Creatine: Benefits, Side Effects, and Research

Meat is rich in creatine, an important energy buffer in muscle cells, and the main constituent of a popular sports supplement used by athletes. However, we’re now finding out that there’s more to it than ‘meats’ the eye.

What is creatine?

Creatine (α-methyl guanidine-acetic acid) is present in our muscle cells. Functionally, it helps our muscles to produce energy for lifting weights, high-intensity exercise, and other strenuous activities. It has enjoyed great popularity as a supplement with athletes and bodybuilders for building muscle, boosting strength and increasing exercise performance.

It was first identified by French chemist Michel Eugène Chevreul in 1832, who isolated it from skeletal muscle. Due to its presence in living tissue, Chevreul named it after the Greek word ρέας (kreas), meaning meat.

In 1912, Otto Folin and Wiley Glover Denis of Harvard University found that ingesting creatine led to a significant increase in intramuscular stores [1], sparking an interest in its potential as an oral supplement.

By the 1930s, German scientists began to study the relationship between creatine levels and muscle contraction, concluding that the more creatine present in muscle cells, the longer they could contract before producing lactic acid [2, 3], allowing for extended training times.

During the 1960s, an interest surged in the possible uses of creatine to treat muscle diseases. In 1964, Fitch et al. were able to show that the skeletal muscles of muscular dystrophy patients have lower concentrations than their normal counterparts, which they attributed to a defect in creatine binding in muscle cells [4, 5].

The potential of creatine as a performance-enhancing supplement came into public scrutiny after the 1992 Barcelona Olympics, in which several gold medalists admitted to taking it during training. Today, supplements exist in a wide variety of forms, and creatine is one of the most widely used nutritional supplements worldwide [6].

What foods contain creatine?

It is produced inside the body from the amino acids glycine and arginine, and it is widely distributed to tissues with high energy demands, such as the brain and muscles. About 95% of the body’s creatine is stored in skeletal muscle, but it is also found in small amounts in the liver, kidneys, and testes.

On average, young adults produce approximately 1 gram of creatine per day [7, 8], while the rest is obtained through diet.

Creatine is naturally occurring in many foods, particularly animal protein, such as meat and fish. One pound of raw beef contains approximately 2.3g of creatine, while one pound of raw salmon contains up to 2g. However, cooking denatures creatine, so without extra-bloody steak or plenty of sashimi, it is difficult to get enough of to benefit from its health properties. Red meat is also high in saturated fat and may increase the risk of all-cause mortality [9, 10], so consuming that much meat to begin with might not be the wisest choice.

Luckily, it is widely available as a health supplement, and is extremely affordable. This is particularly relevant for vegans and vegetarians, whose intake is greatly diminished or absent altogether. These supplements have been found to have increased potency in vegetarians and confer other beneficial effects, such as increased cognitive capacity and performance, compared to omnivores [11, 12]. Recently, some studies have suggested that this might be due to an underlying creatine deficiency [13, 14].

Benefits

Creatine is an important molecule in the maintenance of cellular adenosine triphosphate (ATP) homeostasis, the cell’s balancing act. ATP is essential for the upkeep of physiological processes and is the main transporter of energy for use in metabolism. During exercise, ATP levels in muscle cells deplete very quickly, leading to the accumulation of lactic acid and the onset of cramps.

In order to be able to replenish ATP quickly, muscle cells contain stores of phosphocreatine (PCr), a high-energy phosphate compound which can donate a phosphate group to ADP to quickly form ATP. This reaction is reversible, and during periods of low energy demands, ATP can be used to convert creatine back to phosphocreatine for later use [15-17]. This important “energy reservoir” is what allows it to improve exercise performance.

Not all studies of creatine’s effect on performance have been consistent. In a study with 24 adult male rabbits, researchers aimed to see how adding creatine to their diet would affect their growth and reproductive abilities. The rabbits were split into four groups of six each. The first group was given plain water, while the other three groups received different amounts of creatine monohydrate daily. The findings showed that the groups given creatine grew larger compared to the control group. Their liver weights increased, but their kidney sizes decreased. However, these creatine-fed rabbits showed poorer sperm quality, with reduced sperm count, movement, and viability, and an increase in sperm abnormalities compared to the group that only had water [18].

Another study published in 2024 explored how taking creatine or believing one has taken it affects how well people can do strength exercises. Fifteen young men around 22 years old did squats and bench presses until they couldn’t do any more. They did this four times with different treatments each time: 1) no treatment; 2) fake creatine (placebo); 3) placebo labeled as creatine; 4) real creatine. They checked how many times they could lift the weights and how hard they felt the exercise was. They found that all treatments, including the fake ones, helped the men do more repetitions compared to when they had no treatment. Specifically, both the real and labeled creatine treatments allowed them to do more squats than the no treatment and fake creatine. The study concluded that both believing in and actually taking creatine have a similar positive impact on how well one can perform in these exercises [19].

The use of creatine supplements in combination with strength training has been found to increase muscle fiber size [20, 21] and improve performance in high-intensity repetitive exercise in several studies [22-24]. Other studies have found no beneficial effects on performance, however [25-28]. This inconsistency has recently been attributed to conflicting experimental designs, making the literature on the effects of creatine in humans difficult to interpret.

While many studies have demonstrated that creatine supplementation helps increase strength and muscle size, the effects of creatine on bodyweight, bodyfat, and more endurance-oriented exercise are less consistent.

When it doesn’t help

Fernández-Landa and associates conducted a study examining how taking creatine monohydrateaffects endurance in athletes. These researchers did a detailed review and analysis of previous studies, following strict guidelines. They searched through major medical databases up to May 19, 2022, focusing on experiments that compared creatine’s effects to a placebo in trained individuals. They also checked the quality of these studies.

Out of all the studies they found, 13 met their criteria and were included in their analysis. The results showed that taking creatine monohydrate didn’t really change endurance performance in these athletes. This was consistent even when they only considered the most reliable studies. In conclusion, the study found that for people who are already trained, taking creatine monohydrate doesn’t seem to improve their endurance [29].

Sarcopenia is an age-related disease that results in loss of strength and muscle mass. This loss is even more pronounced in older adults with type 2 diabetes (T2D). One study looked at whether taking creatine, a substance made from amino acids, could help these people. Creatine is known to help healthy older adults get stronger and perform better physically. It also affects how the body uses sugar in people with T2D. However, it was not clear if creatine would help older adults with T2D.

The study tested this by giving some participants creatine and others a placebo for seven days. They checked the participants’ blood sugar levels, muscle strength, endurance, and how well they could do physical tasks before and after taking the supplements. The tests included leg and chest exercises, a hand-grip test, and walking and sitting tests.

In the end, the study found that creatine did not make a difference in blood sugar levels, muscle strength, endurance, or physical performance in older adults with type 2 diabetes [30].

In another study, Darren G. Candow and his research team looked at how lifting weights and taking creatine affect body fat in people under 50. Previous research showed that these activities can lower body fat in people over 50, but it was unclear if this was true for younger adults. The team reviewed existing research and analyzed data from 12 studies involving 266 participants.

They found that adults under 50 who lifted weights and took creatine saw a very small but significant drop in their body fat percentage. However, there was no noticeable change in their total body fat. In summary, for adults under 50, combining weightlifting with creatine supplements slightly reduces body fat percentage, but it doesn’t really change the overall amount of fat in the body [31].

Creatine is an energy buffer

Due to its ability to act as an energy buffer, creatine has also been shown to be neuroprotective against low oxygen levels, preventing neuronal death by regulating NMDA receptor function – a critical channel for the development of the central nervous system – and reducing oxidative stress [32, 33].

There is evidence that impairments in energy production may play a role in the development of neurodegenerative diseases such as Huntington’s [34, 35], and a study exploring the effect of oral administration of creatine on brain lesions found that feeding animals a mixture containing 1% creatine lead to an 83% reduction in lesion volume after two weeks [36]. Other studies have found that it might protect the brain from damage after stroke [37-39] and increase overall cognitive performance in the elderly [40] but not in young adults [41].

A 2024 review or animal studies by Kenekar and colleagues added weight to the role of creatine as a molecule that helps the brain manage its energy needs. This review once again confirmed that creatine can increase lifespan and improve signs of aging. It also protects the brain in situations like low oxygen or low blood sugar and against harmful substances.

This study found that creatine works by changing energy levels and activating certain cell processes. It reduces oxidative stress, a type of cell damage, and prevents cells from dying, especially certain types of brain cells. Creatine also affects brain communication, reducing some signals and enhancing others. This can improve thinking skills in healthy and aging people. It also has potential benefits for various health issues, including metabolic and brain disorders like epilepsy, traumatic brain injury, depression, and diseases like Huntington’s and Parkinson’s [42].

A June 2023 study by Candow’s research team explored the benefits of creatine supplementation for brain health and function. Creatine is a substance that, when added to the diet, can increase the amount of creatine stored in the brain. This increase may explain improvements in thinking, memory, and cognitive abilities, particularly in older adults or during periods when the body is under metabolic stress, like during sleep deprivation.

The study also found that creatine could help in recovery from traumatic brain injuries, including concussions in children. It may also reduce symptoms of depression and anxiety. While creatine shows promise for improving health outcomes in muscular dystrophy, its effects on other neurological diseases like Parkinson’s disease or amyotrophic lateral sclerosis are less clear.

The review aimed to provide a comprehensive overview of current research on creatine’s impact on brain health and function and to discuss whether the effects of creatine differ by sex or age. It also examined how creatine affects brain energy levels, brain health, function, and neurological diseases [43].

Phosphocreatine has also been found to be cardioprotective in several studies, particularly during heart failure, where it becomes the primary source of energy for cardiac tissue [44, 45]. During periods of low oxygen, the creatine kinase system plays an important role in cardiac recovery by providing high-energy phosphate to the heart muscles [46].

Last but not least, creatine may restore skin elasticity and reduce wrinkles by replenishing collagen stores [47, 48] and protecting against UV-induced DNA damage [49, 50]. One study using creatine as a topical skin cream (compounded with glycerol and guarana) found a significant skin-tightening effect and reduction of wrinkles over 6 weeks [51], while another study, which used topical creatine and folic acid, also found notable improvements in skin regeneration and elasticity [52].

Creatine and long COVID

Jelena Slankamenac and her team studied how taking creatine for six months affects people who experienced post-viral tiredness after having COVID-19. In this study, they gave 12 patients either creatine or a placebo. They wanted to see if creatine could change how much of it was in their muscles and brain and if it could help with their tiredness and other symptoms, such as loss of taste, trouble breathing, body pains, headaches, and difficulty concentrating.

They found that patients taking creatine had more of it in their muscles and certain parts of their brains after 3 and 6 months compared to when they started. These patients also felt less tired after 3 months and had fewer symptoms after 6 months compared to before they started taking creatine. This suggests that creatine might help people recover from the extreme tiredness experienced after COVID-19, but more research is needed to be sure [53].

Disclaimer

This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.

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