Creatine: what the science says

Creatine Supplementation for Older Adults: Focus on Sarcopenia, Osteoporosis, Frailty. Bone. Candow et al. September (2022) Vol 162.

The aim of this review was to update the research relating to the effects of creatine supplementation on ageing muscle and bone, and present rationale for its use in the treatment of frailty in older adults.

It presented an analysis of 22 studies of creatine supplementation along with resistance training, including men and women, age range 48-84 years, with intervention from 7 weeks to 1 year.

It also reviewed 10 studies of creatine supplementation without resistance training, including men and women, age range 54-82 years, with intervention from 7 days to 2 years.

The review noted that Sarcopenia, commonly defined as the age-related decrease in strength, muscle mass and functionality, is associated with osteoporosis, frailty and cachexia. Furthermore, Sarcopenia increases the risk of falls, injuries, fractures and premature mortality.

It reported that Creatine (primarily when combined with resistance training) has been shown to increase measures of muscle strength and functionality. Creatine has also been shown to increase bone area and strength, and reduce the rate of bone mineral loss.

It noted that Creatine supplementation (or co-ingestion with whey protein) poses no adverse effect on kidney or liver function in older adults.

In Conclusion: Creatine monohydrate supplementation is a viable lifestyle intervention to improve ageing muscle mass, strength and functionality. This may in turn decrease the risk of falls and fractures in older adults.

Nutritional Supplements to Support Resistance Exercise in countering Sarcopenia of Aging. Nutrients. McKendry et al. (2020) 12,2057

The purpose of this review was to provide an evidence-based account of nutritional strategies to enhance resistance training in an attempt to combat age-related muscle mass loss. In addition, it provided insight on how to incorporate these nutritional strategies that may support the growth or maintenance of skeletal muscle and so extend the healthspan of older individuals.

It noted that older individuals show reduced sensitivity i.e. anabolic resistance to protein ingestion – which makes muscle mass maintenance particularly challenging. Using stable isotopic tracers (instead of old nitrogen balance techniques), research groups have repeatedly demonstrated that older adults require >1.2g/kg/d of protein to maximally stimulate muscle protein synthesis.

It has been shown that animal-derived protein, such as, dairy, eggs, and meat are higher quality protein sources than most plant-based proteins (e.g., soy and wheat). For example, ingestion of whey protein led to a greater muscle protein synthesis than wheat protein, in healthy older men, despite being matched for total protein content. Consuming sufficient high-quality (i.e. leucine rich) protein in combination with resistance exercise appears to be the primary determinant to improve, or at least maintain, skeletal muscle mass and function with advancing age.

Creatine facilitates the transfer of high-energy phosphates in the production, and rapid regeneration, of adenosine triphosphate (ATP). As skeletal muscle cannot make its own creatine it must be either made by the kidneys and liver, or taken in through the diet.
Creatine supplementation, in an older population, has been shown to result in improvements in body composition and to enhance exercise performance. The physiological improvements induced by creatine supplementation may extend to bone and brain tissue.
It concluded that Creatine supplementation offers a safe, well tolerated, and effective nutritional strategy to improve skeletal muscle particularly when carried out with resistance training. It also stated that a more conservative dosing strategy can be employed as opposed to initial studies with a higher loading dose followed by a maintenance dose.

Individuals looking to progress into their later years, unburdened by age-associated complications, should routinely incorporate strategies to offset the decline in skeletal muscle mass and function. Creatine is a nutritional strategy that may support the growth or maintenance of skeletal muscle and subsequently extend the healthspan of older adults.

International Society of Sports Nutrition Position Stand: Safety and Efficacy of Creatine Supplementation in exercise, sport, and medicine. Journal of International Society of Sports Nutrition. Kreider et al. (2017) 14: 18

The purpose of this review was to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).

It stated that significant health benefits may be provided by habitual low dietary ingestion throughout lifespan.

Previous study findings suggest that creatine supplementation can help prevent sarcopenia and bone loss in older individuals.

After reviewing the scientific and medical literature in this area, the International Society of Sports Nutrition conclusions included the following in terms of creatine supplementation as the official Position of the Society:

• Creatine monohydrate supplementation is not only safe, but has been reported to have a number of therapeutic benefits in healthy and diseased populations ranging from infants to the elderly. There is no compelling scientific evidence that the short- or long-term use of creatine monohydrate (up to 30 g/day for 5 years) has any detrimental effects on otherwise healthy individuals or among clinical populations who may benefit from creatine supplementation.

• At present, creatine monohydrate is the most extensively studied and clinically effective form of creatine for use in nutritional supplements in terms of muscle uptake and ability to increase high intensity exercise capacity.

Creatine Supplementation and Aging Musculoskeletal Health. Endocrine. Candow et al. (2014) ;45(3):354–61.

This was a meta-analysis including 405 elderly participants (average age 64 years) who experienced greater gains in muscle mass and upper body strength with creatine supplementation during resistance training compared to training alone.

It concluded that creatine supplementation can help prevent sarcopenia and bone loss in older individuals.

Therefore, the combination of resistance training and creatine supplementation should be considered when developing effective lifestyle interventions for improving ageing musculoskeletal health.

Does Creatine Supplementation Improve Functional Capacity in Elderly Women? Journal of Strength and Conditioning Research. Canete et al. (2006);20(1):22–8.

The purpose of this study was to determine the effects of short term oral creatine supplementation in elderly women during exercise tests that reflect functional capacity during daily living tasks.

Subjects were assigned to either a creatine (included 10 participants with an average age of 67 years) or placebo (included 6 participants with an average age of 68 years) group.

It concluded that in elderly women, short-term oral creatine supplementation did not improve endurance capacity but did increase the ability to perform lower body functional living tasks (measured via the sit to stand test).

Low-dose Creatine combined with Protein during resistance training in Older men. Medicine and Science in Sports Exercise. Candow et al. (2008);40(9):1645–52

The purpose of this study was to determine whether low-dose creatine and protein supplementation during resistance training in older men (aged 59–77 years) is effective for improving strength and muscle mass. 40 healthy older men were randomised into 2 groups; either to receive creatine and protein supplementation or placebo, for a period of 10 weeks.

It concluded that low-dose creatine combined with protein supplementation increased lean tissue mass and upper body strength while decreasing markers of muscle protein degradation and bone resorption in older men.

Creatine Supplementation during resistance training in Older Adults – a meta-analysis. Medicine and Science in Sports Exercise. Devries MC, Phillips SM. (2014);46(6):1194–203.

The aim of this study was to determine whether the addition of Creatine to resistance training increased gains in muscle mass, strength, and function in older adults over resistance training alone by conducting a systematic review and meta-analysis.

The meta-analysis included 357 elderly individuals (average age 64 years) participating in an average 12.6 weeks of resistance training. It found that participants supplementing their diet with creatine experienced greater gains in muscle mass, strength, and functional capacity.

The study concluded that the retention of muscle mass and strength is integral to healthy ageing. The results from this meta-analysis are encouraging in supporting a role for Creatine supplementation during training in healthful ageing by enhancing muscle mass gain, strength, and functional performance over resistance training alone.

Effects of Creatine Supplementation on Cognitive Function of Healthy Individuals. Experimental Gerontology. Avgerinos et al. 108 (2018) 166-173.

The aim of this systematic review was to investigate the effects of oral creatine administration on cognitive function in healthy individuals. It included 6 randomised control trials with a total of 281 participants. 3 of the studies were based in the UK and 1 in each of the USA, Australia and Japan. Study duration ranged from 5 days to 6 weeks, and ages 19-76 years.

It noted that Creatine is an essential compound for the brain and may aid various brain regions in terms of energy supply and neuroprotection. Oral creatine may improve short-term memory and intelligence/ reasoning of healthy individuals.

The study concluded that there is a potential benefit of creatine supplementation for ageing and stressed individuals (younger adults did not show the same benefits – in accordance with studies showing older adults require additional energy for completing cognitive tasks). Also vegetarians responded better than meat-eaters in memory tasks.

Creatine Supplementation and Brain Health. Nutrients. Rochel et al. (2021) 13, 586

The purpose of this review was to provide an update on the effects of creatine supplementation on brain health in humans. It noted that Creatine may be beneficial to brain health and there is potential for creatine supplementation to improve cognitive processing.

Accumulating research shows that creatine supplementation can increase brain creatine content which may help explain some of the preliminary benefits from creatine supplementation on measurements of cognition, depression, concussion, and traumatic brain injury.

A Review of Creatine Supplementation in Age Related Diseases: More than a supplement for athletes. R Smith et al. F1000Research (2014), 3:222

The aim of this study was to explore the mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain ageing and outlining the clinical trials involving creatine to treat these diseases.

It stated that on average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue and protect the brain from neurotoxicity.

Creatine is an endogenous molecule found in all cells in the body and is synthesised in the kidney, liver, and pancreas using the amino acids arginine, glycine and methionine before entering the bloodstream. From the plasma, creatine is transported into the cells via the creatine transporter protein. This transporter is critical for the distribution of creatine throughout the cells as well as for crossing the blood brain barrier, giving creatine access to the central nervous system.

ATP is regenerated using the phosphocreatine system where phosphocreatine donates its phosphate group to adenosine diphosphate (ADP) to form ATP. A 70kg human has a total creatine pool of around 120 grams with 2 grams per day production from both dietary and endogenous (made by the body) sources. Creatine is excreted in the urine as creatinine with a daily turnover of 2 grams per day.

Ageing is associated with lower levels of creatine and phosphocreatine, specifically in the skeletal muscle. Phosphocreatine regeneration rates following exercise fall approximately 8% each decade after age 30.

Analysis of 13 published studies showed creatine had an overall beneficial effect on aged individuals’ muscle mass.

Since the creatine transporter can readily transport creatine from the bloodstream across the blood brain barrier, it is reasonable to suggest that supplementation of creatine would increase concentrations in the brain, where endogenous creatine levels may be reduced as a person ages.

In conclusion; Creatine has potential positive effects on muscle strength and memory. Going forward, one must consider if there are other mechanisms for which creatine acts to be protective and beneficial.

Effects of Creatine Supplementation on Memory in Healthy Individuals – A systematic review and meta-analysis of RCTs. Nutrition Reviews. Prokopidis et al. (2022) Vol 0:1-12

A systematic review and meta-analysis of randomised controlled trials was conducted to determine the effects of creatine supplementation on memory performance in healthy humans.

The rationale being that from an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory.

Ten trials examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for this review.

The study concluded that Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years).

Effects of Creatine Supplementation on Properties of Muscle, Bone, and Brain Function in Older Adults: A narrative review. Journal of Dietary Supplements. Forbes et al. (2022) 19:3, 318-335

The purpose of this review was to examine and summarise the research investigating the effects of creatine supplementation alone on measures of muscle mass and performance, bone mineral and strength, and measurements of brain health in older adults.

Ageing is associated with a reduction in size of type II muscle fibres and creatine may aid in the retention of type II skeletal muscle fibres with age.

Creatine may also directly affect the bone remodelling process (partly by a decrease in bone resorption).

The brain is another tissue impacted by creatine metabolism. Despite the limitations of the blood-brain barrier, creatine supplementation can increase creatine and phosphocreatine in the brain. Creatine within the brain performs several functions such as supporting neurons that require high amounts of ATP for several cellular processes.

This review concluded that, for optimal health benefits combining creatine and exercise is recommended. Also creatine supplementation may present some positive benefits without associated exercise on muscle morphology, function, and cognitive performance in an ageing population.

Importantly, creatine is a very safe supplement and does not negatively impact kidney function.

Efficacy of Creatine Supplementation and Resistance Training on area and density of Bone and Muscle in Older Adults. Medicine and Science in Sports Exercise. Candow et al. (2021) 2388-2395

Interventions which improve bone density may be clinically important for decreasing the risk of falls and fractures in older adults. The purpose of this study was to examine the effects of Creatine supplementation and whole-body resistance training on measures of bone geometry and muscle area and density of the forearm and lower leg in older adults.
70 older adults (men and women over the age of 48 years) were included in this randomised controlled trial, one group given creatine supplementation and one group given a placebo, over one year.
The results showed that creatine supplementation and resistance training had favourable effects on measures of bone area and muscle density in older adults.

Increasing properties of ageing muscle and bone may have application for the treatment of age-related musculoskeletal conditions such as Sarcopenia, Osteoporosis, Osteosarcopenia, Physical frailty and cachexia.

Effects of Creatine and resistance training on Bone health in Postmenopausal Women. Medicine and Science in Sports Exercise. Chilibeck et al. (2015);47(8): 1587–95

The primary purpose of this study was to determine the effect of 12 months of creatine supplementation during a supervised resistance training program on properties of bone in postmenopausal women.

The study stated that osteoporosis is a leading cause of disability in our ageing population. Postmenopausal women experience the highest rate of hip fracture, resulting in disability, loss of functionality, and premature death.

Creatine is a nitrogen-containing compound naturally produced in the body and/or consumed in the diet from red meat and seafood.

Participants were randomised (double-blind) into two groups: resistance training and Creatine supplementation or resistance training and placebo.
It concluded that 12 months of creatine supplementation during resistance training increased strength and preserved femoral neck bone mineral density and increased femoral shaft subperiosteal width in postmenopausal women.

Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults. Nutrients. Candow et al. (2021), 13, 745

The purpose of this narrative review was to evaluate and summarise current research involving creatine, with and without resistance training, on properties of muscle and bone in older adults, and to provide a rationale and justification for future research involving creatine in older adults with osteosarcopenia, sarcopenic obesity, physical frailty.

It was stated that from a healthy ageing perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important.
Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia.

It concluded that as a possible counter measure to sarcopenia and its age-related co-morbidities, creatine has some favourable effects on ageing muscle, bone and fat mass, muscle and bone strength, and physical performance, primarily in healthy populations. Independent of resistance training, creatine can produce some muscle benefits in older adults.