madman
Super Moderator
ABSTRACT
Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults. As a follow-up, the purpose of this paper is to evaluate additional questions and misconceptions about CrM. These include but are not limited to: 1. Can CrM provide muscle benefits without exercise? 2. Does the timing of CrM really matter? 3. Does the addition of other compounds with CrM enhance its effectiveness? 4. Does CrM and caffeine oppose each other? 5. Does CrM increase the rates of muscle protein synthesis or breakdown? 6. Is CrM an anti-inflammatory intervention? 7. Can CrM increase recovery following injury, surgery, and/or immobilization? 8. Does CrM cause cancer? 9. Will CrM increase urine production? 10. Does CrM influence blood pressure? 11. Is CrM safe to consume during pregnancy? 12. Does CrM enhance performance in adolescents? 13. Does CrM adversely affect male fertility? 14. Does the brain require a higher dose of CrM than skeletal muscle? 15. Can CrM attenuate symptoms of sleep deprivation? 16. Will CrM reduce the severity of and/or improve recovery from traumatic brain injury? Similar to our 2021 paper, an international team of creatine research experts was formed to perform a narrative review of the literature regarding CrM to formulate evidence-based responses to the aforementioned misconceptions involving CrM.
2. Can CrM provide muscle benefits without exercise?
* In summary, CrM can provide some muscle performance benefits even without exercise. Populations with lower baseline creatine levels, such as vegans and vegetarians, may experience a greater response to CrM.
3. Does the timing of CrM ingestion really matter?
* In summary, the current body of evidence does not validate that the timing of CrM is critically important in relation to long-term resistance training, as both pre- and post-exercise CrM seem equally effective in promoting resistance training-mediated gains in lean tissue accretion and muscle performance. Consistent ingestion of CrM during a resistance training program is likely the most important variable to consider.
4. Does the addition of other compounds to CrM enhance its effectiveness?
* In summary, there is some evidence that the combination of CrM with other purported ergogenic compounds (i.e. carbohydrate, protein) can accelerate intramuscular creatine accumulation and potentially increase exercise-related training adaptations.
5. Does CrM and caffeine oppose each other?
* In summary, short-term CrM and caffeine ingestion (<5 mg/kg/day) likely does not cause opposing muscle effects. The long-term possible interference effects of CrM and caffeine are unknown. Consider acute caffeine intake after CrM loading for potential performance benefits. Chronic caffeine use, combined with CrM loading, does not result in greater exercise effects. This combined strategy may increase gastrointestinal distress and may indirectly interfere with performance.
6. Does CrM influence the rates of muscle protein synthesis or breakdown?
* In summary, a small body of research shows that CrM does not increase the rates of muscle protein synthesis. However, there is some existing evidence to support the anti-catabolic effects of CrM in men.
7. Is CrM an anti-inflammatory intervention?
* In summary, short-term CrM may reduce some markers of inflammation, primarily in response to aerobic-type activities. Further research is needed to determine the long-term mechanistic effects of CrM on inflammatory responses to exercise.
8. Can CrM increase recovery following injury, surgery and/or immobilization?
* In summary, mechanistic and pre-clinical data suggest that CrM has the potential to enhance recovery following injury, surgery, or immobilization. However, clinical data remain scarce and conflicting. Confounding factors include CrM protocol (short-or long-term), combination with other therapies (exercise rehabilitation), and type of condition (transitory vs. permanent injury; orthopedic vs. neuromuscular injury). Further, well-powered, randomized controlled trials should address these gaps.
9. Does CrM cause cancer?
* In summary, evidence-based research does not support that CrM (3–5 grams/day) in humans increases the formation of carcinogenic compounds or cancer risk (primary or metastasis). It is likely to be beneficial to help protect and/or recover from the skeletal muscle and body composition issues associated with cancer per se and/or the effects of chemotherapy. It is prudent to limit the intake of highly processed and/or overcooked meats/fish (i.e. BBQ) to lower the risk of gastric cancers.
10. Will CrM increase urine production?
* In summary, while CrM may result in higher fluid intake, leading to increased urine production, CrM itself does not independently drive changes in urine volume.
11. Does CrM influence blood pressure?
* In summary, there is no evidence that short-term or chronic CrM adversely affects blood pressure.
12. Is CrM safe to consume during pregnancy?
* In summary, preliminary research involving animal models suggest that CrM during pregnancy does not negatively affect the mother or offspring. However, there is currently no direct evidence available from well-designed and executed randomized controlled clinical trials on the safety and tolerability of CrM during human pregnancy.
13. Does CrM enhance performance in adolescents?
* In summary, CrM can improve measures of sports-specific activities as well as similar indices of physical performance such as power or sprint speed in adolescents. Research in female adolescent athlete populations is significantly lacking. Long-term RCT’s designed to examine changes in training adaptations in adolescent populations from CrM are needed.
14. Does CrM adversely affect male fertility?
* In summary, existing evidence does not suggest that CrM negatively impacts male fertility. In fact, preliminary findings indicate that exposure to creatine may improve human sperm motility and velocity in normospermic men under in vitro conditions.
15. Does the brain require a higher dose of CrM than skeletal muscle?
In summary, it is unclear whether the brain requires higher doses of CrM compared to skeletal muscle. It is well-established that a wide range of CrM protocols (20 grams/day with and without a maintenance dose, 3–5 grams/day) can increase skeletal muscle creatine stores. There is some evidence that different CrM dosing protocols (acute ingestion of 0.35 grams/kg; ≥20 grams/day or 0.3 grams/kg/day for at least 7 days) or lower-dose CrM (4–5 grams/day for several months) can increase brain creatine levels. However, a CrM dose and time-response relationship (if any) remains to be determined.
16. Can CrM attenuate symptoms of sleep deprivation?
* In summary, preliminary evidence suggests that CrM may have a positive effect on cognitive processing under conditions of sleep deprivation in young adults. However, there is no evidence that creatine supplementation improves cognition under conditions of adequate sleep.
17. Will CrM reduce the severity of or improve recovery from traumatic brain injury?
* In summary, the small body of research to date involving animal and patient populations suggest that CrM can potentially reduce severity of and/or improve recovery from TBI. In lieu of data from large RCT’s, for best practice, the totality of evidence suggests that CrM for individuals at high-risk of TBI, such as athletes and military personnel, is sensible.
18. Conclusions
Based on our scientific evaluation of the literature, we conclude that:
(1) CrM may provide benefits to skeletal muscle without exercise. Populations with lower baseline creatine levels, such as vegans and vegetarians, may experience a greater response to CrM.
(2) The timing of CrM does not appear to be a limiting factor on the ergogenic effects of exercise training adaptations. Consistent CrM during an exercise training program is likely the most important variable.
(3) The co-ingestion of CrM with other compounds (i.e. carbohydrates, protein) may accelerate the increase in muscle creatine levels and improve exercise performance.
(4) Short-term creatine and caffeine ingestion (<5 mg/kg/day) likely do not cause opposing effects. Consider acute caffeine intake after CrM loading for potential performance benefits. Chronic caffeine use, combined with CrM does not result in greater exercise effects. This combined strategy may increase gastrointestinal distress and may indirectly interfere with performance.
(5) CrM does not increase the rates of muscle protein synthesis. However, there is some existing evidence to support the anti-catabolic effects of CrM in men).
(6) CrM changes some inflammatory markers following long-duration aerobic type exercise.
97) CrM has the potential to enhance the recovery following injury, surgery or immobilization.
(8) Evidence-based research does not support that CrM in humans (3–5 grams/day)increases the formation of carcinogenic compounds or cancer risk (primary or metastasis). CrM is likely to be beneficial to help protect and/or recover from the skeletal muscle and body composition issues associated with cancer per se and/or the effects of chemotherapy.
(9) CrM does not increase urine production.
(10) There is no evidence that CrM adversely affects blood pressure parameters.
(11) Animal research suggests that CrM during pregnancy does not negatively impact the mother or offspring. However, there are no well-designed or executed randomized controlled clinical trials on the safety and tolerability of CrM during human pregnancy.
(12) In adolescents, CrM can improve measures of sports-specific activities in addition to improving power or sprint speed in adolescents.
(13) CrM does not negatively impact male fertility
.(14) It is unclear whether the brain requires more CrM than skeletal muscle to increase creatine levels.
(15) CrM may positively affect cognition and memory during periods of sleep deprivation in young adults, but not for those with adequate sleep.
(16) CrM has the potential to reduce the severity of and/or improve recovery from TBI
