Effect of omega-3 polyunsaturated fatty acids on the cytoskeleton: an open-label intervention study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) show beneficial effects on cardiovascular health and cognitive functions, but the underlying molecular mechanisms are not completely understood. Because of the fact that cytoskeleton dynamics affect almost every cellular process, the regulation of cytoskeletal dynamics could be a new pathway by which n-3 PUFAs exert their effects on cellular level. METHODS: A 12-week open-label intervention study with 12 healthy men was conducted to determine the effects of 2.7 g/d n-3 PUFA on changes in mRNA expression of cytoskeleton-associated genes by quantitative real-time PCR in whole blood. Furthermore, the actin content in red blood cells was analyzed by immunofluorescence imaging. RESULTS: N-3 PUFA supplementation resulted in a significant down-regulation of cytoskeleton-associated genes, in particular three GTPases (RAC1, RHOA, CDC42), three kinases (ROCK1, PAK2, LIMK), two Wiskott-Aldrich syndrome proteins (WASL, WASF2) as well as actin related protein 2/3 complex (ARPC2, ARPC3) and cofilin (CFL1). Variability in F-actin content between subjects was high; reduced actin content was only reduced within group evaluation. CONCLUSIONS: Reduced cytoskeleton-associated gene expression after n-3 PUFA supplementation suggests that regulation of cytoskeleton dynamics might be an additional way by which n-3 PUFAs exert their cellular effects. Concerning F-actin, this analysis did not reveal unmistakable results impeding a generalized conclusion.

Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease.

Elevated circulating concentrations of total L-homocysteine (thCys) and free asymmetric dimethylarginine (ADMA) are long-established cardiovascular risk factors. Low circulating L-homoarginine (hArg) concentrations were recently found to be associated with increased cardiovascular morbidity and mortality. The biochemical pathways of these amino acids overlap and share the same cofactor S-adenosylmethionine (SAM). In the present study, we investigated potential associations between hArg, L-arginine (Arg), ADMA and thCys in plasma of patients suffering from rheumatoid arthritis (RA), coronary artery disease (CAD) or peripheral artery occlusive disease (PAOD). In RA, we did not find any correlation between ADMA or hArg and thCys at baseline (n = 100) and after (n = 83) combined add-on supplementation of omega-3 fatty acids, vitamin E, vitamin A, copper, and selenium, or placebo (soy oil). ADMA correlated with Arg at baseline (r = 0.446, P < 0.001) and after treatment (r = 0.246, P = 0.03). hArg did not correlate with ADMA, but correlated with Arg before (r = 0.240, P = 0.02) and after treatment (r = 0.233, P = 0.03). These results suggest that hArg, ADMA and Arg are biochemically familiar with each other, but unrelated to hCys in RA. In PAOD and CAD, ADMA and thCys did not correlate.

Vitamin Intake from Food Supplements in a German Cohort - Is there a Risk of Excessive Intake?

Food supplements, if not properly used, may lead to potentially harmful nutrient intake. The purpose of this survey was to examine vitamin intake from food supplements. Taking into account the intake from food, as obtained from the National Nutrition Survey, it was determined whether the tolerable upper intake levels (ULs) were exceeded via supplements alone, or in combination with food. Data from 1070 supplement users (18-93 years) was available. The dietary and supplemental vitamin intakes of three groups were analyzed: average intake (50th percentile food+50th percentile supplements), middle-high intake (50th+95th) and high intake (95th+95th). Vitamin C (53%), vitamin E (45%) and B vitamins (37-45%) were consumed most frequently. Few subjects (n=7) reached or exceeded the ULs through supplements alone. The UL for vitamin A and folate was reached by a few men in the middle-high group, and by a few men and women in the high intake group. Otherwise, even in the high intake group, the recommended vitamin D intake of 20 µg/day (in case of insufficient endogenous synthesis) could not be achieved. The use of food supplements was not associated with excessive vitamin intake in this survey, except in a small number of cases. Vitamin A intake above the UL was the result of high dietary intake which also included the intake of ß-carotene, rather than the result of overconsumption of food supplements. Diets mainly included folate from natural sources, which has no associated risk.

Regulation of lipid metabolism-related gene expression in whole blood cells of normo- and dyslipidemic men after fish oil supplementation.

BACKGROUND: Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the lipid levels of dyslipidemic subjects are widely described in the literature. However, the underlying molecular mechanisms are largely unknown. The aim of this study was to investigate the effects of n-3 PUFAs on the expression of lipid metabolism-related genes in normo- and dyslipidemic men to unveil potential genes and pathways affecting lipid metabolism. METHODS: Ten normo- and ten dyslipidemic men were supplemented for twelve weeks with six fish oil capsules per day, providing 1.14 g docosahexaenoic acid and 1.56 g eicosapentaenoic acid. The gene expression levels were determined by whole genome microarray analysis and quantitative real-time polymerase chain reaction. RESULTS: Several transcription factors (peroxisome proliferator-activated receptor α (PPARα), retinoid X receptor (RXR) α, RXRγ, hepatic nuclear factor (HNF) 6, and HNF1ß) as well as other genes related to triacylglycerol (TG) synthesis or high-density lipoprotein (HDL-C) and cholesterol metabolism (phospholipids transfer protein, ATP-binding cassette sub-family G member 5, 2-acylglycerol O-acyltransferase (MOGAT) 3, MOGAT2, diacylglycerol O-acyltransferase 1, sterol O-acyltransferase 1, apolipoprotein CII, and low-density lipoprotein receptor) were regulated after n-3 PUFA supplementation, especially in dyslipidemic men. CONCLUSION: Gene expression analyses revealed several possible molecular pathways by which n-3 PUFAs lower the TG level and increase the HDL-C and low-density lipoprotein level, whereupon the regulation of PPARα appear to play a central role. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT01089231).

Cardiovascular risk in patients with rheumatoid arthritis: assessment of several traditional risk parameters and a German risk score model.

The present cross-sectional data demonstrate cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). The cross-sectional data were part of an interventional trial that included 100 patients with defined RA. Traditional CV risk parameters and risk score calculation for the German population were used to assess the CV risk profile in the collective given. Proatherogenic lipid profile characterised by increased total cholesterol (≥ 5.2 mmol/l) and LDL cholesterol (≥ 3.5 mmol/l) levels was measured in 85 and 66%, respectively, of the study population. Elevated concentrations of homocysteine (≥ 10 µmol/l) were reached by 67%. The prevalence of patients at high CV risk was 12% and increased up to 42% after using a multiplication factor of 1.5. No association was seen between the CV risk SCORE and DAS 28 or disease duration. RA patients in this study showed a proatherogenic risk profile with regard to the CV risk factors evaluated. The calculation of a 10-year risk using German risk charts might have led to an overall underestimation of the mean CV risk. Cardiovascular co-morbidity in RA patients must be seen as a major prevention and treatment target and should be monitored adequately.