Influence of CReatine Supplementation on mUScle Mass and Strength After Stroke (ICaRUS Stroke Trial): A Randomized Controlled Trial

Abstract

Background/objectives: The acute phase of stroke is marked by inflammation and mobility changes that can compromise nutritional status. This study was a randomized, double-blind, placebo-controlled trial evaluating the effectiveness of creatine supplementation for older people during seven days of hospitalization for stroke compared to usual care.

Method: The primary outcome measures were changes in functional capacity, strength, muscle mass, and muscle degradation. The secondary outcomes were changes in serum biomarkers related to inflammation, fibrosis, anabolism, and muscle synthesis. In addition, a follow-up 90 days after the stroke verified functional capacity, strength, quality of life, and mortality. Following admission for an acute stroke, participants received either creatine (10 g) or a visually identical placebo (10 g) orally twice daily. Both groups received supplementation with protein to achieve the goal of 1.5 g of protein/kg of body weight/day and underwent daily mobility training during seven days of hospitalization.

Results: Thirty older people were included in two similar groups concerning baseline attributes (15-treatment/15-placebo).

Conclusions: Creatine supplementation did not influence functional capacity, strength, or muscle mass during the first 7 days or outcomes 90 days after stroke. There were no serious adverse events associated with creatine supplementation. However, it decreased progranulin levels, raising a new possibility of creatine action. This finding needs further exploration to understand the biological significance of creatine-progranulin interaction.

Keywords: creatine; muscle mass; older people; progranulin; sarcopenia; stroke.

Figure 1

Flowchart of inclusion of participants in the ICaRUS stroke trial from March 2019 to May 2023.

Figure 2

Biochemical markers of older people who participated in the ICaRUS stroke trial in the first 24 h after stroke and on the 7th day of intervention with creatine versus placebo: (a) Moment: estimate (95%CI) (P). (b) Treatment: estimate (95%CI) (P). (c) Interaction of time × treatment: estimate (95%CI) (P). TR: Treatment. PL: Placebo. M1: Moment 1 (24 h after stroke).M2: Moment 2 (7th day of hospitalization). GDF-15: Growth/Differentiation Factor-15. IGF-1: Insulin-like growth factor 1. Performed generalized mixed models using normal and gamma distributions. * Post hoc analysis (Bonferroni) showed a difference between the moments only in the intervention group for progranulin [(difference = 403.3) (p = 0.02) and creatinine [(difference = −0.16) (p = 0.001)].

Figure 3

Functional capacity and muscle strength evaluated by the modified Rankin scale, Timed Up and Go test, handgrip, and 30 s chair stand test of older people who participated in the ICaRUS stroke trial. (a) Moment: estimate (95%CI) (P). (b) Treatment: estimate (95%CI) (P). (c) Interaction of time × treatment: estimate (95%CI) (P). TR: Treatment. PL: Placebo. M1: Moment 1 (24 h after stroke). M2: Moment 2 (7th day of hospitalization). M3: Moment 3 (90 days after stroke). Performed generalized mixed models using normal and gamma distributions.

Figure 4

Kaplan–Meier survival curve of the older people during participation in the Icarus stroke trial. TR: Treatment; PL: Placebo. (p = 0.52).

Figure 5

Adverse events that occurred during the participation of older people in the ICaRUS stroke trial.