To think, act and feel your best, your brain needs constant access to high quality energy. Is it possible that creatine can help our brains regenerate energy, and can this combat foggy thinking, fatigue, poor cognitive performance, dementia, and sleep deficits? In this post, we’re breaking down the powerful new science showing how creatine can influence brain energetics. We’ll talk about mechanisms and the latest clinical research. Note: this is purely for educational purposes, and you should talk to your healthcare provider before taking any supplement.
Let’s Start With a Quick Background on Brain Energetics
The brain, despite its relatively small size, consumes about 20% of the body's total energy, primarily in the form of glucose, which our brain imports through the blood-brain barrier from our bloodstream. Glucose is metabolized through glycolysis and the citric acid cycle, generating ATP (adenosine triphosphate), which powers our neurons. Additionally, the brain can use ketone bodies as an alternative energy source, particularly during periods of low glucose availability, such as fasting. Dysregulation of brain metabolism is implicated in various neurological conditions, especially Alzheimer's disease, where impaired glucose metabolism and mitochondrial dysfunction play significant roles. We’ll come back to this.
What Is Creatine and Where Does it Come From?
Before we get into the technical aspects of creatine, let’s start with the basics of what creatine is. Creatine is a compound made naturally in our bodies out of the amino acids arginine, glycine, and methionine. This synthesis primarily occurs in the liver and in the brain. Creatine also can be found in certain foods, in particular animal foods. It’s notable that for this reason, when compared to omnivores, vegans consume substantially less dietary creatine, and vegetarians may have lower levels of circulating and muscle creatine than omnivores. Over 90% of our creatine stores are located in our skeletal muscle.
Creatine Supplementation
Ok, now let’s shift to talk about taking creatine supplementation. There are over 1000 peer-reviewed papers on this topic. There are several different forms of creatine, but the majority of the data on efficacy and use comes specifically from creatine monohydrate. Creatine monohydrate is highly popular in athletes, and has been extensively studied and deemed relatively safe at doses up to 30 grams a day for up to five years in healthy people, although there are reports of GI issues, muscle cramps and problems with heat tolerance. Though these topics are still being investigated, a recent review entitled “Common questions and misconceptions about creatine supplementation: What does the scientific evidence really show?” looked at popular misconceptions about creatine, finding that in healthy individuals, there’s not much data that creatine is linked to hair loss, kidney issues, muscle cramping or fewer benefits in women, and that oral creatine monohydrate is likely to be the best form, probably around 3-5 grams a day.
Brain Energetic Mechanisms of Creatine
The core pathway identified that tethers creatine to everything from exercise benefits to brain health is a bidirectional reaction where phosphate groups can be added to creatine to allow for the regeneration of energy currency called adenosine triphosphate, or ATP. Here’s the basics of how it works. Creatine can have a phosphate added to it using an enzyme called creatine kinase. The new molecule, called phosphocreatine, can then be used to regenerate ATP from ADP in places of high energy use, specifically the muscle and brain. Creatine is removed by the body after it degrades into creatinine, a molecule that can be excreted through urine.
How does creatine get into the brain? There are several transporters, including the creatine transporter one or CT1 and a sodium chloride protein that allows for dietary creatine and creatine made in our livers to pass the blood-brain barrier, but the CT1 pathway seems to be more important in regulating uptake.
Some research suggests that CT1 receptors may be decreased in the context of high consumption of supplementary creatine, which could potentially limit the ability of supplemental creatine to reach the brain. As a way to bypass this potential resistance, there’s some data suggesting that the consumption of a creatine precursor called guanidinoacetic acid or an analog of creatine called cyclocreatine may help bypass this potential resistance.
How Creatine May Acutely Boost Brain Energy
Let’s now talk about the potential role of creatine under conditions of acute brain stressors. In the course of our days, our brains can experience a host of different stressors like fatigue, lower oxygen, and sleep deprivation. These stressors are believed to affect and be a reflection of brain energetics. Here, research suggests that creatine may have an especially important role. In one 2015 clinical study, young people who experienced oxygen deprivation had improvements in cognition when given placebo. A 2002 study using 8 grams of daily creatine supplementation was found to reduce mental fatigue during math calculations. A small study on sleep-deprived rugby players from 2011 found that creatine supplementation attenuated sleep-related declines in performance, and a new study in Nature Scientific Reports published in 2024 found that creatine supplementation improved cognitive performance and altered brain energetic signals in healthy people after sleep deprivation.
Could Creatine Target States of Chronic Brain Energetic Depletion?
In addition to acute brain stressors that reflect and influence brain energetics, many chronic brain issues are linked to impaired brain energetics. Of these, the best example may be Alzheimer’s disease, a condition that affects almost 60 million people around the world and up to 1 in 3 people over age 85. Alzheimer’s disease is sometimes called “Type 3 diabetes” because it’s been clearly linked to impairments in brain energetics. Specifically, data suggests that a decrease in brain use of glucose (called “cerebral hypometabolism”) is an early indicator of Alzheimer’s disease, and may be a driver of disease progression. Importantly, a decrease in brain glucose utilization has also been found in older adults in general. So how might creatine factor into the conversation?
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Creatine Shows Potential in Treating Brain Disorders
Generally speaking, the research looking at the potential for creatine as a way to benefit brain energetics in Alzheimer’s or age-related cognitive decline is very early and almost exclusively preclinical. However, some promising findings have many researchers invested in continuing pursuit of this emerging science. In a 2023 paper entitled “Creatine as a Therapeutic Target in Alzheimer's Disease,” the authors state that despite the existing lack of clinical data, “Creatine may serve as a potential target for prevention and therapy and Creatine monohydrate supplementation may be beneficial in AD,” and advocate for more clinical data. The good news is that there’s at least one protocol for a pilot study on this very topic now published.
Putting it Together
Creatine is a naturally occurring compound that is found in our food and is synthesized in our bodies under normal states. Creatine’s known mechanism of action indicates that it plays a role in energy regeneration, and this may have significant implications for brain energetics. While the research is still early, there’s some initial signal that creatine may help to offset energetic depletion states in our brains both acutely and long term.
