In the last Workout Nutrition DIY post, I ran through how magnesium and creatine help with sleep deprivation. I think it’s safe enough to say as a general statement there’s a good percentage of people who workout that use creatine, and more concretely, there’s an abundance of peer-reviewed research on it, which brings me to my point – creatine isn’t just for the gym.

Creatine is the Sonny to your Cher, the Ike to your Tina, and the Justin to your Brittany – except it won’t gaslight you or leave you with mental health issues – in fact, it may just help treat those conditions (or at least one of them).

Let’s find out why.

Workout Nutrition DIY: Creatine – It’s Not Just for the Gym [Here’s Why].

If you’ve ever stepped foot inside of a gym or maintained any kind of consistency with your workouts, I’m going to assume you know what creatine is and what it does for your muscles and the body. If you haven’t, here’s a brief summary (and for the love of god – read a book).

Creatine is, like many supplements, another amino acid, and it’s naturally occurring in the body. Formed endogenously, produced and synthesized in the body from reactions which involve non-essential amino acids arginine and glycine and the essential amino acid methionine. The entire process takes place in the brain and the liver so give those two a big round of applause because they earn it on the daily.

You can also get creatine by eating things like seafood, poultry, and red meat, but usually it’s taken as a supplement by gym goers, most often as creatine monohydrate. Personally, I prefer micronized creatine monohydrate for reasons I’ve mentioned in the past and in the nutrition guides – it’s easier for the body to absorb, causing your organs to work less (which means they’ll love you more).

Creatine has also been categorized as a “conditionally essential” nutrient. What are the qualifiers (and what the hell does it mean)?, you’re probably asking.

In order for a nutrient to be “conditionally essential,” it has to normally be produced by the body to meet its physiological requirements; however, certain conditions like brain injury, cardiovascular disease, or other physiologically stressful scenarios (*COUGH*scrolling through Twitter/X*COUGH*) might render production inadequate, causing the body to require supplementation.

Since the early days of researching creatine, we’ve known that creatine benefits muscle size and endurance; it was for the gym, for our bodies as an aid to athletic performance, for our abs and biceps and traps to look great in front of the mirror and just before sex, and that was generally it (you’re LYING if you disagree with that last part).

It never dawned on us that like any other nutrient we’re deficient in, a lack of creatine could compromise physical and mental development (just ask vegans and those ‘carnivore diet’ types), potentially preventing people from maintaining their normal energy flow and making them more vulnerable to cardio-metabolic and neuromuscular diseases.

Creatine being a conditionally essential nutrient isn’t just pseudoscience or some baseless opinion for a sales pitch lineup before you buy some social media influencer’s ‘Get Shredded in 90 Seconds!’ workout plan, either.

No sir/ma’am, this info is taken from data collected by the National Health and Nutrition Examination Survey (NHANES), a highly respected annual event which assesses adults’ and children’s health status in the United States. This also raises the question of…what’s the data set like in other countries???

The Importance of Omnivorous Eating

The NHANES survey results revealed that the average creatine intake among all groups was 0.70 +/- 0.78 grams daily; for context, adults need a minimum of 1 gram a day, normally obtained with omnivorous meals – not for gym related goals like bigger muscles that advertising says creatine is only for, but for general health.

Think about that for a minute. Then consider that you can easily get 1 gram of creatine from things rich in the stuff like:

• Fish, particularly game fish, like salmon, tuna, and herring; a 114 gram serving of herring contains roughly 950 mg of creatine.
• Poultry, like chicken and turkey; a 114 gram serving of chicken contains roughly 450 mg of creatine.
• Pork; a 114 gram serving of pork tenderloin contains roughly 550 mg of creatine.
• Red Meat, like beef; a 114 gram serving of beef contains roughly 500 mg of creatine.
• Dairy products, like cheese and milk also contain creatine, though in smaller amounts.

NHANES discovered that roughly 69% of adults aren’t meeting the creatine metric of 1 gram a day – despite it being so easy to hit that mark.

Research is being conducted to discover even more uses for creatine outside the gym, with a focus on brain function and health. Current research is looking into creatine being used to help with things like traumatic brain injury (TBI), Multiple Sclerosis, Parkinson’s, Alzheimer’s, and neurodegenerative diseases overall.

It’s early days to reach any concrete conclusions for creatine’s use with those conditions though, because while it has shown promise, studies are ongoing.

There are however, 2 things that creatine can help with based on the research results being pretty solid, and those are sleep deprivation and depression (brace yourself amigo, your world’s about to get flipped – in a good way though).

Research on Creatine and Sleep Deprivation

Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Ever stayed up for nearly 52 hours then cried when you dropped a napkin by mistake in that timeframe? Yeah, it’s no party.

It makes sense then, that creatine supplementation should decrease sleep deprivation’s negative effects.

If you’ve been reading my blog for a while, you’ll remember I briefly touched on how creatine can counter sleep deprivation in an earlier blog post and the research article included at the end of it. Here’s two more broken down, one from 2006 and one from 2011:

McMorris et al (2006) Study

This was a double blind study. The study aimed to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on things like cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.

The methodology used was this:

1. Participants (men and women) were divided into creatine and placebo groups. They took 5 grams of creatine monohydrate or a placebo, depending on their group, 4x a day for 7 days, immediately before the experiment.
2. Participants underwent test of verbal and spatial recall, choice reaction time, random movement generation (RMG), static balance and mood state pre-test (0 hours), after 6, 12, and 24 hours of sleep deprivation, with intermittent exercise.
3. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 hours.

The results? At 24 hours, the creatine group demonstrated significantly less change in performance from 0 hours (Δ) in RMG, choice reaction time, balance, and mood state. There were no major differences between the groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 hours than 0 hours, and cortisol levels were lower.

This means that after 24 hours of sleep deprivation, supplementing with creatine had a positive effect on mood state and tasks that place a heavy amount of stress on the prefrontal cortex (like dealing with your mother-in-law).

Having my own bouts of sleep deprivation in my career, using/not using creatine, and seeing a difference despite it not being a ‘stimulant’ like caffeine, I can confidently say I’m not surprised by the results.

Now let’s move onto another study.

Cook et al (2011) Study

I found this study in the Candow et al 2023 research article which covered a range of research on creatine and its effects on brain health and function including:

• Creatine and Brain Bioenergetics
• Creatine and Cognitive Function
• Creatine and Traumatic Brain Injury (TBI)
• Creatine and Neurodegenerative Diseases
• Creatine and Mood Disorders

If you’re interested in reading them all, check out the link to it in the ‘References‘ section at the end of this blog post. For now, I’ve picked this one from the article, which focuses on sleep deprivation and male elite rugby players.

The methodology used was this:

1. Male elite rugby players performed a sport specific skill-based test (passing accuracy) either after normal sleep (7-9 hours) or in a sleep deprived state (3-5 hours).
2. The participants supplemented with a placebo or creatine at two doses – 50 mg per kg and 100 mg per kg, 1.5 hours before testing.
   1. For instance, for a 100 kg rugby player, that’s 5 grams of creatine and 10 grams of creatine, respectively.
3. The repeated rugby passing skill was performed indoors and consisted of a 20 meter sprint where at the 10 meter mark players had to pass a rugby ball through a hanging hoop.

The results? Impaired accuracy as a result of sleep deprivation was decreased in the participants that supplemented with creatine. The players were so overwhelmed, they chest bumped each other, then went home and braided each other’s hair (or lack thereof) while swapping stories of their best tackles.

Overall, this demonstrates that cognitive function can increase in people who supplement with creatine when facing challenges like sleep deprivation or mental fatigue. However, these effects may be dependent on the cognitive function test performed and the intensity and duration of stress conditions.

This probably explains why when I was sleep deprived for all those years in my 20s I could power through despite only getting an average of 4 hours a night – I’ve been taking micronized creatine (and ZMA) for longer than most kids have been at school.

Now let’s look into creatine and its effects on depression.

Research on Creatine and Depression

People can experience some form of Major depressive disorder (MDD) at some point in their lives. When COVID hit, the uptick of this was about 28% with the pandemic increasing depressive disorders. Additionally, those who were forced to sit at home during lockdown and have the entire season of Pretty Little Liars on TV in the background also had a decline in mental health of about 83%.

While there’s different therapies out there, some don’t always hit the mark. Behavioral and talking therapies are known to significantly alleviate symptoms, but only in around 43% to 50% of patients with MDD….and while treatment with antidepressants can reduce symptoms in about 60% of patients, when you find out that placebo treatments do nearly as well as the actual medication (having a 20 to 40% success rate), those numbers don’t look too impressive.

It’s not fair to put all the blame on antidepressants though; the medium success rate overall may be due to the fact that around 28% of patients stop taking treatment after a month because the side effects are disheartening – lack of emotion, potential weight gain, and low sex drive / sexual dysfunction, to name a few.

There’s also the unsettling discovery that the effectiveness of the most regularly prescribed antidepressants – i.e. the ones that work on the brain’s serotonin system (selective serotonin reuptake inhibitors) – has come under scrutiny because of the realization that mood disorders may not actually have anything to do with low levels of serotonin.

Recent research though, has revealed that mood disorders may be related to the levels of creatine in the frontal cortex.

For example, Kondo et al (2016)  reported a significant negative relationship between levels of creatine within a voxel (a “volume element,” i.e. a 3-dimensional chunk or square of brain tissue) encompassing the bilateral frontal pole and ventromedial prefrontal cortex, and scores on the Children’s Depression Rating Scale (CDRS) in females aged 13-20 years with MDD.

Faulkner et al (2021) reported a similarly negative relationship between concentrations of creatine within a voxel in the medial prefrontal cortex and depression scores on the Depression, Anxiety and Stress Scale (DASS) in a sample of 84 participants (men and women) who hadn’t received a diagnosis of MDD, but who showed a wide range of depression scores (which can be considered to be representative of the general population).

Yue et al (2012) reported a small sample of 9 medication-free patients with social anxiety disorder exhibited lower levels of creatine in the left dorsolateral prefrontal cortex than 9 healthy individuals, indicating that levels of creatine within regions of the prefrontal cortex are likely also associated with symptoms of anxiety.

Considering this research ranges from newest to older findings, it would logically make sense then that increasing creatine levels in the prefrontal cortex, and possibly other areas of the brain, may help to alleviate some of the symptoms of anxiety and depression – and that’s exactly what some studies have uncovered.

While it may be true that it’s assumed the brain has low creatine permeability, Dechant et al (1999) successfully increased total levels of creatine in the brain by 8.7% after just 4 weeks; a sample size of 9 healthy individuals supplemented with 20 grams of creatine a day.

Lyoo et al (2012) revealed that just 5 grams a day of creatine for 8 weeks improved the antidepressant effects of the selective serotonin reuptake inhibitor escitalopram in 25 depressed female participants.

Nemets & Levine (2013) got a little lazy with their research. While they reported that taking creatine daily failed to enhance the antidepressant effects of selective serotonin reuptake inhibitors, this is more likely due partially to the fact that the researchers compared the effects of (i) creatine monohydrate 5 grams, (ii) creatine monohydrate 10 grams and (iii) placebo in small groups of only 5, 4, and 9 participants, respectively.

Additionally, Nemets & Levine’s (2013) low doses of creatine were given over only 4 weeks, in comparison to at least 8 weeks with Lyoo et al’s (2012) time frame.

Pulling all the results together, this indicates that taking creatine daily, say 20 grams for at least 4 weeks, or a lower 5 gram dose for at least 8 weeks, is the best documented method to alleviate symptoms of MDD.

More work is needed to come to the optimal dose and treatment method to create antidepressant effects, but the results are promising.

So wrapping up, how is it that creatine can help alleviate or eliminate depression? Based on the research, it looks like taking creatine can increase levels of brain-derived neurotrophic factor, which is known to have antidepressant effects (Pazini et al, 2016).

Additionally, because ATP is used to convert creatine to phosphocreatine, low levels of creatine are associated with a lower release of ATP from astrocytes, which is then considered to promote symptoms of depression and anxiety.

So stop thinking creatine is only for people who want big muscles – and if you’re not ready to invest in micronized creatine just yet, then for your own sake, at least hit your minimum 1 gram a day creatine mark by making sure you have well balanced omnivorous meals; the SUPP UP. No Bull nutrition guides can help you get started immediately.

Nutrition is so important, but often so overlooked.

That’s all folks.

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References

1. Candow, D.G., Forbes, S.C., Ostojic, S.M. et al. 2023. “Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function. Sports Med. 53 (Suppl 1), 49–65. https://doi.org/10.1007/s40279-023-01870-9 
2. Cook CJ, Crewther BT, Kilduff LP, Drawer S, Gaviglio, CM. 2011. Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation: a randomized placebo-controlled trial. J Int Soc Sports Nutr. 8:2
3. Dechent P, Pouwels PJW, Wilken B, Hanefeld F, Frahm J. 1999. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol Regul Integr Comp Physiol. 46:8.
4. Faulkner P, Paioni SL, Kozhuharova P, Orlov N, Lythgoe DJ, Daniju Y, et al. 2021. Relationship between depression, prefrontal creatine and grey matter volume. J Psychopharmacol. 35:1464–72. 
5. Kondo DG, Forrest LN, Shi X, Sung Y-H, Hellem TL, Huber RS, et al. 2016. Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. Amino Acids. 48:1941–54.
6. Korovljev, D., Todorovic, N., Stajer, V., & Ostojic, S. M. (2021). Temporal trends in dietary creatine intake from 1999 to 2018: an ecological study with 89,161 participants. Journal of the International Society of Sports Nutrition, 18(1). https://doi.org/10.1186/s12970-021-00453-1
7. Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, et al. 2012. 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. 169:937–45.
8. McMorris, T., Harris, R.C., Swain, J. et al. 2006. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology. 185, 93–103. https://doi.org/10.1007/s00213-005-0269-z
9. Nemets B, Levine J. 2013. A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression. Int Clin Psychopharmacol. 28:127–33.
10. Pazini FL, Cunha MP, Rosa JM, Colla ARS, Lieberknecht V, Oliveira Á, et al. 2016. Creatine, similar to ketamine, counteracts depressive-like behavior induced by corticosterone via PI3K/Akt/mTOR pathway. Mol Neurobiol. 53:6818–34
11. Post, A., Tsikas, D., & Bakker, S. J. L. (2019). Creatine is a Conditionally Essential Nutrient in Chronic Kidney Disease: A Hypothesis and Narrative Literature Review. Nutrients, 11(5), 1044. https://doi.org/10.3390/nu11051044.
12. Yue Q, Liu M, Nie X, Wu Q, Li J, Zhang W, et al. 2012. Quantitative 3.0T MR spectroscopy reveals decreased creatine concentration in the dorsolateral prefrontal cortex of patients with social anxiety disorder. PLoS ONE. 7:e48105.

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Featured Image & Photo 1, Photo 3: Aleksander Saks
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