Intranasal Oxytocin Improves Lean Muscle Mass and Lowers LDL Cholesterol in Older Adults with Sarcopenic Obesity: A Pilot Randomized Controlled Trial

Abstract

Objectives: Obesity is associated with sarcopenia in older adults, and weight loss can lead to further muscle mass loss. Oxytocin decreases with age, and animal studies suggest that oxytocin administration has trophic effects on skeletal muscle cells and reduces adiposity. We conducted a clinical trial to examine the safety and preliminary efficacy of intranasal oxytocin for older adults with sarcopenic obesity.

Design: A double-blind, placebo-controlled randomized controlled trial of intranasal oxytocin (24 IU 4 times per day) for 8 weeks.

Setting and participants: Twenty-one older (67.5 ± 5.4 years), obese (30-43 kg/m²), sedentary (<2 strenuous exercise per week) adults with slow gait speed (<1 m/s, proxy measure of sarcopenia) were recruited.

Measures: Generalized estimating equations were used to evaluate the effect of oxytocin on safety/tolerability of oxytocin administration and whole body muscle and fat mass.

Results: At baseline, body mass index (BMI) was 36.8 ± 3.6 kg/m², fat mass 46.09 ± 6.99 kg, lean mass 50.98 ± 11.77 kg, fasting plasma glucose (FPG) 92.0 ± 8.9 mg/dL, hemoglobin A1c (HbA1c) 5.7% ± 0.4%, low density lipoprotein (LDL) 111.3 ± 41.5 mg/dL, high-density lipoprotein (HDL) 47.85 ± 10.96 mg/dL, and triglycerides 140.55 ± 83.50 mg/dL. Oxytocin administration was well tolerated without any significant adverse events. Oxytocin led to a significant increase of 2.25 kg in whole body lean mass compared with placebo (P < .01) with a trend toward decreasing fat mass, and a significantly reduced plasma LDL cholesterol by -19.3 mg/dL (P = .023) compared against placebo. There were no significant changes in BMI, appetite scores, glycemia, plasma HDL, triglycerides, or depressive symptoms.

Conclusions and implications: This proof-of-concept study indicates that oxytocin may be useful for the treatment of sarcopenic obesity in older adults. Oxytocin administration may also provide additional cardiovascular benefits.

Keywords: Obesity; body composition; clinical trials; sarcopenia.

Fig. 1.

Change in lean mass (grams) by treatment group, oxytocin versus placebo.

Fig. 2.

Differential change from baseline between oxytocin and placebo based on GEE analysis. *P < .05.