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The effect of omega-3 fatty acids on the atherogenic lipoprotein phenotype in patients with nephrotic range proteinuria.
Bell, S, Cooney, J, Packard, CJ, Caslake, MJ, Deighan, CJ
Clinical nephrology. 2012;(6):445-53
Abstract
AIMS: Patients with nephrotic range proteinuria are known to have an increased risk of cardiovascular disease partly due to possessing the atherogenic lipoprotein phenotype. The aim of this study was to examine the effect of high dose omega-3 fatty acids on atherogenic triglyceride rich lipoproteins in patients with nephrotic range proteinuria, comparing their effect on lipoprotein profiles in age and sex matched controls. METHODS 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Fasting lipids and lipoproteins were measured before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (OmacorĀ®). RESULTS In patients with proteinuria treatment reduced plasma triglyceride by a mean of 0.45 mmol/l (95%CI 0.16 - 0.74, p = 0.005) and plasma very low density lipoprotein cholesterol by a mean of 0.38 (95%CI 0.01 - 0.75, p = 0.04). LDL III concentration fell from 178.8 mg/dl (61.6 - 231.0) to 96.1 mg/dl (49.3 - 204.5), p = 0.05. In patients treatment altered the LDL profile so that LDLIII which was the major subfraction present at baseline was reduced from 49.9% to 29.8% (p = 0.01). Remnant lipoproteins (RLP) also fell with a mean reduction of 3.5 mg/dl in RLP-Cholesterol (95%CI 0.1 - 6.9, p = 0.05) and 12.4 mg/dl in RLP-triglyceride (95%CI 2.6 - 22.2, p = 0.03). There was however a 0.6 mmol/l rise in LDL-C (p = 0.06) in the patients. Treatment did not alter HDL-C. CONCLUSION In patients with nephrotic range proteinuria, omega-3 fatty acids reduced triglyceride rich lipoproteins, LDL III and remnant lipoproteins. A tendency to an increase in LDL-C was observed but this was offset by an alteration in the distribution of the LDL profile towards lighter, larger LDL particles. We propose that treatment with omega-3 fatty acids in conjunction with a statin may be the ideal therapy in these patients.
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Acute supplementation with eicosapentaenoic acid reduces platelet microparticle activity in healthy subjects.
Phang, M, Lincz, L, Seldon, M, Garg, ML
The Journal of nutritional biochemistry. 2012;(9):1128-33
Abstract
BACKGROUND Dietary supplementation with omega-3 fatty acids has been associated with reduced incidence in thrombotic events. In addition, administration of n-3 polyunsaturated fatty acids (PUFAs) has been shown to rectify elevated platelet microparticle (MP) number and procoagulant activity in post myocardial infarction patients. However, it is unknown whether supplementation can alter these parameters in healthy individuals and if such effects are immediate or require long-term supplementation. We have previously demonstrated a gender-specific effect of LCn-3PUFA supplementation on platelet aggregation in healthy human subjects. Here we extend these findings to include the acute effects of supplementation with EPA- or DHA-rich oils on circulating MP levels and activity in healthy subjects. DESIGN A placebo-controlled trial was conducted in healthy males and females (n=30). MP activity, MP levels and platelet aggregation were measured at 0 and 24 h postsupplementation with either a placebo or EPA- or DHA-rich oil. RESULTS Both EPA and DHA effectively reduced platelet aggregation at 24 h postsupplementation relative to placebo (-13.3%, P=.006 and -11.9%, P=.016, respectively), but only EPA reduced MP activity (-19.4%, P=.003). When grouped by gender, males showed a similar reduction in both platelet aggregation and MP activity (-20.5%, P=.008; -22%, P=.008) following EPA, while females showed significantly reduced platelet aggregation (-13.7%, P=.04) but not MP activity after DHA only. CONCLUSION EPA and DHA exert gender-dependent effects on platelet aggregation and platelet MP activity, but not on MP levels. With respect to thrombotic disease risk, males may benefit more from EPA supplementation.
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The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin.
Block, RC, Duff, R, Lawrence, P, Kakinami, L, Brenna, JT, Shearer, GC, Meednu, N, Mousa, S, Friedman, A, Harris, WS, et al
Prostaglandins, leukotrienes, and essential fatty acids. 2010;(2-3):87-95
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Abstract
Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-week supplementation with EPA/DHA (3.4 g/d) with and without aspirin (650 mg). Plasma LPC and LPA species and autotaxin activity were measured. EPA-LPC and DHA-LPC concentrations increased significantly with EPA/DHA supplementation whereas EPA- and DHA-LPA did not. Autotaxin activity was unaffected by any treatment, and aspirin had no effect on any endpoint. Taken together, our data demonstrate that plasma LPC, but not LPA, species can be dynamically regulated by dietary supplementation, and argue against a simple model of LPA generation via LPC hydrolysis.
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Supplementation with long-chain n-3 fatty acids in non-insulin-dependent diabetes mellitus (NIDDM) patients leads to the lowering of oleic acid content in serum phospholipids.
Haban, P, Zidekova, E, Klvanova, J
European journal of nutrition. 2000;(5):201-6
Abstract
BACKGROUND The dietary supplementation with EPA (eicosapentaenoic acid; 20:5n3) and DHA (docosahexaenoic acid; 22:6n3) has been recommended because of their favourable effects on the cardiovascular system (including complications of NIDDM). Oleic acid (18:1n9) from olive oil has some analogous and complementary effects. Potential competitive relations between long-chain n-3 fatty acids (FAs) and the oleic acid would therefore mean a problem. AIM OF THE STUDY We focused primarily on the oleic acid changes in serum phospholipids (SPL) after a supplementation with EPA and DHA. METHODS Thirty-five patients with type 2 diabetes mellitus (NIDDM) were supplemented for 28 days with 1.7 g of EPA plus 1.15 g of DHA/day (as Maxepa capsules, Seven Seas, U. K.). After that, a 3-month wash-out control period with 21 patients followed. A fatty acid composition of serum phospholipids (SPL) was determined by capillary gas-chromatography. Values were calculated as relative percentages of all FAs. RESULTS After the supplementation with the Maxepa capsules, there was a very strong increase in EPA, docosapentaenoic acid (22:5n3) and DHA content in SPL. It was followed by a strong decrease after the wash-out (all p < 0.0001). The oleic acid SPL content after the intervention significantly decreased from 10. 105 +/- 0.307% (mean +/- S. E. M.) to 9.082 +/- 0.276 % (p < 0.0003). During the wash-out, the change was in the opposite direction (p < 0.0001). When the intervention and the wash-out periods were taken together, changes in the oleic acid were inversely correlated with changes in EPA, docosapentaenoic acid and DHA (r = -0.729; r = -0.552; r = -0.629, respectively; p < 0.0001; n = 56). On the background of the overall n-6 FA reduction, the decline in the arachidonic acid after the supplementation (p < 0.0001) and its rise after the wash-out (p < 0.0003) were similar. There were no significant changes in the saturated FA spectrum. CONCLUSIONS Supplementation with long-chain n-3 FAs in NIDDM patients leads to the lowering of oleic acid SPL content. Whereas the reduction of the arachidonic acid may have some desirable aspects (e. g. suppression of thromboxane TxA2 or 4 series leukotriene production), the decline of the former is to be regarded as a potential problem. Therefore, the search for optimally balanced blends of n-3 polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) seems to be more promising than a supplementation with only one type of FA.