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Sad or Tired? Creatine Seems to Help​

You know what it does for you in the gym. Now science is finding startling new uses for creatine monohydrate.​

The creatine pioneers among us who started tinkering around with the stuff 30 years ago never imagined that it would eventually reach the status of a “conditionally essential” nutrient.

So, what the heck is a “nutritionally essential” nutrient? It’s one that’s normally produced in the body to meet its physiological requirements, but certain conditions such as cardiovascular disease, brain injury, or other physiologically stressful situations might render that production inadequate, thus requiring supplementation.

Now, we knew early on what creatine did for athletic performance, muscular endurance, and muscle size, but little did we dream that failure to ingest enough could jeopardize the mental and physical development of both children and adults, preventing them from maintaining normal energy flow and making them more susceptible to neuromuscular and cardiometabolic diseases.

And all this “conditionally essential” nutrient stuff isn’t just conjecture; it’s taken from data collected by the highly respected National Health and Nutrition Examination Survey (NHANES), an annual event that, just as the name implies, assesses the health status of adults and children in the U.S.

The survey determined that the average creatine intake among all age groups was 0.70 +/- 0.78 grams daily. This is relevant because adults need at least 1 gram per day (obtained through an omnivorous diet), and not just for bigger muscles or anything “trivial” like that, but for overall health.

Unfortunately, NHANES found that approximately 68.6% of adults aren’t meeting this creatine metric.

What makes this figure even more grim is that we’re discovering new therapeutic uses for creatine seemingly every month. The newest discoveries involve mostly brain health and function. That means creatine might someday be used to help with cognitive function, traumatic brain injury, Alzheimer’s, Parkinson’s, MS, and neurodegenerative diseases in general.

It’s premature, though, to draw any definitive conclusions regarding creatine’s use in those specific conditions because studies are ongoing. However, I feel fairly confident in discussing two new applications for creatine because the evidence is sufficiently strong:

1. Depression
2. Sleep deprivation

Creatine is just another amino acid, one formed endogenously and produced and synthesized in the human body from reactions involving the dispensable amino acids glycine and arginine and the indispensable amino acid methionine. This process takes place in the liver and the brain. Alternately, creatine can be obtained through eating muscle meats such as red meat and seafood. Or, as is the case with most athletes, it can be obtained as a supplement, most often creatine monohydrate.

Creatine monohydrate has many wannabe rivals, but study after study shows it to be the most effective and bioavailable form. To date, there are more than a hundred peer-reviewed studies lauding creatine monohydrate’s effectiveness.

But enough of that. Let’s look at what creatine does to depression and sleep deprivation.




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A whole lot of people experience some sort of major depressive disorder (MDD) at some point in their lives. COVID didn’t help matters much, either, as the pandemic was credited with increasing depressive disorders by 28% in 2020.

Unfortunately, most therapies come up short. Talking and behavioral therapies significantly alleviate symptoms in only 43 to 50% of patients with MDD. Treatment with antidepressants reduces symptoms in only about 60% of patients, but that number doesn’t look half as good when you discover that placebo treatments did nearly as well as the actual drugs, having a 20 to 40% response rate.

Of course, the poor success rate of antidepressants in general might be explained by about 28% of patients stopping treatment after a month because the side effects are just too daunting: weight gain, lack of emotion (turning Spock-like), or sexual dysfunction (“whisky dick” has nothing on the sexually numbing effects of Prozac, Cipralex, or Zoloft).

Then there’s the disturbing revelation that the usefulness of most commonly prescribed antidepressants – the ones that act on the brain’s serotonin system (selective serotonin reuptake inhibitors) – has been brought into question because of the realization that mood disorders might not have anything to do with low levels of serotonin.

However, recent research has found that mood disorders might be related to the concentrations of creatine in the frontal cortex. One study found that the concentrations of creatine in “voxel” (a “volume element,” i.e., a 3-dimensional chunk or square of brain tissue) had an inverse relationship with depression scores on the Depression, Anxiety, and Stress Scale. Another study found that 9 medication-free patients with anxiety disorder exhibited lower concentrations of creatine in the left dorsolateral prefrontal cortex than 9 healthy individuals.

Given this info, it seems logical that increasing creatine in these and perhaps other areas of the brain might help alleviate some of the symptoms of anxiety and depression, and that’s what some studies have indeed found.

Lyoo, et al. found that daily supplementation of only 5 grams a day of creatine for 8 weeks improved the effects of the selective serotonin uptake inhibitor escitalopram in 25 depressed female patients.

While it’s true the brain is thought to have low creatine permeability, Dechent, et al., was able to increase total brain creatine by 8.7% after 4 weeks by supplementing patients with 20 grams a day.

So, how’s creatine eliminate or ameliorate depression? It seems that creatine can increase levels of brain-derived neurotrophic factor, which is known to have anti-depressive effects. Additionally, creatine augments levels of ATP, low levels of which are considered to promote symptoms of anxiety and depression.




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This is the one I didn’t see coming. It seems that creatine supplementation can supplant extreme sleep deprivation, at least in terms of mental acuity and athletic performance.

I’ll start with an animal study. Firstly, a diet supplemented with 2% creatine for 4 weeks reduced sleep need in male Sprague-Dawley rats.

Now the human studies. Elite male rugby players (male and female) were kept up for 24 hours. Those that had supplemented with creatine (20 grams split into four 5-gram doses) showed significant improvements in movement, verbal and spatial recall, choice reaction time, static balance, and, most surprisingly, mood, when compared to placebo.

The same researchers then decided to increase their torture method, this time requiring subjects to refrain from sleeping for 18, 24, or 36 hours. Half took creatine and half took placebo. All were required to perform intermittent exercise, which included walking, stair climbing, and step-ups.

Interestingly, no changes between placebo and creatine were noticed after 18 and 24 hours, but after 36 hours of no sleep, the creatine group was superior to the placebo group on a number generation task (while changes in tasks engaging mood and effort remained unchanged).

Another study (McMorris et al.), however, found significant improvements in cognitive performance after 24 hours of sleep deprivation.

Clearly, there’s substantial evidence that creatine supplementation can improve cognitive function and performance when subjects are being challenged by sleep deprivation, in addition to mental fatigue.

I find this personally intriguing because even though I don’t seem to need 7 to 9 or even 15 hours of sleep (yeah, I’m talking about you, Mariah Carey, you soprano/sloth hybrid), I often fail to get even 5 because of the demons that haunt me at night. That, or my dogs repeatedly wake me by jostling for position against my warm body.

Even so, that lack of sleep never affects me that much. Maybe it’s the micronized creatine I take. While I don’t take ice-cream-shovel scoops of the stuff as perhaps suggested by some of the research, I take 5 grams a day, which I’ve been mixing into my protein shakes for as long as I can remember and will continue to do so, not only because of its apparent benefits to anxiety and sleep deprivation, but because of its status as a “conditionally” essential nutrient.