Creatine & Brain Health: Hype vs Reality

It isn’t conjecture to say that creatine is THE supplement.

It has been the most well-known, researched, and effective supplement for nearly two decades.

Today, this trend continues with its popularity for brain & cognitive health taking the spotlight.

While there are real benefits to be had here, a lot of the discussion found online in this regard is misguided and sensationalistic.

This article provides an evidence-based look at the brain benefits you can realistically expect from creatine and how to maximize them.

• Primer on creatine

• Creatine in the brain

• Creatine’s effect on memory, cognition, and executive function

• Creatine’s effect on mood disorders

• Creatine’s effect on traumatic injury to the brain

• Dosage of creatine for brain health

• Key take-homes

Primer on creatine

A full explanation of what creatine is and what it does to muscle tissue can be found in our previous review.

Here’s a brief primer:

What it is

Creatine is a modified combination of two amino acids: arginine and methionine.

• Amino acids are small molecules that are the building blocks of peptides, proteins, collagen, hormones, and a ton of other stuff inside your body.

It is produced naturally within our own bodies and can be found in certain foods (primarily meat and fish). However, these sources alone do not completely saturate our tissues with creatine.

Without supplementation, most people sit around ~40-60% of what their total creatine stores can be.

What it does

The body has three energy systems; one is the creatine-phosphate system.

This energy system can produce energy very quickly but not for very long. As a result, in exercise, creatine tends to benefit movements that are short duration and very high intensity.

Examples include heavy lifting, sprinting, jumping, etc.

The limiting factor to this energy system is the amount of creatine available in the tissue to be used for energy production.

Supplementing with creatine serves to saturate the tissues with it, therefore maximizing fuel stores and ‘optimizing’ this energy system.

Creatine in the brain

Creatine is found and used in the brain in much the same way that it is in the muscle.

Similarly, it typically isn’t found in the brain at its maximal storage capacity without deliberate intervention (e.g. supplementation).

Moreover, the brain has a high demand for energy, consuming about ~20% of your entire day’s energy expenditure on average.

Thus, saturating your brain’s creatine stores can serve to enhance the efficiency of the creatine phosphate system.

There is also the argument that your other energy systems can work better due to the creatine-phosphate system being able to handle more of the burden than it was before.

The primary difference in which creatine stores in the brain differ from muscle is in the ease with which creatine can find its way in there.

Your brain has something called a ‘blood-brain-barrier.’

This serves as a club bouncer of sorts; selecting what can or cannot enter the brain.

Creatine can’t cross this barrier on its own, it needs to be transported by a specific transporter; which is conveniently called creatine transporter 1 (CT1). [1]

There are a few issues with this transporter.

1. It isn’t super abundant across the blood brain barrier

2. Your body produces less of it in response to increase creatine intakes from food (annoyingly).

As a result, some have argued for a higher dosage being required to overcome this issue.

Creatine’s effect on memory, cognition, and executive function

In my opinion, there’s one study that kick-started the whole conversation about this online to the size that it is now.

In February 2024, German researchers administered either high dose creatine (0.35 g/kg which is 24 grams for a 150 pound person) or a placebo to subjects and then kept them up all night.

Baseline creatine stores were measured along with baseline cognitive performance using various testing methods (memory recall, multiple choice tests, code deduction, word association, etc.).

As the night went on and subjects became more and more sleep deprived, the group given creatine continued to outperform the placebo group in all cognitive tasks that they were given. Similarly, there was a concordant increase in brain creatine concentration found in those who were administered creatine. [2]

Another study gave subjects either a placebo or 20 grams of creatine per day for 7 days.

Then, the subjects underwent oxygen restriction of 10% oxygen for 90 minutes (normal is ~21%).

The subjects who took the creatine continuously performed better on cognitive tasks as compared to those who took the placebo. [3]

Similarly, in older adults, 20 grams of creatine supplementation for 7 days improved memory recall in various forms as compared to taking placebo. [4]

Now, with all that said, not ALL of the research in this area is showing a benefit.

For instance, in young and healthy individuals, supplementation of creatine at a dose of 0.3 g/kg (21 grams for a 150 pound person) did not improve any measure of cognitive performance compared to placebo. [5]

Bottom line:

Creatine appears to improve cognitive performance when cognition is otherwise impaired.

The examples we covered here include sleep deprivation, advanced age, and oxygen deprivation.

It’s reasonable to expect similar benefits under stress, poor nutrition, or illness.

That said, if you are not of advanced age and are in reasonably good health, I do not think you should discount these cognitive benefits.

You are very likely to find yourself under conditions where these are pertinent at one time or another.

You might not have slept well, have an important presentation to give, not be able to eat for a while, or something else.

When these situations come up, these benefits may be just what you need.

Creatine’s effect on mood disorders

When researchers study the brains of individuals who are either diagnosed with major depressive disorder or experiencing depressive symptoms, they typically find that concentrations of creatine are lower compared to those not experiencing these symptoms. [6,7]

This alone does not mean that lower creatine concentrations are causing depression, but it did spark further investigation.

The evidence here is not as robust and extensive as it is for cognition, but some studies do show promise.

To start, evidence does suggest that creatine concentrations in these individuals can be augmented. Over the course of 4 weeks, 20 grams has been shown to increase brain creatine stores in people with depression. Over 8 weeks, both 5 and 10 grams have demonstrated increases. [8,9]

What’s more interesting is that creatine supplementation has been shown to improve the effectiveness of antidepressants compared to taking antidepressants alone. [9]

At least this has been shown when creatine is taken at a dose of 20 grams for 4 weeks or at a dose of 5 grams for 8 weeks.

Whether creatine reduces the risk of depressive symptoms hasn’t been studied directly, though the broader evidence suggests it likely helps.

The relationship between creatine and mood disorders is meaningful and a valid reason to supplement.

Creatine and brain injury

The form of brain injury that creatine has been most studied for is concussion.

When a concussion occurs there tends to be an alteration of blood flow in the injured area; hindering energy availability to the affected brain tissue. [12]

Moreover, there is some degree of a decrease in creatine concentration in the brain when a concussion occurs. [10]

Creatine supplementation may address both issues by increasing available energy substrates to the affected area.

One study gave youth athletes who had a concussion in sport 0.4 g/kg of creatine per day for 6 months. [11]

The subjects saw improved outcomes in nearly every relevant area including headache frequency and severity, amnesia, and more.

In animal studies, rats who are fed creatine before enduring a concussion tend to fare better than those who were not fed creatine. [1]

It is, hopefully, less likely that you experience a concussion than a poor night’s sleep in the future.

So, this may not be as relevant as a benefit as preserved cognitive function.

However, concussions and other mild traumatic brain injuries are no joke. If one were to happen, it is in your favor to have a physiology more prepared to deal with it than not.

Dosage of creatine for brain health

Most online sources recommend much higher creatine doses than are likely necessary for brain benefits.

• Historically recommended dose of creatine = 5 grams per day

This makes sense from a mechanism perspective. As we discussed before, there are certain guard rails and barriers that seem to make it more difficult for creatine to cross the blood brain barrier.

Furthermore, many of the studies we’ve discussed thus far have used higher doses than normal in their study designs; with 20 grams per day being commonly used.

With all of that said, I don’t think this makes sufficient evidence to recommend these higher-than-usual dosages.

Creatine is not a supplement that has any sort of acute effect. That is, there is no effect 30 minutes after you take it the way there is for caffeine.

It must become saturated in the tissue of interest for it to have any effect on that tissue.

When starting creatine supplementation, you have two options.

1. You can begin taking 5 grams per day from the start, with the full effect setting in about 4 weeks later.

2. You can undergo a ‘loading phase.’ This is a period of increased intake for the purpose of having the full effect set in earlier than 4 weeks later.

If you zoom out a year, though, there’s not going to be any difference between these two approaches.

Many of the studies mentioned thus far are 4 weeks in duration.

In muscle tissue, the full effect would just be starting to set in by the end of the study.

It is possible, given the barriers mentioned before, that even longer may be needed at a normal dose of creatine for the full effect to set in.

If you want to see if there is an effect of creatine on some sort of outcome, you need the full effect to set in sooner.

Thus, the high doses used in research are simply a way to make the most of limited study time.

When discussing the effect of creatine supplementation on mood disorders, I mentioned a study where 20 grams per day for 4 weeks increased brain creatine stores about equally to 5 grams per day for 8 weeks.

Apart from this, there aren’t many other studies looking at creatine’s effect on the brain over long periods of time.

The sleep deprivation study mentioned earlier was a single dose followed by a single night of testing. If the researchers didn’t give them a huge dose, then there wouldn’t be enough of an effect to study.

Bottom line:

Ideally, creatine is something you should supplement for the rest of your life to truly get the benefits. It is probably the most beneficial supplement you can use from both a health and fitness perspective.

Currently, there is evidence to say that normal doses (5 grams per day) over 8 weeks will increase creatine brain stores, but over shorter durations higher doses are needed.

However, if we’re talking about the rest of your life, and you seemingly will increase brain creatine stores over enough time at a normal dose, I don’t see the rationale to base your dosing off of short term studies for this compound.

Until longer duration studies prove me wrong, I am of the opinion that 5 grams per day of creatine (the historically recommended dose) is enough to provide you with all of the benefits aforementioned, over a long enough period of time.

There is no harm in taking more (creatine has absolutely stellar safety data), but there may be no added benefit.

Conclusion

The key take-homes from this article are as follows:

• Creatine improves cognitive function under conditions where your cognitive abilities are otherwise inhibited.

• Creatine has the potential to reduce risk of depressive symptoms and improve treatment outcomes of depressive symptoms.

• Creatine has the potential to reduce severity of concussion and improve recovery after concussion.

• 5 grams per day is probably enough to give you all of these benefits.

References

1. Candow DG, Forbes SC, Ostojic SM, et al. "Heads Up" for Creatine Supplementation and its Potential Applications for Brain Health and Function. Sports Med. 2023;53(Suppl 1):49-65. doi:10.1007/s40279-023-01870-9

2. Gordji-Nejad, A., Matusch, A., Kleedörfer, S. et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep 14, 4937 (2024). https://doi.org/10.1038/s41598-024-54249-9

3. Turner CE, Byblow WD, Gant N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci. 2015;35:1773.

4. McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn.2007;14:517–28.

5. Rawson ES, Lieberman HR, Walsh TM, Zuber SM, Harhart JM, Matthews TC. Creatine supplementation does not improve cognitive function in young adults. Physiol Behav.2008;95:130–4.

6. Faulkner P, Paioni SL, Kozhuharova P, Orlov N, Lythgoe DJ, Daniju Y, et al. Relationship between depression, pre-frontal creatine and grey matter volume. J Psychopharmacol.2021;35:1464–72.

7. Yue Q, Liu M, Nie X, Wu Q, Li J, Zhang W, et al. Quantitative 3.0T MR spectroscopy reveals decreased creatine concentration in the dorsolateral prefrontal cortex of patients with social anxiety disorder. PLoS ONE. 2012;7:e48105.

8. Dechent P, Pouwels PJW, Wilken B, Hanefeld F, Frahm J. Increase of total creatine in human brain after oral supplementation of creatine monohydrate. Am J Physiol Regul Integr Comp Physiol. 1999;46:8.

9. Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, et al. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry. 2012;169:937–45.

10. Forbes SC, Cordingley DM, Cornish SM, Gualano B, Roschel, H, Ostojic SM, et al. Effects of creatine supplementation on brain function and health. Nutrients. 2022;14:921.

11. Dolan E, Gualano B, Rawson ES. Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury. Eur J Sport Sci. 2019;19:1–14.

12. Vedung F, Fahlström M, Wall A, Antoni G, Lubberink M, Johansson J, et al. Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions. Brain Inj. 2022;36:948–60.