A randomized, controlled trial of creatine supplementation as a possible treatment for cachexia in rheumatoid arthritis (RA) showed that treated patients had significant increases in lean muscle mass but not in knee extensor strength, grip strength, or physical function.
The researchers note that restored lean muscle mass is likely to have beneficial effects on immune function even in the absence of increased strength but that resistance training is likely to be necessary to improve strength and physical function in patients with RA.
Thomas J. Wilkinson, BSc, and Andrew B. Lemmey, PhD, Bangor University, United Kingdom, and colleagues published their findings in the June issue of Arthritis Care & Research.
Dr. Lemmey, professor of clinical exercise physiology at Bangor University's School of Sport, Health and Exercise Sciences, told Medscape Medical News they undertook the creatine trial as part of a search for an intervention likely to be more acceptable to patients with RA than progressive resistance training. Prior work by his group had shown that the strength gains associated with twice-weekly resistance training could substantially normalize function and restore ability to perform activities of daily living in patients with established RA.
"However, like the majority of the general population, RA patients do not regularly engage in high-intensity exercise," Dr Lemmey said. "Most studies show that RA patients are even more sedentary than the general population. Hence, the rationale for our creatine supplementation study was to find a more widely acceptable means of increasing muscle mass and improving function in RA patients."
The researchers randomly assigned 40 patients with stable RA to 12 weeks of supplementation with placebo or creatine taken as a loading dose of 20 g of creatine monohydrate (Myprotein) (4x5 g/day) for the initial 5 days, followed by a maintenance dose of 3 g/day for the remainder of the 12-week period. Creatine was mixed with mango-flavored drink powder. The patients in the placebo group received only the flavored drink powder.
Patients were assessed at baseline, day 6, week 12, and week 24. Assessments included body composition (dual x-ray absorptiometry and bioelectrical impedance spectroscopy), strength (isometric maximal voluntary knee extensor strength and handgrip strength), and physical function. The researchers measured physical function with the sit-to-stand in 30 seconds test, the 8-foot up-and-go test, and the 50-foot walk test and used the submaximal Siconolfi step test to estimate aerobic capacity. The investigators used the Disease Activity Score in 28 joints and C-reactive protein levels to assess disease activity and measured physical disability with the Multidimensional Health Assessment Questionnaire.
But Is It Muscle, or Is It Water?
They found that creatine supplementation was associated with a statistically significant mean increase in appendicular lean mass (a surrogate for muscle mass) of 0.52 kg in the creatine group vs no change in the placebo group (between-group P = .004). Total mean lean mass increased by 0.60 kg after creatine supplementation vs no change in the placebo group, although the between-group change was not significant. Intracellular water increased by 0.64 L in the creatine group from baseline to week 12, and this change correlated weakly with the increase in muscle mass (P = .082).
After creatine discontinuation at week 12, these changes regressed back to or toward baseline, and the decline in muscle mass in the creatine group corresponded with reductions in total body water and in intracellular water.
Bruno Gualano, PhD, professor of applied physiology in the Nutrition, Exercise and Genetics Research Group, University of Sao Paulo, Brazil, who was not involved in the study, told Medscape Medical News that the authors might have been slightly misinterpreting the apparent change in lean muscle mass.
"This is an interesting study, but I have a slightly different interpretation. Wilkinson et al's data reveal that a 12-week creatine supplementation intervention alone (ie, without an exercise training program) is ineffective in promoting clinical benefits in RA patients. Also, the increase in lean mass reported in this study could be at least partially accounted for [by] water retention, which might not be translated into muscle hypertrophy (despite some mechanistic studies suggesting it as potential hypertrophy stimulus) or into improvements in functionality," Dr Gualano explained. In the absence of functionality improvement, lean mass might be less clinically relevant, Dr Gualano said.
No Increase in Strength or Function With Creatine Alone
Despite the increase in muscle mass, creatine supplementation did not differ from placebo in effect on isometric knee extensor strength, handgrip strength, or objectively assessed physical function.
Dr Lemmey said, "We were surprised by the lack of effect/benefit on function, as creatine supplementation generally improves function and strength in young and old healthy individuals, and in some clinical populations. Also, we have previously observed some benefits in following protein supplementation in RA patients, and studies comparing creatine supplementation to generic protein supplementation usually find that the former is more efficacious in improving function."
More Lean Muscle Likely to Be Beneficial Even Without More Strength
Even without increased strength, greater lean muscle (LM) mass may benefit patients who have rheumatoid cachexia, according to the authors. "Although the lack of effect on strength and physical function are disappointing, the increase in LM 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. Gualano commented, "In conditions characterized by loss of muscle mass (eg, sarcopenia, cachexia, undernourishment), any intervention able to increase muscle mass, even slightly, is obviously desirable, since this could reflect in functional improvements. However, from these data, I am not confident that creatine can play this role, since (a) water retention rather than muscle hypertrophy may be responsible for the gain in lean mass, and, more importantly, (b) no changes in functionality or disease-related parameters were seen."
This raises the question of whether creatine supplementation might be useful in other conditions, such as cancer cachexia. "Rheumatoid cachexia is characterized by decreased muscle mass and increased fat mass, with little if any change in body mass. This contrasts with cancer, which features loss of body mass, including muscle. In this respect, the body composition changes with RA more closely mirror those typically associated with aging. Whether creatine supplementation will have the same benefit on muscle mass in more cachectic individuals is doubtful," Dr Lemmey explained. He noted that creatine supplementation has not been extensively studied in cancer cachexia and that further studies are warranted.
Creatine in RA: Still No Substitute for Resistance Training
The authors conclude that the lack of effect of creatine supplementation alone on physical function in this study further supports the importance of sustained progressive resistance training for patients with RA wishing to increase muscle mass and restore their strength and physical functioning.
Dr Gualano agreed. He said, "As RA patients may present with weakness and muscle atrophy, resistance exercises are mandatory to counteract these symptoms. Some nutritional interventions (eg, high-quality proteins, creatine) can support anabolism when combined with training. In this context, creatine could be an adjuvant strategy that could enhance the adaptive responses to resistance training (eg, increases in strength, function, mobility, and muscle mass), though the effects of this supplement without any training intervention is controversial. As wisely stressed by the authors, further studies should test the potentiality of creatine in conjunction with resistance training in RA patients."
The study authors and Dr Gualano have disclosed no relevant financial relationships.
Arthritis Care Res. 2016;68:729-737. Abstract
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Cite this: Creatine Increased Muscle Mass, Not Strength, in Patients With RA - Medscape - Jun 08, 2016.