The health benefits of creatine – what does the science say?

Social media is increasingly awash with messaging around the ability of creatine to build muscle and improve athletic performance. More recently, there are claims that the benefits of creatine supplementation may extend beyond sports performance and muscle-building to include, brain health, reproduction and even cancer prevention.

How much truth is in these claims and what does the science say?

Creatine is a compound made naturally in the liver, kidneys and pancreas to deliver energy to muscles during exercise. Almost all (95 per cent) is stored in muscles with small amounts stored in the brain.

A review in the International Journal of Sports Nutrition (2017) outlined how we use up to 3 gram of creatine a day. About half of this comes from protein- rich foods such as meat and oily fish, while our body makes the rest.

Supplements come as powders, tablets or other forms that deliver doses between 3 – 5 g a day, up to 20g. Since about 1kg of meat delivers 5g of creatine, getting these quantities from diet alone would be challenging and expensive.

The potential benefits of creatine supplementation to sports nutrition was first discovered in the 1970s by a biochemist from Aberystwyth University in Wales, Roger Harris. But its potential benefits to brain health are more recent. Over the last two decades the role of creatine in neogenesis – the formation of new neurons in the brain has sparked a whole new generation of research.

Brain health
A paper in Food Science and Nutrition 2023 documented a significant reduction in post Covid-19 fatigue after 3 months of creatine supplementation, and improved scores for other post-Covid-19 symptoms including breathing difficulties, body aches, headaches and concentration at 6-month follow-up compared to controls.

A systematic review in Behavioural Brain Research 2024 examined the evidence for the role of creatine supplementation as a possible aid to improvements in cognition. The researchers found overall evidence of increased brain concentrations of creatinine in those who were taking supplements, but the results for effects on cognition were less clear. The study reported higher levels of creatine content in the brain particularly among stressed individuals, but more research is needed to substantiate impact on cognition.

From an energy perspective, the brain is very demanding. A review of the impact of creatine supplementation on memory performance in Behavioural Brain Research (2024) found significant improvements in older adults (66 to 77 years). The researchers found that creatine dose (from 2g to 20g) or duration of intervention (five days to 24 weeks), did not influence the findings.

The researchers concluded that creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults from 66 to 76 years.

Alzheimer’s disease is the most common neurodegenerative disease affecting growing numbers of people as life expectancy continues to rise. Development of treatment for Alzheimer’s primarily focuses on developing medicines that target amyloid plaques in the brain, a hallmark biomarker that precedes onset of symptoms.

Though recent clinical trails of new drugs that target amyloid have demonstrated promising preliminary results, these medicines have a poor history of developing into treatments for Alzheimer’s.

The critical role of creatine in maintaining brain energy reserves and the disruption of this path in Alzheimer’s was outlined in a paper in Current Developments in Nutrition (2023). Recent studies in mice have demonstrated that creatine supplementation led to improved brain bioenergetics (energy exchange) as well as biomarkers of Alzheimer’s and cognition. Despite these promising findings, human trials have yet to be performed to investigate the potential benefits of creatine supplementation in Alzheimer’s disease.

Creatine may also have benefits to mood. In one study published earlier this year in European Neuropsychopharmacology people with depression were given creatine supplementation combined with a course of cognitive behavioural therapy (CBT). The researchers found that over eight weeks, their symptoms improved more than those who had CBT without creatine.

Sleep deprivation
A recent study published in Scientific Reports (2024) linked creatine supplementation to improved work performance and short-term memory in sleep-deprived people.

Research scientist at the Forschungszentrum Jülich research centre in Germany, Ali Gordjinejad recruited 15 people and gave them a creatine supplement or a placebo at 6pm. He tested their cognitive performance – including reaction times and short-term memories – every two and a half hours until 9am.

Gordjinejad found that processing speed was faster in the creatine group compared with a placebo group, suggesting that sleep deprivation and cognitive tasks put participants’ neurons under stress, and this triggers the body to take in more creatine.

“If the energy demand is high from cells, then phosphocreatine (which provides energy for short bursts of effort) comes in and acts like an energy reservoir,” said Gordjinejad who suggested that dietary supplementation can help this reserve to fill up again.

Though this study was small, the researchers suggest that the findings show that creatine could potentially overcome the negative effects of sleep deprivation in the short-term, until you sleep.

However, the study participants took 10 times the recommended daily dose of creatine – they had 35 g – this is not recommended to be tried at home. The dose, Gordjinjad said would pose a risk to people with kidney problems and could also cause stomach pains in the general population.

The researchers plan to repeat the study with lower doses, suggesting that in the future creatine could be used in this way by people who have an unexpected prolonged period of being awake including emergency workers or students doing exams.

Cancer risk
Creatine supplementation is also being researched for its potential in reducing risk of cancer. One recent study involving 25,000 people found that among people aged 52 and older, for those who had the highest level of creatine in their diets, each additional 0.09g of creatine over a two-day average was linked to a 14 per cent reduction in cancer risk. The study was published in Frontiers in Nutrition earlier this year.

There is also a growing interest in the role of creatine from conception to a baby’s early years of life.

Researchers at Monash University Australia outlined in Nutrients 2022 the role creatine plays as an energy source at every stage of reproduction including sperm motility, uterine and placental development as well as foetal growth and the production of breastmilk.

The study outlined how creatine may also have an important role in reducing damage caused by a lack of oxygen in the womb. Hypoxia can restrict the ability of cells to generate sufficient energy in critical tissues, including the placenta and the foetal brain, which can stunt growth or impair their long-term health. In the short term, creatine can allow cells to release energy without needing oxygen.

However, the safety of supplementing with creatine during pregnancy has not been studied directly in humans.

Though some people might benefit from creatine supplementation, it can come with side effects including water retention, muscle cramping and nausea. Creatine is not suitable for everyone including those with kidney or liver problems or those who are taking certain medications. A recent paper in the Journal of International Society of Sports Nutrition outlined while creatine is thought to be broadly safe and well tolerated, there have been rare cases of major adverse events including liver failure.

Despite a growing research interest, the evidence of health benefits from creatine supplementation is still in its early stages. However, there are promising signs that benefits may extend beyond muscle building and athletic performance to include improvements in brain health, reproduction and even cancer prevention. That evidence is almost within reach.

Author
Dr Catherine Conlon is a public health doctor in Cork and former director of human health and nutrition, safefood.