Creatine Supplements Studied in Alzheimer's Pilot Trial

 

• Creatine monohydrate supplements raised serum creatine values in Alzheimer's disease patients in a pilot trial.
• Preliminary secondary outcome results showed positive trends on brain total creatine and cognition.
• Results from this small, single-arm trial of short duration should be interpreted with caution.

Creatine supplements demonstrated a hint of promise for people with Alzheimer's disease in the pilot CABA trial.

In the single-arm study of 20 Alzheimer's patients who received 20 g/day of creatine monohydrate supplements, the primary outcomes were adherence to the study protocol and change in blood creatine.

Throughout the 8-week study, 19 of 20 participants were protocol compliant. Serum creatine values were elevated at 4 and 8 weeks from baseline (0.6 mg/dL vs 14.0 and 15.0 mg/dL, respectively, P<0.001 for each), reported Matthew Taylor, PhD, RD, of the University of Kansas Medical Center in Kansas City, and colleagues.

At 8 weeks, secondary outcome results suggested positive trends. Brain total creatine increased by a relative 11% from baseline (330.5 vs 366.9 IU, P<0.001) on magnetic resonance spectroscopic imaging (MRSI).

Cognition improved on several components of the NIH Toolbox cognition battery, including total cognition (P=0.02), fluid cognition (P=0.004), list sorting (P=0.001), oral reading (P<0.001), and Flanker inhibitory control and attention (P=0.05) tests, they added. There was no change in crystallized cognition or other cognitive tests.

"Our data suggest that creatine monohydrate supplementation is feasible in Alzheimer's disease and provides preliminary evidence for future efficacy and mechanism studies," the researchers wrote in Alzheimer's & Dementia: Translational Research & Clinical Interventionsopens in a new tab or window.

Creatine helps boost metabolism by regenerating ATP (adenosine triphosphate) from ADP (adenosine diphosphate). Impaired brain energy metabolism, including dysfunction in the creatine system, might play a role in Alzheimer's disease, Taylor and colleagues noted.

Evidence from animal studies suggests that taking creatine monohydrate may be good for brain health, but no studies have looked at supplementation in humans with Alzheimer's disease, they added.

"Creatine may help stabilize energy supply in the brain, possibly improving mitochondrial function," Taylor told MedPage Today. "In addition to energy benefits, creatine might also help reduce inflammation and oxidative stress, which are both common in Alzheimer's. A lot more research is still needed to understand the role of creatine in brain health."

The CABA trialopens in a new tab or window evaluated 20 adults ages 60 and up who were diagnosed with cognitive impairment due to Alzheimer's disease. They had Mini-Mental State Examination score of 17 or higher (scores below 17 indicate severe cognitive impairment) and a study partner who agreed to help them.

Participants were recruited through the University of Kansas Alzheimer's Disease Research Centeropens in a new tab or window. All had plasma phosphorylated tau-217 (p-tau217) measurements to determine their likelihood of Alzheimer's pathology. Before joining the study, participants had to have been on a stable dose of Alzheimer's-related medications like donepezil (Aricept) or memantine (Namenda) for at least 30 days.

Blood draws to measure fasting serum creatine levels occurred at baseline, 4 weeks, and 8 weeks. Trained personnel administered the NIH Toolboxopens in a new tab or window cognition battery at baseline and 8 weeks using an iPad. Each participant had two MRSI scans at approximately the same time of day at baseline and at 8 weeks.

For 8 weeks, participants consumed 20 g of creatine monohydrate daily, split into two 10-g doses. They could stir the creatine monohydrate powder into whatever beverage they liked. Participants who reported at least 80% compliance with their daily supplement intake were considered protocol compliant.

Because the CABA study was a small, single-arm pilot trial of short duration, the preliminary secondary outcome results should be interpreted with caution, Taylor and colleagues noted.

"Brain total creatine concentration increased in 85% of participants, with an overall average total creatine increase of 11%," they wrote. "Magnitude of change in total creatine was variable among participants, which may be partially explained by variations in creatine transport kinetics across the blood–brain barrier, similar to variable transport kinetics in skeletal muscle following creatine monohydrate supplementation."

Creatine supplements are commonly associated with athletes and bodybuilders, but they are promoted for brain health too. With the exception of individuals with significant kidney disease, creatine is safe for most people if it's accurately labeled, noted Pieter Cohen, MD, of Cambridge Health Alliance and Harvard Medical School in Boston, who wasn't involved with the study. "The problem is that's not assured, because all creatine is being sold as dietary supplements," he told MedPage Today.

"Supplements don't get vetted like pharmaceutical or even over-the-counter medications do," Cohen said. "Study after study has demonstrated that what's in a supplement product is not necessarily what's on the label." A good way to prevent that would be to buy a supplement that's verified by a high quality third-party certification program like the U.S. Pharmacopeia (USP) dietary supplement verificationopens in a new tab or window program, he added.

Large clinical trials are not required to promote the benefits of supplements, Cohen pointed out. "Unlike pharmaceutical drugs, a supplement could be promoted as having health benefits, even when none are proven in humans."

Determining whether Alzheimer's patients will benefit from creatine supplementation requires further research, Taylor and co-authors said. "CABA's study design limitations prevent the ability to make conclusions of efficacy; thus we urge caution when interpreting these results."

Disclosures

This study was supported by the Alzheimer's Association and the National Center for Advancing Translational Sciences of the NIH.

Taylor reported research support from the NIH, Alzheimer's Association, and the Avocado Nutrition Center. Co-authors reported relationships with government agencies, industry groups, and pharmaceutical companies.

Cohen has received research support from the Consumers Union and PEW Charitable Trusts, as well as royalties from UptoDate.

Primary Source

Alzheimer's & Dementia: Translational Research & Clinical Interventions

Source Reference: opens in a new tab or windowSmith AN, et al "Creatine monohydrate pilot in Alzheimer's: Feasibility, brain creatine, and cognition" Alzheimer's Dement 2025; DOI: 10.1002/trc2.70101.

https://www.medpagetoday.com/neurology/alzheimersdisease/115813