Supplementation lowered the risk of major coronary events in hemodialysis patients
CVD IS THE major cause of premature mortality in hemodialysis patients. There is some evidence to suggest that higher levels of n-3 fatty acid consumption than is typical in Western diets may reduce risk in the general population. Surveys of the n-3 nutritional status of dialysis patients show that, like the general population, they are generally marginal or deficient, typically due to low consumption of fatty fish (Am J Kidney Dis. 2006;47:1064-1071). The 2005 National Kidney Foundation Kidney Disease Outcomes Quality Initiative for Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients recommended further research in the field. Several studies on n-3 fatty acids effect on CVD in patients have been completed since that report was released.
For example, Perunicic-Pekovic et al. (Nephrology. 2007;12:331-336) found that dialysis patients were deficient in the essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). They were generally mildly malnourished based on global nutritional assessment. At baseline, n-3 fatty acid levels were negatively correlated with interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a), markers of inflammatory status. Patients were supplemented with fish oil capsules containing 2.4 g EPA plus DHA for eight weeks. The supplement increased red blood cell membrane EPA and DHA significantly. Other nutritional markers also improved, including hemoglobin, albumin and HDL cholesterol. IL-6 and TNF-a decreased dramatically.
In a similar design, researchers at AarhusUniversityHospital in Denmark supplemented dialysis patients with 2.4 g PUFA for eight weeks (J Renal Nutr. 2007;17:258-263). They determined that C-reactive protein (CRP) in granulocyte membranes was marginally decreased from 2.46 to 1.47 mg/L and remained unchanged (3.27 vs. 3.14 mg/L) in control patients ingesting olive oil. In another paper (J Renal Nutr. 2007;17:243-249), the same team reported that heart rate variability in 30 dialysis patients with documented CVD was not effected by 1.7 g n-3 fatty acid supplementation for eight weeks.
In a previous study (Clin J Am Soc Nephol. 2006:1:780-786), Svensson et al. randomly assigned 206 hemodialysis patients to either supplementation with 1.7 g n-3 fatty acids or the same amount of olive oil. The primary end point was a composite of total cardiovascular events in the two-year treatment period. During the trial, 121 of the patients reached the primary end point. The n-3 fatty acids had no significant effect on either total cardiovascular events (62 vs. 59) or death (34 vs. 30). However, the researchers observed significant declines in the number of major coronary events in n-3 supplemented patients compared with controls (7 vs. 17). Furthermore, n-3 supplementation was associated with a significant decrease in the number of new MIs (4 vs. 13). The authors hypothesized that earlier intervention or a larger dose of n-3 fatty acids might be more effective.
Friedman and Moe reviewed the effects of n-3 fatty acid supplementation in dialysis patients (Clin J Am Soc. Nephrol. 2006;1:182-192), emphasizing new studies since the 2005 KDOQI report. Their first conclusion was that dialysis patients were generally deficient in n-3 fatty acids, possibly due to low fish consumption. This could be related either to lower palpability of fish or its higher cost. Although not suggested by Friedman and Moe, restriction of dietary protein prior to dialysis could be a contributor.
Overall, their review of the studies to date suggested that n-3 fatty acid supplementation at high doses can reduce triglycerides, but the effects on other lipoproteins are inconsistent. Studies looking at hematologic parameters associated with n-3 fatty acids have found no clear effects on platelet aggregation, blood viscosity, red blood cell survival, and bleeding times, even at high doses. One study, however, revealed a one-year patency rate of 76% for new arteriovenous grafts in hemodialysis patients who took fish oil compared with a 15% rate for those who took placebo. Thus, fish oil may hold promise as an effective prophylaxis against shunt thrombosis. Poor study design and small numbers of studies limit the conclusions that can be made about immunity and inflammatory parameters in dialysis patients.
Two randomized trials comparing n-3 fatty acid supplemention and placebo have found a trend toward an improvement in pruritus symptoms in patients receiving n-3 fatty acids. Data on n-3 fatty acid supplementation have not supported concerns that they upregulate oxidative stress. Adverse effects generally have been limited to GI symptoms such as nausea, vomiting, diarrhea, and abdominal discomfort.
Friedman and Moe concluded that preliminary studies show that n-3 fatty acid supplementation benefits dialysis patients, but more studies are needed to make clinical recommendations. The effects of n-3 fatty acid supplementation were generally positive, with interpretation limited by the small number of studies, small subject number and poor study design.