Bioenergetic data from a creatine monohydrate pilot trial in Alzheimer's disease.
Level 4 - case-series / case-control
Single-arm uncontrolled before-and-after pilot trial
PubMed 41737290 · doi:10.1002/trc2.70228
What was done
Twenty participants with Alzheimer's disease (35% female) received 20 g/day of creatine monohydrate for 8 weeks in an open-label, single-arm pilot trial. Researchers assessed brain concentrations of N-acetylaspartate (NAA) and glutathione (GSH) using 1H magnetic resonance spectroscopy. They also measured platelet and lymphocyte mitochondrial respiration via respirometry, lymphocyte ADP and ATP levels using bioluminescent assays, and lymphocyte reactive oxygen species using flow cytometry.
What was found
Brain NAA and GSH levels showed no significant change (no numerical values reported in the abstract). Lymphocyte ADP (p < 0.02) and ATP (p < 0.001) rose significantly in both sexes, while the ATP/ADP ratio, superoxide, and hydrogen peroxide remained stable. Platelet and lymphocyte mitochondrial respiration increased significantly across multiple respiration states (State 2, State 3, State 3S, Leak, and Maximum oxygen consumption rate) only in female participants (p < 0.05; trends for others). Exact baseline and follow-up numerical values were not provided in the abstract.
Why it matters
The findings provide preliminary peripheral biomarker evidence that high-dose creatine may alter cellular bioenergetics in Alzheimer's disease, with potential sex differences in mitochondrial response.
Limits
The study lacked a randomized control or placebo group, had a small sample size (n = 20, including only 7 females), and lasted only 8 weeks. No changes were observed in brain-specific bioenergetic markers (NAA or GSH), and findings in peripheral blood cells may not reflect central nervous system bioenergetics.
Cited by
- context Studies show that giving approximately 20 grams of creatine to older adults with mild cognitive impairment or early-stage Alzheimer's disease improves cognitive function.