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In frail older adults (mean age 85 years old), a 3-month supplementation with a low dose (6 g/day) of medium-chain triglycerides (MCTs; C8:0 and C10:0) given at a meal increased muscle mass and function, relative to supplementation with long-chain triglycerides (LCTs), but it decreased fat mass. The reduction in fat mass was partly due to increased postprandial energy expenditure by stimulation of the sympathetic nervous system (SNS). However, the extracellular signals to ameliorate sarcopenia are unclear. The following three potential extracellular signals to increase muscle mass and function after MCT supplementation are discussed: (1) Activating SNS-the hypothesis for this is based on evidence that a beta2-adrenergic receptor agonist acutely (1-24 h) markedly upregulates isoforms of peroxisomal proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNAs, promotes mitochondrial biogenesis, and chronically (~1 month) induces muscle hypertrophy. (2) An increased concentration of plasma acyl-ghrelin stimulates growth hormone secretion. (3) A nitrogen-sparing effect of ketone bodies, which fuel skeletal muscle, may promote muscle protein synthesis and prevent muscle protein breakdown. This review will help guide clinical trials of using MCTs to treat primary (age-related) sarcopenia.

Background: Three clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial., Objective: We re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function., Analysis: After adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis., Methods: In a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann-Whitney U test was used to analyze data on right and left knee extension times., Results: MCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 μg)-enriched supplement. In a combined data analysis ( n  = 29 in MCTs, n  = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p  = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm 2 , p  = 0.002), left calf circumference ( p  = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p  = 0.017), right knee extension time ( p  = 0.021), left knee extension time ( p  = 0.034), walking speed ( p  = 0.002), and number of iterations in leg open and close test ( p  < 0.001) and decreased right triceps skinfold thickness ( p  = 0.016)., Conclusion: In frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ezaki and Abe.)

Objectives: Supplementation with 6 g/day of medium-chain triglycerides (MCTs) at dinnertime increases muscle function and cognition in frail elderly adults relative to supplementation with long-chain triglycerides. However, suitable timing of MCT supplementation during the day is unknown., Design: We enrolled 40 elderly nursing home residents (85.9 ± 7.7 years) in a 1.5-month randomized intervention trial. Participants were randomly allocated to two groups: one received 6 g/day of MCTs at breakfast (breakfast group) as a test group and the other at dinnertime (dinner group) as a positive control group., Measurements: Muscle mass, strength, function, and cognition were monitored at baseline and 1.5 months after initiation of intervention., Results: Thirty-seven participants completed the study and were included in the analysis. MCT supplementation in breakfast and dinner groups respectively increased right arm muscle area from baseline by 1.1 ± 0.8 cm2 (P<0.001) and 1.6 ± 2.5 cm2 (P<0.001), left arm muscle area by 1.1 ± 0.7 cm2 (P<0.001) and 0.9 ± 1.0 cm2 (P<0.01), right knee extension time by 39 ± 42 s (P<0.01) and 20 ± 32 s (P<0.05), leg open and close test time by 1.74 ± 2.00 n/10 s (P<0.01) and 1.67 ± 2.01 n/10 s (P<0.01), and Mini-Mental State Examination score by 1.5 ± 3.0 points (P=0.06) and 1.0 ± 2.1 points (P=0.06). These increases between two groups did not differ statistically significantly., Conclusion: Supplementation with 6 g MCTs/day for 1.5 months, irrespective of ingestion at breakfast or dinnertime, could increase muscle mass and function, and cognition in frail elderly adults., Competing Interests: SA, OE, and MS have nothing to disclose.