time. These changes were partially explained by changes in dietary habits, and could potentially help interpret associations of baseline fatty acid composition with future disease risk.

BackgroundCombinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.Methods and findingsWe measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991–1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19–0.29) adjusted for potential confounders and 0.37 (95% CI 0.27–0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.ConclusionsA combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

Consumption of individual saturated fatty acids and the risk of myocardial infarction in a UK and a Danish cohort

Very-long-chain n−3 fatty acids as biomarkers for intake of fish and n−3 fatty acid concentrates

The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition–Netherlands cohort

Dietary intervention studies report neutral effects of stearic acid (18:0) on blood lipids, compared with lauric acid (12:0), myristic acid (14:0) and palmitic acid (16:0). Evidence from observational studies on the associations between intakes of individual saturated fatty acids (SFAs) and risk of CHD is scarce. We prospectively followed 72,102 women in the Nurses’ Health Study (1984-2010) and 42,874 men in the Health Professionals Follow-Up Study (1986-2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by validated food-frequency questionnaire and updated every 4 years. Baseline percentages of energy from total and major 4 subgroups (4:0-10:0, 12:0-14:0, 16:0, and 18:0) of even-chain SFA, were 11.8%, 0.6%, 1.3%, 6.6%, and 3.3% for women, and 10.8%, 0.5%, 1.1%, 6.1%, and 3.1% for men. Spearman correlations among baseline individual SFA intakes ranged from 0.43 (between 4:0-10:0 group and 18:0 in both cohorts) to 0.92 (between 16:0 and 18:0 in women). We generated 18:0 residual by regressing 18:0 on intakes of other SFAs. During 2.6 million person-years of follow-up, 6,843 incident CHD cases were documented. In the multivariate model, intakes of 4:0-10:0, 12:0-14:0, and 16:0, but not 18:0, were positively associated with risk of CHD (P&lt;0.05). After further adjusting for dietary factors, hazard ratios (95% confidence interval, HR[95%CI]) of CHD per 1% energy increase were 1.10 (0.98, 1.22; P=0.10) for 4:0-10:0, 1.11 (1.03, 1.18; P=0.003) for 12:0-14:0, 1.09 (1.04, 1.13; P&lt;0.001) for 16:0, and 0.98 (0.94, 1.01; P=0.22) for 18:0. The HR per 0.2 increase in the ratio of polyunsaturated fat (PUFA) to SFA was 0.93 (0.90, 0.96; P&lt;0.001). The HRs of CHD risk per 1% of energy PUFA replacing SFA were 0.92(0.85,0.99; P=0.03) for 12:0-14:0 and 0.91(0.87,0.95;P&lt;0.001) for 16:0; but PUFA replacing 4:0-10:0 or 18:0 were not associated with CHD risk: HRs were 0.98(0.86,1.11; P=0.74) and 0.97(0.93,1.01; P=0.19), respectively. Our findings indicate that while 12:0-16:0 were associated with increased CHD risk, short-to-medium-chain SFA and 18:0 were not. However, our results need to be interpreted with caution because saturated fatty acids share common food sources and are highly correlated.

The contribution of dietary saturated fatty acids (SFA) to cardiovascular disease (CVD) and mortality remains debated after decades of research. Few previous studies had repeated dietary assessments and power to assess mortality. Evidence for individual SFA is limited. In this large population-based cohort study, we investigated associations between intake of total and individual SFA and risk of total and CVD mortality. Adult residents (mean 41·1 years at baseline) in three Norwegian counties were invited to repeated health screenings between 1974 and 1988 (> 80 % attendance). We calculated cumulative average intakes of macronutrients from semi-quantitative FFQ. Median (interquartile range) intake of SFA was 14·6 % (12·8–16·6 %) of total energy (E%). Hazard ratios (HR) and 95 % CI were estimated using multivariable Cox regression models to assess total, CVD, ischaemic heart disease (IHD) and acute myocardial infarction (AMI) mortality. Among 78 725 participants, 28 555 deaths occurred during a median follow-up of 33·5 years, with 9318 deaths due to CVD. Higher intake of SFA (replacing carbohydrates) was positively associated with all mortality endpoints, including total (HR per 5 E% increment, 1·18; 95 % CI 1·13, 1·23) and CVD mortality (1·16; 95 % CI 1·07, 1·25). Theoretical isoenergetic substitution of SFA with carbohydrates or MUFA was associated with lower risk. Of individual SFA, myristic (14:0) and palmitic acid (16:0) were positively associated with mortality. In summary, dietary SFA intake was strongly associated with higher total and CVD mortality in this long-term cohort study. This supports policies implemented to reduce SFA consumption in favour of carbohydrates and unsaturated fats.