The human body synthesizes about 1 gram of creatine per day, primarily in the liver and kidneys, from the amino acids arginine, glycine, and methionine. An average omnivorous diet contributes an additional gram per day, mainly from red meat, poultry, and fish. Even on an extremely meat-heavy diet, it's almost impossible to consume enough creatine from food alone to maximize the concentration of muscle creatine. Creatine supplementation can boost almost everyone's muscle creatine levels by ~20%.

Although creatine is normally found in animal muscle tissue, creatine supplements are typically made using synthetic ingredients and are acceptable to vegetarians and vegans.

PHYSIOLOGY

The limited amount of ATP in a muscle cell is depleted with several seconds of intense physical activity and then needs to be re-synthesized. The cell must continually re-synthesizes its ATP, the ONLY molecule able to provide energy to the muscle fibers to power their contraction. ATP is continually re-synthesized via one of three metabolic pathways depending on the degree and duration of the physical activity.

• The preferred path is the breakdown of creatine phosphate (CP) - a high transfers its chemical energy to re-synthesize ATP. Like ATP, CP is also stored in finite amounts in the cell and provides at most an additional 5 to 10 seconds of energy which limits its usefulness to sprint type activities.
• Once CP stores have been exhausted, the cell depends on two slightly slower metabolic pathways to re-synthesize its ATP - one is oxygen dependent (aerobic) and the other is not (anaerobic).

Muscle cell ATP is re-synthesized from CP at 4 to 8 times the maximal rate possible from the alternate aerobic pathway. This explains why optimal performance in sprint activities of 5 to 20 second duration is positively correlated with muscle CP levels. For sprints of longer duration, the slower but higher capacity aerobic and anaerobic pathways take over to replenish ATP. Examples of short sprint activities that benefit from high cell ATP (and CP) levels are weightlifting, short track events (100 meter dash), and sports requiring short sprints such as baseball and volleyball. To sustain muscle activity of beyond 10 t0 20 seconds, the cell uses the slower alternate aerobic and anaerobic pathways to replenish its ATP and CP.

Creatine supplements increase the ability to maintain the duration of brief high-intensity bouts of exertion such as a 10 second sprint or other explosive types of exercise like weight lifting where it helps with that final rep. Soccer is an ideal sport to showcase the benefits of creatine supplementation as it intersperses high-intensity activities (sprinting, running, jogging, accelerating, jumping, and changing direction) with low-intensity phases including stopping or walking.

Demant TW and Rhodes EC published one of the first reviews of creatine as a performance enhancer in 1999. To quote "While creatine has been known to man since 1835, when a French scientist reported finding this constituent of meat, its presence in athletics as a performance enhancer is relatively new. Creatine is synthesized from the amino acids glycine, arginine and methionine in the kidneys, liver and pancreas, and is predominantly found in skeletal muscle, where it exists in 2 forms. Approximately 40% is in the free creatine form (Cr free), while the remaining 60% is in the phosphorylated form, creatine phosphate (CP). The daily turnover rate of approximately 2 g per day is equally met via exogenous intake and endogenous synthesis. Although creatine concentration (Cr) is greater in fast twitch muscle fibers, slow twitch fibers have a greater re-synthesis ability due to their increased aerobic capacity. There appears to be no significant difference between men and women as far as creatine levels and training does not appear to effect creatine stores.

Creatine supplementation of 20 g per day for at least 3 days has resulted in significant increases in total Cr for some individuals but not others, suggesting that there are 'responders' and 'nonresponders'. These increases in total concentration among responders is greatest in individuals who have the lowest initial total Cr, such as vegetarians. Increased concentrations of both Cr free and CP are believed to aid performance by providing more short term energy, as well as increase the rate of re-synthesis during rest intervals. Creatine supplementation does not appear to aid endurance and incremental type exercises, and may even be detrimental. Studies investigating the effects of creatine supplementation on short term, high intensity exercises have reported equivocal results, with approximately equal numbers reporting significant and non significant results. The only side effect associated with creatine supplementation appears to be a small increase in body mass, which is due to either water retention or increased protein synthesis."

Another in-depth review as well as two more recent reviews (2025) provide more details on the current status of this supplement.

• one written for serious cyclists
• and another for the AARP generation.

Supplements of creatine do increase muscle cell CP levels. To quote the abstract of one study "The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the pre-supplementation value. During this period, urinary creatine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day. In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is a long term approach likely to be as effective at raising tissue levels as using a loading dose initially."

Is there any benefit to ingesting more than 20 grams per day initially? Casey A and Greenhaff report that "ingestion of creatine monohydrate at a rate of 20 g/d for 5-6 d was shown to increase the total creatine concentration of human skeletal muscle by approximately 25 mmol/kg dry mass, some 30% of this in phosphorylated form as phosphocreatine. However, there is no evidence that increasing intake > 20-30 g/d for 5-6 d has any additional effect on creatine uptake or performance." Another interesting finding was that those already on a high creatine diet will have decreasing benefits from these supplements. In individuals in whom the initial total creatine concentration already approached 150 mmol/kg dry mass, neither creatine uptake nor an effect on phosphocreatine re-synthesis or performance was found after supplementation. And chronic oral supplements may decrease the level of the cell wall transport protein responsible for moving creatine from the blood into the cell, thus minimizing benefits with time (Guerrero-Ontiveros ML, Wallimann)

There is some evidence that carbohydrate supplementation will improve the benefits of a creatine supplementation program. Muscle biopsy, urine, and plasma samples were obtained from 24 males before and after ingesting 5 g Cr in solution (group A) or 5 g Cr followed,30 min later, by 93 g simple CHO in solution (group B) four times each day for 5 days. Supplementation resulted in an increase in muscle phosphocreatine (PCr), Cr, and total creatine (TCr; sum of PCr and Cr) concentration in groups A and B, but the increase in TCr in group B was 60% greater than in group A (P < 0.01). There was also a corresponding decrease in urinary Cr excretion in group B (P < 0.001). This again supports the importance of adequate carbohydrates in any dietary training program.

Higher muscle CP levels also improve performance in repetitive sprint events and activities that require several heats or sets. It's assumed that the additional muscle CP, with recharged phosphate bonds (from the aerobic and anaerobic pathways along with ATP) is responsible for this phenomena.

A summary of creatine supplement use (from an American College of Sports Medicine roundtable) suggests that a loading dose is not needed. "Creatine (Cr) supplementation has become a common practice among professional, elite, collegiate, amateur, and recreational athletes with the expectation of enhancing exercise performance. Research indicates that Cr supplementation can increase muscle phosphocreatine (PCr) content, but not in all individuals. A high dose of 20 g x d(-1) that is common to many research studies is not necessary, as 3 g x d(-1) will achieve the same increase in PCr given time. Coincident ingestion of carbohydrate with Cr may increase muscle uptake; however, the procedure requires a large amount of carbohydrate. Exercise performance involving short periods of extremely powerful activity can be enhanced, especially during repeated bouts of activity. This is in keeping with the theoretical importance of an elevated PCr content in skeletal muscle. Cr supplementation does not increase maximal isometric strength, the rate of maximal force production, nor aerobic exercise performance. Most of the evidence has been obtained from healthy young adult male subjects with mixed athletic ability and training status. Less research information is available related to the alterations due to age and gender. Cr supplementation leads to weight gain within the first few days, likely due to water retention related to Cr uptake in the muscle. Cr supplementation is associated with an enhanced accrual of strength in strength-training programs, a response not independent from the initial weight gain, but may be related to a greater volume and intensity of training that can be achieved. There is no definitive evidence that Cr supplementation causes gastrointestinal, renal, and/or muscle cramping complications. The potential acute effects of high-dose Cr supplementation on body fluid balance has not been fully investigated, and ingestion of Cr before or during exercise is not recommended. There is evidence that medical use of Cr supplementation is warranted in certain patients (e.g.neuromuscular disease); future research may establish its potential usefulness in other medical applications. Although Cr supplementation exhibits small but significant physiological and performance changes, the increases in performance are realized during very specific exercise conditions. This suggests that the apparent high expectations for performance enhancement, evident by the extensive use of Cr supplementation, are inordinate."

Supplements of creatine are just as effectively absorbed as are the equivalent amount in a meal of red meat. The timing of the absorption curve (blood levels) with supplements indicate that the majority of pure creatine (supplements) is absorbed in the upper small intestine.

SUPPLEMENT DOSING

• No loading dose - just start 3 grams per day. This dosing strategy takes a little longer to work. Instead of increasing your muscle creatine levels within a week, it can take around four weeks.
• A loading dose of 20 grams of creatine per day for 5-7 days. Then dial it back to 2-5 grams per day (usually 5) going forward.

What is a reasonable dose for supplementation - using the lowest possible dose to minimize any potential toxicity (very low and if any would most likely be dose related). This review article (with references) again emphasizes that there is a maximal muscle concentration of creatine, and a dose of 3 grams a day will equilibrate at that concentration in 30 days. Any higher dose of supplementation just leads to an increase in urine creatine concentration with no additional benefit.

CREATINE SUPPLEMENTS CAUSE "PSEUDO-WORSENING" OF KIDNEY FUNCTION.

As mentioned above, creatine (Cr) is a naturally occurring compound, primarily stored in skeletal muscle. Phosphocreatine (creatine phosphate, PCr), is creatine plus a high energy phosphate group. During high energy demand (e.g., sprinting, lifting weights), phosphocreatine donates the phosphate to ADP to regenerate ATP.

Approximately half the body's creatine comes from our diet (mostly meat and fish) with the remainder being synthesized in the liver. Approximately 95% of the body's creatine is stored in skeletal muscle cells. The bulk of the remaining 5% is found in brain and heart cells.

The normal muscle concentration of Cr is approximately 125 mmol/kg dry mass. Increasing oral creatine intake can increase the muscles total creatine content (both Cr and PCr) from 10-40%. Both forms go up, but the largest relative jump is in free Cr (often a >50% increase), while PCr rises more modestly (10-20%).

On average, meat/fish eaters average approximately 120 mmol creatine/kg dry muscle weight while vegetarians are closer to ~100 mmol/kg and as a result generally see bigger gains with supplements. Fast-twitch muscle fibers tend (as might be expected) have a higher creatine concentration.

Both typical creatine supplement loading protocols

• 20 g/day (0.3 g/kg/day) for 5-7 days, then 3-5 g/day maintenance
• 3-5 g/day for 3-4 weeks

Creatine is broken down into creatinine at a constant rate of ~1-2% of the total pool/day. This is a simple chemical reaction and no catalyst/enzyme is required for the transformation. T he creatinine (water soluble) then diffuses out of muscle into the blood and is ultimately eliminated from the body by the kidneys.

As almost all creatine is stored in muscle tissue and blood creatinine on a general diet (no supplements) is directly proportional to a person's total muscle mass. Being more muscular means a bigger total body creatine pool which in turn means more creatinine (1 - 2 % of the total pool) is produce per day. A very muscular body builder might have a blood/serum creatinine level of 1.2-1.4 mg/dL while a small-framed woman 0.5-0.7 mg/dL. Let's work through the numbers to see exactly how a supplement will change creatinine production. The example is for an average person on a normal diet with a total lean muscle mass of 20 kg.

Baseline creatinine production:

• 20 kg muscle - estimated total body creatine pool of 80-100 g.
• Daily creatinine production in the range of 1.7% of pool/day
• 90 g creatine x 0.017 = 1.53 g/day of creatinine produced

Now add a creatine supplement of 5 g/day.

• Total muscle creatine storage increases until it approaches the saturation limit of 150-160 mmol creatine/kg dry muscle, an approximately 20% increase in the person's total muscle creatine pool at 30 days.
• Total muscle creatine is now 108 g creatine which x 0.017 equals a daily production of approximately 1.84g creatinine.

A blood test for the biologic molecule Cystatin C, produced at a constant rate by all our cells and, unlike creatinine, unaffected by the total amount of muscle tissue or creatine intake (including supplements) is also filtered by the kidneys and its blood level rises only when filtration of the blood truly decreases. Thus cystatin C provides a more accurate monitor of kidney function in anyone taking creatine supplements.

So if you are taking a creatine supplement, and a physician mentions a change in kidney function on your blood work, be sure to let them know you are taking a supplement. If there is still any question as to the extent of a rise in the blood creatinine level, a Cystatin C could save a lot of worry and the cost of a more extensive evaluation.

SIDE EFFECTS - TOXICITY

What are potential toxicities? As I read the various articles referenced on this page, I looked for comments on side effects from creatine supplement. Finding nine, I did a PubMed search for side effects, toxicity, and any association with cancer. Nothing other than an occasional case report of kidney problems - and one report specifically noted that in randomized studies , creatine has not been shown to be kidney toxic. (I even found a study on the possible use of creatine to protect kidney cells from the damage of chemotherapy). And finally, we have this meta analysis from 2023 once again failing to find any support for kidney toxicity.

There has been no suggestion of toxicity in humans or in an an animal model using doses much higher than advocated in clinical trials of supplementation. That being said, each of us has to make our own decisions on potential risks we are willing to take. An alternative viewpoint is presented in this post with the blogger advocating a more conservative approach.

There have been reports of contamination of imported creatine supplement products with potentially toxic compounds, so looking for the cheapest brand may not be the best strategy.

BICYCLING SPECIFIC STUDIES AND PERIPHERAL BENEFITS.

Although there is tantalizing evidence that creatine supplements may benefit single and repetitive sprint performance in events of 15 to 30 seconds duration, this is far from proven. And there is no solid evidence to support its use in cycling events lasting more than a minute.

Even in endurance cycling, it is not uncommon for the rider to experience moments where a little extra creatine at their disposal could make a difference for intense efforts such as surges, hill climbs, and finishing sprints. I personally think it helps me on the longer climbs on my standard training route - and on enough occasions to feel this is real and not just a placebo effect.

Creatine supplementation may tamp down inflammation (thus improving recovery) after longer, intense events.

And may increase muscle glycogen stores. In healthy volunteers, five days of creatine (Cr) plus carbohydrate (CHO) augmented post-exercise muscle glucose uptake and glycogen storage compared to CHO feeding alone.

THE BOTTOM LINE (FACT VS FICTION)

• sprint activities of 5 to 20 second duration rely on muscle creatine phosphate
• there is no significant difference between males and females in cell CP levels
• training does not appear to effect cell CP levels
• those already on a high creatine diet will have decreasing benefits from supplements
• vegetarians and older athletes are more likely than omnivores to benefit from creatine supplements
• a high carbohydrate diet will improve the benefits of a creatine supplementation program
• there is no evidence that increasing intake > 20-30 g/d for 5-6 d has any additional effect on creatine uptake or performance. Any additional creatine is just eliminated through the urine.
• creatine supplementation , especially when using a loading dose, may lead to weight gain in the first few days, likely due to water retention
• it is likely that only one athlete in many thousand will suffer from kidney problems when taking creatine supplements, and this is more likely in those using mega doses.

UPDATE 2015 - CREATINE SUPPLEMENTATION MAY BENEFIT VEGETARIAN AND OLDER ATHLETES

Those of you who follow my posts know of my skepticism about supplements. But creatine may be an exception. As an almost completely vegetarian (it there is such a thing) as well as an older athlete, I found the following chain of articles fascinating. The initial questions: Can a vegetarian diet lead to underperformance in endurance sports? That is, even if protein requirements are being met on a vegetarian diet, is an athlete still at risk for under performance compared with one who eats meat (omnivores)?

<< The following are a compilation of studies (references provided), direct quotes from them, and my comments.>>

This is the article that suggested that may be the case, at least in older athletes, and got me started on this search of the medical literature. "Consumption of a meat-containing diet contributed to greater gains in fat-free mass and skeletal muscle mass with RT (resistance training) in older men than did an LOV (lacto-ovo vegetarian) diet."

There are several possibilities for this observation -

1. a subtle deficit of basic dietary elements such as carbohydrates and protein or
2. a nutritional component found in a meat based diet but lacking in a vegetarian diet.

This paper raises the possibility that it is a lack of creatine that is the performance risk factor for vegetarians. We know that vegetarians often need to supplement micro-nutrients such as iron, zinc, vitamin B12 (cyanocobalamin), vitamin D and calcium (either by using supplements or altering their dietary intake). But now we add the potential of a creatine deficiency (which cannot be met on a meat free diet). "Creatine supplementation provides ergogenic responses in both vegetarian and non-vegetarian athletes, with limited data supporting greater ergogenic effects on lean body mass accretion and work performance for vegetarians" Creatine is found mostly in meat, fish and other animal products and this does impact vegetarians. "... the levels of muscle creatine are known to be lower in vegetarians."

and

"A vegetarian diet is correlated with a lower muscle creatine."

Not only can creatine levels be low in the muscles of vegetarians, it has found to be lower than in omnivores in the brain as well. And it has been suggested that a lower level may impair memory as well thus putting vegetarians at some small risk. "...in vegetarians rather than in those who consume meat, creatine supplementation resulted in better memory."

A creatine deficit occurs fairly quickly, in less than a month, when switching to a vegetarian diet. "..The results demonstrated that consuming a LOV diet for 21 days was an effective procedure to decrease muscle creatine concentration (p <.01) in individuals who normally consume meat and fish in their diet."

So the question is whether creatine supplementation makes sense for vegetarian athletes? Is it possible to take supplements (assuming that the creatine supplement, probably derived from animal sources, is acceptable to vegetarians). Interestingly, vegetarians as a group, respond more dramatically and in a relatively short period of time to such supplementation. Just 5 days of creatine supplementation increase tissue levels. "The results indicate that VEG have a lower muscle TCr content and an increased capacity to load Cr into muscle following CrS."

The increased responsiveness to creatine supplements is confirmed in this study. "Vegetarians who took Cr had a greater increase in TCr, PCr, lean tissue, and total work performance than nonvegetarians who took Cr (P<0.05). The change in muscle TCr was significantly correlated with initial muscle TCr, and the change in lean tissue mass and exercise performance. These findings confirm an ergogenic effect of Cr during resistance training and suggest that subjects with initially low levels of intramuscular Cr (vegetarians) are more responsive to supplementation."

So we know that tissue creatine levels are lower in vegetarians, that this may be a reason for a decrease in performance, and supplements can fairly quickly reverse this deficit. Are supplements safe? "Creatine is a relatively safe supplement with few adverse effects reported. The most common adverse effect is transient water retention in the early stages of supplementation. When combined with other supplements or taken at higher than recommended doses for several months, there have been cases of liver and renal complications with creatine."

What dosages have been used in these studies? First, the formulation - "Creatine monohydrate is the most studied; other forms such as creatine ethyl ester have not shown added benefits." "0.3 g/kg/d for 5 to 7 days, followed by maintenance dosing at 0.03 g/kg/d....However loading doses are not necessary to increase the intramuscular stores of creatine". "0.1 g/kg of body weight" per day.

There are many articles on the benefits of creatine supplementation in power lifters and for other anaerobic activities such as sprints. This is the only study I could find that addressed aerobic endurance performance... and as in many of these studies, the subjects were a younger population. Remember that the initial article specifically qualified the statement to "older men", who may be more susceptible to the creatine deficit of a vegetarian diet. In this younger group, "...Cr supplementation did not result in any improvement in upper-body maximal strength and in endurance running performance."

So let's switch the focus for a minute to the older, non vegetarian athlete. Interestingly the younger meat eating athlete does not appear to be as responsive to creatine supplementation as the older athlete. Perhaps it is the fact that a minor change in performance is hard to demonstrate statistically and only becomes evident when accentuated by the age factor. Article after article supports the idea that creatine supplementation is beneficial for the older athlete looking to improve performance:

1. "Supplementing with creatine, a high-energy compound found in red meat and seafood, during resistance training has a beneficial effect on aging muscle."

2. "Creatine supplementation is a safe, inexpensive and effective nutritional intervention (particularly when consumed in conjunction with a resistance training regime) for slowing the rate of muscle wasting that is associated with aging."

3. "Data indicate that creatine supplementation without associated training in the elderly could potentially delay atrophy of muscle mass, improve endurance and strength, and increase bone strength, and thus may be a safe therapeutic strategy to help decrease loss in functional performance of everyday tasks. Generally, however, creatine supplementation, without associated resistance training, seems to enhance muscular strength, power and endurance, increase lean body mass (LBM) and improve the functional capacity of the elderly."

4. "Creatine is an inexpensive and safe dietary supplement that has both peripheral and central effects. The benefits afforded to older adults through creatine ingestion are substantial, can improve quality of life, and ultimately may reduce the disease burden associated with sarcopenia and cognitive dysfunction."

I think we now have plenty of evidence that creatine is part of the problem. Are there any other factors (in addition to a relative creatine deficiency) that might the contribute to a performance deficit in the older meat eating athlete? Daily protein requirements (RDA), whether from plant or meats, do increase as we age and may compound the problem of athletic performance for this group. "These results suggest that the RDA for protein may not be adequate to completely meet the metabolic and physiological needs of virtually all older people."

and

"...the recommended dietary allowance of 0.8 g protein x kg(-1) x d(-1) might not be sufficient."

What are my conclusions after this investigation?

1. If you are in that older age group (65-70) creatine supplementation makes sense-for possible positive effect on mental functioning as well as muscle strength. I plan to give it a try for a month although I'm not sure how I will eliminate a placebo effect as I try to decide if it is helpful. Based on the data, even if I am doubtful I will probably continue it if I don't experience any negatives.

2. If you are a vegetarian, or an "almost vegetarian", the age limit where a benefit can be demonstrated decreases. What age? There is no data. But as it is a safe supplement I'd give it to any performance athlete who is a vegetarian.

3. Will this help endurance performance (as opposed to resistance or anaerobic activities) in vegetarians or the older athlete? It may not increase your time to exhaustion in aerobic activities, but if it leads to an increase in muscle mass, strength and the watts of power you can generate should increase as well, which can't help but improve your performance up to that point of exhaustion.

UPDATE 2023 - CREATINE SUPPLEMENTATION MAY PREVENT SARCOPENIA OF AGING.

• Creatine is one of the world's best selling supplements.
• According to the International Society of Sports Nutrition, creatine monohydrate is the single most effective ergogenic supplement available to athletes for increasing exercise capacity and lean body mass during training.
• The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel that, despite the lack of long-term trials, suggested creatine be used for the management of sarcopenia. The recommended dose to achieve muscle saturation is three grams a day.

I'm sticking with my last recommendation. Creatine appears to be a safe supplement with significant potential for long term benefits at a very small cost. It may diminish the loss of muscle mass with aging as well as improve performance in those athletes involved in intense aerobic as well as resistance exercise.

CREATINE AND THE HEART

Animal studies later showed that boosting the creatine system could improve how well the heart contracts. But when scientists tested creatine supplements in people with heart failure, the results were mixed. Most clinical trials and reviews have not found consistent benefits for heart function.

Some research suggested creatine might still be helpful during cardiac rehabilitation - the recovery process after heart problems - by improving skeletal muscle strength, reducing fatigue, and helping these muscles use energy more efficiently. There is clinical evidence to support creatine supplements increasing muscle strength and endurance in people with heart failure, which might make it easier for them to take part in rehab exercises. However, studies looking at whether creatine improves overall exercise capacity or daily functioning have shown only small or inconsistent effects, not enough to change medical guidelines.

In summary, while there is a strong scientific reason to think creatine could help in heart failure, the current evidence does not support using it as a standard treatment.

MY ANNECDOTE

A reader of my FB blog, who trains "by the book" and keeps meticulous records of times and training, told me that he tried it as well. He was originally worried about the weight gain that has been reported, and decided to try a loading dose of ~20 grams for 5 days. Two observations:

• No weight gain
• Increase in interval speed of 3%
  • Prior record for 2 minute interval on his treadmill - 37.2 km/hr, HR 88% MHR
  • After 10 days of creatine - 38.4 km/hr avg, HR 84.2% MHR.

So even though I am not a big advocate of supplements, I am going to stay on my creatine for a bit longer.