A popular dietary supplement commonly used by athletes to build muscle might offer a new way to support brain health in people with Alzheimer’s disease. A small study found that patients who took daily doses of creatine over two months experienced boosts in both brain energy levels and cognitive test scores. The research was published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
Alzheimer’s disease is often associated with a steep decline in how the brain uses energy. The human brain requires massive amounts of fuel to function properly, accounting for a large portion of the body’s daily calorie burn despite its relatively small physical size. Researchers suspect that failing energy systems within brain cells may contribute to the progressive memory loss and confusion seen in patients.
When a cell uses its primary energy currency, a chemical called ATP, it breaks a chemical bond and leaves behind a depleted molecule in its wake. Creatine acts as a biological courier, holding a reserve of chemical parts that it donates to these depleted molecules to rapidly regenerate them into fresh ATP. This rapid recycling process is incredibly important in human tissues that demand massive bursts of energy, like skeletal muscles during exercise. The brain, which constantly fires electrical signals to process thoughts and memories, relies on this exact same recycling system to avoid running out of power.
Inside these cells, creatine shuttles back and forth between different cellular structures. It picks up energy from the mitochondria, often called the microscopic power plants of the cell, and transports it to other areas that desperately need to replenish their power supplies. When cells cannot generate enough power to maintain their basic operations, they become vulnerable to damage and eventually die. This energy failure is one of the earliest signs of Alzheimer’s disease, creating a need for treatments that can restore cellular power.
Current pharmaceutical therapies often target the buildup of toxic protein plaques in the brain, but restoring brain metabolism represents an entirely different approach. While removing toxic plaques might slow the progression of the disease, it does little to repair the broken energy systems inside the surviving neurons. Scientists hope that targeting metabolism could serve as an effective strategy alongside modern drugs. By giving brain cells the tools they need to generate and transport their own power, doctors might be able to help patients maintain independent function for a longer period.
To study this energy transport system, researchers from the University of Kansas Medical Center turned their attention to creatine monohydrate. This specific form of creatine is widely available as an inexpensive dietary powder used by weightlifters seeking to improve their physical performance. Previous laboratory experiments had shown that adding this supplement to the diets of mice with Alzheimer’s-like symptoms improved their spatial memory. The animal studies also showed reductions in brain inflammation and lower 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 might occur in humans with the disease. Up to this point, no clinical trials had specifically tested whether people diagnosed with Alzheimer’s disease could tolerate high doses of creatine under everyday conditions. The research team set out to answer that foundational question while also looking for early signs of cognitive benefit.
The researchers designed an eight-week pilot program involving 20 older adults, ranging in age from 60 to 90. All participants had been clinically diagnosed with progressive dementia due to Alzheimer’s disease. Because doctors’ diagnoses based on symptoms do not always match what is happening biologically inside the tissue, the scientists analyzed the participants’ blood for a biomarker known as p-tau217. This specific protein acts as an accurate indicator of the biological changes that define the condition, particularly the buildup of damaging plaques in the brain.
These specialized blood tests confirmed that the vast majority of the participants had a high biological likelihood of true Alzheimer’s pathology. The team also tested participants for a specific variation of the APOE gene, a known trait that aggressively increases a person’s risk of developing late-onset Alzheimer’s. They found that nearly two-thirds of the study group carried at least one copy of this linked genetic marker. Confirming these traits helped ensure that the study accurately reflected a population facing true Alzheimer’s decline.
The primary goal of the trial was to test whether a daily high-dose supplement regimen would be feasible and safe for these patients. Participants were instructed to dissolve 20 grams of creatine monohydrate powder into a beverage of their choosing every day. They split this amount into two 10-gram doses, taken at different times to maximize the body’s absorption and limit potential digestive issues. The researchers relied on study partners, typically spouses or family members, who used a checklist to track the daily doses over the two-month period.
To objectively confirm that the patients were taking the supplement, the team drew blood at the beginning, middle, and end of the trial to measure blood creatine levels. They also utilized a specialized brain scanning technique called magnetic resonance spectroscopy. Unlike a standard MRI that simply takes pictures of the brain’s physical structure, this advanced imaging method can detect and track the levels of specific chemicals within the brain tissue. In this case, the scanners 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 tissue that protects the brain from harmful substances in the blood, but it also makes delivering treatments difficult. Many targeted treatments fail because they cannot penetrate this protective shield to reach the brain cells inside. Finding that oral creatine supplements can successfully navigate this hurdle in Alzheimer’s patients is a positive technical sign. The brain scanners tracked whether the chemical not only reached the targeted tissue but actually integrated into the existing energy storage systems.
Finally, the participants completed an extensive battery of cognitive tests using a tablet computer. The researchers utilized a standardized collection of tasks designed by medical experts that evaluate different aspects of thinking. The tests measured working memory, which involves holding and manipulating information over short periods, as well as an individual’s ability to switch back and forth between different mental categories. Other assessments tracked attention, processing speed, and language skills before and after the two-month period.
The cognitive assessments evaluated different facets of executive function, which involves the mental processes that enable planning, focusing attention, and juggling multiple tasks. Patients with Alzheimer’s disease often struggle heavily with executive function and working memory as their internal brain structures deteriorate. Researchers suspected that a boost in cellular energy might help delay this specific type of cognitive decline. Identifying a cheap and easy way to support executive function could radically improve the daily lives of patients and their caregivers.
The supplement plan proved highly feasible for the participating patients. All 20 individuals finished the trial without dropping out, and 19 of them successfully consumed at least 80 percent of the required daily doses. The blood tests confirmed that the participants were absorbing the supplement, as their blood creatine levels rose fast after four weeks and stayed elevated throughout the rest of the study.
The intervention appeared to be relatively safe and well-tolerated by the older adults. Some participants reported mild complaints like temporary muscle cramping, occasional diarrhea, or disrupted sleep. Most of these minor issues resolved on their own early in the trial. A comprehensive panel of metabolic blood tests at the end of the study showed no negative impact on the function of the participants’ major internal organs.
The specialized brain scans revealed that the ingested supplement successfully crossed from the bloodstream into the brain. On average, the participants experienced an 11 percent increase in total brain creatine levels over the eight weeks. The researchers observed that a vast majority of the participants experienced at least some measurable increase in their brain’s chemical energy stores.
Alongside this biochemical change, the researchers recorded early improvements in several areas of the patients’ cognitive performance. Overall cognitive test scores climbed by an average of about three points. The participants performed better on tasks related to fluid cognition, which involves solving problems and processing new information quickly. They also showed improvements on a specific working memory task that required them to remember and sort lists of pictured items.
Oral reading recognition, a task that evaluates a person’s ability to correctly read and pronounce visually presented words, saw higher scores by the end of the trial. The researchers also noted improved performance on a test designed to measure a person’s ability to focus on a particular target while actively ignoring distractions. The extent to which a participant’s brain creatine increased tended to align with how much their reading performance improved from the start of the study to the end.
Because this was a small feasibility trial, the research comes with distinct limitations that guide how the results should be evaluated. The trial was single-arm, meaning there was no separate control group taking a fake daily powder for a comparison. Without a placebo group, researchers cannot verify that the supplement directly caused the cognitive improvements. People taking cognitive tests multiple times sometimes perform better on the second try simply because they are more familiar with the testing format.
The short timeline of the trial also prevents scientists from knowing how the supplement acts over periods longer than two months. Moving forward, the research team hopes to launch larger clinical trials that include a placebo element and track patients over a longer timeline. If future research supports these early bioenergetic benefits, this cheap and widely available powder could eventually serve as a tool to support brain health as the disease progresses.
The study, “Creatine monohydrate pilot in Alzheimer’s: Feasibility, brain creatine, and cognition,” was authored by Aaron N. Smith, In-Young Choi, Phil Lee, Debra K. Sullivan, Jeffrey M. Burns, Russell H. Swerdlow, Emma Kelly, and Matthew K. Taylor.
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