Creatine shows potential to boost cognition in Alzheimer’s patients

Athletes have taken the dietary supplement creatine for years seeking to boost energy in their muscles and improve their athletic performance. Now, a preliminary study conducted at the University of Kansas Medical Center suggests that this supplement may have potential for a wholly different health benefit: improving cognition in people with Alzheimer’s disease.

This pilot study, the first to look at the effects of creatine on people with Alzheimer’s or dementia, sought primarily to assess the safety and feasibility of using creatine supplementation in these patients. But the research team also found that the supplements appear to have produced moderate improvements in working memory and executive function.

“These preliminary results suggest that there are good things happening here, that creatine has a benefit,” said Matthew Taylor, Ph.D., assistant professor of dietetics and nutrition at KU School of Health Professions, who led the study, which was known as Creatine to Augment Bioenergetics in Alzheimer's (CABA). “This is a great rationale for doing more clinical trials with larger sample sizes.”

In Alzheimer’s disease, there is a problem with how the brain produces and uses energy. Creatine, an organic compound found mostly in muscle but also found in the brain, is critical to energy metabolism. Mitochondria in the cells convert nutrients and oxygen into energy molecules. Creatine’s job is to transport that energy to where it needs to be. By supplementing the brain with more creatine, the researchers theorize that they can increase brain energy and, they hope, boost memory and thinking processes.

The standard dose people use to boost their muscle strength and athletic performance is 5 grams per day, but because creatine exits the blood into muscles first, the researchers tested a higher dose in this study, in hopes of improving creatine’s odds of making its way to the brain. For this trial, 19 participants with Alzheimer’s disease ages 60-90, recruited through the KU Alzheimer’s Disease Research Center, took 20 grams of creatine monohydrate, a powder they could mix into the beverage of their choice, every day for eight weeks.

Blood draws were conducted at baseline, at four weeks and at eight weeks, and participants underwent magnetic resonance spectroscopy imaging at baseline and at eight weeks to measure creatine in the brain. Besides demonstrating that the supplementation dosage was feasible and well tolerated in the participants, the study also showed an 11% increase in brain creatine levels.

“There has been evidence in other populations that giving a higher dose of creatine does change brain creatine levels, but seeing it change in Alzheimer’s patients was really exciting,” said Taylor. “That (11%) is a significant increase.”

The researchers used the NIH Toolbox Cognition Battery at baseline and at the end of the study to measure cognitive changes in participants. They saw a moderate improvement in working memory, which is task-oriented memory Taylor likened to the memory required for the classic card-matching game Concentration. Participants also demonstrated a moderate boost in executive functioning, another cognitive domain highly affected by Alzheimer’s disease that includes a person’s ability to focus and ignore distractions. “That tends to change in Alzheimer's disease as people progress,” Taylor said. “And we saw what we could call nearly statistically significant improvement in that. They got better at it.”

Taylor cautions that the limitations of the study include, in addition to the sample size, the absence of a control group. But the study serves as the first evidence in humans that creatine supplementation is feasible in people with Alzheimer’s disease and may offer them cognitive benefits.

Future research will also seek to understand the biological mechanisms behind any changes in cognition associated with creatine supplementation, Taylor noted. Moreover, creatine may also play a role in decreasing inflammation and oxidative stress, the progressive accumulation of unstable oxygen-containing molecules known as free radicals and a major mechanism of brain aging and neurodegenerative diseases. “We still have much to learn about the role of this molecule in the brain,” said Taylor.