I remember in high school and college, creatine was becoming a popular supplement for muscle growth.

I took it for a while. I was too young and insensitive to know whether it was truly beneficial or not.

But it was well known at the time that creatine was good for strength, performance, and recovery.

Today it has become one of the most studied supplements on the market. And the research is showing it is extremely safe and effective.

What has also become more popular in recent years, is the benefits of creatine supplementation on brain health.

Creatine & The Brain

Creatine's benefits for the brain and in neurological disorders are a fascinating and growing area of research. The core mechanism behind these benefits relates to creatine's role in energy metabolism.

Creatine and Brain Bioenergetics:

The brain is an incredibly energy-demanding organ, consuming about 20% of the body's total energy despite making up only 2% of body weight. This constant high energy demand is met primarily by adenosine triphosphate (ATP). Creatine plays a crucial role in maintaining ATP levels, particularly during periods of high metabolic demand.

Here's how it works:

Creatine is stored in the brain as phosphocreatine (PCr).
When the brain needs a rapid burst of energy, PCr quickly donates a phosphate group to adenosine diphosphate (ADP) to regenerate ATP. This process is catalyzed by the enzyme creatine kinase (CK), which is also abundant in the brain.
This "creatine-phosphocreatine system" acts as a rapid energy buffer, ensuring a steady supply of ATP to neurons and glial cells, which are constantly engaged in energy-intensive processes like neurotransmission, maintaining ion gradients, and synaptic plasticity.

Cognitive Benefits:

By enhancing the brain's energy reserves, creatine supplementation can lead to several cognitive improvements, especially under conditions of stress or fatigue:

Improved Memory: Studies have shown that creatine can enhance both short-term memory and working memory, which is crucial for tasks like concentration and problem-solving. This benefit appears to be more pronounced in older adults and in situations of mental fatigue or sleep deprivation.
Reduced Mental Fatigue: Creatine can help combat mental fatigue during demanding cognitive tasks, allowing for sustained focus and performance. This is particularly relevant for activities requiring prolonged concentration, such as studying or complex problem-solving.
Enhanced Reasoning and Intelligence: Some research suggests improvements in reasoning abilities and intelligence scores, especially under timed conditions.
Faster Information Processing: There's evidence to suggest improvements in processing speed.
Beneficial in "Metabolic Stress" Conditions: The cognitive benefits seem to be amplified when the brain is under metabolic stress, such as during sleep deprivation, hypoxia (low oxygen), or acute stress.
Vegetarians/Vegans: Individuals who consume little to no dietary creatine (e.g., vegetarians and vegans) often show greater cognitive benefits from supplementation, as their baseline brain creatine levels may be lower.

Neurological Disorders and Neuroprotection:

The potential of creatine in neurological disorders stems from its neuroprotective properties, primarily by supporting cellular energy levels and reducing oxidative stress. Low brain creatine levels are often observed in various neurodegenerative disorders, and the severity of the deficiency can correlate with disease progression.

Here's a breakdown of its potential in specific areas:

Traumatic Brain Injury (TBI) and Concussion:
- Brain trauma, including concussions, can severely impair the brain's energy metabolism.
- Creatine supplementation has shown promise in animal models and some human studies for improving recovery after TBI. It's hypothesized that by boosting brain energy reserves, creatine can help neurons recover and repair more effectively.
- It may also reduce inflammation and oxidative stress, which are common in TBI.
Neurodegenerative Diseases (e.g., Alzheimer's, Parkinson's, Huntington's, ALS):
- Many neurodegenerative diseases are characterized by impaired brain energy metabolism and increased oxidative stress.
- Alzheimer's Disease: A pilot study in Alzheimer's patients showed that creatine supplementation increased brain creatine levels and led to moderate improvements in working memory and executive function. This suggests a potential strategy for boosting brain energy in a disease where energy utilization is compromised.
- Huntington's Disease (HD): Animal models of HD have shown significant neuroprotective effects of creatine, including extended survival, improved motor performance, and reduced striatal atrophy. It's thought to protect against the specific neuronal damage seen in HD.
- Parkinson's Disease (PD): Creatine has been in clinical trials for PD due to its neuroprotective potential, showing promise in improving Unified Parkinson's Disease Rating Scale scores in some earlier trials.
- Amyotrophic Lateral Sclerosis (ALS): In mouse models of ALS, creatine has shown to extend survival and improve motor function.
- Spinocerebellar Ataxia Type 3: Creatine supplementation has shown to slow disease progression and improve motor dysfunction in mouse models.
- Mechanism: Creatine's neuroprotective effects in these conditions are believed to involve:
  - Maintaining ATP levels: Ensuring neurons have enough energy to function and repair.
  - Antioxidant effects: Scavenging free radicals and reducing oxidative stress, which contributes to neuronal damage.
  - Stabilizing mitochondrial function: Protecting mitochondria, the "powerhouses" of the cells, from damage.
  - Anti-excitotoxicity: Protecting neurons from excessive stimulation that can lead to damage.
Depression and Mood Disorders:
- Population studies have linked lower dietary creatine intake to increased depression risk.
- Lower creatine levels in the prefrontal cortex (a brain region involved in mood regulation) have been associated with low mood.
- Some human trials have shown that adding creatine to antidepressant medications can lead to improved mood within a few weeks. Animal studies also strongly support its antidepressant-like effects, possibly through pathways like mTORC1 activation.
Cerebral Creatine Deficiency Syndromes: These are rare genetic disorders where the body cannot properly synthesize or transport creatine to the brain. They lead to severe developmental delays, intellectual disability, seizures, and autism-like behaviors. In some cases, creatine supplementation can partially reverse these severe symptoms, highlighting the critical role of creatine in brain development and function.

Important Considerations for Brain Benefits:

Dosing: While much of the cognitive research has used doses similar to those for muscle benefits (e.g., 5g/day or loading phases of 20g/day), the optimal dosing schedule for specific brain benefits and neurological conditions is still being investigated. Brain creatine levels tend to increase more slowly and to a lesser extent than muscle creatine levels with supplementation.
Blood-Brain Barrier: Creatine needs to cross the blood-brain barrier (BBB) to enter the brain. While it does cross, the efficiency can vary, and this is an active area of research.
Research Stage: While promising, much of the research on neurological disorders is still in its early stages (animal models, pilot human studies). Larger, long-term, well-controlled clinical trials are needed to confirm these benefits and establish optimal protocols for specific conditions.
Not a Cure: Creatine is not a cure for neurodegenerative diseases but shows potential as a supportive therapy to improve symptoms, slow progression, or enhance quality of life.

In conclusion, the emerging evidence strongly suggests that creatine is not just for muscles but plays a vital role in brain health and has significant potential as a therapeutic agent for a range of cognitive impairments and neurological disorders, primarily by optimizing brain energy metabolism and offering neuroprotection.

Sources

PNAS

www.pnas.org

Appraising the brain's energy budget - PNAS

In the average adult human, the brain represents about 2% of the body weight. Remarkably, despite its relatively small size, the brain accounts for about 20% ...

PNAS

www.pnas.org

Tightly coupled brain activity and cerebral ATP metabolic rate - PNAS

Adenosine triphosphate (ATP), a high-energy phosphate (HEP) compound, is the universal energy currency in living cells for supporting the energy needs of ...

Drink Harlo

drinkharlo.com

Phosphocreatine (PCr) and System: Energizing Muscles with Creatine's P - Drink Harlo