The limited amount of ATP stored in the muscle cell is depleted with several seconds of physical activity if not replaced or re-synthesized. To sustain physical activity beyond these few seconds, the cell continually re-synthesizes its ATP (which is the ONLY molecule able to act as an intermediary to provide the energy to the muscle fibers to power their contraction). ATP is 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) - another high energy, phosphate bearing molecule stored in the muscle cell - which then supplies 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 is an amino acid found mainly in the muscle tissue of fish and meats. In man, creatine is found in skeletal muscle, heart, brain, retina, testes and the uterus. Normally less than 1 gram per day is supplied by the diet and another gram is synthesized (mainly by the kidneys). Synthesis is the only source for vegetarians and suggests a possible role for creatine supplementation in this group of athletes as compared to omnivores (those that also have meat in their diet). Creatine is eliminated through the kidneys which does raise a concern that high doses might potentially injure the kidneys. However, unless one is using mega-doses, no adverse affects have been demonstrated.

Demant TW and Rhodes EC published a nice review on creatine. 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 (Crfree), 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 Crfree 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."

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 will also improve performance in repetitive sprint events and activities that require several heats or sets. Presumably 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 would indicate that the majority of pure creatine (supplements) is absorbed in the upper small intestine. This is important as one suggested toxicity results from a bacterial degradation product of creatine. As supplements are well (and early on) absorbed, the risk of TMAO toxicity should be minimized compared with creatine in meat which, being less easily digested, is delivered to the colon (where the vast majority of bacterial degradation takes place) in greater amounts.

SUPPLEMENT DOSING

SIDE EFFECTS - TOXICITY

The potential toxicities are acute (short term over days to months, perhaps dose related) and longer term (over years).

• Short term - the most commonly mentioned is kidney inflammation. As mentioned, other than an occasional case report (note toxicity as an allergic type reaction can occur from any medication) there was no cluster of events. 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.
• Long term - the two most commonly mentioned possibilities would be cancer or CV disease from the creatine degradation product TMAO. But as mentioned above, pure creatine in supplements is well absorbed, and very little if any should make it to the colon to be degraded by the bacteria residing there. In my mind, the risk of toxicity from eating red meat (which contains creatine and is not completely digested) is greater than from any supplement.

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

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 evidence to support its use in cycling events lasting more than a minute.

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 ALL 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.

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.