Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment.

BACKGROUND: Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI). METHODS: The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). RESULTS: Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). DISCUSSION AND CONCLUSION: These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.

A combination of palm oil tocotrienols and citrus peel polymethoxylated flavones does not influence elevated LDL cholesterol and high-sensitivity C-reactive protein levels.

BACKGROUND/OBJECTIVES: Lipid-lowering and anti-inflammatory effects have been individually described for tocotrienols (TTs) and polymethoxylated flavones (PMFs). This study investigated low-density lipoprotein-cholesterol (LDL-C)- and high-sensitivity C-reactive protein (hsCRP)-reducing effects of combined TT-PMF treatment in low doses in hypercholesterolemic individuals with subclinical inflammation. SUBJECTS/METHODS: In the double-blind, placebo-controlled study, 240 Caucasians with LDL-C ⩾3.36 mmol/l and hsCRP ⩾1 mg/l were enrolled and randomized into group S1 (12 mg/day TT and 103 mg/day PMF), group S2 (27 mg/day TT and 32 mg/day PMF) or placebo. RESULTS: Twenty-three subjects dropped out of the study, 13 were excluded from the analysis because of lack of compliance. A total of 204 subjects per-protocol analysis were included. After 12 weeks of treatment, no significant differences in LDL-C levels (primary outcome) were observed between groups. LDL-C levels significantly decreased in all intervention groups (S1: -5.2%, S2: -4.8% and P: -4.2%). Total cholesterol and hsCRP (secondary outcome) did not change significantly. CONCLUSIONS: PMF-TT supplements had no effect beyond that of placebo on elevated LDL-C and hsCRP levels.

Moderate doses of EPA and DHA from re-esterified triacylglycerols but not from ethyl-esters lower fasting serum triacylglycerols in statin-treated dyslipidemic subjects: Results from a six month randomized controlled trial.

Recently, in a supplementation study over six months, it has been demonstrated that re-esterified omega-3 fatty acid triacylglycerols (n3-FA-rTAGs) led to a higher increase in omega-3-index compared to identical doses of n3-FA ethyl-esters (n3-FA-EEs), suggesting a better long-term bioavailability. The aim of this study was to examine whether differences occur between the two forms in affecting fasting serum lipid levels. 150 dyslipidemic statin-treated participants were randomized to corn oil as a placebo or fish oil either as rTAG or EE in identical doses (1.01g EPA+0.67g DHA). No changes in total cholesterol, HDL or LDL levels were observed. In the rTAG-group, but not in the EE-group, fasting serum TAG levels were significantly reduced from baseline after three and six months. There was no significant difference between the two n3-FA-groups. However, serum TAG levels were significantly lowered after six months in the rTAG-group compared to the placebo-group in contrast to the EE-group.

Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.

BACKGROUND: There is a debate currently about whether different chemical forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are absorbed in an identical way. The objective of this study was to investigate the response of the omega-3 index, the percentage of EPA+DHA in red blood cell membranes, to supplementation with two different omega-3 fatty acid (n-3 FA) formulations in humans. DESIGN: The study was conducted as a double-blinded placebo-controlled trial. A total of 150 volunteers was randomly assigned to one of the three groups: (1) fish oil concentrate with EPA+DHA (1.01 g+0.67 g) given as reesterified triacylglycerides (rTAG group); (2) corn oil (placebo group) or (3) fish oil concentrate with EPA+DHA (1.01 g+0.67 g) given as ethyl ester (EE group). Volunteers consumed four gelatine-coated soft capsules daily over a period of six months. The omega-3 index was determined at baseline (t(0)) after three months (t(3)) and at the end of the intervention period (t(6)). RESULTS: The omega-3 index increased significantly in both groups treated with n-3 FAs from baseline to t(3) and t(6) (P<0.001). The omega-3 index increased to a greater extent in the rTAG group than in the EE group (t(3): 186 versus 161% (P<0.001); t(6): 197 versus 171% (P<0.01)). CONCLUSION: A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.