Mike Montemarano, Associate Editor 03.30.21
Creatine, an amino acid which can be found in meat and dietary supplements, and is also produced endogenously from arginine, glycine, and methionine, is a highly popular dietary supplement among athletes and gymgoers, due to evidence that it can improve muscle mass, performance, and recovery when used in conjunction with training. However, while over 500 peer-reviewed publications investigating the health benefits of creatine on muscle development, cognitive function, and more have been published, questions regarding the efficacy and safety of creatine remain. Furthermore, many widespread misconceptions regarding the amino acid and its role in nutrition remain.
The authors, all members of the International Society of Sports Nutrition (ISSN) of a recent review, published in the Journal of the International Society of Sports Nutrition, analyzed the known research so far as it relates to a number of common questions and misconceptions, still being posed by researchers, or held by consumers, respectively. The studies cited for the review analyzed consumption which is well-tolerated and advised, roughly 3-5 g per day, or 0.1g/kg of body mass daily.
In short, the paper provides an evidence-based review of literature examining the effects of creatine supplementation on performance, recovery, injury prevention, exercise tolerance and rehabilitation, neuroprotection, aging, clinical and disease state populations, and pregnancy. The paper is framed by the questions on creatine’s associations with water retention, relationship with steroids, kidney damage/renal dysfunction, hair loss, dehydration/cramping, children and adolescent health, body fat, health benefits for older adults, and more.
Water Retention
On whether creatine causes water retention, ISSN states that water retention is possible within the first several days of creatine supplementation, but that based on these short-term responses, the notion that creatine increases water retention over the long-term is widely accepted.
“Creatine is an osmotically active substance. Thus, an increase in the body’s creatine content could theoretically result in increased water retention. Creatine is taken up into muscle from circulation by a sodium-dependent creatine transporter. Since the transport involves sodium, water will also be taken up into muscle to help maintain intracellular osmolality. However, considering the activity of the sodium-potassium pumps, it is not likely that intracellular sodium concentration is dramatically affected by creatine supplementation.”
Furthermore, other studies suggest creatine does not alter total body water relative to muscle mass over longer periods of time. As a result, creatine supplementation may not lead to water retention.
Kidney Function
The authors also addressed questions and concerns surrounding creatine supplementation and kidney damage/renal dysfunction.
“in terms of pervasive misinformation in the sport nutrition arena, the notion that creatine supplementation leads to kidney damage/renal dysfunction is perhaps second only to the myth that protein supplementation and high habitual protein intake causes kidney damage. Today, after > 20 years of research which demonstrates no adverse effects from recommended dosages of creatine supplements on kidney health, unfortunately, this concern persists,” the authors said.
While creatine supplementation does increase blood or urinary creatinine concentrations, there has not been evidence to date sufficient to conclude that if the kidneys are “forced” to excrete higher than normal levels of creatine or creatinine, kidney damage or renal dysfunction would take place. While one case study in 1998 involved one creatine supplement user experiencing renal dysfunction, several trials evaluating creatine supplementation and kidney function analysis failed to replicate the health effects of this case study to date.
“If the link between creatine supplementation and kidney health was valid, there would be an expected increase in kidney damage/ renal dysfunction in low risk (i.e. young, physically fit, healthy) individuals since 1992 after Harris et al. published their seminal work,” the authors said.
Hair Loss
ISSN concluded that the current body of evidence does not indicate that creatine supplementation increases total testosterone, free testosterone, or DHT, hormonal changes which would result in hair loss or baldness. Therefore, they do not suspect that there is an association between creatine and hair loss in its users. While one study, which evaluated week-long supplementation of creatine in college-aged male rugby players, found that the supplementation increased DHT concentrations by 56% over the seven-day loading period (and DHT is theorized to be linked to baldness).
However, 12 other studies investigating the effects of creatine supplementation found no significant changes to either testosterone, free testosterone, or DHT.
Dehydration and Muscle Cramping
ISSN said that questions surrounding a link between creatine and dehydration and muscle cramping likely were based on speculation, when the American College of Sports Medicine (ACSM) recommended avoiding creatine supplementation in individuals controlling their weight or exercising intensely, or in hot environments. The rationale behind the theory is that creatine is an osmotically active substance found primarily in skeletal muscle and may alter whole-body fluid distribution in the short term.
While plausible in situations of body water loss such as severe sweating, the bound intracellular fluid could in theory be detrimental to hydration, however, most evidence supporting the theory involved self-reporting in surveys, while, experimental and clinical evidence suggests no detriment. One study (Greenwood et al.) found that Division 1 baseball and football players who used creatine had significantly less cramping, heat illnesses, dehydration, muscle tightness, muscle strains, and total injuries compared to a sport drink placebo group.
“In summary, experimental and clinical research does not validate the notion that creatine supplementation causes dehydration and muscle cramping,” the authors said.
Children and Adolescents
“The overwhelming majority of evidence in adult populations indicates that creatine supplementation, both short- and longer-term, is safe and generally well tolerated,” the authors of the study said. “The physiological rationale supporting the potential ergogenic benefits of creatine supplementation in children and adolescents was first postulated by Unnithan and colleagues in 2001; which established a strong basis for future applications of creatine for younger athletes. More recently, in a comprehensive review examining the safety of creatine supplementation in adolescents, Jagim et al., summarized several studies that examined the efficacy of creatine supplementation among various adolescent athlete populations and found no evidence of adverse effects. However, it is important to note that none of the performance-focused studies included in the Jagim et al. review provided data examining specific markers of clinical health and whether or not they were impacted by the supplementation protocols.”
Additionally, based on a survey of 270 high school boys and girls in which 21% of boys and 3% of girls reported supplementing with creatine, the authors of the study suggest that its use among youth and adolescents is relatively widespread, a trend which warrants additional research to determine with greater certainty that creatine supplementation, both acute and longer-term, is safe for children and adolescents.
“In summary, based on the limited evidence, creatine supplementation appears safe and potentially beneficial for children and adolescents.
Additional Findings
The authors of the study state that, based on the existing evidence, that while creatine can possibly increase body mass, in the clinical trials where this occurs, there is no increase in body fat, but only fat-free mass. The lack of effect on body fat composition was true in both short- and long-term studies, they said, including in trials which lasted several weeks across several demographics. “Recently, Forbes et al. conducted a systematic review and meta-analysis on randomized controlled trials involving creatine supplementation in conjunction with resistance training on fat mass in older adults (>50 yrs). Nineteen studies with a total of 609 participants were also included. Participants supplementing with creatine had a greater reduction in body fat percentage. There was no significant difference in absolute fat mass loss; however the creatine group lost ~0.5 kg more fat mass compared to those on placebo.
Additionally, “Accumulating evidence indicates that you do not have to ‘load creatine,” the authors said. “Lower, daily dosages of creatine supplementation (i.e. 3-5 g/day) are effective for increasing intramuscular creatine stores, muscle accretion, and muscle performance/recovery.”
From a clinical and healthy aging perspective, ISSN also believes that creatine supplementation, combined with resistance training, is beneficial to older adults, however, more evidence from clinical trials involving frail populations and longer-term follow-ups are needed. There is therapeutic potential for “cachexia, myopathies, post-surgery rehabilitation, bed rest, other muscle/bone wasting conditions/diseases/ and brain health.”
Creatine, while predominantly used and researched for performance benefits in high-intensity interval training, might have a wider array of benefits to other types of athletic events, too. Citing trials showing that supplementation of creatine in conjunction with carbohydrates and proteins can help regulate glycogen during endurance events, and a possible role in both musculoskeletal and neurological injury prevention, should be further researched.
While females have a higher resting creatine concentration in muscle tissue, which might be linked to diminished responsiveness or performance effects in female athletes, the authors cited a number of studies in which creatine was evaluated for roles in fetal development, cognitive health, and postmenopausal muscle mass, concluding that “there is accumulating evidence that creatine supplementation has the potential to be a multifactorial therapeutic intervention across the lifespan in females, with little to no side effects.”
Lastly, the authors concluded based on existing evidence that creatine in monohydrate powder, the most popular form of creatine as a dietary supplement ingredient, is likely the most efficacious, even though other formats, such as creatine salts, creatine complexed with other nutrients, creatine dipeptides, etc. have been marketed as more effective sources.
Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at mmontemarano@rodmanmedia.com.
The authors, all members of the International Society of Sports Nutrition (ISSN) of a recent review, published in the Journal of the International Society of Sports Nutrition, analyzed the known research so far as it relates to a number of common questions and misconceptions, still being posed by researchers, or held by consumers, respectively. The studies cited for the review analyzed consumption which is well-tolerated and advised, roughly 3-5 g per day, or 0.1g/kg of body mass daily.
In short, the paper provides an evidence-based review of literature examining the effects of creatine supplementation on performance, recovery, injury prevention, exercise tolerance and rehabilitation, neuroprotection, aging, clinical and disease state populations, and pregnancy. The paper is framed by the questions on creatine’s associations with water retention, relationship with steroids, kidney damage/renal dysfunction, hair loss, dehydration/cramping, children and adolescent health, body fat, health benefits for older adults, and more.
Water Retention
On whether creatine causes water retention, ISSN states that water retention is possible within the first several days of creatine supplementation, but that based on these short-term responses, the notion that creatine increases water retention over the long-term is widely accepted.
“Creatine is an osmotically active substance. Thus, an increase in the body’s creatine content could theoretically result in increased water retention. Creatine is taken up into muscle from circulation by a sodium-dependent creatine transporter. Since the transport involves sodium, water will also be taken up into muscle to help maintain intracellular osmolality. However, considering the activity of the sodium-potassium pumps, it is not likely that intracellular sodium concentration is dramatically affected by creatine supplementation.”
Furthermore, other studies suggest creatine does not alter total body water relative to muscle mass over longer periods of time. As a result, creatine supplementation may not lead to water retention.
Kidney Function
The authors also addressed questions and concerns surrounding creatine supplementation and kidney damage/renal dysfunction.
“in terms of pervasive misinformation in the sport nutrition arena, the notion that creatine supplementation leads to kidney damage/renal dysfunction is perhaps second only to the myth that protein supplementation and high habitual protein intake causes kidney damage. Today, after > 20 years of research which demonstrates no adverse effects from recommended dosages of creatine supplements on kidney health, unfortunately, this concern persists,” the authors said.
While creatine supplementation does increase blood or urinary creatinine concentrations, there has not been evidence to date sufficient to conclude that if the kidneys are “forced” to excrete higher than normal levels of creatine or creatinine, kidney damage or renal dysfunction would take place. While one case study in 1998 involved one creatine supplement user experiencing renal dysfunction, several trials evaluating creatine supplementation and kidney function analysis failed to replicate the health effects of this case study to date.
“If the link between creatine supplementation and kidney health was valid, there would be an expected increase in kidney damage/ renal dysfunction in low risk (i.e. young, physically fit, healthy) individuals since 1992 after Harris et al. published their seminal work,” the authors said.
Hair Loss
ISSN concluded that the current body of evidence does not indicate that creatine supplementation increases total testosterone, free testosterone, or DHT, hormonal changes which would result in hair loss or baldness. Therefore, they do not suspect that there is an association between creatine and hair loss in its users. While one study, which evaluated week-long supplementation of creatine in college-aged male rugby players, found that the supplementation increased DHT concentrations by 56% over the seven-day loading period (and DHT is theorized to be linked to baldness).
However, 12 other studies investigating the effects of creatine supplementation found no significant changes to either testosterone, free testosterone, or DHT.
Dehydration and Muscle Cramping
ISSN said that questions surrounding a link between creatine and dehydration and muscle cramping likely were based on speculation, when the American College of Sports Medicine (ACSM) recommended avoiding creatine supplementation in individuals controlling their weight or exercising intensely, or in hot environments. The rationale behind the theory is that creatine is an osmotically active substance found primarily in skeletal muscle and may alter whole-body fluid distribution in the short term.
While plausible in situations of body water loss such as severe sweating, the bound intracellular fluid could in theory be detrimental to hydration, however, most evidence supporting the theory involved self-reporting in surveys, while, experimental and clinical evidence suggests no detriment. One study (Greenwood et al.) found that Division 1 baseball and football players who used creatine had significantly less cramping, heat illnesses, dehydration, muscle tightness, muscle strains, and total injuries compared to a sport drink placebo group.
“In summary, experimental and clinical research does not validate the notion that creatine supplementation causes dehydration and muscle cramping,” the authors said.
Children and Adolescents
“The overwhelming majority of evidence in adult populations indicates that creatine supplementation, both short- and longer-term, is safe and generally well tolerated,” the authors of the study said. “The physiological rationale supporting the potential ergogenic benefits of creatine supplementation in children and adolescents was first postulated by Unnithan and colleagues in 2001; which established a strong basis for future applications of creatine for younger athletes. More recently, in a comprehensive review examining the safety of creatine supplementation in adolescents, Jagim et al., summarized several studies that examined the efficacy of creatine supplementation among various adolescent athlete populations and found no evidence of adverse effects. However, it is important to note that none of the performance-focused studies included in the Jagim et al. review provided data examining specific markers of clinical health and whether or not they were impacted by the supplementation protocols.”
Additionally, based on a survey of 270 high school boys and girls in which 21% of boys and 3% of girls reported supplementing with creatine, the authors of the study suggest that its use among youth and adolescents is relatively widespread, a trend which warrants additional research to determine with greater certainty that creatine supplementation, both acute and longer-term, is safe for children and adolescents.
“In summary, based on the limited evidence, creatine supplementation appears safe and potentially beneficial for children and adolescents.
Additional Findings
The authors of the study state that, based on the existing evidence, that while creatine can possibly increase body mass, in the clinical trials where this occurs, there is no increase in body fat, but only fat-free mass. The lack of effect on body fat composition was true in both short- and long-term studies, they said, including in trials which lasted several weeks across several demographics. “Recently, Forbes et al. conducted a systematic review and meta-analysis on randomized controlled trials involving creatine supplementation in conjunction with resistance training on fat mass in older adults (>50 yrs). Nineteen studies with a total of 609 participants were also included. Participants supplementing with creatine had a greater reduction in body fat percentage. There was no significant difference in absolute fat mass loss; however the creatine group lost ~0.5 kg more fat mass compared to those on placebo.
Additionally, “Accumulating evidence indicates that you do not have to ‘load creatine,” the authors said. “Lower, daily dosages of creatine supplementation (i.e. 3-5 g/day) are effective for increasing intramuscular creatine stores, muscle accretion, and muscle performance/recovery.”
From a clinical and healthy aging perspective, ISSN also believes that creatine supplementation, combined with resistance training, is beneficial to older adults, however, more evidence from clinical trials involving frail populations and longer-term follow-ups are needed. There is therapeutic potential for “cachexia, myopathies, post-surgery rehabilitation, bed rest, other muscle/bone wasting conditions/diseases/ and brain health.”
Creatine, while predominantly used and researched for performance benefits in high-intensity interval training, might have a wider array of benefits to other types of athletic events, too. Citing trials showing that supplementation of creatine in conjunction with carbohydrates and proteins can help regulate glycogen during endurance events, and a possible role in both musculoskeletal and neurological injury prevention, should be further researched.
While females have a higher resting creatine concentration in muscle tissue, which might be linked to diminished responsiveness or performance effects in female athletes, the authors cited a number of studies in which creatine was evaluated for roles in fetal development, cognitive health, and postmenopausal muscle mass, concluding that “there is accumulating evidence that creatine supplementation has the potential to be a multifactorial therapeutic intervention across the lifespan in females, with little to no side effects.”
Lastly, the authors concluded based on existing evidence that creatine in monohydrate powder, the most popular form of creatine as a dietary supplement ingredient, is likely the most efficacious, even though other formats, such as creatine salts, creatine complexed with other nutrients, creatine dipeptides, etc. have been marketed as more effective sources.
Mike Montemarano has been the Associate Editor of Nutraceuticals World since February 2020. He can be reached at mmontemarano@rodmanmedia.com.
