Early evidence shows that daily creatine supplementation may help Alzheimer’s patients preserve muscle strength and size, offering a low-cost strategy worth testing in larger trials.
Study: Eight weeks of creatine monohydrate supplementation is associated with increased muscle strength and size in Alzheimer’s disease: data from a single-arm pilot study. Image credit: Olena Yakobchuk/Shutterstock.com
A recent study published in Frontiers in Nutrition examined the muscular benefits of eight weeks of creatine monohydrate (CrM) supplementation in Alzheimer’s disease (AD) patients.
Muscle strength, Alzheimer’s disease and creatine monohydrate
Reduced muscle mass and strength are often seen in AD patients, acting both as a consequence of the disease and a contributor to its risk and progression. Research has shown that neuromuscular dysfunction can emerge before cognitive impairment in AD patients, and six months of resistance training enhanced muscle benefits in older adults with mild cognitive impairment. In mouse models, direct manipulation of skeletal muscle improved cognition. This provides evidence that muscle could be a modifiable node in the disease process.
Existing research documents the role of CrM in improving muscle strength and size. Creatine (Cr) is primarily found in skeletal muscle as phosphocreatine (PCr) and is crucial in maintaining intracellular energy levels. Supplementation with CrM promotes PCr formation and adenosine triphosphate (ATP) regeneration during high-intensity muscle contractions, potentially driving improvements in muscle strength and size. However, the existing literature lacks information regarding the effects of CrM supplementation on skeletal muscle in the context of AD.
About the study
This single-arm pilot trial was conducted at the University of Kansas. It analyzed how 20 g/day CrM supplementation for eight weeks altered muscle strength, muscle size, and neuromuscular junction (NMJ) integrity in 20 participants with a clinical diagnosis of probable AD-dementia. The dose was divided into two 10-gram doses, mixed with beverages chosen by the participants. The participants were between 60 and 90 years, and exclusion criteria included a recent cardiac event, insulin-dependent diabetes, presence of another neurodegenerative disease, chemotherapy or radiation within the past five years, inability to undergo MRI, and participation in a clinical trial within 30 days of screening.
For all the participants, a calibrated Jamar hand dynamometer was used to measure handgrip strength on the participant’s dominant hand. Additionally, 10 participants underwent a lower-body strength assessment, which included peak torque measurements recorded over five repetitions. Muscle size assessment (rectus femoris and vastus medialis) and muscle thickness (the rectus femoris, vastus medialis, and vastus lateralis) were measured for 18 individuals. Plasma C-terminal agrin fragment (CAF) levels were noted in 19 participants to gauge NMJ integrity. All assessments were measured at baseline and eight weeks.
Study findings
The study sample consisted of 65% men, and regarding race, White individuals formed 85% of the sample. They tolerated the CrM intervention well and showed excellent adherence, with 95% of participants achieving ≥80% compliance and an average adherence of 90%. They did not report signs of withdrawal.
Between baseline and eight weeks, handgrip strength increased from an average of 33.5kg to 35.5kg. This represented a 6% gain, which the authors noted was clinically meaningful because grip strength is linked to quality of life and mortality in older adults.
Only 10 participants completed the leg strength test, during which peak torque did not change at any of the tested velocities. Men showed higher baseline strength than females, but no differences were noted by sex for changes in either hand or leg strength.
The muscle cross-sectional area (mCSA) increased in the rectus femoris and vastus medialis. No change was noted in muscle thickness. Similarly, mean echo intensity (mEI) analysis did not show significant changes. However, the rectus femoris and the vastus lateralis regions showed reduced subcutaneous fat. Such a reduction was not noted in the vastus medialis region. The ultrasonography measures did not show any differences by sex.
Anthropometrics and body composition measures showed that the body mass index (BMI) did not change from baseline to 8 weeks and stayed at the average value of around 25. Similarly, the waist circumference and the percent lean body mass showed no significant changes. Despite men having a greater percentage of lean body mass at baseline, no differences by sex for changes in percentage of lean body mass were noted. For NMJ integrity, plasma CAF concentrations did not change between baseline and the eight-week mark, with the average value around 2.5 ng/mL. There were no differences by sex for changes in CAF.
Conclusions
The results showed that 20 g/day CrM supplementation was associated with modest skeletal muscle benefits in AD patients. Improvement in handgrip strength and localized increases in muscle size may help offset the accelerated muscle loss often seen in AD. This finding prompts further research on the potential for CrM to prevent AD-related decline in muscle function. However, the findings should be interpreted with caution as they do not provide definitive evidence.
The results of this investigation are limited by a lack of racial and sex diversity data. A small sample size, the absence of a control group, and a brief study duration also limit the strength of the conclusions. Furthermore, some mid-study protocol changes were required due to mechanical issues with the dynamometer, which prevented standardized familiarization trials.
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