95% of the body’s creatine stores are found within skeletal muscle tissue, with the remaining 5% being distributed in the brain, liver, kidney, and testes [6].

Creatine plays a role in ATP production, serving as an important regulator of cellular energy metabolism and maintaining cellular energy levels.

One placebo-controlled study had subjects complete five 30-second bouts of maximum muscle contractions. The authors found that the subjects who consumed 20 grams of creatine for 5 days, peak-torque production increased in the final ten repetitions of the first bout and throughout the of the rest of the bouts [2].

Another study on D1 college football athletes showed increases in bench press volume, total volume, and total work completed during the initial bouts of a repeated sprint cycling protocol after supplementation with creatine combined with carbohydrates for 28 days [2].

Another review of 22 studies looking at the combined effects resistance training plus creatine supplementation found that the average increase in muscular endurance was 14% greater than that following placebo ingestion and resistance training alone [2].

Many more studies have consistently found that creatine supplementation leads to increases in work output in each set of repetitions, increased power output in each set, and increased total work volume [2].

One study put subjects on a 5-day creatine supplementation protocol (at 20 g of creatine per day) and had them participate in a resistance exercise program that included back squats. They found both significant improvements in average anaerobic power and back squat strength after the 5-day loading protocol compared to training alone. However, the same benefits were not found after 2 days of creatine loading, which indicates that greater than 2 days of creatine loading might be required to elicit benefits in strength and power [13].

A review of studies noted that short-term benefits have also been reported in young adult males who were who no prior recent history of resistance training. After 10 days of creatine supplementation, they found improvements in bench press, squat strength, and power output. What’s interesting is that subjects did not participate in a resistance training program during the supplementation period, yet this ergogenic benefits were still present [2].

Another review found that creatine supplementation during 8 weeks of resistance training in healthy aging men resulted in “significantly greater gains in leg press and total lower-body strength, muscle thickness, and some measures of peak torque and physical performance” [1]

According to one review of 22 studies on resistance training combined with creatine supplementation, the total increase in muscular strength was approximately 8% greater than that from resistance training alone [2].

Sprinting

• Studies have shown improvements in sprinting performance in several sports: handball [15], soccer [14], football [16], ice hockey [17], and track [18].

Football

• One study on college football players found that creatine supplementation combined with carbohydrates significantly increased bench press strength, vertical jump, 100 yd dash time, and fat-free weight compared to placebo when combined with resistance exercise [16].

Swimming

• A study on competitive swimmers found that creatine supplementation significantly reduced 100 m sprint times compared to placebo. They also found that total sprint time to complete 3 rounds of 100-m sprints was reduced in the creatine group and not the placebo group [19].

Track and Field

• 36 collegiate track and field athletes were divided into a creatine supplementation group and a placebo group and placed on a preseason conditioning program where they underwent various sport-specific exercises. The authors found that after 6 weeks, the creatine supplementation group experienced significant gains in vertical jump height, vertical jump power index, average cycle peak power, total work volume, and lean body mass compared to the placebo group [20].

For example, one study reported that 20 grams of creatine per day for 5 days in a group of runners who participated in a 30-km race resulted in reduced levels of muscle damage, muscle soreness, and markers of inflammation [21].

Another study reported reduced levels of creatine kinase, which is a common marker of muscle damage, after a bout of leg exercises in subjects who supplemented with creatine for 5 days leading up to the exercises [2].

25 athletes were assigned to either a placebo group or a creatine supplementation group for 7 days at which point they were subjected to repeated bouts of sprint exercises. The authors reported inhibition of TNF-a and C-reactive protein (common markers of inflammation) in the creatine group compared to placebo. However, there were no differences in markers of oxidative stress between the groups [22].

They mentioned one study that reported augmented regeneration of muscle tissue after a 10-week rehabilitation program  following cast immobilization in patients who supplemented with creatine [2].

They do note that results among studies are mixed, however, and that not all studies show a benefit.

Study after study has shown increases in lean body mass, skeletal muscle mass, and muscular strength when combining creatine supplementation with resistance training.

For example, one study reported that 8 weeks of creatine supplementation combined with resistance exercise in untrained healthy aging men resulted in significant gains in leg press and total lower body strength, muscle thickness, and total performance [1].

Another study showed significant gains in fat-free mass and bench press 1 rep max strength in recreational male bodybuilders who followed a creatine supplementation program for 5 weeks in combination with a resistance exercise program compared to a placebo group [25].

Similar results were shown in another study where 51 college football players were supplemented with either a placebo, carbohydrates + placebo, or a combination of carbohydrates + protein + creatine. The two groups that consumed creatine experienced the greatest gains in muscle mass as well as strength compared to the groups that did not consume creatine [26].

Multiple other studies have consistently shown increases in strength, muscle mass, and training volume in college football players who supplemented with creatine during training compared placebo [26][27].

Several mechanisms have been proposed as to how creatine may confer these anabolic benefits.

One review mentions that “increased intracellular osmolarity from augmented creatine storage may cause cell swelling and the concomitant stimulation of anabolic signaling pathways, independently of exercise” [2]. It has also been suggested that increases in total body mass are largely due to the increased intracellular water content.

Another review says that “it may indirectly stimulate protein synthesis through upregulation of growth factors and increased production of myosatellite cells, which may contribute to muscle hypertrophy” [6]

“The mechanisms underlying creatine’s enhancement of memory likely involve several biological pathways. Firstly, creatine increases the energy supply to brain cells, particularly in the form of phosphocreatine (PCr), which is crucial for maintaining cellular ATP levels in the energy-demanding brain (35). Secondly, creatine may enhance memory by improving neurotransmitter function, such as by increasing the synthesis of neurotransmitters like acetylcholine (36). Additionally, creatine may function as a neuromodulator, potentially affecting synaptic efficacy and plasticity, which are vital for learning and memory processes. Furthermore, creatine may exhibit neuroprotective properties by mitigating oxidative stress damage to brain cells” [9]

Creatine supplementation of 5 grams per day for 6 weeks was shown to increase working memory and processing speed [28].

Another study reported significant improvements in random number generation, forward spatial recall, and long-term memory tasks in participants supplementing with creatine [1].

A lot of the studies showing enhancements in cognition are done on the elderly, people with disease, and people following a plant-based diet so these results should be taken with a grain of salt. However, if you are someone experiencing issues with cognition, it might be worth trying. Creatine is very inexpensive.

Moreover, if you are someone who is physically active, older than 60, or someone who doesn’t consume much animal protein, it might be worth trying creatine supplementation to see if it provides any benefit.

Immediately following a concussion or a TBI, the brain’s ability to generate energy is compromised and brain creatine levels decrease significantly. Thus, creatine supplementation in this scenario serves to maintain the brain’s creatine levels, mitigating any declines in energy-generating ability the brain might experience.

The evidence is so strong, in fact, that the International Society of Sports Nutrition recommended that all athletes who are involved in sports with risk to TBI should take creatine to reduce the severity of this type of injury [1].

Animal studies demonstrate that creatine supplementation prior to a TBI reduces damage by up to 50% [6].

A rat study found that rats who received creatine for 2 weeks prior to a controlled head injury had tissue sparing in certain parts of the brain compared to rats who received a placebo [8].

Another study found that creatine supplementation for 5 days prior to TBI decreased the amount of brain damage by 36% in rats and 50% in mice compared to placebo [1].

One study showed that following 24 hours of sleep deprivation, creatine supplementation “resulted in less change in performance from baseline in random movement generation, choice reaction time, balance and mood state” [8].

In a similar experiment, the same group also found that creatine supplementation “attenuated sleep-deprived loss of complex central executive function” [8], meaning that creatine was able to mitigate the negative effects sleep deprivation has on executive function.

Another review of studies concluded that “a deficit in performance caused by sleep deprivation was significantly improved following acute supplementation of creatine just 90 min prior to activity” [6].

For example, in a mouse model of epilepsy, creatine supplementation attenuated seizure activity and reduced depressive-like behaviors [8].

Creatine has also been shown to have anti-depressive effects in a mouse model of Alzheimer’s disease-related depression [8].

One study in mice showed that a single dose of creatine resulted in improvements in depressive-like behaviors induced by chronic corticosterone administration [8].

One literature review on this topic concluded that “when looking at both the preclinical research and the limited number of small-scale human trials, the research suggests a possible role for creatine supplementation in the treatment of different forms of depression” [8].

The authors did note that more studies were needed, however.

An example of this would be those women with methylation issues. Methylation plays a vital role during pregnancy, influencing fetal development, maternal adaptations, and potentially impacting pregnancy outcomes and long-term health. Creatine biosynthesis is estimated to consume 70% of the body’s methyl donors [29].

Thus, supplementing with creatine could improve methylation by reducing the amount of creatine the body needs to produce and allowing the body to redirect available methyl donors to other important processes.

Creatine supplementation during pregnancy has been shown to improve neonatal survival and organ function during asphyxia in animals [1]. This means that creatine can potentially offer protection for newborns against damage that can come from oxygen deprivation.

A review of studies concluded that creatine supplementation may improve reproductive and perinatal outcomes [1].

Lastly, creatine is a key player in energy metabolism, and its supplementation may help support the energy demands of both the mother and the developing fetus.

One common biomarker of undermethylation is elevated homocysteine.

It is estimated that around 70% of the body’s methyl groups go toward generating creatine [29].

Therefore, by supplementing with creatine, we can improve methylation by reducing our body’s reliance on endogenous creatine synthesis, which in turn lowers the demand for methyl groups, leaving more methyl groups available for the body to use to convert homocysteine back into methionine, reducing the excess buildup and leading to a reduction in homocysteine levels.

Where does oxidative stress come from?

Some oxidative stress is normal and even necessary for certain bodily functions. Free radicals, for example, are a normal byproduct of the body’s conversion of food into energy. However, issues arise when levels of oxidative stress become too high for the body to deal with.

Here are some common things that lead to excess oxidative stress in the body:

• Poor diet (ultra-processed foods, sugar, seed oils, etc.)
• Environmental toxins (e.g. air pollution, pesticides, household cleaning products, personal care products, mold, heavy metals)
• Alcohol
• Smoking

Numerous studies have shown that creatine supplementation acts as a direct antioxidant, scavenging free radicals, protecting cells from damage, and reducing oxidative stress in the body [31][32][33][34].

Sarcopenia has been associated with a significantly increased risk of all-cause mortality, meaning death from any cause, as well as chronic disease states such as insulin resistance and autoimmunity [30].

Maintaining our muscle mass as we age is one of the most effective ways we can reduce our risk of chronic disease and extend our lifespan.

Multiple meta-analyses have found that creatine supplementation, particularly when combined with resistance exercise, counteracts sarcopenia and leads to greater gains in muscle mass, strength, and functional capacity when compared to resistance exercise alone [1][6][23].

This means that simply supplementing with creatine in addition to lifting weights can help stave off some of these age-related deficits in body composition and strength, increasing our overall health and significantly improving our quality of life.

After being produced by the organs, creatine enters systemic circulation where it is taken in by muscle cells. Once inside the cell, creatine is converted into phosphocreatine (PCr), where it is rapidly broken down “via catalysis by creatine kinase (CK) to facilitate adenosine triphosphate (ATP) regeneration, thereby serving as a crucial element in energy transfer” [9].

Interestingly, while our organs produce the majority of our endogenous creatine, almost all of it, around 95%, is stored in our skeletal muscle, with the remaining 5% being distributed among the brain, liver, kidney, and testes [1][6].

Oral supplementation with creatine monohydrate has been shown to increase the intramuscular creatine stores by 10%–40% [2].

Our bodies produce about 50% of our daily creatine needs which means the rest must be obtained through our diet and/or supplementation in order to maintain normal tissue levels [1].

How much creatine do we need to consume in order to maintain normal levels?

According to science, the body uses about 1-2% of its intramuscular creatine stores per day. In people who are more physically active and who have a higher muscle mass, this rate is much higher. Based on this information, it is recommended that a normal-sized individual consume around 2-3 grams per day of creatine to maintain normal levels depending on diet, muscle mass, and activity levels [1].

Vegetarians and vegans have been reported to have 20-30% lower muscle creatine stores than people following an omnivorous diet, so their daily intake needs are higher, upwards of 4 grams per day to achieve normal levels [1][12].

Creatine is exclusively found in animal foods, and a lot of plants are too low in the amino acids necessary to synthesize sufficient amounts of creatine.

However, certain plant foods offer higher amounts of glycine, methionine, and arginine, the building blocks of creatine, than others and should be prioritized on a plant-based diet.

For those following a plant-based diet, here are some good sources of those amino acids:

• 1. Soybeans
• 2. Spinach
• 3. Quinoa
• 4. Pumkin Seeds
• 5. Walnuts
• 6. Sesame seeds
• 7. Almonds
• 8. Asparagus
• 9. Spirulina
• 10. Chickpeas
• 11. Legumes

Since plant foods do not contain creatine and people following a vegan or vegetarian diet tend to have significantly lower levels of creatine compared to those who follow an omnivorous diet [1][12], experts recommend that vegans and vegetarians supplement with creatine monohydrate.

The good news is that people following a plant-based diet tend to respond better to creatine supplementation with studies showing greater increases in lean muscle mass and exercise performance when compared to omnivores supplementing with creatine [12].

Not everyone responds to creatine supplementation the same way.

Some people see significant increases in intramuscular creatine stores while others see little to no increase.

Scientists refer to these people as responders and non-responders, with the latter being people who experience minimal or no increase in muscle creatine levels despite creatine supplementation.

Scientists suggest that this is partially due to individual variation in absorption rate [2].

Luckily, scientists have discovered a way to enhance the absorption rate.

Numerous studies have demonstrated that co-ingesting creatine with carbohydrates leads to significantly greater increases in muscle creatine levels compared to taking creatine alone [1][2][3][4][5][6][8].

Why does this happen?

Creatine uptake is influenced by glucose and insulin [1][4].

Insulin is released in response to carbohydrate consumption where it plays a role in transporting glucose into cells, but it also facilitates the transport of other nutrients, including creatine, into cells.

Consuming carbohydrates leads to an increase in blood sugar levels, triggering the release of insulin.

The increased insulin levels, in turn, facilitate the transport of creatine across the muscle cell membrane, leading to greater creatine uptake and storage within the muscle tissue.

For example, one study showed that co-ingesting creatine with 94g of carbohydrates resulted in a 60% greater increase in muscle creatine levels compared to ingesting creatine alone [5].

Other studies recommend combining creatine with carbohydrates AND protein for an even greater effect [1][2][5][8].

Creatine is an osmotically active substance, meaning as creatine accumulates inside our cells, it draws water into the cells causing water retention.

However, studies have shown that creatine supplementation does not lead to increased water retention over longer periods of time.

For example, resistance-training subjects who supplemented with creatine at a dose of 20 g/day for 7 days followed by 4 weeks at 5 g/day experienced no significant change in intracellular water, extracellular water, or total body water [7].

A similar study had resistance trained males consume 20 g/day for 7 days followed by 5 g/day for 21 days and also found no significant increase in intracellular water, extracellular water, or total body water [7].

To summarize, while creatine supplementation seems to lead to water retention in the short term, say several days, there are several other studies suggesting it does not lead to water retention over longer periods of time.

According to a panel of researchers, “Today, after > 20 years of research which demonstrates no adverse effects from recommended dosages of creatine supplements on kidney health, unfortunately, this concern persists” [7].

They say this is a common myth perpetuated by a poor understanding of creatine metabolism.

The way it works is creatine is degraded into creatinine, which is transported to the blood and excreted in the urine. Healthy kidneys filter creatine from the blood, where it would otherwise accumulate. Thus, blood creatinine levels are typically used as a proxy for kidney function.

However, creatine levels in the blood are directly related to muscle mass and dietary intake, i.e. someone with more muscle mass would have higher levels of creatinine in their blood compared to someone with less muscle mass.

By the same logic someone supplementing with creatine would have higher levels of creatinine in their blood compared to someone not supplementing with creatine.

The researchers note, however, that there seems to be a misunderstanding that if the kidneys are forced to excrete higher than normal levels of creatinine, too much strain will be placed on the kidneys causing them to become damaged and dysfunctional [7].

In reality, transient increases in blood creatinine levels due to creatine supplementation are unlikely to reflect a decline in kidney function, they say [7].

They also note that if creatine supplementation did lead to kidney damage, we would expect to see an increase in causes of kidney damage/renal dysfunction is low risk individuals (i.e. young, fit, & healthy) since the early 90’s when creatine use was beginning to get popular. No such evidence exists, however.

In summary, the researchers conclude that “in healthy individuals, there appears to be no adverse effects from consuming recommended doses of creatine supplements on kidney/renal function” [7].

Lower doses of 3-5 g/day of creatine supplementation have been proven effective for increasing intramuscular creatine stores.

However, forgoing the loading phase delays the maximum intramuscular saturation of creatine.

A study was done comparing a loading phase (20 g/day) vs a daily maintenance dose (3 g/day), and the authors found that both strategies led to identical creatine accumulation in muscle tissue (a 20% increase).

However, the 20% increase took 28 days to achieve in the 3 g/day group and only 6 days to achieve in the 20 g/day group [7]. Thus, while both strategies are equally effective at raising intramuscular creatine stores, the loading phase speeds up this process substantially.

Sarcopenia is associated with a wide range of adverse health outcomes including “poor overall and disease-progression free survival rate, postoperative complications, and longer hospitalization in patients with different medical situations as well as falls and fracture, metabolic disorders, cognitive impairment, and mortality in general populations” [35].

It has been widely demonstrated that creatine supplementation, in combination with resistance training, leads to increases in muscle mass, muscle strength, and mobility in older individuals. There have also been studies showing increased bone mineral content.

In addition to resistance and power-related activities, creatine supplementation has been shown to:

• Promote greater muscle glycogen storage leading to optimal glycogen levels
• Reduce muscle damage and enhance recovery from exercise
• Reduce inflammation
• Increase total work volume
• Help prevent training-related injuries
• Reduce the amount of muscle atrophy from immobilization following injury
• Enhance tolerance to exercise in the heat
• Protect the brain from oxidative stress
• Reduce the severity of TBIs [7]
• And much more

Aside from the benefits described previously, there is accumulating evidence that creatine may have a supportive role for females during menses, pregnancy, post-partum, perimenopause, and postmenopause [7].

According to scientists, hormone changes that take place during these different stages of female reproduction cause changes in endogenous creatine synthesis, therefore highlighting the positive implications for creatine supplementation in females.

In addition, maternal creatine supplementation during pregnancy in animal studies has been shown to:

• Offer protective effects against fetal death and organ damage resulting from hypoxia
• Enhance brain cell uptake of creatine in offspring
• Support mitochondrial integrity in offspring
• Reduce intra- and post-partum complications associated with cellular energy depletion
• Offer an alternative way to maintain optimal levels of creatine if unable to eat meat due to nausea
• Potentially protect against post-partum depression [7]