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Creatine supplementation significantly improved cognitive function by nearly 5% in Alzheimer's patients over just 8 weeks, a new study shows.
In the first-ever trial of its kind, Alzheimer's patients supplementing with high-dose creatine (20 grams per day) saw an 11% increase in total brain creatine levels. Cognitive scores improved by 4.4%, driven by substantial gains in working memory, fluid cognition, inhibitory control and attention, and oral reading recognition.
While creatine boosted cognition broadly, the greatest improvements correlated with higher increases in brain creatine stores.
Creatine's cognitive benefits likely stem from its critical role in brain energy metabolism, addressing core bioenergetic deficits linked to Alzheimer's like dysfunctional mitochondria, impaired glucose metabolism, reduced ATP, and disrupted brain creatine systems—hallmarks of disease that creatine supplementation appears to counteract.
These promising yet preliminary results position creatine as an inexpensive and safe therapeutic option, potentially slowing Alzheimer's disease progression when combined with broader lifestyle and neuroprotective strategies.
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Creatine increases total brain creatine stores and improves cognition
For the study—the first-ever to investigate creatine supplementation for Alzheimer's disease patients—20 adults were supplemented with 20 grams of creatine monohydrate per day for 8 weeks. Creatine was taken in 10-gram doses twice per day and all participants (or their caregivers) documented when and how much they took—a step that ensured compliance with the protocol.
All study participants were in the early stages of Alzheimer's disease—they were taking Alzheimer's disease medication and had pathological signs of Alzheimer's disease, indicated by elevated levels of phosphorylated tau-217.
Cognitive function was assessed before and after the intervention using two tools: the mini-mental state examination (MMSE), a test that reliably detects cognitive impairment, and the NIH Toolbox, another validated test that measures cognitive function in areas like attention, category switching, episodic memory, working memory, processing speed, written language, and auditory language. It's also validated for detecting cognitive impairment in adults.
After 8 weeks of supplementation, brain creatine stores increased by an average of 11%, with 17 out of the 20 participants (85%) experiencing an increase in levels of brain total creatine.
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Cognitive function also improved after creatine supplementation.
Total cognition scores increased by 4.4% (an absolute increase of 3.3 points). Several other measures of cognitive function improved including:
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Fluid cognition (a 7.4% or 4.4-point increase)
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Working memory (a 17.1% or 8-point increase)
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Oral reading recognition (a 5.1% or 5-point increase)
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Inhibitory control and attention (a 7.2% or 4-point increase)
Those scores came from the NIH Toolbox. In contrast, participants didn't improve their scores on the MMSE, the other test battery used in the study.
The improvements in some of these cognitive measures, such as oral reading recognition and crystalized cognition, correlated with changes in total brain creatine—larger changes in brain creatine were associated with greater improvements in cognitive function among these domains.
These results are promising—they suggest that creatine supplementation is feasible, safe, and most importantly effective in treating Alzheimer's disease symptoms.
Why might creatine have such beneficial effects for neurodegenerative diseases? There are plenty of explanations.
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For a short dive into the many benefits associated with creatine and a breakdown of its side effects and how to avoid them, check out this video from our clips channel on YouTube:
Should You Supplement With Creatine?
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I talk about my own approach to creatine supplementation and optimal dosing protocols in Premium Member Q&A episodes #63:
Q&A #63 with Dr. Rhonda Patrick (10/12/2024)
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04:25 - How much creatine do I take daily?
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07:15 - Which creatine brand do I use?
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1:12:12 - Do brain benefits of creatine require high doses (15-20 grams)?
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1:13:41 - Optimal creatine dosing for long-term brain health
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Alzheimer's Disease as a Metabolic Condition (and Why Creatine Might Come to the Rescue)
In Alzheimer's disease brain energy metabolism—or brain bioenergetics—is compromised. Metabolic disruption is a key hallmark of the disease, preceding and persisting throughout its symptomatic stages, and coinciding with hallmark pathological changes, most notably the presence of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Metabolic impairments are considered significant upstream contributors, potentially initiating or accelerating Alzheimer's disease pathology and the major bioenergetic impairments associated with it.
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Dysfunctional mitochondria are central to Alzheimer's disease bioenergetic impairments. Defects mainly occur in the electron transport chain (that's where most of our energy is produced). Animal studies reveal that mitochondrial deficits emerge early and often exhibit sex-dependent differences, typically appearing earlier in females.
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Brain insulin resistance is increasingly recognized in Alzheimer's disease pathology, which impairs glucose uptake and utilization. Decreased glucose metabolism in the brain has been detected decades before clinical symptoms and pathological changes appear—making it a potential canary in the coalmine of Alzheimer's. Furthermore, amyloid-beta peptides directly impair glucose transport into neurons throughout the brain.
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Lower adenosine triphosphate (ATP)—the primary energy source for neuronal survival and energy production—is observed early in Alzheimer's disease and contributes to altered amyloid-beta processing and its subsequent accumulation, exacerbating neurotoxicity. Depletion of ATP levels occurs very early in Alzheimer's disease and is attributed to amyloid-beta exposure, among other effects.
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The brain’s creatine system, essential for ATP regeneration through phosphocreatine (PCr), is significantly disrupted in Alzheimer's disease. Studies highlight reduced PCr levels with substantial declines in the creatine kinase enzyme that's specific to the brain (BB-CK), especially in later disease stages. Furthermore, lower creatine levels have been detected in cognitively healthy older adults carrying the APOE4 allele, a major genetic risk factor for Alzheimer's disease, correlating with poorer cognitive performance.
These bioenergetic impairments collectively represent a profound energy crisis within the Alzheimer's disease brain, and it's why bioenergetic restoration (potentially through creatine supplementation) represents a promising therapeutic target. It's also why physical exercise is one of the most potent ways to lower one's risk for Alzheimer's disease. There's even some convincing evidence that exercise—particularly aerobic exercise—can stabilize cognition and slow brain volume loss even among people who already have Alzheimer's disease!
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Final Thoughts
It's important to recognize the merits of this study while also curbing our enthusiasm for its results.
Since this was a pilot study, there was no placebo (control) group, and the sample size was relatively small—both important limitations. A control group would allow us to compare and clearly identify if creatine preserves, slows, or improves cognitive function beyond the expected decline seen in Alzheimer's. Without this comparison, we can't confidently separate the effects of creatine from typical disease progression.
Nevertheless, this study is promising. Creatine is inexpensive and generally side-effect-free. And currently there are few effective non-pharmacological treatments for Alzheimer's disease. In the early stages, intervening with creatine may slow the biology of the disease, effectively manage the symptoms, and support the brain in the process.
Let's talk about dose. Would I recommend that everyone start taking 20 grams of creatine per day? Probably not. Here's what the latest evidence suggests:
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5-10 grams of creatine per day is sufficient for most people to saturate their creatine stores and optimize muscle strength and performance outcomes.
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Higher daily creatine doses (approximately 10 grams/day) may be optimal for maximizing cognitive and neurological benefits.
- Under acute stress (sleep deprivation, jet lag, intense cognitive load), single higher doses (~20 grams/day for short periods) might further enhance cognitive performance and brain resilience. (Creatine expert Dr. Darren Candow explained this in episode #100 of the FoundMyFitness podcast).
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Higher doses (8-10 grams/day) might also offer additional bone health benefits, particularly when combined with mechanical loading through exercise. Lower doses (2-3 grams/day) have demonstrated limited or no significant benefits for bone outcomes.
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Check out Premium Member Q&A episode #56 to learn all about combining creatine with resistance training and other frequently asked questions about this supplement:
Q&A #56 with Dr. Rhonda Patrick (2/10/2024)
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1:08:19 – Can creatine speed up muscle recovery after workouts?
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1:11:13 – Are there negative side effects to taking creatine?
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1:13:49 – Does creatine affect testosterone levels?
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1:23:11 – Is creatine supplementation safe during pregnancy?
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We can't expect creatine to be a single solution to a complex disease—it's just one supplement that's part of a larger picture of Alzheimer's disease management. That means the benefits will be maximized when it's added to a lifestyle that includes other neuroprotective features like physical activity, a polyphenol-rich diet, cognitive training, and the effective management of cardiometabolic risk factors.
This study adds to the ever-growing list of things that creatine might be good for. It's a supplement everyone should be using—just don't expect miracles.
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