Docosahexaenoic Supplementation Research Articles

Differential effects of high dose omega-3 fatty acids on metabolism and inflammation in patients with obesity: eicosapentaenoic and docosahexaenoic acid supplementation.

Obesity is complicated by low-grade chronic inflammation characterised by increases in inflammatory proteins and cells in peripheral blood. It has been known that omega-3 fatty acids (FA) like eicosapentaenoic (EPA) and docosahexaenoic (DHA) could modulate the inflammatory process and improve metabolic markers. This study aimed to determine the effect of high-dose omega-3 FA on metabolic and inflammatory markers among patients with obesity and healthy volunteers. This prospective study included 12 women with obesity (body mass index [BMI] ≥ 35.0 kg/m2) and 12 healthy women (BMI < 24.0 kg/m2) who were supplemented with a dose of 4.8 g/day (3.2 g EPA plus 1.6 g DHA) for 3 months followed by no treatment for 1 month. Plasma metabolic and inflammatory markers and levels of mRNA transcripts of CD4+ T lymphocyte subsets were determined monthly. None of the participants exhibited changes in weight or body composition after study completion. EPA and DHA supplementation improved metabolic (insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], triglyceride [TG]/ high-density lipoprotein [HDL] ratio, TG, and arachidonic acid [AA]/EPA ratio) and tumor necrosis factor-alpha (TNF-α). Moreover, the levels of mRNA transcripts of T CD4+ lymphocyte subsets (TBX21, IFNG, GATA-3, interleukin [IL]-4, FOXP3, IL-10 IL-6, and TNF-α), were down-regulated during the intervention phase. After 1 month without supplementation, only insulin, HOMA-IR and the mRNA transcripts remained low, whereas all other markers returned to their levels before supplementation. Supplementation with high-dose omega-3 FAs could modulate metabolism and inflammation in patients with obesity without weight loss or changes in body composition. However, these modulatory effects were ephemeral and with clear differential effects: short-duration on metabolism and long-lasting on inflammation.

Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose-response meta-analysis of observational and experimental studies.

Randomized controlled trials (RCTs) testing supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have failed to provide evidence supporting a suggested inverse association between fish intake and dementia risk. Dose-response analyses were conducted to evaluate associations between fish intake, all-cause dementia or Alzheimer's Disease (AD), and the effect of EPA/DHA supplementation on cognitive performance. PubMed, Scopus and Web of Science databases were searched for original research evaluating either associations between fish intake and dementia or AD, or the impact of EPA and/or DHA supplementation on the risk of cognitive decline. Data were collected on study characteristics and methods; number of cases/deaths (for observational studies); categories of exposure; model covariates; risk estimates from the most-adjusted model; type and dosage of supplementation (from RCTs); fatty acid levels in blood; and differences in cognition test results before and after supplementation. Risk of bias was assessed through the ROBINS-E and RoB2.0 tools for observational and experimental studies, respectively. Weighted mixed-effects models were applied, allowing for the inclusion of studies with 2 levels of exposure. Based on findings with low/moderate risk of bias, fish intake of up to 2 portions (250 g) per week was associated with a 10% reduction (95% confidence interval [CI]: 0.79, 1.02, Ν = 5) in all-cause dementia and a 30% reduction (95% CI: 0.54, 0.89, Ν = 3) in AD risk. Changes in EPA and DHA body status had a positive impact on participants' executive functions, but not on their overall cognitive performance. The protection offered by fish intake against cognitive decline levels off at intakes higher than 2 portions/week and likely relates to the impact of EPA and DHA on the individual's executive functions, although there remain questions about the mechanisms linking the short- and long-term effects. PROSPERO registration no. CRD42019139528.

Low Dietary n6/n3 Ratio Attenuates Changes in the NRF 2 Gene Expression, Lipid Peroxidation, and Inflammatory Markers Induced by Fructose Overconsumption in the Rat Abdominal Adipose Tissue.

The objective of this study was to examine the benefits of different n6/n3 polyunsaturated fatty acid ratios on the lipid metabolism, insulin resistance, and oxidative stress in the adipose tissue of rats fed a high-fructose diet. Male and female rats were divided into four groups: a control group (CON) (n6/n3 ratio ~7), a high-fructose group (HF) (n6/n3 ratio ~7), an N6-HF group (n6/n3 ratio ~50), and the DHA-HF group (n6/n3 ratio ~1, with the addition of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid). The CON group received plain water and the HF group received 15% fructose in their drinking water. Fructose induced an increase in the content of serum triglycerides, serum cholesterol, and HOMA-IR index. Among the fatty acids, elevated proportions of C18:1n9 and C16:1n7, as well as an increase in total monounsaturated fatty acid (MUFA), were found in the adipose tissue of the HF group. Fructose treatment also changed oxidative parameters, including a marked increase in the serum malondialdehyde (MDA) content. Meanwhile, DHA supplementation caused a significant decrease in the serum MDA concentration in comparison with the HF group. In addition, DHA/EPA supplementation attenuated oxidative stress by increasing NRF 2 gene expression. Fructose treatment also significantly decreased the adiponectin level, while DHA supplementation ameliorated it. The changes observed in this trial, including the decrease in the content of DHA and EPA, the decreased EPA/ARA ratio, and the increase in the expression of inflammatory genes, are characteristics of the low-grade inflammation caused by fructose treatment. These changes in the rat adipose tissue could be prevented by dietary intervention consisting of DHA supplementation and a low n6/n3 ratio.

Effects of docosahexaenoic acid or arachidonic acid supplementation on gene expression and contractile force of rat cardiomyocytes in primary culture

While fatty acids play essential roles in the physiology of the myocardium, conventional culture media contain little lipid. We previously revealed that rat neonatal myocardium mainly contains docosahexaenoic (DHA), linoleic (LA), and arachidonic (AA) acids as polyunsaturated fatty acids (PUFAs), and these contents in cultured cardiomyocytes derived from fetal rats were markedly lower than those in the neonatal myocardium. In this study, we first assessed the effects of supplementation of DHA, LA, or AA on the fatty acid contents and the percentage change of contractile area in primarily cultured rat cardiomyocytes. Based on this assessment, we then evaluated the effects of DHA or AA supplementation on mRNA expression and further directly measured the contractile force of cardiomyocytes with the supplementations. This study revealed that percentage change of contractile area was maximized under 20 μM DHA or 50 μM AA supplementation while LA supplementation did not affect this contraction index, and that a widespread upregulation tendency of the mRNA expression related to differentiation, maturity, fatty acid metabolism, and cell adhesion was seen in the cultured cardiomyocytes with supplementation of DHA or AA. In particular, upregulation of the gene expression of cellular adhesion molecules connexin43 and N-cadherin were remarkable, whereas the effects on differentiation and maturation were less pronounced. Correspondingly, the increase of the percentage change of the contractile area of cardiomyocyte clusters in culture dishes with the supplementations was significant, whereas the enhancement of the contractile force was modest. These results suggest that supplementation of DHA or AA to the fetal cardiomyocyte culture may play effective roles in preventing the de-differentiation of the cardiomyocytes in culture and that the enhancement of the contractile performance may be mainly attributed to the improvement of intercellular connection.

Genetic risk prediction of the plasma triglyceride response to independent supplementations with eicosapentaenoic and docosahexaenoic acids: the ComparED Study

BackgroundWe previously built a genetic risk score (GRS) highly predictive of the plasma triglyceride (TG) response to an omega-3 fatty acid (n-3 FA) supplementation from marine sources. The objective of the present study was to test the potential of this GRS to predict the plasma TG responsiveness to supplementation with either eicosapentaenoic (EPA) or docosahexaenoic (DHA) acids in the Comparing EPA to DHA (ComparED) Study.MethodsThe ComparED Study is a double-blind, controlled, crossover trial, with participants randomized to three supplemented phases of 10 weeks each: (1) 2.7 g/day of DHA, (2) 2.7 g/day of EPA, and (3) 3 g/day of corn oil (control), separated by 9-week washouts. The 31 SNPs used to build the previous GRS were genotyped in 122 participants of the ComparED Study using TaqMan technology. The GRS for each participant was computed by summing the number of rare alleles. Ordinal and binary logistic models, adjusted for age, sex, and body mass index, were used to calculate the ability of the GRS to predict TG responsiveness.ResultsThe GRS predicted TG responsiveness to EPA supplementation (p = 0.006), and a trend was observed for DHA supplementation (p = 0.08). The exclusion of participants with neutral TG responsiveness clarified the association patterns and the predictive capability of the GRS (EPA, p = 0.0003, DHA p = 0.01).ConclusionResults of the present study suggest that the constructed GRS is a good predictor of the plasma TG response to supplementation with either DHA or EPA.Trial registrationClinicalTrials.gov, NCT01810003. The study protocol was registered on March 4, 2013.

DHA supplementation decreases resting metabolic rate in healthy young females.

This study examined the independent effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid supplementation on resting metabolic rate (RMR) and substrate oxidation in young healthy females and males. EPA or DHA supplementation had no effect on RMR and substrate oxidation in males, while DHA reduced RMR by ∼7% (p < 0.01) in females. In conclusion, these data establish potential sex differences on RMR in response to DHA supplements. Novelty Supplementing with DHA decreases resting energy expenditure in healthy young females but not males.

Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid

BackgroundRecent studies suggest that eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have distinct effects on cardiometabolic risk factors. The Omega-3 Index (O3I), which is calculated as the proportion of EPA and DHA in red blood cell (RBC) membranes, has been inversely associated with the risk of coronary heart diseases and coronary mortality. The objective of this study was to compare the effects of EPA and DHA supplementation on the O3I in men and women with abdominal obesity and subclinical inflammation. MethodsIn a double-blind controlled crossover study, 48 men and 106 women with abdominal obesity and subclinical inflammation were randomized to a sequence of three treatment phases: 1–2.7g/d of EPA, 2–2.7g/d of DHA, and 3–3g/d of corn oil (0g of EPA+DHA). All supplements were provided as 3×1g capsules for a total of 3g/d. The 10-week treatment phases were separated by nine-week washouts. RBC membrane fatty acid composition and O3I were assessed at baseline and the end of each phase. Differences in O3I between treatments were assessed using mixed models for repeated measures. ResultsThe increase in the O3I after supplementation with DHA (+5.6% compared with control, P<0.0001) was significantly greater than after EPA (+3.3% compared with control, P<0.0001; DHA vs. EPA, P<0.0001). Compared to control, DHA supplementation decreased (−0.8%, P<0.0001) while EPA increased (+2.5%, P<0.0001) proportion of docosapentaenoic acid (DPA) in RBCs (DHA vs. EPA, P<0.0001). The baseline O3I was higher in women than in men (6.3% vs. 5.8%, P=0.011). The difference between DHA and EPA in increasing the O3I tended to be higher in men than in women (+2.6% vs. +2.2% respectively, P for the treatment by sex interaction=0.0537). ConclusionsThe increase in the O3I is greater with high dose DHA supplementation than with high dose EPA, which is consistent with the greater potency of DHA to modulate cardiometabolic risk factors. The extent to which such differences between EPA and DHA in increasing the O3I relates to long-term cardiovascular risk needs to be investigated in the future.

Effects of dietary Docosahexaenoic, training and acute exercise on lipid mediators.

BackgroundEicosanoids mediate initiation and resolution of inflammation. Our aim was evaluating the effects of training, exercise and docosahexaenoic (DHA) supplementation on plasma eicosanoids levels and peripheral blood mononuclear cells (PBMCs) eicosanoids production.MethodsFifteen male footballers were distributed to placebo and experimental groups. Experimental group consumed DHA-enriched beverage (1.16 g DHA/day) for 8 weeks, placebo group consumed a placebo beverage. Blood samples were taken before and after the nutritional intervention in basal conditions and 2 h after acute exercise.ResultsTraining increased basal Prostaglandin E1 (PGE1) plasma levels and PBMCs cyclooxygenase 2 (COX-2) protein levels in both groups, but COX-1 protein levels only in the experimental group. Acute exercise increased plasma PGE2 and PBMCs active NFκβ levels. Lipopolysaccharide (LPS)-stimulated PBMCs increases eicosanoids production (PGE1, PGE2, RvD1) in both groups and increased LPS-stimulated PBMCs active NFκβ. DHA supplementation increased COX-2 levels but decreased LPS-stimulated PBMCs PGE1 and PGE2 production. Neither DHA supplementation nor acute exercise altered the expression of NFκβ, COX-2, 15-LOX2, 5-LOX, or IL-1β genes in PBMCs.ConclusionsThe increase of PGE1 plasma levels after training promoted systemic anti-inflammatory and vasodilator environment. Exercise and DHA supplementation acted synergistically by increasing plasma PGE2 with anti-inflammatory effects. Exercise primed PBMCs to enhance PGE1, PGE2 and RvD1 production in response to LPS.Trial registrationThe project was registered at ClinicalTrial.gov (NCT02177383).

N-3 Fatty acids regulate the inflammatory-state related genes in the lung epithelial cells exposed to polycyclic aromatic hydrocarbons.

Chronic airway inflammation is coordinated by a complex of inflammatory mediators, including eicosanoids. The aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbons (PAHs) on the human lung epithelial carcinoma A549 cells supplemented with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. We analyzed the influence of DHA, EPA and/or benzo(a)pyrene (BaP), chrysene (Chr), fluoranthene (Flu) and benzo(a)anthracene (Baa) treatment on the fatty acids (FAs) profile and the formation of isoprostanes. We studied the cyclooxygenase-2, FP-receptor, peroxisome proliferator-activated receptors PPARδ and PPARγ, transcription factor NF-кB p50 and p65 expression by Western blot, phospholipase A2 (cPLA2) activity, as well as aryl hydrocarbon receptor (AHR), cytochrome P450 (CYP1A1), phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR. DHA or EPA supplementation and BaP or Baa treatment resulted in a higher level of PGF3α. COX-2 expression was decreased while PPARδ expression and cPLA2 activity was increased after fatty acid supplementation and PAHs treatment. DHA and EPA up-regulated AHR and PLA2G4A genes. Supplementation with n-3 FAs resulted in changes of inflammatory-state related genes in the lung epithelial cells exposed to PAHs. The altered profile of lipid mediators from n-3 FA as well as repression of the COX-2 protein by n-3 PUFAs in A549 cells incubated with PAHs suggests anti-inflammatory and pro-resolving properties of DHA and EPA. It remains to be shown whether these pleiotropic and protective actions of n-3 FAs contribute to fish oil's therapeutic effect in asthma.

Fatty Acid Desaturase Single Nucleotide Polymorphisms Modify the Effect of Prenatal Supplementation with Docosahexaenoic Acid on Birth Weight

Maternal single nucleotide polymorphisms (SNP) in the Fatty Acid Desaturase genes (FADS) modulate the conversion of biologically inactive dietary polyunsaturated fatty acids (PUFA) into arachidonic and docosahexaenoic (DHA) acid, which are essential for fetal development. We assessed if four FADS SNPs (rs174445, rs174556, rs174602, rs498793) modified the association of prenatal DHA supplementation with birth weight (BW). 1,094 pregnant women in Cuernavaca, Mexico were randomized to supplementation with 400 mg/day of DHA or a placebo from 18‐22 w of gestation through delivery. We included 677 live births with maternal genotype information available (65% of the original sample). Mean (±SD) BW was 3,210 g (±466) and BW for gestational age z‐scores (WAZ) relative to the WHO Growth Standards was ‐0.24 (±1.00). There were no intent‐to‐treat differences in birth weight. We found a significant interaction by SNP rs174602 (p=0.02), where offspring of carriers of alleles TT and TC in the intervention group were heavier than those in the placebo (WAZ = ‐0.14±0.14 and ‐0.18±0.07 vs.‐0.55±0.14 and ‐0.40±0.8, respectively); while the opposite was observed among the offspring of rs174602 CC homozygotes (WAZ= ‐0.23±0.09 intervention vs. ‐0.02 ±0.08 placebo). We found no significant effect modification by the other three FADS SNPs. Differential responses to prenatal DHA supplementation trials based on target populations' genetic makeup and PUFA dietary intake could explain the mixed evidence of the impact of DHA on BW. Funded by NIH and the Nutricia Research Foundation.

Fatty acids and bipolar disorder

Fatty acids and bipolar disorder

Docosahexaenoic acid elevates trans-18:1 isomers but is not directly converted into trans-18:1 isomers in ruminal batch cultures

Pathways of docosahexaenoic (DHA) biohydrogenation are not known; however, DHA is metabolized by ruminal microorganisms. The addition of DHA to the rumen alters the fatty acid profile of the rumen and milk and leads to increased trans-18:1 isomers, particularly trans-11 18:1. This study included 2 in vitro experiments to identify if the increase in trans-11 C18:1 was due to DHA being converted into trans-11 18:1 or if DHA stimulated trans-11 products from biohydrogenation of other fatty acids. In each experiment, ruminal microorganisms collected from a lactating Holstein cow were incubated in 10-mL batch cultures for 0, 6, 24, and 48h and a uniformly 13C-labeled DHA was added to the cultures at 0h as a metabolic tracer. Experiment 1 tested 0.5% DHA supplementation and experiment 2 examined 1, 2, and 3% DHA supplementation to determine if the level of DHA effected its conversion into trans-11 18:1. In both experiments, any fatty acid that was enriched with the 13C label was determined to arise from DHA. Palmitic (C16:0), stearic (C18:0), all trans-18:1, eicosanoic (C20:0), and docosanoic (C22:0) acids were examined for enrichment. In experiment 1, the amount of trans-18:1 isomers increased 0.415mg from 0 to 48h; however, no label was found in trans-18:1 at any time. Docosanoic acid was highly enriched at 24h and 48h to 20.2 and 16.3%. Low levels of enrichment were found in palmitic and stearic acids. In experiment 2, trans-18:1 isomers increased 185, 256, and 272% from 0 to 48h when DHA was supplemented at 1, 2, and 3%, respectively; however, as in experiment 1, no enrichment occurred of any trans-18:1 isomer. In experiment 2, low levels of label were found in palmitic and stearic acids. Enrichment of docosanoic acid decreased linearly with increased DHA supplementation. These studies showed that trans-18:1 fatty acids are not produced from DHA, supporting that DHA elevates trans-18:1 by modifying biohydrogenation pathways of other polyunsaturated fatty acids.

EPA or DHA Supplementation Increases Triacylglycerol, but not Phospholipid, Levels in Isolated Rat Cardiomyocytes

It is well recognized that a high dietary intake of long-chain polyunsaturated fatty acids (LC-PUFA) has profound benefits on health and prevention of chronic diseases. In particular, in recent years there has been a dramatic surge of interest in the health effects of n-3 LC-PUFA derived from fish, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Notwithstanding, the metabolic fate and the effects of these fatty acids once inside the cell has seldom been comprehensively investigated. Using cultured neonatal rat cardiomyocytes as model system we have investigated for the first time, by means of high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy in combination with gas chromatography (GC), the modification occurring in the cell lipid environment after EPA and DHA supplementation. The most important difference between control and n-3 LC-PUFA-supplemented cardiomyocytes highlighted by HR-MAS NMR spectroscopy is the increase of signals from mobile lipids, identified as triacylglycerols (TAG). The observed increase of mobile TAG is a metabolic response to n-3 LC-PUFA supplementation, which leads to an increased lipid storage. The sequestration of mobile lipids in lipid bodies provides a deposit of stored energy that can be accessed in a regulated fashion according to metabolic need. Interestingly, while n-3 LC-PUFA supplementation to neonatal rat cardiomyocytes causes a huge variation in the cell lipid environment, it does not induce detectable modifications in water-soluble metabolites, suggesting negligible interference with normal metabolic processes.

151 Docosahexaenoic and Eicosahexaenoic N-3 Fatty Acids Inhibit DNA Synthesis and Cell Proliferation in Colorectal Cancer Cells Independent of the Responsible Underlying Molecular Pathways

Introduction: The intestinal epithelium undergoes a constant and fast renewal that is maintained in check thanks to a tight equilibrium between cell death and proliferation. An alteration of this equilibrium in the colonic epithelium can result in colorectal cancer development. Nutrients capable of either inducing programmed cell death or decreasing the proliferative rate of this epithelium could presumably be useful as either chemo preventive or even adjuvant therapeutic elements in colorectal cancer. Fish oil, through its main fatty acids, Docosahexaenoic (DHA) and Eicosahexaenoic (EPA) has shown some promising effects in colorectal cancer both, epidemiologically and experimentally. We have previously shown that DHA and EPA induce apoptosis in colorectal cancer cells. We also showed that both, the intrinsic and extrinsic pathways are involved though the down-regulation of two key elements: FLIP and XIAP. Aims: The aims of this study were: to determine if the n-3 fatty acids DHA and EPA can regulate colorectal cancer cell proliferation; to determine if this regulation is dependent on the type of molecular alterations present in these cells and; to determine if any phase of the cell cycle is affected in this potentially anti neoplastic effect. Methods: Non-confluent HCT116, LoVo, SW480, Caco-2 and HT-29 human colorectal cancer cells were grown in their regular media and, 24 h before the experiments, they were synchronized by feeding them with sera-free media supplemented with DHA, EPA or vehicle at final concentrations of 30 to 50 uM according to the type of cell studied. Cell proliferation was assessed by MTT analysis at 24 and 48h after fatty acid supplementation. Cell cycle phases were analyzed by flow citometry through propidium iodide staining. Results: DHA and EPA supplementation resulted in a decrease in the proliferation rate of most colorectal cancer cells, independently of APC, p53 or mismatch repair status. This coincided with a significant decrease in the DNA synthesis of these cells. Neither DHA nor EPA was able to stop proliferation of the metastatic LoVo cells. DNA synthesis was preserved in the latter cells as opposed to the non-metastatic cells. Conclusions: DHA and EPA can exert an anti neoplastic effect in colorectal cancer not only through a significant apoptosis induction but also through a significant decrease in cell proliferation and in DNA synthesis. These effects are independent of the responsible underlying molecular pathways. Metastatic colorectal cancer cells may have developed mechanisms that make these cells resistant to the anti proliferative effects of DHA and EPA.

N-3 polyunsaturated fatty acids supplementation decreases asymmetric dimethyl arginine and arachidonate accumulation in aging spontaneously hypertensive rats.

Plasma accumulation of asymmetric dimethyl arginine (ADMA) is considered as a risk factor for endothelial dysfunction and a strong predictor for coronary heart diseases. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) increasing plasma levels have been positively associated with reduced cardiovascular mortality with a mechanism( s) yet unclear. We hypothesised that ADMA reduction might be a part of EPA and DHA beneficial effects on the cardiovascular system. To verify this hypothesis we measured ADMA plasma levels in aged spontaneously hypertensive rats (SHR) supplemented for 8 weeks with EPA and DHA. 16-month-old SHR were supplemented with EPA and DHA (EPA-DHA) or with olive oil (1 g/kg/day; OLIVE). At the end of the treatments, the plasma of each animal was analysed for 1) the total fatty acid composition, by gas-cromatography, 2) ADMA levels, by high pressure liquid chromatography, 3) nitrite and homocysteine concentration by chemiluminescence and by polarisation immunoassay respectively. Moreover, the activity of dimethyl arginine dimethyl amino hydrolase, the main enzyme involved in ADMA metabolism, was measured spectrophotometrically in the kidney from each rat. Animals supplemented with EPA and DHA showed: 1) lower ADMA and arachidonate plasma levels (587.4 +/- 113.7 nM and 0.49 +/- 0.11 mM respectively) than the values found in OLIVE rats (1365 +/- 399 nM and 1.07 +/- 0.07 mM respectively) 2) higher nitrite content (0.73 +/- 0.05 microM) than OLIVE (0.23 +/- 0.08 microM). EPA and DHA supplementation reduced ADMA accumulation in SHR in parallel with a decrease of arachidonate availability. This finding suggests that the control of the inflammatory ground of endothelium might play an important role in EPA and DHA effect on this novel and highly predictive cardiovascular risk factor.

Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet.

Blood lipid studies are reported in 25 adults and 2 adolescents with PKU who had been on phenylalanine-restricted diets for a mean period of 22.6 years (range 7-39 years). Measurements included plasma concentrations of phenylalanine, cholesterol, lipoproteins, triglycerides and fatty acid profiles, including the analysis of seven fatty acids in plasma and red blood cells. Lipid screening identified 7 subjects with significantly elevated cholesterol/HDL ratios ranging from 5.6 to 10.3. Triglyceridaemia was documented in 5 of these 7, with concentrations ranging between 0.24 and 4.5 mmol/L (219-402 mg/dl) with a mean of 3.5 mmol/L (310 mg/dl). The fatty acid analyses demonstrated slight but statistically significant reductions in the concentrations of long-chain polyunsaturated fatty acids (LCPUFA), including plasma docosahexaenoic (DHA) and arachidonic acid (AA), and red blood cell DHA concentrations. The pattern resembles that reported previously in children, but alterations in the mean levels are less severe. In six of the adult patients plasma DHA or AA concentrations were less than 50% of controls. Since DHA and AA have important physiological roles, including brain and retinal function, it is recommended that blood lipid concentrations be monitored in all patients with PKU, including adults, and that DHA and AA supplementation be provided, particularly in those patients in whom the blood concentrations of these substances are reduced significantly.

Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men

Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk. This study aimed to determine whether eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have differential effects on serum lipids and lipoproteins, glucose, and insulin in humans. In a double-blind, placebo-controlled trial of parallel design, 59 overweight, nonsmoking, mildly hyperlipidemic men were randomly assigned to receive 4 g purified EPA, DHA, or olive oil (placebo) daily while continuing their usual diets for 6 wk. Fifty-six men aged 48.8 +/- 1.1 y completed the study. Relative to those in the olive oil group, triacylglycerols fell by 0.45 +/- 0.15 mmol/L ( approximately 20%; P = 0.003) in the DHA group and by 0.37 +/- 0.14 mmol/L ( approximately 18%; P = 0.012) in the EPA group. Neither EPA nor DHA had any effect on total cholesterol. LDL, HDL, and HDL(2) cholesterol were not affected significantly by EPA, but HDL(3) cholesterol decreased significantly (6.7%; P = 0.032). Although HDL cholesterol was not significantly increased by DHA (3. 1%), HDL(2) cholesterol increased by approximately 29% (P = 0.004). DHA increased LDL cholesterol by 8% (P = 0.019). Adjusted LDL particle size increased by 0.25 +/- 0.08 nm (P = 0.002) with DHA but not with EPA. EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA. DHA supplementation increased DHA and EPA in plasma and platelet phospholipids. Both EPA and DHA increased fasting insulin significantly. EPA, but not DHA, tended to increase fasting glucose, but not significantly so. EPA and DHA had differential effects on lipids, fatty acids, and glucose metabolism in overweight men with mild hyperlipidemia.