Journal Title (Medline/Pubmed accepted abbreviation): Am J Clin Nutr
Page numbers: 402-412
doi (if applicable): 10.3945/ajcn.110.005611
Summary of Background and Research Design
Background:Age-related loss of skeletal muscle mass may result, in part, from a blunted muscle protein synthesis response (ie, anabolic resistance). Defects in the anabolic signaling cascade, mediated by increased inflammatory activity, may contribute to anabolic resistance. Some evidence for omega-3 supplementation to activate the anabolic signaling cascade and prevent loss of muscle mass exists from animal studies. However, there is currently no evidence from clinical studies.
Hypothesis/purpose of study: The hypothesis was that dietary omega-3 fatty acid supplementation would increase the stimulatory effect of hyperaminoacidemia-hyperinsulinemia on anabolic signaling and protein synthesis in muscles. The study evaluated the effect of omega-3 fatty acid supplementation on muscle protein synthesis rate and anabolic signaling cascade in older adults.
Subjects:The study included 16 older, healthy adults (10 men and 6 women) age 71 ± 2 years who did not participate in regular exercise and had a body mass index < 30 kg/m2.
Experimental design:Single-institution, randomized, controlled study.
Treatments and protocol:Participants were randomized to receive omega-3 fatty acid (4 g Lovaza®/day, containing 1.86 g eicosapentaenoic acid [EPA] and 1.5 g docosahexaenoic acid [DHA]) or corn oil (control). All participants had 2 testing sessions, 1 before receiving supplementation and 1 after 8 weeks of supplementation. A standardized meal was ingested the evening before each testing. Participants received amino acid and glucose tracers for 4 hours before the start of the hyperaminoacidemia-hyperinsulinemia clamp. During the 3-hour clamp, human insulin and amino acids (Travasol, 105 mg amino acids/kg fat-free mass) were infused at a rate to simulate meal consumption. Blood samples were collected before tracer and every 30 minutes following tracer infusion up to 7 hours for assessment of insulin levels and appearance and disappearance of labelled amino acid and glucose tracers. Muscle biopsies were collected 60 and 240 minutes after tracer (baseline) and at 420 minutes (3 hr after clamp initiation) for protein synthesis rate and phosphorylated signal transduction protein levels.
Summary of research findings:
- Baseline patient characteristics were similar in both supplementation groups.
– Low-density lipoprotein and TNF-α levels increased following supplementation in both groups (main effect of time, P < .05); no significant group × time interaction.
- Insulin, glucose, and amino acid levels were not different between supplementation groups at any timepoint during the study.
- Muscle protein synthesis rates at baseline were increased by the hyperaminoacidemia-hyperinsulinemia clamp (P < .001); no effects for group or interaction between groups.
- Omega-3 supplementation did not affect the basal rate of muscle protein synthesis, but doubled the anabolic response to the amino acid and insulin infusion (P < .001).
– Corn oil had no effect on either assessment
- 2 phosphorylated signaling proteins involved in muscle cell growth and protein synthesis were increased after omega-3 supplementation (mTORSer2448 and p70s6KThr389), although phosphorylation of another protein was not affected (AktThr308).
– Corn oil had no effect on any of the signaling proteins.
Interpretation of findings/Key practice applications:
The baseline levels of muscle protein synthesis induced during the hyperaminoacidemia-hyperinsulinemia clamp in this study were compared with data reported from a similar clamp study in younger, healthy adults and were found to be 2-fold lower. Although the comparison was not head-to-head, the results suggest that the anabolic response is blunted in older adults. The results of this study suggest that omega-3 supplementation can attenuate anabolic resistance in older adults and may be a useful therapeutic agent in the treatment of sarcopenia. Although the exact mechanism of this effect is unknown, the results also suggest that activation of the mTOR-p70s6K signaling pathway may be involved. Upstream activators of this pathway that omega-3 may affect were not identified.