Creatine monohydrate is important for sustaining phosphocreatine stores in tissues such as muscle and brain. Phosphocreatine is an important source of energy in these tissues. Supplementation with creatine monohydrate is effective in healthy and clinical populations for improving muscle and brain function. The purpose of our study is to determined whether creatine supplementation is effective during resistance training for improving muscle and brain function in people recovering from stroke.

The purpose of this study is to determine the effects of creatine supplementation and supervised resistance training in stroke survivors. It is hypothesized that creatine supplementation and resistance training will increase whole-body lean tissue mass, limb muscle thickness, muscle strength, tasks of functionality and cognition and decrease symptoms of depression and anxiety compared to placebo and resistance training.

Stroke is characterized by an abrupt disturbance in cerebral circulation causing a neurological deficit. It is a major cause of adult neurological disability in North America, often resulting in significant muscle loss, weakness and functional limitations. Disability associated with stroke limits independent living and social participation in at least half of all stroke survivors. A sedentary lifestyle after stroke can increase the risk for recurrent stroke, cardiovascular disease, and diabetes mellitus. All factors may adversely affect independence and quality of life. The majority of stroke survivors have residual impairments such as hemiparesis, spasticity, cognitive dysfunction, and aphasia, with full recovery reached in a small portion of these individuals. One of the major consequences of these impairments is physical inactivity which inevitably contributes to muscle loss, decreased muscle function (i.e. strength, endurance) and impaired functionality. One intervention which may help improve muscle mass, muscle function and functionality in stroke survivors is supervised resistance training. Resistance training does not lead to muscle spasticity in stroke survivors and has been shown to improve the ability to perform activities of daily living. Another intervention which may be beneficial for stroke survivors is creatine supplementation. Creatine has been shown to increase muscle mass, muscle function and tasks of functionality when combined with resistance training, possibly by influencing cellular hydration status, high-energy phosphate metabolism, muscle protein kinetics, satellite cells, anabolic growth factors, and inflammation. Creatine has also shown promise for improving cognition and symptoms of depression and anxiety; however, no study has examined the combined effects of creatine supplementation and resistance training in stroke survivors.

The study will be a double-blind, repeated measures design. In order to minimize group differences, participants will be matched according to age, gender, and type of stroke and then be randomized on a 1:1 basis to one of two groups, creatine monohydrate or placebo (corn-starch maltodextrin). Creatine and placebo will be similar in taste, color, texture and appearance. A research assistant will be responsible for randomization and another research assistant will prepare study kits. Each study kit will contain the participants supplement for the duration of the study, detailed supplementation instructions, as well as measuring spoons. For days 1-7, participants will ingest 0.3g/kg of creatine or placebo (0.075 g/kg x 4 times daily). This creatine dosing strategy has been shown to be effective for increasing intramuscular creatine stores. For subsequent days, participants will consume 0.1 g/kg/day of creatine or placebo as this creatine dosage is effective for increasing muscle mass. On training days, participants will consume their supplement within 5 minutes after each training session. On non-training days, supplements will be consumed at the participants leisure. Adherence with creatine supplementation, placebo, and resistance training will be assessed by training and supplementation compliance logs. A retrospective treatment identification will be administered to all participants upon completion of the study in order to assess whether participants thought they were administered creatine, placebo, or unsure about what supplement they consumed.

The dependent variables that will be measured at baseline and after the intervention include: (1) whole-body lean tissue mass (dual energy x-ray absorptiometry) (2) muscle thickness (elbow and knee flexors and extensors; ultrasonography), (3) muscle strength (1-repetition maximum leg press and chest press), (4) tasks of functionality (berg balance scale, 6-minute walk test) (5) cognition (Montreal Cognitive Assessment), (6) depression (The Center for Epidemiologic Studies- Depression Scale) and anxiety (Generalized Anxiety Disorder 7-item). Participants will also complete a 3-day food log at baseline and during the last week of supplementation and training to determine whether total calories consumed as well as macronutrient intake changed over the duration of the study. Participants will be instructed to record all food and beverages consumption during these 3 days. Food records will be analyzed using MyFitnessPal.

Inclusion Criteria:

• At least 6 months post-stroke

Exclusion Criteria:

• creatine supplementation within the past 12 weeks
• medications affecting muscle function within the past 12 weeks
• kidney disorders
• liver disorders