High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients.
Protein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (ω-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) ω-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation.



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 ω-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.



Compared with placebo, ω-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (-31, [interquartile range, -98--13] versus 26 [interquartile range, 13-87] µg/100 ml per min; P=0.01), which remained significant after multivariate adjustment (-46, [95% confidence interval, -102 to -1] µg/100 ml per min). ω-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 ω-3 supplementation on whole body protein synthesis or breakdown.



High-dose ω-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.
Divisions of *Nephrology, and.|Clinical Science Research and Development, Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee.
Serpil Muge
SM
Deger
Divisions of *Nephrology, and.|Clinical Science Research and Development, Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee.
Adriana M
AM
Hung
Divisions of *Nephrology, and.
Charles D
CD
Ellis
Divisions of *Nephrology, and.
Cindy
C
Booker
Biostatistics, and.
Aihua
A
Bian
Biostatistics, and.
Guanhua
G
Chen
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; and.
Naji N
NN
Abumrad
Divisions of *Nephrology, and.|Clinical Science Research and Development, Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee.
T Alp
TA
Ikizler
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D019587:Dietary Supplements; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005542:Forearm; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000628:therapy
D000596:Amino Acids; D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D009124:Muscle Proteins; D002097:C-Reactive Protein
Forearm; Homeostasis; Humans; Inflammation; Muscle Proteins; diabetes mellitus; hemodialysis; muscle protein turnover; omega-3 fatty acids; protein energy wasting