This study will examine the impact of creatine supplementation on muscle function and cognitive performance in young and older subjects.

This is a randomised, double-blind study of the effects of creatine supplementation on muscle energetics and cognitive function, using 31P-MRS and fMRI. 31P-MRS data will be acquired continuously during exercise phase and in the post-exercise metabolic recovery phase. Participants will undergo a fMRI scan of the brain to record changes in the blood oxygen level dependent (BOLD) signal during a series of cognitive tests. In addition, participants will undergo a resting state BOLD scan and a structural MRI scan for localization of brain regions.

Inclusion Criteria:

• Healthy volunteer: Group 1: male; Group 2: male or female.
• Aged 18-35 years (Group 1), or 50-70 years (Group 2).
• Dietary protein intake at or near the current recommended daily amount (0.75 to 0.85 g protein/kg/day).
• Participation in regular physical activity (aerobic and resistance training) 2-3 times a week for at least 6 months before the study starts (Group 1 only).
• Willingness to maintain a stable lifestyle throughout the study.

Exclusion Criteria:

• Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
• Impaired endocrine, thyroid, hepatic, respiratory, neurological, or renal function, diabetes mellitus, cardiovascular disease, coagulation disorder, autoimmune disease, phenylketonuria, hyperlipidaemia, or history of any psychotic mental illness.
• Any impairment affecting mobility and muscle metabolism of the lower limbs (such as arthritis).
• Surgery (eg stomach bypass) or medical condition that might affect absorption of supplements.
• Inability to complete the structured exercise program.
• Blood pressure and heart rate in seated position at the screening examination outside the ranges 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 35-100 beats/min (Group 1) or 40-100 beats/min (Group 2).
• Metal implants that may affect the MRI scan, eg gold tooth or other metal dental devices (normal dental fillings are allowed), pacemaker, mechanical heart valve, replacement joint, shrapnel. If any metal in the body is identified, the investigators will make a decision, as to whether the subject should participate in the study.
• History of claustrophobia or subject feels unable to lie still on their back for a period of 90 mins in the MRI scanner, or subject unable to perform the required muscle exercise in the MRI scanner.