The benefits of omega-3 (n-3) fatty acids in renal populations were last discussed in this column in 2007. Much additional research has occurred since that time. N-3 polyunsaturated fatty acids (PUFAs) have demonstrated cardioprotective effects and reduce risks for death from cardiovascular disease (CVD) in a number of studies.
The two most potent forms include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and these fatty acids are most easily obtained through the consumption of fatty cold-water fish. They are often associated with reduced triglyceride values as well as reductions in oxidative stress.
The mechanism of action often involves the regulation of pro-inflammatory eicosanoid and prostaglandin pathways, in which omega-6 (n-6) fatty acids and n-3 fats are both involved (Biomed Res Int 2013; published online ahead of print). As the ratio of n-6/n-3 tends to decrease, eicosanoid and prostaglandin metabolism begins to favor a more pro-inflammatory nature. Patients with renal disease are at increased risk for CVD-related mortality and high rates of inflammation, and thus n-3 interventions have grown in interest.
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Observational data
Plasma adiponectin is directly associated with n-3 fatty acids and negatively associated with n-6 fatty acids (Clin Nephrol 2011;75:195-203). Long chain n-3 PUFA concentrations are low in hemodialysis (HD) populations while n-6 fats tend to predominate (Am J Nephrol 2012;36:451-458; Ren Fail 2011;33:819-823). HD patients who supplement with n-3 fatty acids tend to have higher erythrocyte DHA and EPA, but the overall elevated n-6 levels result in a reduced overall ratio of n-6/n-3 compared with healthy controls (J Ren Nutr 2009;19:267-274).
An observational study of HD, peritoneal dialysis (PD), and kidney transplant recipients (KTR) assessed the blood erythrocyte fatty acid differences between groups. Although both arachidonic acid and DHA were significantly higher in the KTR group, the n-6/n-3 was reduced in the KTR group (Transplant Proc 2012;44:2932-2935. A prospective HD cohort has indicated an association between blood DHA content and a reduced risk of all-cause mortality and CVD (Am J Nephrol 2011;33:105-110; Clin Nephrol 2009;71:508-513).
A six-year prospective study of n-3 versus n-6 intake in dialysis patients found that each 1-unit increment in n-6/n-3 ratio was associated with a 0.55 mg/L increase in C-reactive protein levels. In the lowest n-6/n-3 quartile, there was a 61% decrease in all-cause mortality (Am J Kidney Dis 2011;58:248-256).
Interventions
In a study of PD patients, triglycerides were found to significantly decrease after supplementation with 2.4 g DHA and 1 g EPA per day for eight weeks (Ren Fail 2010;32:1031-1035). Similarly, a combination of high fish intake and n-3 supplementation was shown to significantly decrease triglyceride values in an HD population after three months (Nephrol Dial Transplant 2008;23:2918-2924).
Likewise, 2.1 g of n-3 was shown to significantly decrease serum triglycerides but no other blood lipid factors (Ren Fail 2011;33:892-898). A placebo-controlled trial found that a two-month intervention with 3 g/day of n-3 found significant increases in glutathione peroxidase, superoxide dismutase, and ferric-reducing antioxidant power and reduced malondialdehyde levels (Iran J Kidney Dis 2010;4:322-326).
Another study found supplementation to significantly reduce TNF-α using 3 g/day of a pharmaceutical grade n-3 supplement protocol for two months (Saudi J Kidney Dis Transpl 2012;23:500-506). Researchers found no significant improvements in blood lipids with supplementation of 920 mg EPA and 760 mg DHA over four weeks (J Ren Nutr 2011;21:479-484). However, 2.4 g (1.8 g EPA, 600 mg DHA) given three times per week has been shown to improve the LDL-C/HDL-C ratio compared with controls. A four-month intervention with 2 g/day n-3 fatty acids resulted in significant decreases in blood pressure (J Nephrol 2008;21:99-105).
One group of investigators found that serum DHA was negatively associated with atrial fibrillation, but supplementation with 1.7 g/day n-3 PUFA did not improve QTc interval compared with controls (Br J Nutr 2012;107:903-909). A placebo-controlled trial found that supplementation of 1 g/day of fish oil significantly decreased rates of uremic pruritis (Iran Red Crescent Med J 2012;14:515-522. A dose of 460 mg EPA and 380 mg DHA (comparable to 3 g fish oil) significantly increased 1,25 (OH) vitamin D and fetuin-A (Nutr Res 2012;32:495-502).
Another study found that supplementation with n-3 resulted in increased erythrocyte DHA and EPA and decreased oleic and saturated fatty acids (Prostaglandins Leukot Essent Fatty Acids 2012;86:29-34). Intravenous administration of 4 g n-3 PUFAs during dialysis does temporarily increase plasma content and is incorporated into platelets, but no improvements in nutritional parameters have been found at this time (J Parenter Enteral Nutr 2011;35:97-106; (J Ren Nutr 2009;19:487-493).
Conclusion
It appears that n-3 supplementation can be used to improve blood lipid parameters, measures of oxidative stress, blood pressure, arrhythmia, and pruritus abnormalities. Dosage varies among studies, but generally 3 g/day of n-3 fatty acids is capable of achieving beneficial results.
One should also consider the incorporation of fatty cold-water fish to help improve n-3 fat intake as well as increase protein for improved outcomes. Due to the easy lipid peroxidation of PUFAs, lower cooking temperatures are suggested and excessive deep frying and grilling is discouraged.
