Patients with rheumatoid cachexia had significant improvement in lean muscle mass with creatine supplementation but no gains in strength or function in a new, small, placebo-controlled clinical trial.
Rheumatoid arthritis (RA) often leads to substantial loss of lean mass, a condition known as rheumatoid cachexia. The loss of lean mass adversely affects strength and physician function, a characteristic feature of RA. Currently available therapies for RA, including newer biologic agents, do not reverse the loss of lean mass or fully restore functional ability, Jeremy G. Jones, MD, Honorary Research Fellow, School of Sport, Health and Exercise Sciences, Bangor University, Gwynedd, Wales, United Kingdom, and colleagues explained in their report published in Arthritis Care & Research.1
Studies of high-intensity exercise—particularly progressive resistance training—have demonstrated restoration of lean mass and functional ability in patients with RA. However, low rates of uptake and adherence to such exercise have limited its acceptance.
Among nutritional supplements evaluated in patients with RA, creatine has demonstrated greater potential for increasing lean mass and improving physical function compared with generic protein supplementation, the authors continued. However, only 1 previous study specifically evaluated creatine supplementation in patients with RA, and, because of several limitations, yielded inconclusive results.
Dr Jones and colleagues enrolled 40 patients with RA and evidence of rheumatoid cachexia in a randomized, placebo-controlled trial to evaluate the impact of 12 weeks of creatine supplementation on body composition, strength, and physical function. Patients were followed for an additional 12 weeks after completing randomized treatment.
Patients assigned to active treatment consumed 20 g of creatine monohydrate daily for the first 5 days, followed by 3 g daily for the remainder of the 12-week period; to improve taste, the creatine was dissolved into a fruit-flavored drink. Patients who were randomized to placebo consumed the drink without creatine supplementation.
Patient assessments occurred at baseline, on day 6, week 12, and week 24. Each clinical assessment included evaluation of body composition (dual x-ray absorptiometry and bioelectrical impedance spectroscopy), strength (voluntary knee extensor and hand grip), and physical function (sit-to-stand in 30 seconds test, 8-foot up and go agility test, and 50-foot walk test).
After 12 weeks of treatment, the creatine group’s mean appendicular lean mass increased by 0.52 kg compared with 0.05 kg in the placebo group. Total lean mass also exhibited numerical improvement in the creatine group.
Measures of lower leg and hand grip strength did not differ significantly between the groups at the end of the study, nor did the scores for 3 objective assessments of physical function.
The lack of improvement in strength or physical function contrasted with several prior studies demonstrating positive associations between creatine supplementation and strength, functional ability, or both, in different patient populations, Dr Jones and colleagues acknowledged. However, the cumulative evidence for a favorable effect of creatine on strength and function has been equivocal, they said.
“Although the lack of effect on strength and physical function are disappointing, the increase in LM [lean mass] we demonstrated suggests that creatine supplementation may be beneficial in patients with severe rheumatoid cachexia, since a marked loss of LM both impairs the body’s ability to fight infection, due to limited expendable protein reserve for immune cell production, and increases the risk of mortality,” Dr Jones and colleagues concluded.
“The lack of efficacy demonstrated on physical function in this study further emphasizes that sustained PRT [progressive resistance training] should be performed by RA patients wishing to substantially increase LM, and, subsequently, restore their strength and physical functioning,” they added.
Baseline characteristics did not differ between the 2 groups, although the patients assigned to creatine supplementation were older (aged 63.0 years vs 57.2 years), had a lower body mass index (24.7 kg/m2 vs 27.8 kg/m2), and had less lean mass (45.9 kg vs 50.1 kg) than those receiving placebo. RA-specific parameters, such as Disease Activity Score in 28 joints, did not differ significantly between the groups.
The primary assessment occurred at week 12. At that point, the between-group difference in appendicular lean mass—a surrogate for muscle mass—achieved statistical significance (P = .004). Total lean mass increased by 0.60 kg in the creatine versus the placebo group (P = .158).
The values for isometric knee extensor strength (P = .408) and hand grip strength (P = .833) did not differ significantly between the groups. In addition, scores for the 3 principal tests of physical function also did not differ significantly (P = .335 to P = .764).
- Wilkinson TJ, Lemmey AB, Jones JG, et al. Can creatine supplementation improve body composition and objective physical function in rheumatoid arthritis patients? A randomized controlled trial. Arthritis Care Res (Hoboken). 2016;68:729-737.