Introduction 

We have all heard the word ‘creatine’ being thrown around when it comes to building muscle or going to the gym. But what is creatine? Creatine is a compound made when protein in our body is broken down. It stores energy that enables muscles to move. Although most of the body’s creatine is found in muscle, it acts as a backup energy source for the brain, especially for intense mental activities.¹ Over the past decade, there has been a shift in attention from the role of creatine in building muscle to the role it has in maintaining brain energy and neurological function. 

The basics of brain energy and metabolism 

The brain requires a lot of energy to function, taking up to 20% of the body’s total energy.¹ To meet this demand, the brain uses mainly glucose and oxygen to produce ATP (adenosine triphosphate), the energy currency of cells. It gives energy for a process called neurotransmission, which allows neurons to send signals to each other and even supports the strengthening of connections between these neurons. It also maintains ion gradients across cells, which power and transmit electrical impulses. Mitochondria (known as the powerhouse of the cell) are the source of this energy production by taking in nutrients and oxygen and producing ATP. If mitochondria are unable to produce ATP, that would mean reduced brain activity, which would lead to impairment and neurological diseases. Therefore, ATP is crucial in maintaining brain function, which is vital for the human body as the brain is not only responsible for mental activities such as thinking, memory, but also maintains bodily functions such as our digestion, heart rate, and movement. 

Creatine’s role in brain energy metabolism

Creatine is produced internally by different organs such as the liver, kidneys and pancreas.² It facilitates the recycling of ATP, which helps the cell reuse energy so it does not run out. It is stored and used in organs that use a lot of energy, which are mainly the skeletal muscles (95% creatine storage), and the rest (5%) is found in the brain, liver, kidney and testes. 

Energy synthesis in the brain via the creatine system helps the brain in various ways:

• Transmits chemical or physical signals through the central (brain and spinal cord) and peripheral nerves
• Maintains the electrical difference across neuronal membranes (membrane potential)
• Maintains neuronal cell volume and function (osmotic regulation) 
• Works as a neuromodulator^, which means it fine-tunes the activity of neurons by influencing the strength and timing of their communication over a longer time duration (unlike neurotransmitters, which rapidly send signals across neurons) 
• Responsible for neuroprotection (protection of nerves from damage and degeneration)³ 

The brain is not working at full capacity when required to do a task, and blood flow increases gradually to the regions of the brain that need it. This means that energy to the brain is provided as and when needed, saving energy in the long run. Creatine helps by providing a backup source of energy to maintain ATP levels, especially for high-energy demands during cognitive tasks.⁴ 

Creatine crosses the blood-brain barrier via creatine transporters like CRT1, which facilitate the uptake of creatine in cells. The brain regions with high levels of creatine are those with high energy needs, such as the cerebral cortex, hippocampus, and thalamus.^5.6 The cerebral cortex is divided into four lobes: frontal, temporal, parietal and occipital lobes, which are responsible for a major portion of human characteristics, such as personality, cognitive functions, decision making, problem solving, intelligence, memory, learning, perception of touch, spatial mapping, and vision, to name a few. The hippocampus is mainly responsible for long-term memory and spatial navigation. The thalamus is mainly responsible for exchanging motor and sensory information, alertness, movement and consciousness. All these regions are responsible for high brain activity and function, requiring high levels of energy. 

Effects of creatine on brain function

Cognitive performance 

Cognition is the mental process by which one gains and processes information, knowledge and understanding through thought, experiences and senses. For example, cognitive performance includes attention, processing, memory, understanding, language and perception. Creatine may improve cognitive performance by increasing cell energy reserves and reducing cell damage.⁷

Memory 

Research has shown that creatine supplementation significantly improves memory in adults and older populations.^7,8,11 Creatine is responsible for many biological processes that enhance memory ability. One, it supplies energy to the brain, particularly in the form of phosphocreatine, which rapidly uses energy reserves, maintaining ATP levels required for high-energy demands.⁹ Secondly, it improves the function of neurotransmitters, especially acetylcholine, which is highly responsible for memory formation and consolidation in the hippocampus.⁹ Additionally, creatine acts as a neuromodulator and neuroprotector, which strengthens the connections between neurons and reduces damage to the cells, respectively.⁷  

Attention and information processing 

Interestingly, there hasn't been a large improvement in attention levels, but some studies show that creatine can improve information processing speed while doing tasks.⁷ This is because of creatine’s ability to produce high-energy metabolism in the brain. Therefore, it can play a vital role in learning, especially for certain populations like students and professionals. 

Neuroprotection 

Creatine is also known for its neuroprotective properties when it comes to brain injury and ischemic conditions (reduced blood flow to a part of the body, causing a shortage of oxygen and nutrients), such as ischemic stroke.¹⁰ Studies have shown that creatine supplementation has positive effects on cerebral ischemia, stroke, and traumatic brain injury by reducing the level of brain damage and better recovery outcomes.¹¹ Moreover, researchers have found creatine to significantly improve traumatic headaches, dizziness and fatigue with no side effects in children and adolescents during intensive care stay.¹² Thus, creatine is shown to reduce oxidative stress (causing damage to neurons) and decrease the risk of neurodegenerative diseases. 

Emotional regulation 

Mental health conditions such as depression and anxiety are widespread, affecting a significant portion of the world. Deficiencies in brain creatine are linked to various neurodevelopmental and psychiatric disorders.¹ Low levels of creatine in the brain’s prefrontal cortex have been associated with depressive symptoms, suggesting that creatine supplementation could improve symptoms alongside antidepressant treatment.¹³ There has also been some evidence around creatine improving symptoms of both anxiety and post-traumatic stress disorder (PTSD).^14,15 Some animal studies have shown that creatine triggers a specific pathway (mTORC1), which is involved in cellular growth, repair and synaptic plasticity, which are all linked to emotional health and stability.¹⁶ Although this area of research warrants further clinical trials and reviews.  

Creatine in neurological disorders

Neurological disorders are a wide range of conditions that affect the brain, spinal cord and nerves. These include neurodegenerative disorders, neuromuscular conditions and other brain conditions such as epilepsy, traumatic brain injury and stroke. 

Neurodegenerative disorders 

A group of conditions is characterised by progressive loss in structure and function of neurons, leading to impaired movement, cognition and loss of other neurological functions. Some common examples are Alzheimer's disease, Huntington's disease, and Parkinson's disease. Emerging research has shown that supplementation of creatine in the early stages of Alzheimer’s disease may help improve brain energy metabolism.¹⁷ Creatine is also well tolerated by patients with Huntington’s disease and has shown decreased oxidative injury to DNA, suggesting a protective effect.¹⁸ People with Parkinson’s disease have tremors, difficulty walking and maintaining posture. Creatine supplementation has been shown to improve mitochondrial function and reduce oxidative stress, which helps slow down the progression of the disease.¹⁹ Although there is more evidence demonstrating the positive effects of creatine on depressive symptoms in people with Parkinson’s.²⁰  

Neuromuscular diseases 

Neuromuscular diseases are conditions where the nerves and muscles are affected, causing muscle weakness and other symptoms like pain, spasms, and difficulty moving. Creatine has been shown to improve function and bone health in Duchenne and Becker's muscular dystrophy, making it easier for people to walk independently, improving their posture and overall quality of life.¹⁰ Interestingly, there has been evidence showing improved muscle strength in neuromuscular diseases after creatine supplementation.^21,22 There is much-needed evidence to show the effects of creatine on paediatric neuromuscular disorders. 

Creatine supplementation 

Creatine is naturally found in foods like poultry, red meat and fish, and it is produced by our body in small quantities. For supplementation, creatine monohydrate is the most studied and effective form. In terms of dosage, a common and safe amount to take is 3-5 grams per day for maintenance. Long-term use of creatine in the right amounts is generally safe for adults, but consider talking to your doctor if you have any health conditions. 

Conclusion 

Creatine is not only used for muscle performance but is also an essential supplement for brain energy and neurological function. It plays a powerful role in brain health, from cognitive function and emotional health to neuroprotection against neurological diseases. Research has shown various ways in which creatine is beneficial in improving symptoms of some neurological conditions, such as Alzheimer's, Parkinson’s and Becker's muscular dystrophy, to name a few. It is highly beneficial to older populations. More research needs to be carried out on the potential therapeutic benefits of creatine.