Creatine as a Nootropic

A popular ingredient in sports nutrition supplements, creatine may also have potent nootropic properties.

• Maintain a healthy brain energy metabolism. This may improve cognitive performance and help with degenerative brain concerns.
• Protect the brain from oxidative damage. Creatine’s antioxidant properties may help alleviate the high levels of oxidative stress in the brain.

Overview

Creatine is a naturally occurring organic acid compound found in both animals and humans. Creatine serves a wide variety of functions in the body, but its main role is to increase the supply of energy to skeletal muscle and the brain – two tissues with high energy requirements. This explains why 95% of the body’s creatine is stored in muscle, along with significant concentrations in the brain.¹

Creatine is best known as a dietary supplement used to improve athletic performance, with decades of research to back up its effectiveness and safety. Nevertheless, recent medical studies suggest that creatine also plays an equally important role in brain function.

Thus far, trials done in animals and humans show promising results, including evidence of reduced mental fatigue, enhanced brain function, protection against brain injury, improvement of neurodegenerative illnesses such as Huntington’s and Alzheimer’s, and amelioration of mood disorders such as depression.²³

As one recent review paper summarizes, “the role of creatine in developing and maintaining brain health cannot be understated. This accumulation of positive reports should encourage scientific inquiry among psychology, neuroscience and nutrition communities to further clarify the importance of creatine in cognition and emotion.”¹

Creatine’s Possible Bio-Activities for the Brain

Brain Energy Production

Creatine’s most important and best-understood biological activity is its support of a healthy energy metabolism. This activity is surprisingly similar in both muscle and brain tissue, where creatine works by increasing the availability of adenosine triphosphate (ATP) – the body’s main energy molecule.

ATP rapidly depletes during intense activity, and turns into the molecule ADP. This is where creatine comes in – once it enters the body, it turns into phosphocreatine (PCr), which can then in turn convert ADP back into ATP. This allows ATP to regenerate faster during intense activity.⁵

By quickly replenishing ATP, creatine helps meet the brain’s changing energy demands and maintain healthy function.²

Meanwhile, impairment of this brain energy metabolism is one the leading explanations for the development of a large array of both neurodegenerative and mental disorders. Indeed, studies done in both animals and humans have shown creatine supplementation to be at least somewhat effective for disorders including Alzheimer’s, Parkinson’s, and depression.⁷

Novel Mood Support

What’s more exciting is that creatine appears to be a promising new therapy for people with treatment-resistant depression in particular.⁸⁹

In addition, researchers believe this bio-activity is also largely responsible for enhanced brain function in healthy individuals, especially in situations that elicit mental fatigue. For example, one study found that participants given creatine scored better on intelligence and memory tests, while subjects in another study performed better on a continuous math calculation test.¹⁰¹¹

Meanwhile, several other studies have reported that creatine appears to improve mood and cognitive performance after a period of sleep deprivation. ¹²

Brain Protective Antioxidant Activity

Creatine’s antioxidant action is another major biological activity beneficial to brain health. Antioxidant compounds combat oxidative stress caused by reactive oxygen species (ROS) which can cause damage to brain cells, and in turn contribute to the development of neurodegenerative disorders such as Parkinson’s disease. However unlike creatine’s role in energy balance, this activity is yet to be fully explored.¹³

Brain Cell Survival Support

Another potential biological activity of creatine is the inhibition of mitochondrial permeability transition pores (MPTP); these pores can cause cell death following traumatic brain injury (TBI). Several studies in both animals and humans have found creatine to act as a protector against brain damage following TBI.¹⁴¹⁵

Research

Ultimately, although human trials of creatine have been overwhelmingly positive in terms of ameliorating brain disorders and improving overall brain function and health, some studies reported no effect.¹⁷As such, further research is still needed to confirm ideal dosage and to understand why creatine has not been as effective in humans as it is in animals.

Animal Research

Animal research of creatine supplementation suggests that it has potent neuroprotective qualities, defending against a multitude of neurodegenerative conditions such as Parkinson’s disease, Huntington’s disease, and ALS. Specific findings indicate that creatine may:

• Have an “antidepressant-like” effect in rats¹⁸
• Provide “significant protection” against brain damage in mice and rats following traumatic brain injury¹⁴
• Be a possible “new therapeutic strategy for ALS,” a common brain disorder which causes the death of neurons²⁰
• Be a possible “novel therapeutic strategy to slow or halt the progression of neurodegeneration in HD [Huntington’s]”²¹
• “Limit, if not prevent, damage caused” by inadequate blood and oxygen supply in the brains of mice²²

Human Research

Promising results of creatine supplementation for brain health and performance in animals have spurred a multitude of human trials. Although these have been overwhelmingly positive, thus far creatine appears to be less effective in humans.

Creatine (0.4 g/kg) may improve symptoms of traumatic brain injury

This study examined the neuroprotective effects of creatine on children and adolescents with traumatic brain injury (TBI). Thirty-nine children were given either placebo or creatine (0.4 g/kg body weight) daily for 6 months. The creatine group had a significant improvement in headaches, dizziness, and fatigue associated with TBI.

• The researchers concluded that “There is no doubt that the supply of Cr to patients with TBI needs further investigation, with more patients in double-blind studies and with longer follow-up”²³

Creatine 3-5 g may improve depression in treatment-resistant patients

This study recruited 8 patients with unipolar and 2 patients with bipolar depression who were resistant to medical treatment. They were given creatine daily (3-5 g) for 4 weeks in addition to their existing medication. The 8 patients with unipolar depression improved considerably, while the 2 bipolar patients had a switch to manic behavior.

• The researchers concluded that “creatine, a brain energy metabolism enhancer, may be an efficacious, well tolerated and fast-acting treatment for depression. We hope that larger, controlled trials will continue to explore the potential of this treatment”²⁴

Creatine 8 g could be a potential therapy for Huntington’s

This study tested the effectiveness of creatine as a therapy for Huntington’s (HD). Sixty-four patients with HD were given either placebo or creatine (8 g daily) for 16 weeks. The trial found that the creatine group had a reduction in 8OH2’dG levels, a compound which is indicative of oxidative damage to DNA and is elevated in patients with HD.

• The researchers concluded that “Serum 8-hydroxy-2′-deoxyguanosine (8OH2’dG) levels, an indicator of oxidative injury to DNA, were markedly elevated in HD and reduced by creatine treatment”²⁵

Long-term creatine supplementation appears to enhance mood and mental activity in patients with Parkinson’s

Sixty Parkinson’s patients received either placebo or creatine daily for 2 years. Creatine was first given at a loading dose of 20 g daily for 6 days, then 2 g for 6 months, and 4 g for the remaining period.

The creatine group was found to have improved mood, mental activity and behavior. The researchers also discovered that the CR group required smaller dosage increases for dopamine therapy, which is one of the main ways PD is currently treated.

• The researchers concluded that “Cr improved patient mood and led to a smaller dose increase of dopaminergic therapy but had no effect on overall Unified Parkinson’s Disease Rating Scale scores or dopamine transporter SPECT”²⁶

Creatine 8g may counteract mental fatigue

This study examined the effectiveness of creatine in fighting mental fatigue. The researchers gave 24 participants tablets containing either placebo or creatine monohydrate (1g) taken 8 times daily for 5 days. The subjects also performed a mathematical calculation test created specifically to induce mental fatigue before and after taking the tablets. The study found that the group given creatine performed significantly better after supplementation. In addition, the creatine group had higher brain oxygen use.

• The researchers concluded that “dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when subjects repeatedly perform a simple mathematical calculation”¹¹

Creatine 20g appears to improve mood and mental performance following 24 hours of sleep deprivation

Nineteen subjects were first divided into a placebo or creatine (20g daily) group for a week. Next, they underwent 24 hours of sleep deprivation, during which their mood, memory, cognitive function, and psychomotor skills were tested at 0, 6, 12, and 24 hours. With exception of the verbal and spatial short-term memory tests, the study found that at the 24 hour mark, the creatine group had significantly better performance than placebo on mood, cognition, and psychomotor tests.

• The researchers concluded that “the results of this experiment provide evidence of a positive effect of creatine supplementation on cognitive and psychomotor performance and mood state, following 24 h of sleep deprivation”²⁸

Creatine 5g daily may enhance brain function

This frequently-cited study tested whether increasing brain creatine levels could have a positive effect on cognitive performance. The researchers chose vegetarian and vegan participants because their brain creatine levels may be lower than those who consume meat, and could theoretically respond better to supplementation. Forty-five adults were given placebo or 5 g creatine daily for 6 weeks, and then for another 6 weeks after a washout period.

The trial found that creatine supplementation improved brain function, as shown by improved scores on the Raven’s Advanced Progressive Matrices (RAPM) intelligence test, and the Wechsler Auditory memory test.

• The researchers concluded that “This trial of creatine supplementation showed beneficial effects of creatine on mental performance. These effects may add to the physical enhancement gained by athletes supplementing creatine levels…”¹⁰
• The researchers also suggested that the effect would be the same for people who consume meat

Dosage Notes

Because research on the role of creatine in brain function is still relatively new, experts have yet to decide on the best dosage. However, research suggests that doses of anywhere from 5-20 g or even more may be effective, similar to those already used for optimizing muscle energetics.

Side Effects

Creatine does not appear to have any side effects, although it may result in minor short-term weight gain due to creatine retaining water in muscles.³¹

Available Forms of Creatine

Creatine is available in many different powder forms. It is typically sold by itself, in a mixture of multiple creatine formulations, or with other performance-boosting compounds.

Creatine Monohydrate (CM) – Creatine with a water molecule. CM is the most common and extensively studied form of creatine with clinically proven results.

Micronized Creatine – Same as CM, except the molecules of creatine have been reduced in size, making it easier to absorb.

Buffered Creatine / Kre-Alkalyn® – A patented form which has been “buffered” to reach a higher pH, which is advertised as protecting creatine from converting into the waste byproduct creatinine.

Creatine Anhydrous (CA) – Creatine with the water molecule removed, allowing for higher creatine concentrations.

Creatine Hydrochloride – Creatine bound to a hydrochloride salt group. This form is marketed as being more soluble in water than CM; because of this, most commercial products recommend taking smaller doses.

Creatine Magnesium Chelate / Creatine Magna Power® – Similar to Kre-Alkalyn, this patented form of creatine is advertised as protecting creatine from turning into creatinine.

Creatine Phosphate (CP) – Also known as phosphocreatine, this is the primary form of creatine found in both muscle and brain tissue.

Creatine Nitrate (CN) – Creatine bound to nitrate.

Creatine Pyruvate – CM combined with pyruvic acid.

Creatine Citrate – Creatine bound to citric acid.

Creatine Effervescent – This form is advertised as having better absorption.

References