Plasma Phospholipid Fatty Acid Levels Research Articles

Associations between Fatty Acid Intakes and Plasma Phospholipid Fatty Acid Concentrations in the European Prospective Investigation into Cancer and Nutrition.

The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort (n = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels. Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain n-3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for n-3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)). Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study

Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

Circulating plasma phospholipid fatty acid levels and breast cancer risk in the Cancer Prevention Study-II Nutrition Cohort.

Prospective studies that objectively measure circulating levels of fatty acids are needed to clarify their role in the etiology of breast cancer. Thirty-eight phospholipid fatty acids were measured using gas chromatograph in the plasma fraction of blood samples collected prospectively from 2718 postmenopausal women (905 breast cancer cases) enrolled in the Cancer Prevention Study II Nutrition Cohort. Associations of 28 fatty acids that passed quality control metrics (modeled as per 1-SD increase) with breast cancer risk were assessed using multiple variable conditional logistic regression models to compute odds ratios (OR) and 95% confidence intervals (CI). The false discovery rate (q value) was computed to account for multiple comparisons. Myristic acid levels were positively associated with breast cancer risk (OR, 1.17, 95% CI: 1.07-1.28; q value=0.03). Borderline associations were also found for palmitoleic acid (OR, 1.14, 95% CI: 1.04-1.24) and desaturation index16 (OR, 1.10, 95% CI: 1.01-1.20) at nominal P values (<.03) (q values>0.05). These findings suggest that higher circulating levels of myristic acid, sourced from dietary intake of palm kernel oils along with increased de novo synthesis of fatty acids, may increase breast cancer risk. Additional studies are needed to investigate de novo synthesis of fatty acid in breast cancer tissues.

Abstract LB079: Circulating plasma phospholipid fatty acid levels &amp; breast cancer risk in the CPS-II Nutrition Cohort

Abstract Circulating plasma phospholipid fatty acid levels and breast cancer risk in the CPS-II Nutrition Cohort Background The association between dietary fat intake and breast cancer risk has been a source of controversy with conflicting results reported in past decades. Additional prospective studies that objectively measure circulating levels of fatty acids are now needed to better understand the associations between dietary fat and breast cancer development. MethodsWe assessed the relation between breast cancer risk and plasma levels of 60 phospholipid fatty acids in a nested case-control study of 2,718 postmenopausal women (905 breast cancer cases and 1,813 matched controls) enrolled in the Cancer Prevention Study II (CPS-II) Nutrition Cohort. Blood samples were collected at baseline (1997-1998). Multivariable-adjusted conditional logistic regression models that included established breast cancer risk factors (alcohol use, postmenopausal hormone use, smoking status, waist circumference, body mass index, and weight change from age 18 years to blood draw) were used to compute odds ratios (OR) and 95% confidence intervals (CI). The false discovery rate (FDR; q-value) was computed to control for multiple comparisons. ResultsAfter adjustment for multiple comparisons and in continuous log-transformed multivariable models, plasma levels of myristic acid (a saturated fatty acid) were positively associated with breast cancer risk (OR per log-value, 1.17, 95% CI: 1.07-1.28; q-value = 0.03), with similar magnitude associations found for estrogen receptor (ER) positive and ER negative breast cancer (p-interaction = 0.39). Positive associations were also found for plasma levels of monounsaturated fatty acid (OR per log-value, 1.09, 95% CI: 1.00-1.18; q-value = 0.24), palmitoleic acid (OR per log-value, 1.14, 95% CI: 1.04-1.24; q-value = 0.09), palmitic acid (OR per log-value, 1.12, 95% CI: 1.01-1.24; q-value = 0.17), dihomo-γ-linolenic acid (OR per log-value, 1.14, 95% CI: 1.04-1.25; q-value = 0.09), and adrenic acid (OR per log-value, 1.13, 95% CI: 1.03-1.24; q-value = 0.11) with breast cancer risk; however, after adjustment for multiple comparisons these associations did not reach the threshold of statistical significance. Similarly, inverse associations between plasma levels of trans α-linolenic acid (OR per log-value, 0.85, 95% CI: 0.76-0.96; q-value = 0.09), heptadecanoic acid (OR per log-value, 0.90, 95% CI: 0.82-0.99; q-value = 0.17), and vaccenic acid (OR per log-value, 0.88, 95% CI: 0.80-0.97; q-value = 0.11) with breast cancer risk were not statistically significant after adjustment for multiple comparisons. ConclusionThese findings suggest that higher circulating levels of myristic acid, that can be sourced from dietary intake of dairy foods or via de novo synthesis, may increase breast cancer risk. Additional studies are needed to replicate this finding and provide mechanistic insights. Citation Format: Michele Matta, Emily Deubler, Veronique Chajès, Marc Gunter, Neil Murphy, Mia M. Gaudet. Circulating plasma phospholipid fatty acid levels &amp; breast cancer risk in the CPS-II Nutrition Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB079.

Plasma Phospholipid Fatty Acids, FADS1 and Risk of 15 Cardiovascular Diseases: A Mendelian Randomisation Study.

Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs. We performed a secondary analysis of the association between a functional variant (rs174547) in FADS1, which encodes 𝛥5-desaturase (a key enzyme in the endogenous FA synthesis), and CVD. Genetic predisposition to higher plasma α-linolenic, linoleic, and oleic acid levels was associated with lower odds of large-artery stroke and venous thromboembolism, whereas higher arachidonic and stearic acid levels were associated with higher odds of these two CVDs. The associations were driven by SNPs in or close to FADS1. In the secondary analysis, the minor allele of rs174547 in FADS1 was associated with significantly lower odds of any ischemic stroke, large-artery stroke, and venous thromboembolism and showed suggestive evidence of inverse association with coronary artery disease, abdominal aortic aneurysm and aortic valve stenosis. Genetically higher plasma α-linolenic, linoleic, and oleic acid levels are inversely associated with large-artery stroke and venous thromboembolism, whereas arachidonic and stearic acid levels are positively associated with these CVDs. The associations were driven by FADS1, which was also associated with other CVDs.

Plasma phospholipid fatty acids, bone mineral density and fracture risk: Evidence from a Mendelian randomization study.

Available epidemiological evidence on the associations of individual fatty acids (FAs) with bone mineral density and fracture risk is inconsistent and scarce. We conducted a two-sample Mendelian randomization study to explore these relationships. Summary-level data from up to 426824 individuals in UK Biobank for estimated bone mineral density (eBMD) derived from heel quantitative ultrasound and bone fractures were used in this study. Single-nucleotide polymorphisms associated with plasma phospholipid FA levels at genome-wide significance were exploited as instrumental variables. Analyses were conducted using the inverse-variance weighted method. Eight of ten FAs were associated with eBMD and fracture risk. Specifically, genetic predisposition to higher plasma α-linolenic acid, linoleic acid, palmitoleic acid, and oleic acid levels was positively associated with eBMD and inversely associated with the odds of fracture, whereas the opposite directions were observed for plasma arachidonic acid, eicosapentaenoic acid, docosapentanenoic acid, and stearic acid levels. Most of the associations were driven by single-nucleotide polymorphisms within or nearby the FADS1 and FADS2 genes, which explained the largest proportion of variance in FA levels. The associations of arachidonic acid and palmitoleic acid with eBMD remained after exclusion of the variants in the FADS1-FADS2 gene regions. FADS encodes fatty acid desaturases, which have a major role in FA metabolism. Genetic variations in plasma levels of several FAs were associated with eBMD and fracture risk. Variants in FADS1-FADS2 were the major determinants of the observed associations, except the associations of arachidonic acid and palmitoleic acid with eBMD.

Plasma Phospholipid Fatty Acids and Risk of Atrial Fibrillation: A Mendelian Randomization Study.

Available evidence on the associations of dietary and circulating levels of long-chain n-3 fatty acids, which have potential antiarrhythmic properties, and other fatty acids with atrial fibrillation is conflicting and limited. We conducted a Mendelian randomization study to assess the associations between plasma phospholipid fatty acid levels and atrial fibrillation. Summary-level data of atrial fibrillation were available from 65,446 cases and 522,744 non-cases included in the Atrial Fibrillation Consortium. Sixteen single-nucleotide polymorphisms associated with ten fatty acids at significance level of p < 5 × 10−8 were identified as instrumental variables from the hitherto largest genome-wide association studies for plasma fatty acids. The fixed-effects inverse-variance weighted method was used to assess the association of individual plasma fatty acids and atrial fibrillation risk. The random-effects inverse-variance weighted method, weighted median method, and Mendelian randomization (MR)-Egger method were employed as the sensitivity analyses. Genetic predisposition to higher levels of any of the ten individual fatty acids was not associated with atrial fibrillation risk.

Trans-fatty Acids and Survival in Renal Transplantation

High consumption of trans-fatty acids (TFAs) is associated with increased mortality. Observational cohort study of 1.988 Norwegian renal transplant recipients with a median follow-up time of 9.6 years. We assessed multivariable adjusted associations between plasma levels of industrial and ruminant TFAs with patient and graft survival. Plasma phospholipid fatty acid levels were determined by gas chromatography at 10 weeks after transplantation. During follow-up, there were 595 deaths, and 805 grafts were lost. Plasma industrial TFA levels dropped from 0.3 wt% in years 1999-2004 to reach a plateau of 0.2 wt% from year 2005 and beyond, whereas plasma levels of ruminant TFAs remained stable throughout the study period. In the former era (years 1999 to 2004, n=902), we found multivariable adjusted associations between plasma industrial TFA levels and mortality (hazard ratio 4.44, P=.02) and graft loss (hazard ratio 4.22, P=.01). In the latter era (years 2005 to 2011, n=1,086), there were no associations between plasma industrial TFA levels and patient or graft survival. Plasma ruminant TFAs were not associated with mortality or graft loss in either eras. In this Norwegian transplant cohort, plasma industrial TFA levels dropped from around 0.3 wt% in the former era to 0.2 wt% in the latter era. While plasma industrial TFA was significantly associated with survival in the former era, no associations were found with survival in the latter era. This finding suggests that lowering industrial TFA consumption from modest to low levels could possibly influence health beneficially after renal transplantation.

Preconception Plasma Phospholipid Fatty Acids and Fecundability.

Fatty acids (FAs) are important for reproductive processes, including steroidogenesis, though associations with fecundability, as measured by time to pregnancy (TTP), are unclear. To investigate the relationship between preconception plasma phospholipid FA (PPFA) levels and time to human chorionic gonadotropin-pregnancy among women with prior pregnancy loss. Prospective cohort of 1228 women attempting pregnancy (aged 18 to 40 years, with one or two prior pregnancy losses) followed for up to six cycles at four US university medical centers during 2006 to 2012. PPFA levels were measured at baseline. Associations with fecundability overall and by body mass index (BMI) group after adjusting for confounders were estimated using fecundability odds ratios (FORs) and 95% CIs. False discovery rate (FDR) was used to account for multiple comparisons. Monounsaturated fatty acids (MUFAs) were associated with increased fecundability or shorter TTP [FOR, 1.08 (95% CI, 1.01 to 1.16) per unit increase in percentage of total FAs], whereas polyunsaturated fatty acids (PUFAs) were associated with decreased fecundability or longer TTP [FOR, 0.95 (95% CI, 0.91 to 1.00) per 1% change], though associations only remained significant after FDR adjustment among women with BMI <25 kg/m2. Saturated FA and trans FA were not associated with fecundability. Omega-3 FAs and omega-6 linoleic acid were not associated with fecundability. We observed associations between preconception MUFA and PUFA levels and fecundability among women with normal BMI, highlighting the importance of FA composition among normal-weight women with prior pregnancy loss.

Development of Kidney Transplant Fibrosis Is Inversely Associated With Plasma Marine Fatty Acid Level

We assessed associations between plasma levels of polyunsaturated fatty acids (PUFAs) and degree of inflammation and interstitial fibrosis in transplanted kidneys. The design of the study was single center cohort study. A study population of 156 patients who received a kidney transplant at Oslo University Hospital during2010. Kidney transplant biopsies were obtained at 2months and 1year after transplantation. Degree of inflammation and interstitial fibrosis in the cortex of transplanted kidneys were estimated semi-quantitatively. Plasma phospholipid fatty acids levels were measured in a stable phase 2months posttransplant. We used multivariate linear regression to assess associations between plasma levels of PUFAs and degree of inflammation and interstitial fibrosis at 2months and 1year postoperatively and change in degree of interstitial fibrosis during the first year after transplantation, adjusting for inflammation and fibrosis risk factors. Higher plasma marine n-3 PUFA levels were associated with less development of interstitial fibrosis in the kidney transplant (unstandardized β-coefficient -1.12, standardized β-coefficient -0.18, P=.03) during the first year after transplantation. Plasma levels of alpha linoleic acid, linoleic acid, and arachidonic acid were not associated with development of interstitial fibrosis. No associations were found between plasma levels of PUFAs and inflammation inside fibrotic areas or outside fibrotic areas in the kidney transplant at neither 2months nor 1year postoperatively. Linolenic acid levels in plasma were positively associated with change in renal function during the first year after transplantation. The inverse association between plasma marine n-3 PUFA levels and development of interstitial fibrosis during the first year after kidney transplantation suggests that marine fatty acid consumption might halt progression of fibrosis.

Associations of Plasma Phospholipid Omega-6 and Omega-3 Polyunsaturated Fatty Acid Levels and MRI Measures of Cardiovascular Structure and Function: The Multiethnic Study of Atherosclerosis

Background. The association between plasma omega-6 fatty acids and cardiovascular disease (CVD) is unclear, and discrepancy remains concerning the cardiovascular benefit of the omega-3 fatty acid alpha-linolenic acid. Methods. Associations of plasma phospholipid fatty acid levels (arachidonic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid (DHA), and alpha-linolenic acid) with cardiac magnetic resonance imaging measures of left ventricular (LV) mass, LV volume, ejection fraction, stroke volume, and aortic distensibility were investigated in 1,274 adults. Results. Results of multivariate analysis showed no statistically significant associations of plasma omega-6 or omega-3 levels with cardiac magnetic resonance imaging measures. Stratification by gender revealed a positive association between DHA and LV mass in women (β = 1.89, P = 0.02; P interaction = 0.003) and a trend for a positive association between DHA and ejection fraction in men (β = 0.009, P = 0.05; P interaction = 0.03). Conclusion. Additional research is warranted to clarify the effects of plasma DHA on cardiac structure and function in women versus men.

Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations

Limited information is available with respect to the association between age and the plasma phospholipid fatty acid profile. Therefore we investigated the association between plasma phospholipid fatty acid status and age after correction for sex, smoking, alcohol use, BMI and fish intake. Plasma phospholipid fatty acid composition was measured and information on fish intake and other potential covariates was collected in 234 participants of the Maastricht Aging Study. The participants were healthy individuals of both sexes with an age range between 36 and 88 years. Hierarchical linear regression analyses were applied to study the relationship between age and fatty acid concentrations. After correction for fish consumption and other relevant covariates, a significant positive relationship was observed between age of the subjects and their plasma phospholipid concentrations of DHA (22 : 6n-3, P = 0.006) and EPA (20 : 5n-3; P = 0.001). Age contributed 2.3 and 3.9 % to the amount of explained variance, respectively. The higher n-3 long-chain PUFA status at advanced age was confirmed by lower concentrations of their putative 'shortage marker' Osbond acid (ObA, 22 : 5n-6; P = 0.022 for the relationship with age after correction for covariates and fish intake, R2 0.022). Concentrations of linoleic acid (LA; 18 : 2n-6) were negatively associated with age (P < 0.001; R2 0.061). In conclusion, DHA and EPA concentrations appeared to be higher in older age groups, partly because of a higher fish intake and partly because of another age-associated mechanism, possibly involving the well-known competition with LA.

Relation between plasma phospholipid saturated fatty acids and hyperinsulinemia

We determined whether plasma phospholipid fatty acid levels, an indicator of fatty acid composition in the diet, are associated with fasting serum insulin concentrations (a marker of insulin resistance). We examined cross-sectionally 4,304 middle-aged adults free of diabetes. Plasma fatty acid composition was quantified by gas chromatography. Fasting insulin was strongly and positively associated with the saturated fatty acid percentage in plasma phospholipids, moderately and inversely associated with the monounsaturated percentage, and not appreciably associated with the polyunsaturated percentage. Fasting insulin adjusted for age, smoking status, alcohol consumption, and sports participation, for example, was 29% higher in men and 33% higher in women per 1.9% greater level of saturated fatty acids (the interquartile range). After adjustment for body mass index (BMI) and other covariates, these estimates were 12% and 15% ( P < .01 for the difference from zero). A 1.9% greater increment in saturated fatty acid level was also associated with a 2.4-fold higher odds of hyperinsulinemia (fasting insulin ≥ 143.5 pmol/L). These data are consistent with studies showing that fatty acid composition of cell membranes modulates insulin action, and support the hypothesis that increased habitual saturated fat intake or a related dietary pattern is a risk factor for hyperinsulinemia.