High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients

Abstract

Background and Objectives Protein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (v-3) fatty acids have anti-inflammatory properties and have been shown to improve protein homeostasis. We hypothesized that administration of high-dose (2.9 g/d) v-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation.Design, setting, participants & measurements This is a substudy from a randomized, placebo-controlled study (NCT00655525). Patients were recruited between September 2008 and June 2011. Primary inclusion criteria included signs of chronic inflammation (average C-reactive protein of $5 mg/L over three consecutive measurements), lack of active infectious or inflammatory disease, no hospitalization within 1 month prior to the study, and not receiving steroids (.5 mg/d) and/or immunosuppressive agents. The primary outcomes were forearm muscle and whole body protein breakdown and synthesis before and after the intervention. The patients received v-3 (n=11) versus placebo (n=9) for 12 weeks. Analysis of covariance was used to compare outcome variables at 12 weeks. Models were adjusted for a propensity score that was derived from age, sex, race, baseline high sensitivity C-reactive protein, diabetes mellitus, and fat mass because the groups were not balanced for several characteristics.Results Compared with placebo, v-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (231, [interquartile range, 298-213] versus 26 [interquartile range, 13-87] mg/100 ml per min; P=0.01), which remained significant after multivariate adjustment (246, [95% confidence interval, 2102 to 21] mg/100 ml per min). v-3 Supplementation resulted in decreased forearm muscle protein synthesis while the rate in the placebo group increased; however, there is no longer a statistically significant difference in skeletal muscle protein synthesis or in net protein balance after multivariate adjustment. There was no statistically significant effect of v-3 supplementation on whole body protein synthesis or breakdown.Conclusions High-dose v-3 supplementation over 12 weeks in MHD patients with systemic inflammation was associated with attenuation of forearm muscle protein breakdown but did not influence skeletal muscle protein synthesis, skeletal muscle net protein balance or any component of the whole-body protein balance. These results should be interpreted cautiously given the imbalance in the two groups and the short duration of the intervention.

Update on the Impact of Omega 3 Fatty Acids on Inflammation, Insulin Resistance and Sarcopenia: A Review

“…No difference was observed in FBG, LDL, homeosis model assessment insulin resistance (HOMA-IR), insulin, leptin or adiponectin [ 21 ]. No effects of higher doses of omega 3 FA (1914 mg EPA and 957 mg DHA daily supplementation compared to placebo for 12 weeks), were also observed for FBG level and HOMA-IR [ 22 ]. A small dose of omega 3, consisting in 80 mg EPA and 120 mg DHA daily for 10 weeks, was compared with a placebo condition using vit E [ 23 ].…”

Effects of Omega‐3 Fatty Acids on Markers of Inflammation in Patients With Chronic Kidney Disease: A Controversial Issue

“…Overall, it indicated that the change of serum CRP level was not different among the two groups. In another study performed by Himmelfarb et al, serum CRP data were expressed in the form of a histogram, and it also indicated no significant difference in the treatment and control group .…”

“…These 12 studies included a total of 487 patients, among which 254 were treated with omega-3 fatty acids and a control group included 233 treated with placebo. These studies also provided the outcomes reflected in the levels of CRP (22,(25)(26)(27)(28)(29)(30)32,33,35), IL-6 (25,(29)(30)(31)(32)(33)35) and TNF-α (29,31,32,34). Among these, four studies included CKD patients who did not receive dialysis (22,27,31,34).…”

“…Ten studies described the effect of omega-3 fatty acid supplementation on the serum CRP levels (22,(25)(26)(27)(28)(29)(30)32,33,35). The pooled results of seven trials indicated that omega-3 fatty acids intake had no statistical difference in the levels of serum CRP (SMD, −0.20; 95% CI, −0.44 to 0.05; P = 0.11; Fig.…”

“…Six studies were included pertaining to the changes in serum IL-6 levels (25,29,(31)(32)(33)35). Four articles were included in the pooled analysis, which suggested that serum IL-6 levels were not significantly different in the group receiving omega-3 fatty acids supplementation compared with the controls (SMD, 0.00; 95% CI, −0.33 to 0.33; P = 0.99; Fig.…”