A popular nutritional supplement often used by athletes to build muscle may offer a new way to support brain health in Alzheimer’s patients. A small study found that patients who took creatine daily for two months experienced improvements in both brain energy levels and cognitive test scores. The study was published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
Alzheimer’s disease is often associated with a sharp decline in the brain’s energy expenditure. Despite its relatively small physical size, the human brain requires large amounts of fuel to function properly and accounts for a large portion of the body’s daily calorie expenditure. Researchers suspect that defects in the energy systems within brain cells may be contributing to the progressive memory loss and confusion seen in patients.
When cells use their primary energy currency, a chemical called ATP, chemical bonds break, leaving behind depleted molecules. Creatine acts as a biological messenger, holding a reserve of chemical moieties available for these depleted molecules and quickly regenerating them into fresh ATP. This rapid recycling process is critical in human tissues that require large bursts of energy, such as skeletal muscles during exercise. The brain, which constantly emits electrical signals to process thoughts and memories, relies on this very same recycling system to avoid running out of power.
Within these cells, creatine moves between different cellular structures. It receives energy from the mitochondria, often referred to as the cell’s microscopic power plants, and transports it to other areas in dire need of replenishing the power supply. When cells cannot generate enough power to maintain basic operations, they become susceptible to damage and eventually die. This energy failure is one of the early signs of Alzheimer’s disease, creating a need for treatments that can restore cellular power.
While current drug treatments often target the buildup of toxic protein plaques in the brain, restoring brain metabolism takes an entirely different approach. Removal of toxic plaques may slow disease progression, but it is unlikely to repair broken energy systems within surviving neurons. Scientists hope that targeting metabolism may work as an effective strategy alongside modern drugs. By giving brain cells the tools they need to generate and transport their own power, doctors may be able to help patients maintain independent function for longer periods of time.
To study this energy transport system, researchers at the University of Kansas Medical Center turned to creatine monohydrate. This particular form of creatine is widely available as an inexpensive powdered food used by weightlifters looking to improve their physical performance. Previous laboratory experiments have shown that adding the supplement to the diet of mice with Alzheimer’s disease-like conditions improves spatial memory. Animal studies have also shown that it reduces brain inflammation and lowers levels of harmful protein clumps associated with the disease.
Aaron N. Smith, Matthew K. Taylor, and their scientific colleagues wanted to see if similar bioenergetic benefits would occur in humans with this disease. Until now, no clinical trials have specifically tested whether people diagnosed with Alzheimer’s disease can tolerate high doses of creatine under everyday conditions. The research team set out to answer that basic question, looking for early signs of cognitive benefits.
Researchers designed an eight-week trial program for 20 older adults aged 60 to 90. All participants had been clinically diagnosed with progressive dementia due to Alzheimer’s disease. Because doctors’ diagnoses based on symptoms don’t always match what’s happening biologically inside the tissue, the scientists analyzed the participants’ blood for a biomarker known as p-tau217. This particular protein serves as an accurate indicator of condition-defining biological changes, particularly the buildup of damaging plaques in the brain.
These specialized blood tests confirmed that the majority of participants had a high biological likelihood of true Alzheimer’s disease. The research team also tested participants for specific mutations in the APOE gene, a known trait that significantly increases the risk of developing late-onset Alzheimer’s disease. They found that nearly two-thirds of the study group carried at least one copy of this associated genetic marker. By confirming these characteristics, we were able to ensure that the study accurately reflected the population facing a true decline in Alzheimer’s disease.
The primary objective of this study was to test whether daily high-dose supplement therapy is feasible and safe for these patients. Participants were instructed to dissolve 20 grams of creatine monohydrate powder in their favorite beverage every day. They split this amount into two 10-gram doses and take them at different times to maximize absorption in the body and limit potential digestive problems. Researchers relied on study partners (usually spouses or family members) to track daily doses over a two-month period using a checklist.
To objectively confirm that patients were taking the supplement, the team measured blood creatine levels by drawing blood at the beginning, middle, and end of the trial. They also used a special brain scanning technique called magnetic resonance spectroscopy. Unlike standard MRI, which simply takes pictures of the physical structures of the brain, this advanced imaging method can detect and track the levels of specific chemicals within brain tissue. In this case, the scanner measured the total amount of creatine present in the frontal and parietal regions of the brain.
The blood-brain barrier is a tightly woven network of blood vessels and tissues that protects the brain from harmful substances in the blood, but it also makes it difficult to administer treatments. Many targeted therapies fail because they cannot penetrate this protective shield to reach the brain cells inside. The finding that oral creatine supplements can successfully overcome this hurdle in Alzheimer’s disease patients is a positive sign for the technology. The brain scanner tracked whether the chemicals not only reached the target tissue but were actually integrated into existing energy storage systems.
Finally, participants completed a series of extensive cognitive tests using a tablet computer. The researchers utilized a collection of standardized tasks designed by medical professionals that assess different aspects of thinking. The test measured working memory, which retains and manipulates information over short periods of time, and an individual’s ability to move back and forth between different mental categories. Other assessments tracked attention, processing speed, and language skills before and after a two-month period.
Cognitive assessments assessed various aspects of executive function. This involves the mental processes that allow us to plan, focus our attention, and juggle multiple tasks. People with Alzheimer’s disease often have significant problems with executive function and working memory as the brain’s internal structures deteriorate. Researchers wondered if increased cellular energy might help slow this particular type of cognitive decline. Identifying inexpensive and easy ways to support executive function could fundamentally improve the daily lives of patients and their caregivers.
This supplementation plan proved to be highly feasible for the participating patients. All 20 people completed the study without dropping out, and 19 of them were able to take at least 80 percent of their daily dose. Blood tests confirmed that the participants were absorbing the supplement, and blood creatine levels rose rapidly after four weeks and remained high throughout the remainder of the study.
This intervention appeared to be relatively safe and well tolerated by older adults. Some participants reported mild symptoms, including temporary muscle spasms, occasional diarrhea, and trouble sleeping. Most of these minor issues resolved themselves early in the trial. A comprehensive panel of metabolic blood tests performed at the end of the study showed that the functions of the participants’ major internal organs were not adversely affected.
Special brain scans revealed that the ingested supplements successfully passed from the bloodstream to the brain. On average, participants increased total brain creatine levels by 11% over eight weeks. The researchers observed that the majority of participants experienced at least some measurable increase in their brain’s chemical energy stores.
In addition to this biochemical change, the researchers recorded early improvements in several areas of patients’ cognitive abilities. Overall cognitive test scores increased by about 3 points on average. Participants performed better on tasks related to fluid cognition, such as solving problems and processing new information quickly. They also showed improvements in certain working memory tasks that required remembering and sorting lists of items depicted in pictures.
Higher scores were seen by the end of the test on oral reading recognition, a task that assesses a person’s ability to correctly read and pronounce visually presented words. Researchers also noted improved performance on tests designed to measure the ability to focus on a specific goal while actively ignoring distractions. The amount of increase in creatine in the participants’ brains tended to match how much their reading performance improved from the start of the study to the end.
Because this was a small-scale feasibility trial, this study comes with clear limitations on how the results should be evaluated. This study was conducted in a single group. That is, there was no separate control group taking fake daily powder for comparison. Without a placebo group, researchers cannot verify that the supplement directly caused improvements in cognitive function. People who have taken a cognitive test more than once may perform better on their second attempt simply because they are more familiar with the test format.
The short trial schedule also prevents scientists from knowing how the supplements will work over a period of two months or more. The research team now hopes to start larger clinical trials that include a placebo component and follow patients over a longer schedule. If future studies confirm these initial bioenergetic benefits, this inexpensive and widely available powder may ultimately serve as a tool to support brain health as the disease progresses.
The study, “Piloting Creatine Monohydrate in Alzheimer’s Disease: Feasibility, Brain Creatine, and Cognition,” was authored by Aaron N. Smith, Inyoung Choi, Phil Lee, Debra K. Sullivan, Jeffrey M. Burns, Russell H. Swerdlow, Emma Kelly, and Matthew K. Taylor.
Heading options
- Creatine supplements show initial promise for boosting brain energy in Alzheimer’s patients
- Popular muscle supplement may help strengthen brain cells malfunctioning in Alzheimer’s disease
- Can an inexpensive training powder improve memory in Alzheimer’s patients?
- Researchers are testing whether creatine supplements can safely restore brain energy
- Daily creatine intake is associated with improved cognitive scores in dementia in pilot study
- Alzheimer’s patients experience improved memory after taking daily creatine supplements
- How common fitness supplements combat energy loss in Alzheimer’s disease
- Creatine monohydrate safely increases brain energy stores in small Alzheimer’s disease trial
- Targeting brain metabolism with creatine may slow cognitive decline
- Free up your brain’s energy stores with daily creatine powder
