Blood fatty acid analysis reveals similar n-3 fatty acid composition in non-pregnant and pregnant women and their neonates in an Israeli pilot study.

Maternal docosahexaenoic acid (DHA) is required during pregnancy to supply for normal fetal growth and development. This pilot study aimed to assess the unknown fatty acid (FA) composition in a cohort of non-pregnant and pregnant Israeli women at term and their offspring on a normal diet without n-3 FA supplementation. The fatty acid profile, analyzed using gas chromatography, showed significantly higher plasma monounsaturated (MUFA) and lower n-6 FA percent distribution with similar n-3 index, in pregnant compared to non-pregnant women. RBC exhibited significantly higher MUFA with similar n-3 index, in pregnant compared to non-pregnant women. N-3 FA significantly correlated between neonates' plasma, with higher n-3 index, and pregnant women's DHA. Conclusion: DHA levels in non-pregnant and pregnant Israeli women at term were comparable and the DHA in pregnant women's plasma positively correlated with their neonate's level, suggesting an efficient mother-fetus FA transfer and/or fetal fatty acid metabolism to longer FA products.

Association between erythrocyte membrane n-3 and n-6 polyunsaturated fatty acids and carotid atherosclerosis: A prospective study.

BACKGROUND AND AIMS: The relationship of polyunsaturated fatty acids (PUFAs) with cardiovascular risk is still controversial. We aimed to determine whether erythrocyte n-3 and n-6 PUFAs are related to the risk of carotid atherosclerosis. METHODS: From 2008 to 2019, baseline erythrocyte n-3 and n-6 PUFAs were determined in a cohort of 4040 Chinese adults (40-75 ys). The intima-media thickness (IMT) at the common carotid artery (CCA) and bifurcation of the carotid artery (BIF) and carotid plaque were assessed using ultrasonography at baseline and every 3 years. RESULTS: During a median follow-up of 8.8 years, we identified the following newly diagnosed cases: 535 cases of CCAIMT thickening, 654 cases of BIFIMT thickening, and 850 cases of carotid plaque. Higher erythrocyte docosahexaenoic acid (DHA) and arachidonic acid (ARA) and lower gamma-linolenic acid (GLA) were associated with decreased risks of BIFIMT thickening. N-3 eicosatrienoic acid (ETrA), docosapentaenoic acid (DPA), and n-6 dodecylthioacetic acid (DTA) presented a significant beneficial association with carotid IMT thickening in the short-term (2.8 y) follow-up (all p trend <0.02), although the association was attenuated in the relatively long-term (8.8 y) follow-up. In addition, carotid plaque risk was found to be inversely associated with ETrA and DHA but positively associated with alpha-linolenic acid (ALA). N-6 linolenic acid (LA) and eicosadienoic acid (EDA) were not significantly associated with carotid atherosclerosis risk. CONCLUSIONS: Higher erythrocyte very-long-chain n-3 and n-6 PUFAs (especially DHA and ARA) and lower erythrocyte GLA are associated with lower carotid atherosclerosis risk, suggesting potential cardioprotective roles of very-long-chain PUFAs.

Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils.

BACKGROUND: Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of É£-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-É£-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively. OBJECTIVES: The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleotide polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA, and ARA. METHODS: Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Merr.; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention. RESULTS: SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03, 2.85) in TT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA. CONCLUSIONS: The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils. This trial was registered at clinicaltrials.gov as NCT02337231.

Is There a Link between Zinc Intake and Status with Plasma Fatty Acid Profile and Desaturase Activities in Dyslipidemic Subjects?

The prevalence of obesity and dyslipidemia has increased worldwide. The role of trace elements in the pathogenesis of these conditions is not well understood. This study examines the relationship between dietary zinc (Zn) intake and plasma concentrations of Zn, copper (Cu) and iron (Fe) with lipid profile indicators, fatty acid composition in plasma phospholipids and desaturase enzyme activities in a dyslipidemic population. The role of the newly proposed biomarker of Zn status, the linoleic:dihomo-gama-linolenic acid (LA:DGLA) ratio, in predicting Zn status of dyslipidemic subjects has been explored. The study included 27 dyslipidemic adults, 39-72 years old. Trace elements were determined using atomic absorption spectrometry and fatty acid composition by a liquid gas chromatography. Desaturase activities were calculated from product-precursor fatty acid ratios. Dietary data were obtained using 24 h recall questionnaires. Insufficient dietary intake of Zn, low plasma Zn concentrations and an altered Cu:Zn ratio is related to modified fatty acid profile in subjects with dyslipidemia. Plasma Zn status was associated with obesity. There was no correlation between dietary Zn intake and plasma Zn status. The LA:DGLA ratio was inversely linked to dietary Zn intake. Cu, in addition to Zn, may directly or indirectly, affect the activity of desaturase enzymes.

ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.

Serum n-6 polyunsaturated fatty acids and risk of death: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Background: The cardioprotective properties of linoleic acid (LA), a major n-6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. Relatively little is also known about how the minor n-6 PUFAs-γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)-relate to mortality risk. Objective: We investigated the associations of serum n-6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations. Design: We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y at baseline in 1984-1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease. Results: During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend < 0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend < 0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend = 0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction > 0.13). Conclusions: Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.

Different effects of γ-linolenic acid (GLA) supplementation on plasma and red blood cell phospholipid fatty acid composition and calcium oxalate kidney stone risk factors in healthy subjects from two race groups with different risk profiles pose questions about the GLA-arachidonic acid-oxaluria metabolic pathway: pilot study.

Fatty acid (FA) composition of phospholipids in plasma and red blood cells (RBC) can influence calciuria, oxaluria and renal stone formation. In this regard, the ratio of arachidonic acid (AA) and its precursor linoleic acid (LA) appears to be important. Administration of γ-linolenic acid (GLA) has been shown to increase the concentration of dihomo-gamma linoleic acid (DGLA) relative to AA indicating that it may attenuate biosynthesis of the latter. Such effects have not been investigated in race groups having difference stone occurrence rates. Black (B) and white (W) healthy males ingested capsules containing linoleic acid (LA) and GLA, for 30 days. Plasma and RBC total phospholipid (TPL) FA profiles, serum and 24 h urine biomarkers of hypercalciuria and urinary stone risk factors were determined on days 0 and 30. Data were tested for statistical significance using GraphPadInstat version 3.02. Concentration and percentage content of DGLA in plasma TPL increased in W but not in B. Arachidonic acid (AA) did not change in either group. There was no change in calcium excretion in either group but oxalate and citrate excretion increased in W. We suggest that elongation of GLA to DGLA may occur more rapidly than desaturation of DGLA to AA in W and that depressed activity of the enzyme elongase may occur in B. Calciuric and citraturic effects may be dependent on the quantity of LA or on the mass ratio of LA/GLA in the FA supplement. Questions about the mooted DGLA-AA-oxaluria pathway arise. We speculate that there exists a potential for using GLA as a conservative treatment for hypocitraturia. The observation of different responses in B and W indicates that such differences may play a role in stone formation and prevention.

Metabolic pathways of oleic and palmitic acid are intensified in PCOS patients with normal androgen levels.

CONTEXT: The aetiology and pathogenesis polycystic ovary syndrome (PCOS) remain uncertain and thus the relative studies are still crucial. OBJECTIVE: Our aim was to analyse the fatty acids profiles of the main phospholipids species in serum from women with PCOS classified into phenotypes, and to diagnose women more susceptible to the occurrence of inflammatory state. DESIGN: PCOS screening tests were performed in The Clinic of Gynecology and Urogynecology of Pomeranian Medical University in the 2014-2015 years. SETTING: The study are designed for general community and a primary care or referral center. PATIENTS: 39 patients with PCOS, diagnosed according to Rotterdam's criteria, and 14 healthy women, as a control group, participated in this study. Fatty acid profiles were investigated using gas chromatography. A total of 36 fatty acids and their derivatives were identified and quantified. MAIN OUTCOME MEASURE: Changes in fatty acids profile in plasma from women with PCOS phenotypes are not identical. RESULTS: The analyses showed lowered level of total SFA, increase in the concentration of caprylic acid and the activation of palmitic and oleic acids pathways. The level of nervonic acid was several times higher than in the control group, and the levels of behenic and tricosanoic acids were reduced. CONCLUSIONS: In both phenotypes the alternative metabolic pathways of oleic acid were activated, but they were more pronounced in women with proper level of androgens. Gamma-linolenic acid (C18:3n6) can be a factor protecting hyperandrogenic women.

High Serum Phospholipid Dihomo-γ-Linoleic Acid Concentration and Low Δ5-Desaturase Activity Are Associated with Increased Risk of Type 2 Diabetes among Japanese Adults in the Hitachi Health Study.

Background: The association between the circulating fatty acid (FA) composition and type 2 diabetes (T2D) has been reported in Western populations, but evidence is scarce among Asian populations, including Japanese, who consume large amounts of fish.Objective: The objective of the present study was to prospectively examine the association between circulating concentrations of individual FAs and T2D incidence among Japanese adults.Methods: We conducted a nested case-control study in a cohort of 4754 employees, aged 34-69 y, who attended a comprehensive health checkup in 2008-2009 and donated blood samples for the Hitachi Health Study. During 5 y of follow-up, diabetes was identified on the basis of plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case by sex, age, and date of checkup were randomly chosen by using density sampling, resulting in 336 cases and 678 controls with FA measurements. GC was used to measure the FA composition in serum phospholipids. Cox proportional hazards regression was used to estimate the HRs and 95% CIs after adjusting for potential confounders. We examined the association of T2D risk with 25 different individual and combinations of FAs.Results: T2D risk was positively associated with serum dihomo-γ-linoleic acid concentration (highest compared with the lowest quartile-HR: 1.49; 95% CI: 1.04, 2.11; P-trend = 0.02) and inversely associated with Δ5-desaturase activity (highest compared with the lowest quartile-HR: 0.72; 95% CI: 0.52, 0.99; P-trend = 0.02), independent of body mass index (BMI). There were also inverse associations between T2D risk with serum total n-6 (ω-6) polyunsaturated fatty acids (PUFAs), linoleic acid, and cis-vaccenic acid, but these were attenuated and became nonsignificant after adjustment for BMI. Serum n-3 (ω-3) PUFAs and saturated fatty acids (SFAs) were not associated with T2D risk.Conclusions: T2D risk was associated with circulating concentrations of the n-6 PUFA dihomo-γ-linoleic acid and Δ5-desaturase activity but not with n-3 PUFA or SFA concentrations in Japanese adults.

Associations of estimated Δ-5-desaturase and Δ-6-desaturase activities with stroke risk factors and risk of stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study.

Stroke is a leading cause of morbidity and mortality. The role of PUFA in reducing the risk of stroke is uncertain. The concentrations of PUFA in the human body are determined both by dietary intake and by activities of desaturase enzymes. Desaturase enzymes have been associated with chronic diseases, but little is known about their association with stroke risk. We investigated the associations of Δ-6-desaturase (D6D) and Δ-5-desaturase (D5D) activities with stroke risk factors and risk of stroke among 1842 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD at baseline in 1984-1989. ANCOVA and Cox regression models were used for the analyses. Whole serum desaturase activities were estimated as product:precursor ratios - γ-linolenic acid:linoleic acid for D6D and arachidonic acid:dihomo-γ-linolenic acid for D5D. Higher D6D activity was associated with higher systolic and diastolic blood pressure, BMI, serum insulin and TAG concentrations and worse homoeostatic model assessment (HOMA) indices. In contrast, higher D5D activity was associated with lower systolic and diastolic blood pressure, BMI, serum insulin, LDL-cholesterol, TAG and C-reactive protein concentrations, higher HDL-cholesterol concentration, and better HOMA indices. During the mean follow-up of 21·2 years, 202 stroke cases occurred. Neither D6D activity (multivariable-adjusted extreme-quartile hazard ratios (HR) 1·18; 95 % CI 0·80, 1·74) nor D5D activity (HR 1·06; 95 % CI 0·70, 1·60) were associated with stroke risk. In conclusion, higher D5D activity was favourably associated and higher D6D activity unfavourably associated with several stroke risk factors, but not with the risk of incident stroke.

Clinical Benefits of n-3 PUFA and ɤ-Linolenic Acid in Patients with Rheumatoid Arthritis.

(1) Background: Marine n-3 polyunsaturated fatty acids (PUFA) and ɤ-linolenic acid (GLA) are well-known anti-inflammatory agents that may help in the treatment of inflammatory disorders. Their effects were examined in patients with rheumatoid arthritis; (2) Methods: Sixty patients with active rheumatoid arthritis were involved in a prospective, randomized trial of a 12 week supplementation with fish oil (group I), fish oil with primrose evening oil (group II), or with no supplementation (group III). Clinical and laboratory evaluations were done at the beginning and at the end of the study; (3) Results: The Disease Activity Score 28 (DAS 28 score), number of tender joints and visual analogue scale (VAS) score decreased notably after supplementation in groups I and II (p < 0.001). In plasma phospholipids the n-6/n-3 fatty acids ratio declined from 15.47 ± 5.51 to 10.62 ± 5.07 (p = 0.005), and from 18.15 ± 5.04 to 13.50 ± 4.81 (p = 0.005) in groups I and II respectively. The combination of n-3 PUFA and GLA (group II) increased ɤ-linolenic acid (0.00 ± 0.00 to 0.13 ± 0.11, p < 0.001), which was undetectable in all groups before the treatments; (4) Conclusion: Daily supplementation with n-3 fatty acids alone or in combination with GLA exerted significant clinical benefits and certain changes in disease activity.

Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to attenuate valproic acid-induced autism-like features.

The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups. The pups were scrutinized on the accounts of behavioral, biochemical, and inflammatory markers, and the results suggested that the GLA can impart significant protection in comparison to ALA against VPA-induced autism features. When scrutinized histopathologically, the cerebellum of the GLA-treated animals was evident for more marked protection toward neuronal degeneration and neuronal loss in comparison to ALA. Concomitant administration of ALA and GLA with VPA demonstrated a marked cutdown in the Pgp 9.5 expression with GLA having more pronounced effect. Henceforth, it can be concluded that ALA and GLA can impart favorable protection against the VPA-induced autism-like features with GLA having pronounced effect.

Serum n-6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: The role of n-6 (ω-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations. OBJECTIVES: We investigated the associations of serum n-6 PUFAs and activities of enzymes involved in PUFA metabolism, Δ5 desaturase (D5D) and Δ6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations. DESIGN: The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y and free of T2D at baseline in 1984-1989. T2D was assessed by self-administered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations. RESULTS: During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74; P-trend < 0.001) and higher concentrations of total n-6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73; P-trend < 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70; P-trend < 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85; P-trend = 0.007) had a lower risk and those with higher concentrations of γ-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68; P = 0.021) and dihomo-γ-linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84; P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97; P-trend < 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04). CONCLUSIONS: Higher serum total n-6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D.

Determination of sex-based differences in serum γ-linolenic [corrected] acid and dihomo-γ-linolenic [corrected] acid using gas chromatography-mass spectrometry.

Because serum unsaturated fatty acids can provide useful information on disease diagnosis, the simultaneous determination of several fatty acids in small volumes of human serum would be beneficial for clinical applications. In the present study, serum fatty acids were extracted with n-heptane/chloroform from 10µL of serum collected from 26 healthy Japanese subjects (11 men, ages 23-37 years; 15 women, ages 18-37 years) after deproteinization with perchloric acid, derivatization to their methyl ester using p-toluenesulfonic acid as an acid catalyst, and subsequent separation and measurement by gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode. Nine types of fatty acids (palmitoleic acid [PLA], oleic acid [OA], linoleic [corrected] acid [LA], γ-linolenic acid [GLA], α-linolenic acid [ALA], dihomo-GLA [DGLA], arachidonic acid [AA], eicosapentaenoic acid [EPA], and docosahexaenoic acid [DHA]) were analyzed in the serum within 35 min by GC-MS. The concentrations of these fatty acids in serum ranged from 3.64±0.38µM (GLA) to 413±26.3 µM (LA). Among these nine fatty acids, GLA and DGLA levels were significantly lower in women than in men (p=0.0034 and 0.0012, respectively), suggesting that there may be sex-based differences in the biosynthetic production or metabolic processes of GLA and DGLA in humans.

Importance of fatty acid compositions in patients with peripheral arterial disease.

OBJECTIVE: Importance of fatty acid components and imbalances has emerged in coronary heart disease. In this study, we analyzed fatty acids and ankle-brachial index (ABI) in a Japanese cohort. METHODS: Peripheral arterial disease (PAD) was diagnosed in 101 patients by ABI ≤0.90 and/or by angiography. Traditional cardiovascular risk factors and components of serum fatty acids were examined in all patients (mean age 73.2±0.9 years; 81 males), and compared with those in 373 age- and sex-matched control subjects with no evidence of PAD. RESULTS: The presence of PAD (mean ABI: 0.71±0.02) was independently associated with low levels of gamma-linolenic acid (GLA) (OR: 0.90; 95% CI: 0.85-0.96; P = 0.002), eicosapentaenoic acid∶arachidonic acid (EPA∶AA) ratio (OR: 0.38; 95% CI: 0.17-0.86; P = 0.021), and estimated glomerular filtration rate (OR: 0.97; 95% CI: 0.96-0.98; P<0.0001), and with a high hemoglobin A1c level (OR: 1.34; 95% CI: 1.06-1.69; P = 0.013). Individuals with lower levels of GLA (≤7.95 µg/mL) and a lower EPA∶AA ratio (≤0.55) had the lowest ABI (0.96±0.02, N = 90), while the highest ABI (1.12±0.01, N = 78) was observed in individuals with higher values of both GLA and EPA∶AA ratio (P<0.0001). CONCLUSION: A low level of GLA and a low EPA∶AA ratio are independently associated with the presence of PAD. Specific fatty acid abnormalities and imbalances could lead to new strategies for risk stratification and prevention in PAD patients.

Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index. METHODS: The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography. RESULTS: A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008). CONCLUSION: The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.

n-3 and n-6 Fatty acids are independently associated with lipoprotein-associated phospholipase A2 in the Multi-Ethnic Study of Atherosclerosis.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor for CVD and has been proposed as a marker of vascular inflammation. Polyunsaturated n-3 fatty acids (FA) and several n-6 FA are known to suppress inflammation and may influence Lp-PLA2 mass and activity. The associations of n-3 and n-6 plasma FA with Lp-PLA2 mass and activity were analysed using linear regression analysis in 2246 participants of the Multi-Ethnic Study of Atherosclerosis; statistical adjustments were made to control for body mass, inflammation, lipids, diabetes, and additional clinical and demographic factors. Lp-PLA2 mass and activity were significantly lower in participants with the higher n-3 FA EPA (ß = - 4·72, P< 0·001; ß = - 1·53; P= 0·023) and DHA levels (ß = - 4·47, ß = - 1·87; both P< 0·001). Those in the highest quintiles of plasma EPA and DHA showed 12·71 and 19·15 ng/ml lower Lp-PLA2 mass and 5·7 and 8·90 nmol/min per ml lower Lp-PLA2 activity than those in the first quintiles, respectively. In addition, lower Lp-PLA2 mass and activity were associated with higher levels of n-6 arachidonic acid (ß = - 1·63, ß = - 1·30; both P< 0·001), while γ-linolenic acid was negatively associated with activity (ß = - 27·7, P= 0·027). Lp-PLA2 mass was significantly higher in participants with greater plasma levels of n-6 linoleic (ß = 0·828, P= 0·011) and dihomo-γ-linolenic acids (ß = 4·17, P= 0·002). Based on their independent associations with Lp-PLA2 mass and activity, certain n-3 and n-6 FA may have additional influences on CVD risk. Intervention studies are warranted to assess whether these macronutrients may directly influence Lp-PLA2 expression or activity.

n-3 fatty acids, γ-linolenic acid, and antioxidants in sepsis.

The usefulness of n-3 fatty acids, γ-linolenic acid and antioxidants in the critically ill is controversial. I propose that adverse outcome in the critically ill is due to excess production of proinflammatory cytokines and eicosanoids from polyunsaturated fatty acids (PUFAs), while generation of anti-inflammatory products of PUFAs may lead to a favorable outcome. Hence, I suggest that measurement of plasma levels of various cytokines, free radicals, and proinflammatory and anti-inflammatory products of PUFAs and correlating them to the clinical picture may pave the way to identify prognostic markers and develop newer therapeutic strategies to prevent and manage critical illness.

Effects of EPA, γ-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial.

The main objective of the present study was to determine the potential of n-3 and n-6 fatty acids or coenzyme Q10 (CoQ10) to alter serum prostate-specific antigen (PSA) levels in normal healthy men. A total of 504 healthy men with serum PSA level ≤ 2·5 ng/ml were recruited into the study. Serum PSA values were not segregated by decade of age. Participants were randomly assigned to a daily dietary supplement containing n-3 fatty acids (1·12 g of EPA and 0·72 g of DHA per capsule) (group 1, n 126), n-6 fatty acid (600 mg γ-linolenic acid (GLA) each capsule) (group 2, n 126), CoQ10 (100 mg per capsule) (group 3, n 126) or a similar regimen of placebo (group 4, n 126) for 12 weeks. Study medication was administered as two capsules to be taken twice daily. Serum levels of PSA, EPA, DHA, GLA, lipid profile and reproductive hormones were also measured. EPA treatment significantly reduced serum PSA level by 30·0 (95 % CI 25, 36) % (P= 0·004) from baseline. In contrast, GLA therapy significantly increased serum PSA concentration by 15·0 (95 % CI 11, 20) % (P= 0·02). CoQ10 therapy also significantly reduced serum PSA level by 33·0 (95 % CI 27, 40) % (P= 0·002). In multivariable analysis, serum values of PSA were strongly correlated with duration of EPA (r - 0·62; 95 % CI - 0·42, - 0·77; P= 0·003), n-6 (r 0·42; 95 % CI 0·31, 0·58; P= 0·02) and CoQ10 use (r - 0·77; 95 % CI - 0·56, - 0·87; P= 0·001). There were also significant correlations between serum values of DHA, EPA, GLA and CoQ10 and serum PSA levels. The present study demonstrates that dietary supplements containing EPA, GLA or CoQ10 may significantly affect serum PSA levels.

Metabolomics of dietary fatty acid restriction in patients with phenylketonuria.

BACKGROUND: Patients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA). Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. METHODOLOGY/PRINCIPAL FINDINGS: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18) in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS). Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re-) absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6) a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2) and thromboxane B(3) release did not differ from that of healthy controls. CONCLUSION/SIGNIFICANCE: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta-oxidation. No functional influence on unsaturated fatty acid metabolism and platelet aggregation in patients with PKU was detected.