Creatine guide. Part 4: Risks, Side Effects & Benefits
Is creatine safe for women, children, the pregnant or the elderly?
Following the example set by the sports medicine and exercise physiology fields, the creatine field has principally concentrated on male subjects between the ages of 18 and 35 years. Scientific studies conducted on this age group have typically demonstrated enhancements in physical performance during repeated bouts of maximal effort, particularly during later repetitions when the accumulation of lactic acid becomes appreciable, contributing significantly to the onset of muscle fatigue. Therefore, since one of the major ergogenic contributions of creatine is to lessen the buildup of lactic acid, exercise capacity increases as a result of creatine supplementation. Other contributions of creatine to the total ergogenic package have been discussed previously and have to do with increases in anaerobic energy reserves (ATP and Phosphocreatine), muscle cell proliferation and increases in the production of contractile and metabolic (energy-producing) proteins.
Although, the effects of creatine in children, the elderly and women has been studied much less, there is no a priori reason to think that creatine’s basic mechanism of action should differ with age or gender. However, subtle differences may exist in how creatine supplementation effects these distinct categories of individuals and special considerations may thus apply; some aspects of creatine supplementation in these populations may be detrimental and be a valid basis for concern, whereas others aspects of creatine supplementation may render a clear benefit to the individual supplementing. These considerations will be discussed below.
Children: Whether creatine is safe for children is our second most commonly asked question. And expectedly, the nature of creatine's side effects is our most frequent inquiry. Most creatine experts are of the opinion that it is best to postpone creatine supplementation until after puberty, particularly since the long-term consequences of creatine supplementation are still largely unknown. In other words, if adverse consequences to creatine supplementation do exist, then the younger an athlete starts the practice, the more likely potential side effects are to manifest within their lifetime.
A more pertinent question might be, however: “Should children push themselves beyond the normal limits of play?” Remember, creatine supplementation primarily enhances an athlete's ability to generate near maximal force during repetitive bouts of intense exercise. Given that some experts have warned that excessive mechanical stress might have deleterious consequences on a skeletal frame that is rapidly growing, I would advise against creatine supplementation before reaching puberty. This is just my personal opinion, the opinion of other experts may differ.
Adolescents: Creatine studies conducted on adolescents have given both positive and null results creating a bit of confusion in the field. The simple truth is, however, that too few studies exist to objectively state just how great an effective creatine supplementation has in the adolescent population. "Nonresponders" are observed even in the most heavily studied age group (18-35 years of age) and hence, the statistical uncertainty may merely reflect the fewer number of studies conducted on adolescents.
Elderly: Our muscular phosphocreatine levels decline as we age beyond our fifth decade. Such a decline in muscle creatine content may partially explain the decrease in strength and predisposition to fatigue that is observed in the elderly. Creatine supplementation might therefore prove especially worthwhile in the individuals over 50. In support of this notion several recent studies have demonstrated accentuated performance enhancement in healthy individuals in their 50s, 60s and early 70s. That is, creatine supplementation produces relatively greater gains in middle-aged subjects than in younger subjects.
Oddly, an effect of creatine supplementation (over physical performance) in individuals in their late 70s and 80s has been somewhat harder to resolve. Age-related decreases in activity-level, anabolic hormones, or type II (fast) muscle mass may all contribute to the reduced responsiveness of the elderly to creatine supplementation. Foremost, since type II muscle is the class of muscle fiber that is most responsive to creatine supplementation, a selective loss of this muscle class can largely account for the "apparent" insensitivity of elderly subjects to acute (one time) creatine supplementation.
The elderly, however, are not without recourse in combating this age-related decline in creatine responsiveness over physical performance. On the one hand, undertaking certain proactive measures can increase one's sensitivity to creatine in later life. Adopting a more healthful lifestyle, including regular exercise and eating a balanced diet can help maintain more youthful anabolic hormone levels for longer in life and hence, preserve one's sensitivity to creatine. Maintaining an active lifestyle also helps prevent against the loss of existing muscle tissue, which should also translate into greater responsiveness to creatine supplementation. Therefore, exercise and good nutrition slows the normal aging process and should prolong one's sensitivity to creatine for longer in life.
On the other hand, recent evidence is now indicating that creatine supplementation per se helps maintain anabolic hormone levels and type II muscle mass - independently of lifestyle changes. Therefore, creatine supplementation may act directly to slow physical aging and hence, maintain its physiological relevance.
Clearly, creatine supplementation is a worthwhile endeavor in later life. Many aspects of creatine supplementation may prove particularly beneficial for older athletes. For instance, creatine supplementation may reduce the chances of developing coronary heart disease as well as several neurological disorders that plague the elderly.
Women: Several recent studies have examined the effects of creatine supplementation in women of diverse fitness levels. And, although creatine clearly enhanced exercise performance in women, the documented effects were less pronounced than those observed in males of the same study. Specifically, gender differences were observed at the level of muscle protein turnover; creatine supplementation appears to have a greater anti-catabolic action in males. Differences in the anabolic-androgenic sex hormone, namely the predominance of testosterone in males, may underlie this distinct response to creatine in females.
Pregnancy: It is not known whether the levels of creatine in breast milk increase during supplementation. Until this information becomes available, women nursing infants are advised to abstain from using creatine. The point of this recommendation is to avoid inadvertently exposing the infant to abnormally elevated levels of creatine that might alter key metabolic processes during child development.
A red flag, however, was raised by studies examining rat fetal development. A region of the placenta known as the decidua was found in rodents to express very high levels of the enzyme, AGAT (L-Arginine:GlycineAmidinoTransferase). AGAT is first of two enzymes used in the synthesis of creatine from common amino acids. AGAT catalyzes the union of arginine and methionine to form GuanidinoAcetic Acid, or GAA, in the kidneys; ornithine is the other product of this synthetic reaction. GAA is then transported in the blood stream to the liver where it is activated by the addition of a methyl group (from methionine) to produce creatine. This second step is one of the principal methylation reactions undertaken by the body (also see A Drop in Cellular Methylation Status Characterizes Normal Aging for the importance of this fact).
Most importantly, the expression of AGAT has been shown to be suppressed (downregulated) by the presence of elevated creatine in the blood stream. Supplementing during pregnancy may therefore, interfere with the endogenous role of AGAT in fetal development. Although provocative, this result needs to be expanded upon and corroborated in the placenta of pregnant human females.
A similar concern arose from the finding that the expression level of the creatine transporter changes dramatically during the first few weeks of life in certain animal species. For instance, in rabbit pups the level of creatine transporter expressed on neurons within the brain drops by 60% between the first 5 to 15 days of life. That is, after birth. Given the fact that serum creatine levels have been shown to influence the expression of the creatine transporter, the possibility thus exists that exogenous creatine supplementation may upset an inherent developmental program based on natural changes in serum creatine levels. Again, this phenomenon remains to be demonstrated in humans.
Understandably, "What are creatine's side effects?" is my most frequently asked question. While several classes of side effects have unequivocally been linked to creatine consumption, others have not. I will begin this section by describing those side effects which have been clearly linked to creatine use and end with a discussion of the side effects often attributed to creatine consumption, but largely unexplained based on our current knowledge of creatine's accepted mechanisms of action, and give some possible explanations.
Most of the substantiated side effects arising from creatine use involve the propensity for creatine to draw water into the body compartments where it has accumulated. Scientifically speaking, creatine is osmotically active. This may not sound too serious, but if NOT compensated for with adequate fluid intake, other body tissues may be deprived of much needed fluids, especially during strenuous exercise. It is thus very important that you remain well hydrated while supplementing. Drink at least 1-2 ounces of water daily per kilogram of body weight while supplementing. Other possible side effects have to do with the body's ability, or rather, inability to clear creatine and its associated by-products from the body.
Volumizing: An increase in body weight is the most widely accepted side effect attributed to creatine use. As much as 3 kilograms (6.6 pounds) of added body weight have been reported during the first weeks of supplementation. This rapid increase in body mass is almost exclusively due to the movement of water from the blood stream into skeletal muscle. Such an increase in body mass is simply too rapid to be due to an increase in "dry" muscle mass (proteins). This form of muscle growth is known as Muscle Volumizing because our muscles increase in volume as they inflate with water. Some types of athlete (bodybuilders, for example) may not consider this side effect a negative, and, in fact, may find it a desirable characteristic. By contrast, other athletes (endurance athletes, for example), may find that muscle volumizing interferes with their athletic performance. It is easy to imagine how a few extra "kilos" may hinder one's performance in a marathon. In any case, creatine-based energy production bestows little benefit during endurance events.
Later stages of muscle growth, on the other hand, do involve the acquisition of new muscle proteins, but will be smaller in magnitude and more protracted in time when compared to the increase in body mass attributed to Muscle Volumizing. The proportion of gains that persist, moreover, will increase by combining creatine with essential B vitamins and other important nutrients.
Dehydration: Again, it's imperative that you remain well-hydrated while supplementing. Adequate hydration is important since much of our body water follows creatine into skeletal muscle, possibly depriving our remaining tissues of much needed fluid, especially when exercising in hot and humid environments. Down the road this may lead to impaired thermoregulation and subsequent heat exhaustion. This precaution is especially valid in combative sports (wrestling, etc) where athletes strive to make weight before competition. Weight loss under these circumstances is often achieved through fluid restriction, which, in combination with creatine use, could lead to excessive dehydration.
Gastrointestinal Distress: Gastrointestinal distress is the secondly most common side effect reported. Incidences of stomach cramps, nausea, flatulence, and diarrhea are more commonly reported during the loading phase when greater amounts of creatine are consumed each day. These side effects are principally due to the presence of large quantities of undissolved creatine particles residing within the intestinal compartment. Remember, creatine has the propensity to draw water into the body compartment where it is found (see above). If the body compartment in question is the large intestine, then excessive water absorption may lead to diarrhea and intestinal cramps. These side effects can often be largely circumvented by making sure that creatine is completely dissolved in at least 16 ounces of water (or juice) and never consuming more than the recommended dosing amount.
The presence of additives or contaminants may also be a source of gastrointestinal discomfort. These days, it seems as if every creatine manufacturer is trying to distinguish their particular product from the rest of the crowd. Each day new marketing twists are appearing with the main objective of making their particular products appear superior to all the rest. As a result more and more extraneous agents are being added to the growing list of creatine products (see above). People who experience gastrointestinal discomfort from creatine may merely be sensitive to these additives and not to the creatine per se. If your particular brand of creatine gives you an upset stomach, switch to a source of pure creatine monohydrate. It's thus important that you purchase your creatine from a reputable creatine provider.
Flatulence: The large amounts of sugars often consumed with creatine may lead to flatulence, complicate gastric emptying and result in gastric cramps. Mechanistically, certain classes of carbohydrates, particularly when consumed in large quantities, may pass undigested through the small intestine and ultimately collect (nearly intact) in the large intestine. Here, intestinal bacteria decompose the sugar, releasing gas. If sufficiently large amounts of gas are produced to exert pressure within the intestinal compartment, then cramps may ensue. Flatulence is the expelling of this gas produced by the bacteria.
Fructose and sorbitol are especially notorious in this respect. Therefore, avoid mixing your creatine in juices containing mainly fructose.
Muscle strains, cramps and tears: These side effects are sometimes reported in chat rooms and in the popular press. As a result, these incidences are sometimes dismissed as anecdotal and unfounded. Similar incidences, although rare, have also been reported during controlled scientific studies. Nevertheless, the validity of these side effects is still being debated in the creatine scientific community. This is due, in great part, to appearance of scientific studies showing no, or even a positive, effect of creatine over the incidence of muscle injury. The problem may be that most of the before mentioned studies used highly-trained college-aged athletes. The body's of such individuals have adapted quite well to a demanding exercise load.
Muscle cramping might result from an electrolyte imbalance downstream of possible creatine-induced dehydration. Alternatively, muscle lesions might result from one over-reaching their physical capacity. In other words, during creatine supplementation the amount of force we are able to generate may increase faster than our muscle's (ligaments, tendons, etc) ability to adapt to the increased load; a weakest link phenomena. Again, drink plenty of fluids while taking creatine!
Renal Stress: Sensible creatine use doesn't appear to adversely influence kidney function in healthy individuals. There is some concern, however, that "creatine abuse" may place undue stress on the kidneys, particularly during the loading phase when large quantities of creatine are being ingested on a daily basis. During loading the kidneys must work harder to clear unabsorbed creatine from the blood stream. Persons with pre-existing kidney disorders, or predisposed to renal dysfunction, such as diabetics or the elderly, should minimally omit the loading phase of supplementation, or abstain from creatine use altogether. These individuals, should they choose to supplement, should also be checked by their doctors on a regular basis.
Blood Pressure: There was some concern that creatine-induced fluid retention could reduce blood pressure. This was the topic of a recent scientific study demonstrating that acute creatine use does not alter blood pressure. Importantly, some blood pressure medications may negatively interact with creatine-induced muscle fluid retention.
Cholesterol & Protein Synthesis: Not all of creatine's reputed side effects are detrimental. For example, recent research has shownt that creatine supplementation may improve our serum cholesterol levels. In addition, muscle volumizing may directly stimulate the production of new muscle proteins. There are also indications that creatine may possess antioxidant properties on its own. Finally, and most importantly for overall health, creatine supplementation may reduce serum homocysteine levels by sparring the body's methyl reserves. Reducing serum homocysteine levels, in turn, will greatly improve physical and mental health.
Contaminants: Pure creatine monohydrate is not toxic. Certain impurities, however, may be potentially harmful. Creatine monohydrate is produced commercially by mixing sodium sarcosine and cyanamide in a heated water bath. Although seemingly straightforward certain chemical by-products may be formed, especially if inferior quality starting materials are used or sufficient care isn't exercised during synthesis. These contaminants are particularly evident for cheaper brands of creatine. Moreover, some of the impurities present in poorer quality brands of creatine are potentially toxic and may give rise to adverse side effects.
The presence of contaminants is particularly worrisome during the loading phase when much greater amounts of creatine are consumed each day. A person loading with a poorer quality creatine product may actually be taking in grams of potentially toxic impurities each week.
Finally, some cheaper (or less scrupulous) creatine products have been shown to contain trace amounts of certain anabolic steroids. The presence of steroids in some cheaper creatine products may account for incidences of false-positives in some creatine users. Importantly, under the new Anabolic Steroid Control Act of 2005 (USA), ignorance is no excuse. If you test positive for any banned agent you may be barred from receiving federal financial aid as well as be declared ineligible for further athletic competition. This is no joking matter. In essence, cheaper brands of creatine literally dilute the amount of "real creatine" with contaminants making them pointless, potentially harmful, possibly illegal and a huge waste of money.
Rumors & Unexplained Side EffectsSide effects that cannot be explained from what is scientifically known about creatine are sometimes reported. Whether these side effects represent fact or fiction is still a matter of controversy. Some unexplained side effects may be merely rumor and arise from creatine being mistakenly associated with anabolic steroids. On the other hand, other incidences of unexplained side effects may be real and stem from contaminants or additives present in cheaper brands of creatine. This second set of unexplained side effects may have previously escaped detection owing to the fact that most scientific studies use only the highest-grade creatine products, WITHOUT unstudied additives that could confound the analysis of the data.
Unsubstantiated side effects reported include breast formation in men (gynecomastia), a reduction in penis size, hair loss (men), hair growth (women), acne and stunted growth in children. Unexplained incidences of aggression have also been sometimes linked to creatine use.
Misconceptions: Oh, Fat is Fat and Muscle is Muscle, "and never the twain shall meet"...
Muscle will not convert to fat after stopping creatine supplementation. It simply can't. Muscle and fat are two completely different tissue types.
Our muscles initally grow in response to creatine use as a result of increased hydration (aka, muscle volumizing) and later on because of an increase in muscle protein content (aka, protein synthesis). After stopping creatine supplementation any gains in muscle size that were attributed to muscle volumizing will be lost. This is unavoidable. Remember, however, that this is only muscle water that is being lost, not muscle proteins. On the other hand, any gains you made as a result of increased muscle protein content will be more enduring.
The only way you can create body fat is to consume more calories than you burn with physical activity. Therefore, if your activity level decreases significantly after stopping creatine supplementation, while your caloric intake remains the same (or increases), you will gain fat.
Long-term consequences of creatine use?
The use of creatine in the athletic arena is a relatively recent practice, less than two decades. Consequently, the long-term consequences of creatine supplementation aren't fully understood. In other words, the phenomenon of athletic creatine supplementation is much too recent for a complete epidemiological profile to be available. Of particular concern, however, is the time required for synthesis and transporter function to fully recover after prolonged exposure to elevated creatine levels. This information is simply not known for humans. It is therefore that I advise that the loading phase not exceed 5 days.
Clinical situations, however, do exist where low doses of creatine have been used for several years with no signs of adverse side effects. For example, Gyrate Atrophy is a disease of the eye (retina) that is characterized by progressive narrowing of the visual fields. A secondary component of the disease is a deficiency in creatine synthesis. Consequently, this disease is also characterized by a reduction in the size of fast muscle fibers. Creatine supplementation has been shown to alleviate the muscular symptoms associated with this disease, although the visual symptoms persist. Other than mild weight gain, however, low doses of creatine (1.5 grams/day) when administered for the duration of several years produced no obvious adverse effects.
On the other hand, with each passing day it is becoming increasingly apparent that creatine supplementation possesses long-term benefits, especially when accompanied by B-vitamin supplementation. These "unexpected long-term benefits" have to do with an enhancement in cellular methylation rate that accompanies creatine supplementation.
Can creatine help those with Muscular Dystrophy?
Neuromuscular disease: Creatine has been used in clinical trials for several classes of neuromuscular disorder. The neuromuscular disorders with which creatine has been used with some clinical success include Duchenne muscular dystrophy, Becker muscular dystrophy, fascioscapulohumeral muscular dystrophy, sarcoglycan-deficient limb girdle muscular dystrophy, Mitochondial cytopathies, Gyrate Atrophy, McArdle disease (myophosphorylase deficiency) and Myasthenia Gravis. Creatine has also been used in animal models for Huntington's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and spinocerebellar ataxia. Obviously, creatine has caught the attention of the medical community and will continue to do so for quite some time. In fact, these applications are what got me involved in the creatine field in the first place.
Interestingly, a common feature of many these neuromuscular disorders is a reduction in muscular phosphocreatine levels. Therefore, although not representing a cure per se, creatine supplementation may improve the quality of life of individuals inflicted with these disorders. In support of this conclusion, preliminary studies have demonstrated that creatine supplementation improves strength and endurance in patients with several classes of neuromuscular disorder.
Physical rehabilitation: Creatine has also been used postoperatively on patients recovering from orthopedic surgery. As a result of the success of these initial trials it is my opinion that creatine use during rehabilitation will become increasingly common.
Neurological disorders: Creatine metabolism has also been implicated in certain neurological disorders. Systemic defects in either creatine synthesis or creatine transport are often characterized by severe mental retardation. Not surprisingly, the neurological symptoms arising from inherited creatine disorders are often more devastating than the corresponding muscular symptoms; clearly indicating that creatine-based energy production plays a major role in the nervous system. Creatine has been used with some success in reversing the neurological symptoms of human patients exhibiting defects in creatine synthesis. Creatine has also been shown to exert a neuroprotective (preventing brain cell death) effect in mouse models of Huntington's disease, Amyotrophic lateral sclerosis (ALS) and Parkinson's disease.
Here is a page specifically dedicated to discussing the ongoing clinical trials investigating the possible benefits of creatine to states of human disease: www.creatinemonohydrate.net/creatine_trials.html
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