Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review
Open accessAbstract
In 2011, we published a paper providing an overview about the bioavailability, efficacy, and regulatory status of creatine monohydrate (CrM), as well as other “novel forms” of creatine that were being marketed at the time. This paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM, and that CrM was recognized by international regulatory authorities as safe for use in dietary supplements. Moreover, that most purported “forms” of creatine that were being marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy. We also provided examples of several “forms” of creatine that were being marketed that were not bioavailable sources of creatine or less effective than CrM in comparative effectiveness trials. We had hoped that this paper would encourage supplement manufacturers to use CrM in dietary supplements given the overwhelming efficacy and safety profile. Alternatively, encourage them to conduct research to show their purported “form” of creatine was a bioavailable, effective, and safe source of creatine before making unsubstantiated claims of greater efficacy and/or safety than CrM. Unfortunately, unsupported misrepresentations about the effectiveness and safety of various “forms” of creatine have continued. The purpose of this critical review is to: (1) provide an overview of the physiochemical properties, bioavailability, and safety of CrM; (2) describe the data needed to substantiate claims that a “novel form” of creatine is a bioavailable, effective, and safe source of creatine; (3) examine whether other marketed sources of creatine are more effective sources of creatine than CrM; (4) provide an update about the regulatory status of CrM and other purported sources of creatine sold as dietary supplements; and (5) provide guidance regarding the type of research needed to validate that a purported “new form” of creatine is a bioavailable, effective and safe source of creatine for dietary supplements. Based on this analysis, we categorized forms of creatine that are being sold as dietary supplements as either having strong, some, or no evidence of bioavailability and safety. As will be seen, CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety. Additionally, CrM is the source of creatine recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.
AI snapshot
Written from the paper’s full text.
TL;DR
This critical review concludes that creatine monohydrate (CrM) remains the only creatine source with strong evidence of bioavailability, efficacy, and safety, while no marketed alternative has been shown to be superior. Other purported forms have limited or no supporting evidence and are often less bioavailable, less effective, or not regulatory-approved as dietary ingredients.
Key findings
- CrM supplementation increases muscle creatine retention by 20–40% and brain creatine by 5–15%; high-intensity exercise performance is generally increased by 10–20%, with greater effects in those starting with lower muscle creatine. CrM is nearly 100% bioavailable, and 5 g orally raises plasma creatine to about 800 µmol/L after 1 h.
- No alternative form has demonstrated greater bioavailability, efficacy, or safety than CrM. For example, creatine ethyl ester (CEE) increased serum creatinine more than two-fold and produced smaller muscle creatine increases than CrM; creatine nitrate at 1.5–3 g produced lower plasma creatine AUC than 5 g CrM; buffered CrM at recommended doses did not significantly increase muscle creatine; creatine serum contained <10 mg creatine and 69 mg creatinine per 5 mL and had no effect on plasma or muscle creatine.
- The review categorizes CrM as having strong evidence; creatine salts, magnesium creatine chelate, CEE, creatine HCl, creatine nitrate, and buffered CrM as having some evidence; and other creatine salts, creatine serum, creatyl-L-leucine, and creatinol-O-phosphate as having no evidence to support bioavailability, efficacy, and safety.
- CrM is the only creatine form listed on the FDA’s GRAS inventory and is approved for sale in major markets including Australia, Canada, China, the EU, Japan, and South Korea; creatine nitrate is FDA-approved only at 750 mg/day, below levels expected to increase muscle creatine.
Methods
- Systematic review of literature from PubMed on creatine sources in dietary supplements, food products, and beverages, covering solubility, stability, bioavailability, supplementation, and performance.
- Additional searches included patents from the USPTO, European Patent Office, Japan Patent Office, and WIPO; company websites; publicly available court documents; and regulatory agencies including FDA, TGA, Health Canada, China’s State Administration for Market Regulation, EU Commission, Japan MHLW, and Korea FDA.
- Findings were summarized with a PRISMA flow chart; no new primary data were collected.
Limitations
- The paper states that a creatine nitrate crossover study used only a 7-day washout, which may have confounded results because muscle creatine can take about 4 weeks to return to normal; it also notes that some creatine HCl studies were in non-indexed journals and had methodological issues, and that many forms lack direct data on muscle or brain creatine content.
- The review is a critical narrative synthesis rather than a meta-analysis, and it relies partly on non-peer-reviewed reports, company materials, patents, and litigation documents; these limitations are evident from the described methods and sources.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
83 of 183 cited sources checked · 46 supported · 1 flagged · accuracy not yet measured
- Premisecitation
CrM is very stable in powder form, showing no signs of degradation to creatinine over years, even at elevated temperatures.
“Creatine monohydrate is very stable in powder form, showing no signs of degradation to creatinine over years, even at elevated temperatures [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- Premisecitation
CrM is considered the gold standard to compare other purported sources of creatine because of its well-known physiochemical properties, high bioavailability, stability, low cost, and a large number of studies that have demonstrated efficacy and safety.
“Creatine monohydrate is considered the gold standard to compare other purported sources of creatine because of its well-known physiochemical properties, high bioavailability, stability, low cost, and a large number of studies that have demonstrated efficacy and safety [15,25].”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
The Bioavailability section (page unavailable) describes creatine monohydrate as the most studied form, reports near-complete absorption of creatine, and finds no evidence that other forms provide greater retention. The Safety and ISSN Position sections (pages unavailable) support its efficacy and safety. The copy does not establish low cost as a reason for treating it as the comparison standard; it also qualifies stability by noting that creatine is stable in solid form but degrades in some solutions. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
The Introduction describes creatine monohydrate (CM) as the comparator for newer forms, while the Bioavailability, Physio-chemical properties, and Summary sections support its high absorption, characterized properties, stability, and well-studied efficacy and safety. Our copy does not establish low cost as a reason for treating CM as the benchmark (pages unavailable). (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
Increased creatine levels have been reported to enhance high-intensity exercise performance and exercise training adaptations.
“The increased creatine levels have been reported to enhance high-intensity exercise performance and exercise training adaptations [14,15,24].”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [14] Kerksick, 2018, ISSN exercise & sports nutrition review update: Research & recommendations, J. Int. Soc. Sports Nutr. source
- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- cites [24] Wax, B., Kerksick, C.M., Jagim, A.R., Mayo, J.J., Lyons, B.C., and Kreider, R.B. (2021). Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations. Nutrients, 13. source
- Premisecitation
Creatine degrades to creatinine in solution at a faster rate as pH decreases and temperature increases.
“Generally, creatine degrades to creatinine in solution at a faster rate as pH decreases and temperature increases [25,52,53,54].”
Quote in the paperSubstantial claim1 of 4 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- cites [52] Howard, A.N., and Harris, R.C. (1999). Compositions Containing Creatine. (No. 5,969,544, Application No. 08/866,517), U.S. Patent.
Not checked in the free run.
- cites [53] Edgar, 1925, The equilibrium between creatine and creatinine, in aqueous solution: The effect of hydrogen ion, J. Am. Chem. Soc. source
- cites [54] Cannon, 1990, Acute phase reponse in exercise: Interaction of age and vitamin E on neutrophils and muscle enzyme release, Am. J. Physiol. source
- Premisecitation
CrM is the gold standard to compare other purported forms of creatine due to its known bioavailability, pharmacokinetics, efficacy, and safety.
“CrM is the gold standard to compare other purported forms of creatine due to its known bioavailability, pharmacokinetics, efficacy, and safety [5,14,15,25,62].”
Quote in the paperSubstantial claim5 of 5 sources checked- cites [5] Kreider, R.B., and Stout, J.R. (2021). Creatine in Health and Disease. Nutrients, 13. source
The Introduction and §4 (General Health Benefits; pages unavailable) describe creatine supplementation as well studied and effective, and §4 discusses research on its safety. However, our copy does not establish that creatine monohydrate is the gold-standard comparator for other forms or give its known bioavailability and pharmacokinetics as the reason. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [14] Kerksick, 2018, ISSN exercise & sports nutrition review update: Research & recommendations, J. Int. Soc. Sports Nutr. source
The Background section on muscle-building supplements calls creatine monohydrate the most extensively studied and clinically effective form for muscle uptake and exercise capacity, and reports its safety. This supports using it as a comparator, but the copy does not identify it as a gold standard on the basis of known pharmacokinetics. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- cites [62] Antonio, 2021, Common questions and misconceptions about creatine supplementation: What does the scientific evidence really show?, J. Int. Soc. Sports Nutr. source
- Findingcitation
There are no data showing that any other purported form of creatine is more effective in increasing tissue creatine content than CrM.
“There are no data showing that any other purported form of creatine is more effective in increasing tissue creatine content than CrM [62].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [62] Antonio, 2021, Common questions and misconceptions about creatine supplementation: What does the scientific evidence really show?, J. Int. Soc. Sports Nutr. source
- Premisecitation
CrM loading or low-dose long-term intake increases brain creatine content by 5-15%.
“and brain creatine content by 5–15% [72,73,74,75,76,77].”
Quote in the paperSubstantial claim2 of 6 sources checked- cites [72] Choi, 2009, Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation, Eur. J. Neurosci. source
The Results section reports that a 2% creatine diet increased brain creatine by about 11% in the medulla of mice, which falls within the claimed range. It also reports an increase of about 25% in the cerebellum and no significant increase in the cortex, so this source does not support 5–15% as a general brain-wide range or establish the claim for loading or low-dose intake. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [73] Lyoo, 2003, Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate, Psychiatry Res. source
- cites [74] Roschel, H., Gualano, B., Ostojic, S.M., and Rawson, E.S. (2021). Creatine Supplementation and Brain Health. Nutrients, 13. source
Section 2 reports that nine of twelve studies found significant increases in brain creatine, averaging about 5–10%, rather than establishing a 5–15% range. It also says the optimal supplementation strategy is unclear and does not establish that either loading or low-dose long-term intake reliably produces that increase. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [75] Dolan, 2019, Beyond muscle: The effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury, Eur. J. Sport Sci. source
- cites [76] Gualano, 2016, Creatine supplementation in the aging population: Effects on skeletal muscle, bone and brain, Amino Acids source
- cites [77] Rawson, 2011, Use of creatine in the elderly and evidence for effects on cognitive function in young and old, Amino Acids source
- Premisecitation
The 2011 paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM.
“This paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- Premisecitation
CrM is the most effective ergogenic nutrient currently available to athletes in terms of increasing high-intensity exercise capacity and lean body mass during training.
“the ISSN concluded that CrM is the most effective ergogenic nutrient currently available to athletes in terms of increasing high-intensity exercise capacity and lean body mass during training [8,15].”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [8] Buford, 2007, International Society of Sports Nutrition position stand: Creatine supplementation and exercise, J. Int. Soc. Sports Nutr. source
- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- Premisecitation
Galvan and coworkers found no adverse effects after 28 days of creatine nitrate supplementation (3 g/day).
“Galvan and coworkers [29] also found no adverse effects after 28 days of supplementation (3 g/day).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] Galvan, 2016, Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance, J. Int. Soc. Sports Nutr. source
The Study 2 Results report no significant treatment-related differences in side effects or blood safety markers over 28 days, but participants did report minimal side effects. The Supplementation protocol also specifies that the 3 g/day creatine nitrate dose began on day 8; the high-dose group received 12 g/day during the first seven days. Thus, neither ‘no adverse effects’ nor 3 g/day throughout the 28 days accurately describes the study. (LLM, conf=0.90)
Experimental — accuracy not yet measured
- Interpretationcitation
The clinically significant increase in creatinine levels observed with CEE should raise concerns about potential safety of CEE.
“the clinically significant increase in creatinine levels observed should raise some concerns about potential safety of CEE as has reported two case studies [195,196].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [195] Law, 2019, Elevation of serum creatinine in a renal transplant patient following oral creatine supplementation, Clin. Kidney J. source
The Case Report documents a substantial rise in serum creatinine after the patient switched to CEE. But the Abstract and Discussion explain that CEE can elevate measured creatinine without impairing kidney function; investigations found no allograft damage. The paper supports concern about interpreting the test result, not a conclusion that the rise indicates a safety risk from CEE. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [196] Velema, 2011, Elevated plasma creatinine due to creatine ethyl ester use, Neth. J. Med.
- Premisecitation
Jagim and colleagues found that neither recommended doses of CrM-Alk nor loading and maintenance equivalent doses of CrM-Alk to CrM promoted greater changes in muscle creatine content, body composition, strength, or anaerobic capacity than creatine monohydrate.
“Results revealed that neither recommended doses of CrM-Alk or loading and maintenance equivalent doses of CrM-Alk to CrM promoted greater changes in muscle creatine content, body composition, strength, or anaerobic capacity than CrM (see Figure 13).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] Jagim, 2012, A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate, J. Int. Soc. Sports Nutr. source
- Findingcitation
CEE supplementation did not promote greater changes in body composition, strength, or anaerobic power during training compared to CrM supplementation.
“CEE supplementation did not promote greater changes in body composition, strength, or anaerobic power during training compared to CrM supplementation.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] Spillane, 2009, The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels, J. Int. Soc. Sports Nutr. source
- Premisecitation
Joy and colleagues reported that 28 days of creatine nitrate supplementation (1 and 2 g/day) during training had no adverse effects on clinical blood chemistries compared to a non-supplemented group.
“Joy and colleagues [212] reported that 28 days of CrN supplementation (1 and 2 g/day) during training had no adverse effects on clinical blood chemistries compared to a non-supplemented group.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [212] Joy, 2014, 28 days of creatine nitrate supplementation is apparently safe in healthy individuals, J. Int. Soc. Sports Nutr. source
The Methods (Experimental design; page not provided) describe 1 and 2 g/day creatine nitrate groups and an unsupplemented control over 28 days. The Abstract (Conclusion; page not provided) says the measured safety markers generally remained within normal range, but notes that BUN could rise beyond that range in participants with previously elevated levels. The Methods (Participants; page not provided) require participants to be recreationally active; they do not describe a training intervention during supplementation. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
Dalton and colleagues reported that ingesting 3 and 6 g/day of creatine nitrate for 5 days significantly improved some measures of strength and muscle endurance compared to placebo.
“Dalton and colleagues [36] reported that ingesting 3 and 6 g/day of CrN for 5 days significantly improved some measures of strength and muscle endurance compared to placebo.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [36] Dalton, R.L., Sowinski, R.J., Grubic, T.J., Collins, P.B., Coletta, A.M., Reyes, A.G., Sanchez, B., Koozehchian, M., Jung, Y.P., and Rasmussen, C. (2017). Hematological and Hemodynamic Responses to Acute and Short-Term Creatine Nitrate Supplementation. Nutrients, 9. source
The Results (§4.3) report improvements after five days in some strength and endurance measures with creatine nitrate. But they report no significant treatment-by-time effects for those measures, and the observed leg-press endurance increase was not different among treatments. The claim overstates the evidence by saying both doses significantly improved those measures compared with placebo. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Jagim and colleagues found that muscle creatine content was not significantly increased after 7 or 28 days of CrM-Alk supplementation at recommended doses.
“In fact, muscle creatine content was not significantly increased after 7 or 28 days of supplementation at recommended doses (−6.4 ± 37.8; 13.7 ± 42.2 %, respectively).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] Jagim, 2012, A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate, J. Int. Soc. Sports Nutr. source
- Premisecitation
Galvan and colleagues found that nitrate AUCs in the creatine nitrate groups were significantly greater than placebo and creatine monohydrate in a dose-related manner.
“Conversely, the nitrate AUCs in the CrN groups were significantly greater than the placebo and CrM treatments in a dose related manner.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] Galvan, 2016, Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance, J. Int. Soc. Sports Nutr. source
In Results, Study 1: acute supplementation (page not provided), plasma nitrate AUC was significantly greater than placebo and creatine monohydrate for CrN-High. CrN-Low showed only a trend and was not significantly different from either comparator, so the claim overstates the finding for the CrN groups as a whole. (LLM, conf=0.93)
Experimental — accuracy not yet measured
- Premisecitation
A toxicology study found that CLL did not cause mortality, toxic effects, or adverse effects in rats administered CLL for 90 days by oral gavage at doses of 1250, 2500, and 5000 mg/kg/day.
“This study found that CLL did not cause mortality, toxic effects, or adverse effects in rats administered CLL for 90-days by oral gavage at doses of 1250, 2500, and 5000 mg/kg/day.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [220] Reddeman, 2018, A Toxicological Assessment of Creatyl-l-Leucine, Int. J. Toxicol. source
- Premisecitation
Rats fed CLL did not increase blood, muscle, and brain creatine content above rats fed a control diet.
“Additionally, rats fed CLL did not increase blood, muscle, and brain creatine content above rats fed a control diet.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [221] da Silva, R.P. (2022). The Dietary Supplement Creatyl-l-Leucine Does Not Bioaccumulate in Muscle, Brain or Plasma and Is Not a Significant Bioavailable Source of Creatine. Nutrients, 14. source
- Premisecitation
Some improvement in exercise performance was reported with acute and 8-week supplementation of a pre-workout supplement containing 2 g/day of creatine nitrate.
“Some improvement in exercise performance was also reported with acute [210] and 8-weeks [211] supplementation of a pre-workout supplement containing 2 g/day of CrN.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [210] Jung, 2017, Effects of acute ingestion of a pre-workout dietary supplement with and without p-synephrine on resting energy expenditure, cognitive function and exercise performance, J. Int. Soc. Sports Nutr. source
The Methods (Testing sequence; page unavailable) describe acute testing of a pre-workout supplement containing 2 g of creatine nitrate. The Results (Performance assessment; page unavailable) report only a trend toward greater bench-press volume with the p-synephrine formulation, and the Discussion says there was no clear ergogenic benefit or statistically significant performance improvement. This citation is attached to the acute claim; the separate 8-week claim is cited to another source. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [211] Jung, 2017, Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males, J. Int. Soc. Sports Nutr. source
- Findingcitation
CEE significantly increased serum creatinine levels by more than two-fold after 6, 27, and 48 days of supplementation compared to the placebo and CrM groups.
“CEE significantly increased serum creatinine levels by more than two-fold after 6, 27, and 48 days of supplementation in comparison to the placebo and CrM groups (Figure 10B).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] Spillane, 2009, The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels, J. Int. Soc. Sports Nutr. source
The Results (Serum creatinine; page not provided) report higher creatinine in the CEE group than in the placebo and creatine monohydrate groups, and significant elevations within CEE at days 6, 27, and 48. The Discussion (Serum Creatinine; page not provided) specifies significant between-group increases at days 6 and 48 and an approximately three-fold rise after loading. It does not establish a more-than-two-fold increase or a significant between-group difference at day 27. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Findingcitation
CrM supplementation promotes greater training adaptations.
“CrM supplementation increases muscle phosphagen levels, improves repetitive high-intensity exercise performance, and promotes greater training adaptations [15].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- Premisecitation
Several of these NDI notifications were initially objected to by the FDA citing that the form of creatine may not be a legal dietary ingredient, inadequate safety information, and/or a lack of information about the chemical identity of the creatine form.
“Several of these notifications were initially objected to by the FDA citing: (1) the form of creatine may not be a legal dietary ingredient as defined by the FD&C Act §201(ff); (2) inadequate safety information to conclude that the form of creatine is reasonably expected to be safe; and/or (3) a lack of information about the chemical identity of the creatine form [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- Premisecitation
The regulatory status of CrM is unequivocal in the global markets as a dietary or food supplement.
“The regulatory status of CrM is unequivocal in the global markets as a dietary or food supplement [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- Interpretationcitation
As of this writing, creatine monohydrate is the only form of creatine that is listed on the FDA's inventory of GRAS notices.
“As of this writing, CrM is the only form of creatine that is listed on the FDA’s inventory of GRAS notices [239] (see Table 5).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [239] Dwyer, J.T., Coates, P.M., and Smith, M.J. (2018). Dietary Supplements: Regulatory Challenges and Research Resources. Nutrients, 10. source
Section 2.2 discusses FDA regulation of dietary supplements and new dietary ingredient notifications, but not the FDA’s inventory of GRAS notices. Searches for creatine, creatine monohydrate, and GRAS found no passage addressing whether creatine monohydrate is the only creatine form listed. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Findingcitation
CrM supplementation increases muscle phosphagen levels.
“CrM supplementation increases muscle phosphagen levels, improves repetitive high-intensity exercise performance, and promotes greater training adaptations [15].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- Findingcitation
CrM supplementation improves repetitive high-intensity exercise performance.
“CrM supplementation increases muscle phosphagen levels, improves repetitive high-intensity exercise performance, and promotes greater training adaptations [15].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- Findingreasoning
Different creatine-related compounds shown in Table 1 contain less creatine by molecular weight than CrM, assuming a full creatine molecule is contained and liberated as creatine in circulation.
“different creatine-related compounds shown in Table 1 contain less creatine by molecular weight than CrM, assuming that a full creatine molecule is contained in the compound and would be liberated as creatine in circulation.”
Quote in the paperSubstantial claim- The authors state this as an assumption: A full creatine molecule is contained in each creatine-related compound and would be liberated as creatine in circulation.
- Findingnone given
Creatine citrate (CC) contains 53.9% less creatine by molecular weight than CrM.
“creatine citrate (CC) contains 53.9% less creatine by molecular weight than CrM.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: A full creatine molecule is contained in each creatine-related compound and would be liberated as creatine in circulation.
- Findingreasoning
There is no evidence that CPY is more effective than CrM in increasing muscle creatine content and/or performance.
“there is no evidence that CPY is more effective than CrM in increasing muscle creatine content and/or performance.”
Quote in the paperSubstantial claim - Findingnone given
Creatine ethyl ester (CEE) has only 6.3% less creatine by molecular weight than CrM.
“Creatine ethyl ester (CEE) has only 6.3% less creatine by molecular weight than CrM.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: A full creatine molecule is contained in each creatine-related compound and would be liberated as creatine in circulation.
- Findingown data
Analysis of the structure of creatyl-L-leucine indicates that CLL does not contain a creatine molecule.
“Analysis of the structure of CLL (see Figure 15) indicates that CLL does not contain a creatine molecule.”
Quote in the paperSubstantial claim - Findingcitation
Available studies suggest that orally ingested CEE is converted to creatine in vivo less efficiently than proponents have assumed.
“While proponents of CEE have assumed that all orally ingested CEE is converted to creatine in vivo, available studies suggest it is less efficient.”
Quote in the paperSubstantial claim - Findingcitation
Ingestion of 3 g/day of Cr-HCl did not promote greater gains in performance or hormonal responses than 3 or 20 g/day of CrM.
“Results revealed that ingestion of 3 g/day of Cr-HCl did not promote greater gains in performance or hormonal responses than 3 or 20 g/day of CrM as claimed.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [202] Tayebi, 2020, Is creatine hydrochloride better than creatine monohydrate for the improvement of physical performance and hormonal changes in young trained men?, Sci. Sports source
- Findingreasoning
The creatine content based on molecular weight in the dosages used was 35.1 g in the Cr-HCl group compared to 131.9 g in the CrM group over the 30-day period.
“given the creatine content based on molecular weight in these dosages was 35.1 g in the Cr-HCl group compared to 131.9 g in the CrM group over the 30-day period.”
Quote in the paperSubstantial claim - Findingnone given
Some forms of creatine have clearly rearranged the creatine molecule.
“Some have clearly rearranged the creatine molecule.”
Quote in the paperSubstantial claim - Findingnone given
CrM is approved for use with accompanying health claims in the EU.
“CrM remains the only source of creatine that has substantial evidence of bioavailability, efficacy and safety and is considered GRAS by the U.S. FDA, is approved for use with accompanying health claims in the EU, has been extensively reviewed and approved by Health Canada, and is approved to be sold in major global markets.”
Quote in the paperNot a substantial claim - Findingnone given
Most of the forms of creatine listed in Table 1 have been chemically altered in some way (e.g., covalently binding or complexing) to the creatine molecule.
“Most of the forms of creatine listed in Table 1 have been chemically altered in some way (e.g., covalently binding or complexing) to the creatine molecule.”
Quote in the paperSubstantial claim - Findingreasoning
CrM is the only source of creatine with strong/substantial evidence of bioavailability, efficacy, and safety.
“Pure CrM is the only source of creatine with strong evidence of bioavailability, efficacy, and safety and considered as GRAS by the FDA, approved for use in the EU and Australia, and evaluated for safety by Health Canada.”
- Also stated in: § 12. Summary · boosted
“CrM remains the only source of creatine that has substantial evidence of bioavailability, efficacy and safety and is considered GRAS by the U.S. FDA, is approved for use with accompanying health claims in the EU, has been extensively reviewed and approved by Health Canada, and is approved to be sold in major global markets.”
Quote in the paperSubstantial claim - Also stated in: § 12. Summary · boosted
- Findingnone given
Only nine of the newer forms of creatine are listed in the IND notification inventory.
“Yet, as described above, only nine of these newer forms are listed in the IND notification inventory.”
Quote in the paperSubstantial claim - Findingreasoning
CrM remains the only source of creatine that is approved for sale in Australia, Canada, China, the European Union, Japan, and South Korea.
“As can be seen, CrM remains the only source of creatine that is approved for sale in Australia, Canada, China, the European Union, Japan, and South Korea.”
Quote in the paperNot a substantial claim - Findingnone given
Based on a press release, we identified one self-affirmed GRAS affirmation for a creatine chelated with Mg (Creatine MagnaPower®).
“Based on a press release, we identified one self-affirmed GRAS affirmation for a creatine chelated with Mg (Creatine MagnaPower®).”
Quote in the paperNot a substantial claim - Findingnone given
Some other forms of creatine marketed as ingredients for dietary supplements are not permitted to be included in dietary supplements in their country due to a lack of safety data.
“Some of the other forms of creatine marketed as ingredients for dietary supplements are not permitted to be included in dietary supplements in their country due to a lack of safety data.”
Quote in the paperSubstantial claim - Findingnone given
CrM is the only source of creatine that has approved health claims in the European Union, Canada, Japan, and South Korea.
“Additionally, it is the only source of creatine that has approved health claims in the European Union, Canada, Japan, and South Korea.”
Quote in the paperNot a substantial claim - Findingreasoning
Many alternative forms of creatine have little to no data supporting bioavailability and/or efficacy despite making bold claims that the source is more bioavailable, effective, and/or safer than CrM.
“Even then, many have little to no data supporting bioavailability and/or efficacy despite making bold claims that the source is more bioavailable, effective, and/or a safer form of creatine than CrM.”
Quote in the paperSubstantial claim - Findingnone given
No significant side effects other than weight gain have been reported from CrM supplementation despite widespread use throughout the world.
“No significant side effects other than weight gain have been reported from CrM supplementation despite widespread use throughout the world.”
Quote in the paperNot a substantial claim - Findingnone given
CrM is considered GRAS by the U.S. FDA.
“Pure CrM is the only source of creatine with strong evidence of bioavailability, efficacy, and safety and considered as GRAS by the FDA, approved for use in the EU and Australia, and evaluated for safety by Health Canada.”
- Also stated in: § 12. Summary · plain
“CrM remains the only source of creatine that has substantial evidence of bioavailability, efficacy and safety and is considered GRAS by the U.S. FDA, is approved for use with accompanying health claims in the EU, has been extensively reviewed and approved by Health Canada, and is approved to be sold in major global markets.”
Quote in the paperSubstantial claim - Also stated in: § 12. Summary · plain
- Findingreasoning
CrM is approved to be sold in major global markets.
“CrM remains the only source of creatine that has substantial evidence of bioavailability, efficacy and safety and is considered GRAS by the U.S. FDA, is approved for use with accompanying health claims in the EU, has been extensively reviewed and approved by Health Canada, and is approved to be sold in major global markets.”
Quote in the paperSubstantial claim - Findingnone given
CrM has been evaluated for safety by Health Canada.
“Pure CrM is the only source of creatine with strong evidence of bioavailability, efficacy, and safety and considered as GRAS by the FDA, approved for use in the EU and Australia, and evaluated for safety by Health Canada.”
Quote in the paperNot a substantial claim - Premisecitation
CC and CPY had less permeability than CrM across caco-2 monolayers, a model used to assess intestinal absorption.
“Gufford et al. [179] reported that CC and CPY had less permeability than CrM across caco-2 monolayers cells, which is used as a model to assess intestinal absorption.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [179] Gufford, 2010, Physicochemical characterization of creatine N-methylguanidinium salts, J. Diet. Suppl. source
- Interpretationreasoning
It would take a greater amount of most other creatine-related sources to provide equivalent amounts of creatine delivered from CrM if those other sources were bioavailable.
“Consequently, it would take a greater amount of most of these sources of creatine in a dietary supplement to provide equivalent amounts of creatine delivered from CrM if the other sources were indeed bioavailable.”
Quote in the paperSubstantial claim- The authors state this as an assumption: A full creatine molecule is contained in each creatine-related compound and would be liberated as creatine in circulation.
- The authors state this as an assumption: The other creatine-related sources would be bioavailable.
- Interpretationreasoning
Claims that a given form of creatine is more effectively absorbed than CrM because it is more soluble in water are unsupported.
“Therefore, claims that a given form of creatine is more effectively absorbed than CrM because it is more soluble in water is unsupported marketing hyperbole.”
Quote in the paperSubstantial claim - Premisecitation
Ingesting 3 g/day of CrM for 35 days resulted in a gradual 16.7% increase in muscle creatine content.
“(3) ingesting 3 g/day of CrM for 35 days (i.e., low dose supplementation strategy) resulted in a gradual 16.7% increase in muscle creatine content.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Hultman, 1996, Muscle creatine loading in men, J. Appl. Physiol. source
- Interpretationreasoning
Creatine salts would have less stability than CrM in solution because adding acid to creatine decreases pH to ranges that promote greater formation of creatinine over time.
“However, creatine salts would also have less stability than CrM in solution since adding the acid to creatine decreases pH to ranges that would promote greater formation of creatine to creatinine in solution over time.”
Quote in the paperSubstantial claim - Premisecitation
CrM supplementation (e.g., 5 g/day for 5-7 days or 3-5 g/day for 30 days) increases blood, muscle, and tissue levels of creatine and PCr by 20-40%.
“Over the last 30 years, several studies have shown that CrM supplementation (e.g., 5 g/day for 5–7 days or 3–5 g/day for 30 days) increases blood, muscle, and tissue levels of creatine and PCr by 20–40% [11,12,19,20].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [11] Hultman, 1996, Muscle creatine loading in men, J. Appl. Physiol. source
- cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
- cites [19] Casey, 1996, Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans, Am. J. Physiol. source
- cites [20] Green, 1996, Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans, Am. J. Physiol. source
- Interpretationcitation
Provision of equimolar amounts of CC and CPY can serve as a bioavailable source of creatine.
“Results support contentions that provision of equimolar amounts of CC and CPY can serve as a bioavailable source of creatine.”
Quote in the paperSubstantial claim - Interpretationreasoning
CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety.
“As will be seen, CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety.”
Quote in the paperSubstantial claim - Interpretationreasoning
Purported forms of creatine that do not increase blood creatine concentrations, do not increase uptake of creatine through tissue-specific creatine transporters, and ultimately do not increase tissue creatine levels by physiologically meaningful amounts would not affect creatine-related metabolic function.
“Purported forms of creatine that do not increase blood creatine concentrations, do not increase uptake of creatine through tissue-specific creatine transporters, and ultimately do not increase tissue creatine levels by physiologically meaningful amounts would not affect creatine-related metabolic function.”
Quote in the paperSubstantial claim - Interpretationreasoning
It is unlikely that the small differences in blood creatine levels observed with CC and CPY would promote greater creatine retention and/or a bioenergetic advantage.
“However, it is unlikely that the small differences in blood creatine levels observed would promote greater creatine retention and/or a bioenergetic advantage.”
Quote in the paperSubstantial claim - Premisecitation
CrM loading or low-dose long-term intake increases muscle creatine retention typically by 20-40% depending on initial muscle creatine content.
“Prior studies indicate that CrM loading (i.e., 4 × 5 g/day for 5–7 days) or low-dose long-term intake (e.g., 3–6 g/day for 4–12 weeks) increases muscle creatine retention typically by 20–40% depending on initial creatine content in the muscle [12,22,68,69,70,71]”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
- cites [22] Greenwood, 2003, Differences in creatine retention among three nutritional formulations of oral creatine supplements, J. Exerc. Physiol. Online
Not checked in the free run.
- cites [68] Nelson, 2001, Muscle glycogen supercompensation is enhanced by prior creatine supplementation, Med. Sci. Sports Exerc. source
- cites [69] Tarnopolsky, 1999, Direct measurement of high-energy phosphate compounds in patients with neuromuscular disease, Muscle Nerve source
- cites [70] McKenna, 1999, Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance, J. Appl. Physiol. source
- cites [71] Greenhaff, 1994, Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis, Am. J. Physiol. source
- Premisecitation
Both 2.5 g CrM in solution and 408 g lightly cooked steak containing 5.4 g creatine resulted in similar increases in area under the curve (AUC) values (507 ± 205 and 518 ± 153 μmol/h/L, respectively).
“Nevertheless, both strategies resulted in similar increases in area under the curve (AUC) values (507 ± 205 and 518 ± 153 µmol/h/L, respectively).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] Harris, 2002, Absorption of creatine supplied as a drink, in meat or in solid form, J. Sports Sci. source
- Premisecitation
Oral ingestion of CrM is nearly 100% bioavailable (i.e., it's either absorbed by tissue or excreted in urine).
“Since oral ingestion of CrM is nearly 100% bioavailable (i.e., it’s either absorbed by tissue or excreted in urine), whole-body creatine retention with CrM supplementation can also be estimated as the difference between daily intake of CrM and urinary creatine output [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Greenwood, 2003, Differences in creatine retention among three nutritional formulations of oral creatine supplements, J. Exerc. Physiol. Online
Not checked in the free run.
- Interpretationreasoning
Purported sources of creatine that do not deliver similar increases in muscle creatine content than equivalent doses of CrM are less bioavailable sources of creatine than CrM.
“Purported sources of creatine that do not deliver similar increases in muscle creatine content than equivalent doses of CrM are less bioavailable sources of creatine than CrM.”
Quote in the paperSubstantial claim - Interpretationreasoning
A supplement would need to provide 9.3 g of CC to equal a typical supplementation dose of 5 g of CrM if CC had similar bioavailability.
“Therefore, a supplement would need to provide 9.3 g of CC to equal a typical supplementation dose of 5 g of CrM if it had similar bioavailability.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: A full creatine molecule is contained in each creatine-related compound and would be liberated as creatine in circulation.
- The authors state this as an assumption: Creatine citrate would have similar bioavailability to CrM.
- Interpretationreasoning
An increase in plasma creatine alone does not provide definitive proof that a purported source of creatine is bioavailable or effective.
“However, an increase in plasma creatine alone does not provide definitive proof that a purported source of creatine is bioavailable or effective.”
Quote in the paperSubstantial claim - Interpretationreasoning
None of the creatine-containing compounds with some evidence supporting bioavailability, efficacy, and/or safety have been shown to promote greater creatine retention in muscle than creatine monohydrate.
“As described above, while some effects were observed compared to placebo ingestion and in some instances have comparable effects on performance as CrM, none of these forms have been shown to promote greater creatine retention in muscle than CrM.”
Quote in the paperSubstantial claim - Interpretationreasoning
There is some evidence showing creatine nitrate may serve as a bioavailable and effective source of creatine.
“Based on this analysis, there is some evidence showing CrN may serve as a bioavailable and effective source of creatine.”
Quote in the paperSubstantial claim - Interpretationnone given
We are not aware of any study that has evaluated whether oral creatinol-O-phosphate has any effect on muscle creatine levels or exercise performance.
“We are also not aware of any study that has evaluated whether oral COP has any effect on muscle creatine levels or exercise performance.”
Quote in the paperNot a substantial claim - Interpretationcitation
Results are conflicting on whether short- or long-term creatine nitrate supplementation (3 g/day) significantly increases muscle creatine levels.
“Nevertheless, results are conflicting on whether short- or long-term CrN supplementation (3 g/day) significantly increase muscle creatine levels.”
Quote in the paperSubstantial claim - Premisenone given
As of this writing, only two published articles have assessed the safety and/or efficacy of CLL.
“As of this writing, only two published articles have assessed the safety and/or efficacy of CLL.”
Quote in the paperSubstantial claim - Premisecitation
Creatine serum ingestion at recommended and equivalent doses had no effects on muscle free creatine, phosphocreatine, total creatine content, or ATP concentrations.
“However, CS ingestion at recommended and equivalent doses had no effects on muscle free creatine, phosphocreatine, total creatine content, or ATP concentrations.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Kreider, 2003, Effects of serum creatine supplementation on muscle creatine content, J. Exerc. Physiol. Online
Not checked in the free run.
- Interpretationreasoning
Little to no data are available on several other creatine salts listed in Table 1.
“While there is some bioavailability, efficacy, and safety data on CC and CPY, little to no data are available on several other creatine salts listed in Table 1.”
Quote in the paperSubstantial claim - Interpretationnone given
There is limited data available on creatine nitrate bioavailability.
“In terms of bioavailability, there is limited data available.”
Quote in the paperNot a substantial claim - Premisereasoning
Ingesting 1 g of creatine nitrate would theoretically provide 0.675 g of creatine and 0.325 g of nitrate.
“Therefore, ingesting 1 g of CrN would theoretically provide 0.675 g of creatine and 0.325 g of nitrate.”
Quote in the paperNot a substantial claim - Interpretationreasoning
There is no evidence that oral creatinol-O-phosphate ingestion has any effect on muscle creatine content or creatine-related metabolism.
“There is no evidence that oral COP ingestion has any effect on muscle creatine content or creatine-related metabolism.”
Quote in the paperSubstantial claim - Premisecitation
Jung and associates reported no adverse effects of participants consuming a pre-workout supplement containing 2 g/day of creatine nitrate for 8 weeks.
“Finally, Jung and associates reported no adverse effects of participants consuming a pre-workout supplement containing 2 g/day of CrN for 8 weeks.”
Quote in the paperSubstantial claim - Interpretationnone given
The FDA-approved 750 mg/day level of creatine nitrate is below any meaningful level expected to increase muscular creatine levels and performance.
“However, CrN has only been approved as a dietary supplement by the U.S. FDA at levels of 750 mg per day, which is below any meaningful level expected to increase muscular creatine levels and performance.”
Quote in the paperSubstantial claim - Premisenone given
By molecular weight, creatine nitrate contains 67.5% creatine.
“By molecular weight, CrN contains 67.5% creatine.”
Quote in the paperNot a substantial claim - Premisecitation
Researchers found that creatine serum contained <10 mg of creatine and 69 mg of creatinine per 5 mL dose in multiple samples and lot numbers.
“However, when researchers evaluated the creatine content of CS, they found that CS contained <10 mg of creatine and 69 mg of creatinine per 5 mL dose in multiple samples and lot numbers [38].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] Harris, 2004, The creatine content of Creatine Serum and the change in the plasma concentration with ingestion of a single dose, J. Sports Sci. source
- Interpretationreasoning
CLL is listed in the no-evidence category.
“Therefore, CLL is listed in the no evidence category.”
Quote in the paperSubstantial claim - Interpretationreasoning
It is unclear whether the strength and muscle endurance changes reported by Dalton and colleagues were primarily due to creatine and/or nitrate.
“However, it is unclear whether these changes were primarily due to creatine and/or nitrate.”
Quote in the paperNot a substantial claim - Interpretationreasoning
For CEE to act like creatine it would have to be de-ethylated and an H+ added back to the NH of the molecule at nearly 100% efficiency to deliver 94% of an equivalent CrM dose.
“For CEE to act like creatine it would have to be de-ethylated and an H+ added back to the NH of the molecule at nearly 100% efficiency to deliver 94% of an equivalent CrM dose.”
Quote in the paperNot a substantial claim - Interpretationcitation
As of this writing, we are aware of no data showing bioavailability and/or efficacy of creatine orotate supplementation.
“However, as of this writing, we are aware of no data showing bioavailability and/or efficacy of CO supplementation [216].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [216] (2022, January 05). Creatine Orotate. Available online: https://www.exercise.com/supplements/creatine-orotate/.
Not checked in the free run.
- Interpretationcitation
Creatine nitrate appears to be safe when taken in the amounts and timeframes studied.
“Thus, CrN appears to be safe when taken in these amounts and timeframes.”
Quote in the paperSubstantial claim - Interpretationreasoning
The non-peer-reviewed report does not validate claims that buffered creatine monohydrate is a more bioavailable, efficacious, or safer form of creatine than creatine monohydrate.
“Thus, the report does not validate claims than CrM-Alk supplementation is a more bioavailable, efficacious, or safer form of creatine than CrM.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [215] Affouras, A., Vodenicharova, K., Shishmanova, D., Goranov, K., and Stroychev, K. (2006). Clinical Trial Comparing Kre-Alkalyn to Creatine Monohydrate, Medical Center.
Not checked in the free run.
- Premisecitation
Cr-HCl does not appear to be a more effective source of creatine than CrM.
“The authors concluded that Cr-HCl does not appear to be a more effective source of creatine than CrM.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [202] Tayebi, 2020, Is creatine hydrochloride better than creatine monohydrate for the improvement of physical performance and hormonal changes in young trained men?, Sci. Sports source
- Premisecitation
Creatinol-O-phosphate was initially studied in the 1970s to intravenously deliver phosphate to improve myocardial function and reduce arrhythmias during ischemic conditions.
“Rather, it was initially studied in the 1970s to intravenously deliver phosphate to improve myocardial function and reduce arrhythmias during ischemic conditions [227,228,229,230].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [227] Guglielmi, 1979, A controlled clinical study of the use of creatinol-O-phosphate in subjects with deficient myocardial circulation, Clin. Ter.
- cites [228] Melloni, 1979, Acute clinical tolerance of creatinol-O-phosphate, Arzneimittelforschung
Not checked in the free run.
- cites [229] Godfraind, T., Ghiradi, P., Ferrari, G., and Cassagrande, C. (1983). Creatinol-O-Phopshate Having Therapeutical Action. (No. 4,376,117, Application No. 198,263), U.S. Patent.
Not checked in the free run.
- cites [230] Marzo, 1979, Pharmacological and toxicological properties of creatinol O-phosphate. A review, Arzneimittelforschung
- Premisenone given
Creatine nitrate has only been approved as a dietary supplement by the U.S. FDA at levels of 750 mg per day.
“However, CrN has only been approved as a dietary supplement by the U.S. FDA at levels of 750 mg per day, which is below any meaningful level expected to increase muscular creatine levels and performance.”
Quote in the paperNot a substantial claim - Interpretationreasoning
MgCr-C is listed in the some evidence to support bioavailability, efficacy, and safety category.
“For this reason, MgCr-C is listed in some evidence to support bioavailability, efficacy, and safety category.”
Quote in the paperSubstantial claim - Premisecitation
The European Food and Safety Authority has expressed concerns about the potential cancerogenic effects of orotic acid.
“The European Food and Safety Authority has also expressed concerns about the potential cancerogenic effects of orotic acid [176,177].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [176] Andres, 2017, Creatine and creatine forms intended for sports nutrition, Mol. Nutr. Food Res. source
- cites [177] European Food Safety Authority (2009). Orotic Acid Salts as Sources of Orotic Acid and Various Minerals Added for Nutritional Purposes to Food Supplements, Scientific Opinion of the Panel on Food Additives and Nutrient Sources Added to Food (ANS). EFSA J., 7, 1187. source
- Interpretationreasoning
Creatine monohydrate is considered GRAS for inclusion as a dietary ingredient in dietary supplements, energy drinks, protein bars and powders, milkshakes, meal replacement powders and bars, meat replacement products, powdered drink mixes, and functional foods.
“Consequently, CrM is considered GRAS for inclusion as a dietary ingredient in dietary supplements, energy drinks, protein bars and powders, milkshakes, meal replacement powders and bars, meat replacement products, powdered drink mixes, and functional foods.”
Quote in the paperSubstantial claim - Interpretationreasoning
Misleading claims that lower doses of an alternate form of creatine are as effective as CrM may limit the benefits consumers may achieve from creatine supplementation.
“Additionally, misleading claims that lower doses of an alternate form of creatine are as effective as CrM may limit the benefits consumers may achieve from creatine supplementation.”
Quote in the paperSubstantial claim - Interpretationnone given
The scientific basis and regulatory status of other forms of creatine continues to be less clear.
“However, the scientific basis and regulatory status of other forms of creatine continues to be less clear.”
Quote in the paperSubstantial claim - Interpretationnone given
The AHPA NDIN database does not include notifications for creatine maleate, creatine fumarate, creatine tartrate, creatine ascorbate, creatine citrate, magnesium creatine chelate, creatine HCL, alkaline creatine, creatine serum, CLL, or COP.
“The AHPA NDIN database does not include notifications for creatine maleate, creatine fumarate, creatine tartrate, creatine ascorbate, creatine citrate, magnesium creatine chelate, creatine HCL, alkaline creatine (although it is a buffered form of CrM), creatine serum, CLL, or COP.”
Quote in the paperNot a substantial claim - Interpretationreasoning
CrM remains the gold standard to compare other forms of creatine with the strongest bioavailability, efficacy, and safety portfolios.
“Consequently, despite marketing hyperbole, CrM remains the gold standard to compare other forms of creatine with the strongest bioavailability, efficacy, and safety portfolios.”
Quote in the paperSubstantial claim - Interpretationreasoning
The legal status of other purported sources of creatine is less clear.
“The legal status of other purported sources of creatine is less clear.”
Quote in the paperNot a substantial claim - Premisecitation
According to the FDA's NDI Notification database, since 1995, NDI Notifications for creatine pyruvate, creatine ethyl ester, creatine ethyl ester HCL, tri-creatine orotate, β-creatine, creatine nitrate, and creatine acesulfame have been submitted.
“According to the FDA’s NDI Notification database, since 1995, NDI Notifications for creatine pyruvate (1998), creatine ethyl ester (2003), creatine ethyl ester HCL (2004), tri-creatine orotate (2003), β-creatine (2010), creatine nitrate (2011 and 2017), and creatine acesulfame (2018) have been submitted.”
Quote in the paperNot a substantial claim - Interpretationcitation
Since all other purported sources of creatine described were introduced into the U.S. marketplace after October 15, 1994, they are considered NDIs.
“Since all of the other purported sources of creatine described above were introduced into the U.S. marketplace after 15 October 1994, they are considered NDI’s and manufacturers and distributors were expected to notify the FDA about these ingredients”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [235] EAS (2022, February 07). Product Phosphagen™ Marketed by Experimental and Applied Sciences (EAS™). Available online: https://www.eas.com.
Not checked in the free run.
- Premisecitation
In the US, a major factor in determining whether an NDI notification is required to be submitted to the FDA is whether the NDI has been present in the food supply and/or has been chemically altered from its original form.
“In the US, a major factor in determining whether an NDI notification is required to be submitted to the FDA is whether the NDI has been present in the food supply and/or has been chemically altered from its original form [26].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Kreider, 2003, Effects of serum creatine supplementation on muscle creatine content, J. Exerc. Physiol. Online
Not checked in the free run.
- Interpretationreasoning
Except for CrM, one cannot assume that the purported other sources of creatine described above can be legally sold as a dietary supplement in all countries.
“Therefore, except for CrM, one cannot assume that of the purported other sources of creatine described above can be legally sold as a dietary supplement in all countries.”
Quote in the paperSubstantial claim - Interpretationreasoning
Since some of these sources of creatine are ingredients in dietary supplements, any company selling these nutrients would have to have documentation that the ingredient was on the market in the U.S. before October 15, 1994 or is present in the food supply in a form that is not chemically altered.
“Since some of these sources of creatine are ingredients in dietary supplements, any company selling these nutrients would have to have documentation that the ingredient was on the market in the US before 15 October 1994 or is present in the food supply in a form that is not chemically altered.”
Quote in the paperNot a substantial claim
- May combine two claims. 111
- Classified as probably not a substantial claim. 28
May combine two claims.
FindingcitationPeak concentrations of creatine were significantly higher with creatine pyruvate (CPY) than with CrM or CC, while AUC values did not significantly differ among treatments.
“Peak concentrations of creatine were significantly higher with CPY (CrM 761.9 ± 107.7, CC 855.3 ± 165.1, CPY 972.2 ± 184.1 µmol/L) while AUC values did not significantly differ among treatments (2384 ± 376.5, 2627 ± 506.8, 2985 ± 540.6 mM/h, respectively).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [63] Harris, 2007, Comparison of new forms of creatine in raising plasma creatine levels, J. Int. Soc. Sports Nutr. source
The Results report that peak creatine concentration was significantly higher with creatine pyruvate than with creatine citrate (p = 0.010), but not significantly higher than with creatine monohydrate (p = 0.075). Table 3 reports a significant overall difference in AUC among treatments (ANOVA p = 0.023), contrary to the claim that AUC values did not significantly differ. The quoted concentration values come from the one-hour measurements in Table 2, not the peak-concentration measurements in Table 3. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationThere is no evidence that micronized CrM is more bioavailable than normal mesh CrM or that consuming CrM in effervescent fluid promotes greater creatine retention or performance benefits.
“There is also no evidence that supplementation of micronized versions of CrM (i.e., CrM with smaller mesh size particles) are more bioavailable than CrM with normal mesh sized particles [138,139,140] or consuming CrM in effervescent fluid promotes greater creatine retention or performance benefits [22,141].”
Quote in the paperSubstantial claim1 of 5 sources checked- cites [138] Pakulak, A., Candow, D.G., Totosy de Zepetnek, J., Forbes, S.C., and Basta, D. (2021). Effects of Creatine and Caffeine Supplementation During Resistance Training on Body Composition, Strength, Endurance, Rating of Perceived Exertion and Fatigue in Trained Young Adults. J. Diet. Suppl., 1–16. source
- cites [139] Tibirica, 2019, Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets, Fundam. Clin. Pharmacol. source
- cites [140] Moraes, 2014, Effects of dietary creatine supplementation on systemic microvascular density and reactivity in healthy young adults, Nutr. J. source
The Methods section says the study used micronized creatine monohydrate, but it does not compare its bioavailability with normal-mesh creatine monohydrate. The cited paper therefore does not establish the claim attached to this citation. The separate claim about effervescent fluid is cited to other sources. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [22] Greenwood, 2003, Differences in creatine retention among three nutritional formulations of oral creatine supplements, J. Exerc. Physiol. Online
Not checked in the free run.
- cites [141] Falk, 2003, Effects of effervescent creatine, ribose, and glutamine supplementation on muscular strength, muscular endurance, and body composition, J. Strength Cond. Res. source
May combine two claims.
PremisecitationFor a dietary source of creatine to be bioavailable, creatine must be absorbed as creatine into the blood and transported to tissues, transported into tissue via tissue-specific creatine transporter genes, and increase tissue and cellular creatine and PCr content by a physiologically meaningful amount (e.g., 20-40% in muscle and 10-20% in brain).
“For a dietary source of creatine to be bioavailable, creatine must be: (1) absorbed as creatine into the blood and transported to tissues [2,25]; (2) transported into tissue via tissue-specific creatine transporter genes (e.g., CRT1 or SLC6A8 in muscle) [6,7]; and (3) increase tissue and cellular creatine and PCr content by a physiologically meaningful amount to influence metabolic activity (e.g.,”
Quote in the paperSubstantial claim6 of 10 sources checked- cites [2] Brosnan, 2016, The role of dietary creatine, Amino Acids source
- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- cites [6] Wallimann, 2011, The creatine kinase system and pleiotropic effects of creatine, Amino Acids source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites [7] Bonilla, D.A., Kreider, R.B., Stout, J.R., Forero, D.A., Kerksick, C.M., Roberts, M.D., and Rawson, E.S. (2021). Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review. Nutrients, 13. source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites [5] Kreider, R.B., and Stout, J.R. (2021). Creatine in Health and Disease. Nutrients, 13. source
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites [20] Green, 1996, Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans, Am. J. Physiol. source
- cites [24] Wax, B., Kerksick, C.M., Jagim, A.R., Mayo, J.J., Lyons, B.C., and Kreider, R.B. (2021). Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations. Nutrients, 13. source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured - cites [47] Vandenberghe, 1997, Long-term creatine intake is beneficial to muscle performance during resistance training, J. Appl. Physiol. source
May combine two claims.
PremisecitationCrM is the most extensively studied and effective form of creatine found in nutritional supplements that professional organizations recommend for use.
“The most extensively studied and effective form of creatine found in nutritional supplements that professional organizations recommend for use is creatine monohydrate (CrM) [14,15,17,18].”
Quote in the paperNot a substantial claim3 of 4 sources checked- cites [14] Kerksick, 2018, ISSN exercise & sports nutrition review update: Research & recommendations, J. Int. Soc. Sports Nutr. source
- cites [15] Kreider, 2017, International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine, J. Int. Soc. Sports Nutr. source
- cites [17] Thomas, 2016, Position of the Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine: Nutrition and Athletic Performance, J. Acad. Nutr. Diet source
- cites [18] Maughan, 2018, IOC Consensus Statement: Dietary Supplements and the High-Performance Athlete, Int. J. Sport Nutr. Exerc. Metab. source
The 'Supplement Proposed Mechanism of Action Evidence for Efficacy' section identifies creatine monohydrate and gives a recommended dose; the 'Overview' describes performance benefits from creatine loading. Our copy does not establish that monohydrate is the most extensively studied or most effective form relative to other forms, or that multiple professional organizations recommend it. (LLM, conf=0.86)
Experimental — accuracy not yet measured
May combine two claims.
InterpretationcitationMixing CrM in common juices and beverages with pHs ranging from 2.5-3.5 would enhance solubility but would also promote the conversion of creatine to creatinine over time.
“Additionally, while mixing CrM in common juices and beverages with pHs ranging from 2.5–3.5 [61] would enhance solubility, it would also promote the conversion of creatine to creatinine over time [66].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [61] Reddy, 2016, The pH of beverages in the United States, J. Am. Dent. Assoc. source
- cites [66] Howard, A.N., and Harris, R. (1999). Compositions Containing Creatine and Aloe Vera Extract. (No. 6,168,802), U.S. Patent.
Not checked in the free run.
May combine two claims.
PremisecitationThe solubility of creatine in water increases linearly with increasing temperature; about 6 g of creatine dissolves in one liter of water at 4 °C, 14 g/L at 20 °C, 34 g/L at 50 °C, and 45 g/L at 60 °C.
“The solubility of creatine in water increases linearly with increasing temperature. In this regard, about 6 g of creatine dissolves in one liter of water at 4 °C (39.2 °F) while 14 g/L are dissolved at 20 °C (68 °F), 34 g/L are dissolved at 50 °C (122 °F); and, 45 g/L are dissolved at 60 °C (140 °F) [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
May combine two claims.
PremisereasoningSince stomach acid is generally less than 2.5, less than 1% of CrM is degraded to creatinine during digestion and 99% of creatine is taken up by tissue or excreted in urine after ingestion.
“Since stomach acid is generally less than 2.5, less than 1% of CrM is degraded to creatinine during digestion and 99% of creatine is taken up by tissue or excreted in urine after ingestion [12,25,58,59].”
Quote in the paperSubstantial claim2 of 4 sources checked- cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
The Stability section (page unavailable) says pH below 2.5 can prevent creatine degradation and that conversion to creatinine in the gastrointestinal tract is minimal. The Bioavailability section (page unavailable) says intestinal absorption of creatine monohydrate is close to 100% and discusses tissue uptake and urinary excretion. It does not give the claimed thresholds of less than 1% degraded or 99% taken up by tissue or excreted, nor state that stomach acid is generally below pH 2.5. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [58] Persky, 2003, Pharmacokinetics of the dietary supplement creatine, Clin. Pharmacokinet. source
- cites [59] Deldicque, 2008, Kinetics of creatine ingested as a food ingredient, Eur. J. Appl. Physiol. source
The Discussion estimates that at stomach pH near 2, about 1% of a 2 g dose converts to creatinine within the first hour, and describes gastrointestinal conversion overall as negligible. It also says creatine appearing in blood is taken up by tissues or eliminated in urine. But it does not establish less than 1% conversion throughout digestion: it says a larger proportion may degrade during the longer intestinal transit. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationCreatinine levels significantly increased throughout training with MgCr-C compared to placebo, and this increase was higher than reported in long-term CrM studies during training in hot and humid environments.
“creatinine levels were also significantly increased throughout training with MgCr-C (0.83 to 1.87 mmol/L) compared to placebo (0.92 to 0.82 mmol/L), which is higher than reported in other long-term CrM studies during training in hot and humid environments that administered 5–10 g/day of CrM for 21 months in well-trained athletes [144].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [191] Zajac, A., Golas, A., Chycki, J., Halz, M., and Michalczyk, M.M. (2020). The Effects of Long-Term Magnesium Creatine Chelate Supplementation on Repeated Sprint Ability (RAST) in Elite Soccer Players. Nutrients, 12. source
The Results report that creatinine rose significantly from 0.83 at baseline to 1.87 after four weeks of MgCr-C, while it did not change significantly in the placebo group. The increase did not continue throughout training: creatinine fell to 1.38 by week 16. The Results give the placebo endpoint as 0.85, not 0.82, and the Discussion gives the creatinine unit as mg/dL, not mmol/L. Our copy does not support the claimed comparison with CrM studies conducted in hot and humid environments. (LLM, conf=0.91)
Experimental — accuracy not yet measured - cites [144] Greenwood, 2003, Creatine supplementation during college football training does not increase the incidence of cramping or injury, Mol. Cell. Biochem. source
May combine two claims.
PremisecitationCrM provides a powder containing 87.9% creatine that readily dissociates into creatine and water upon oral ingestion.
“This provides a powder containing 87.9% creatine that readily dissociates into creatine and water upon oral ingestion.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
The Physio-chemical properties section (page unavailable) states that creatine monohydrate contains 87.9% creatine and has one molecule of water of crystallization per molecule of creatine. The Solubility section says it dissolves in water, but our copy does not establish that it readily dissociates into creatine and water upon oral ingestion. (LLM, conf=0.84)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationMost purported forms of creatine marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy.
“Moreover, that most purported “forms” of creatine that were being marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
May combine two claims.
PremisecitationCreatine monohydrate (CrM) is not degraded into creatinine during normal digestion, is nearly 100% bioavailable, and markedly increases blood and tissue creatine content.
“Research has clearly shown that CrM is not degraded into creatinine during normal digestion, it is nearly 100% bioavailable [12,25,58,59], and markedly increases blood and tissue creatine content.”
Quote in the paperSubstantial claim2 of 4 sources checked- cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
- cites [58] Persky, 2003, Pharmacokinetics of the dietary supplement creatine, Clin. Pharmacokinet. source
- cites [59] Deldicque, 2008, Kinetics of creatine ingested as a food ingredient, Eur. J. Appl. Physiol. source
May combine two claims.
PremisecitationCrM supplementation improves acute exercise performance particularly in intermittent high-intensity exercise bouts and enhances training adaptations in adolescents, young adults, and older individuals.
“CrM supplementation has been reported to improve acute exercise performance particularly in intermittent high-intensity exercise bouts as well as enhance training adaptations in adolescents [78,79,80,81,82], young adults [29,55,83,84,85,86,87,88,89,90,91,92], and older individuals [8,77,93,94,95,96,97,98,99,100,101].”
Quote in the paperSubstantial claim1 of 10 sources checked- cites [78] Cornish, 2006, The effect of creatine monohydrate supplementation on sprint skating in ice-hockey players, J. Sports Med. Phys. Fit.
Not checked in the free run.
- cites [79] Dawson, 2002, Effects of 4 weeks of creatine supplementation in junior swimmers on freestyle sprint and swim bench performance, J. Strength Cond. Res. source
- cites [80] Grindstaff, 1997, Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers, Int. J. Sport Nutr. source
- cites [81] Juhasz, 2009, Creatine supplementation improves the anaerobic performance of elite junior fin swimmers, Acta Physiol. Hung. source
- cites [82] Silva, 2007, Effect of creatine on swimming velocity, body composition and hydrodynamic variables, J. Sports Med. Phys. Fit.
Not checked in the free run.
- cites [29] Galvan, 2016, Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance, J. Int. Soc. Sports Nutr. source
The Methods describe young adult men undertaking resistance training, and the Results report increased lean mass in the CrM group. However, the Results (Study 2: chronic supplementation) say only the high-dose creatine nitrate group improved bench-press outcomes relative to placebo, and there were no significant treatment effects in the intermittent sprint test. This paper therefore does not support the claimed CrM performance benefit over placebo, particularly for intermittent high-intensity exercise; it also did not study adolescents or older individuals. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [55] Kreider, 1998, Effects of creatine supplementation on body composition, strength, and sprint performance, Med. Sci. Sports Exerc. source
- cites [83] Stone, 1999, Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players, Int. J. Sport Nutr. source
- cites [84] Bemben, 2001, Creatine supplementation during resistance training in college football athletes, Med. Sci. Sports Exerc. source
- cites [85] Hoffman, 2006, Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes, Int. J. Sport Nutr. Exerc. Metab. source
May combine two claims.
PremisecitationCrM was the first source of creatine marketed as a dietary supplement and remains the most common source of creatine found in dietary supplements.
“Creatine monohydrate was the first source of creatine marketed as a dietary supplement and remains the most common source of creatine found in dietary supplements [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Jager, 2011, Analysis of the efficacy, safety, and regulatory status of novel forms of creatine, Amino Acids source
May combine two claims.
Findingcitation5.5 g/day of MgCr-C supplementation during 16 weeks of soccer training improved repeated sprint ability performance compared to placebo, but the study did not compare MgCr-C to CrM and performance changes were consistent with other CrM studies.
“Zajac et al. [191] reported that 5.5 g/day of MgCr-C supplementation during 16 weeks of soccer training improved repeated sprint ability performance compared to placebo.”
- Also stated in: § 9.2. Magnesium Creatine Chelate · plain
“this study did not compare the effects of consuming MgCr-C to CrM, and performance changes were consistent with other studies conducted on CrM supplementation.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [191] Zajac, A., Golas, A., Chycki, J., Halz, M., and Michalczyk, M.M. (2020). The Effects of Long-Term Magnesium Creatine Chelate Supplementation on Repeated Sprint Ability (RAST) in Elite Soccer Players. Nutrients, 12. source
- Also stated in: § 9.2. Magnesium Creatine Chelate · plain
May combine two claims.
FindingcitationSome creatine salts are less stable than CrM; storage of tri-creatine citrate at 40 °C for 28 days results in formation of 770 ppm of creatinine compared to no measurable amount with CrM powder.
“Some creatine salts are less stable when compared to CrM. For example, storage of tri-creatine citrate at 40 °C (104 °F) for 28 days results in formation of 770 ppm of creatinine compared to no measurable amount with CrM powder [63].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [63] Harris, 2007, Comparison of new forms of creatine in raising plasma creatine levels, J. Int. Soc. Sports Nutr. source
The Methods (Supplementation Protocol; page not provided) say that all three creatine products contained less than 100 ppm creatinine, but give no storage conditions or stability comparison. Searches for 770 ppm, 40 °C, 28 days, and storage stability found no passage supporting the claimed result. (LLM, conf=0.76)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationOstojic et al. found that peak serum creatine increased to a greater degree with CrN + CrM supplementation, while muscle creatine increased to a greater degree with CrN ingestion.
“The researchers found that peak serum creatine increased to a greater degree with CrN + CrM supplementation (CrM 118.6 ± 12.9, CrN 163.8 ± 12.9; CrN + CrM 183.7 ± 15.5 µmol/L) while muscle creatine increased to a greater degree with CrN ingestion (CrM 2.1%, CrN 8.0%, CrN + CrM 9.6%).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [209] Ostojic, 2019, Searching for a better formulation to enhance muscle bioenergetics: A randomized controlled trial of creatine nitrate plus creatinine vs. creatine nitrate vs. creatine monohydrate in healthy men, Food Sci. Nutr. source
The Results (Single-dose experiment) report the quoted peak serum creatine values, and the Results (5-day intervention) report the quoted muscle-creatine increases. But the combination tested was creatine nitrate plus creatinine (CN-CRN), not creatine nitrate plus creatine monohydrate (CrN + CrM). The greatest muscle-creatine increase was also with CN-CRN (9.6%), rather than creatine nitrate alone (8.0%). (LLM, conf=0.90)
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationThe Alraddadi et al. study is only a theoretical modeling study and did not directly compare Cr-HCl to CrM intake on plasma or tissue creatine content.
“First, this is only a theoretical modeling study. The researchers did not directly compare Cr-HCl to CrM intake on plasma or tissue creatine content.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [199] Alraddadi, E.A., Lillico, R., Vennerstrom, J.L., Lakowski, T.M., and Miller, D.W. (2018). Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth. Pharmaceutics, 10. source
The Methods (§2.2) describe an experimental rat study that administered creatine monohydrate and measured plasma and tissue samples, so the paper was not only a theoretical modeling study. The Results (§3.4) show that the creatine hydrochloride versus monohydrate comparison was simulated rather than directly tested, supporting the second sentence. (LLM, conf=0.90)
Experimental — accuracy not yet measured
May combine two claims.
Study design and conductcitationJagim and colleagues conducted a double-blind trial in which 36 resistance-trained participants were randomly assigned to creatine monohydrate, CrM-Alk at recommended doses, or CrM-Alk at equivalent doses to CrM.
“In a double-blind manner, 36 resistance-trained participants were randomly assigned to ingest CrM (4 × 5 g/day for 7-days, 5 g/day for 21-days), CrM-Alk at recommended doses (1.5 g/day for 28-days), or CrM-Alk with equivalent doses to CrM (4 × 5 g/day for 7-days, 5 g/day for 21-days).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] Jagim, 2012, A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate, J. Int. Soc. Sports Nutr. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationRecommended nitrate dosages generally range between 300-600 mg ingested 1-2 h prior to exercise.
“Recommended dosages generally range between 300–600 mg ingested 1–2 h prior to exercise [204,205,206].”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [204] Tan, R., Cano, L., Lago-Rodríguez, Á., and Domínguez, R. (2022). The Effects of Dietary Nitrate Supplementation on Explosive Exercise Performance: A Systematic Review. Int. J. Environ. Res. Public Health, 19. source
The Introduction (page unavailable) recommends at least ~6 mmol of nitrate, a dose within the claimed 300–600 mg range. But it specifies ingestion 2–3 hours before exercise, not 1–2 hours, and does not recommend 300–600 mg as a general dosage range. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [205] Gao, 2021, The effects of dietary nitrate supplementation on endurance exercise performance and cardiorespiratory measures in healthy adults: A systematic review and meta-analysis, J. Int. Soc. Sports Nutr. source
The Results (Subgroup analyses; page unavailable) say there were insufficient data to analyze effects by daily nitrate dose. The Discussion’s athlete perspective describes a personal protocol of 500 ml of beetroot juice 2–3 hours before exercise, not a recommendation of 300–600 mg 1–2 hours beforehand. Searches for those dose and timing ranges found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [206] Macuh, M., and Knap, B. (2021). Effects of Nitrate Supplementation on Exercise Performance in Humans: A Narrative Review. Nutrients, 13. source
Section 2.1 gives a likely effective dose of 5–9 mmol (310–560 mg), broadly consistent with the claimed 300–600 mg range. It recommends taking an acute dose 2–3 hours before exercise, not 1–2 hours, and says effects are not statistically significant when nitrate is taken less than 2 hours beforehand. No page number is provided in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measured
May combine two claims.
InterpretationcitationCreatine nitrate can be a bioavailable source of creatine proportional to the amount of creatine delivered during the loading phase, but not more bioavailable than creatine monohydrate when equivalent doses are ingested.
“These findings suggest that CrN can be a bioavailable source of creatine proportional to the amount of creatine delivered during the loading phase (i.e., 54.6 g for CrN-High versus 73.8 g for CrM), but not more bioavailable than CrM when equivalent doses are ingested.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] Galvan, 2016, Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance, J. Int. Soc. Sports Nutr. source
The Results (Study 2: chronic supplementation) show that CrN-High increased muscle creatine after seven days, supporting CrN as a source of creatine; the increase was smaller than with CrM. However, the Methods (Testing methodology) describe equal masses of the two supplements, not equivalent amounts of creatine, so the study does not directly establish their relative bioavailability at equivalent creatine doses. The cited 54.6 g and 73.8 g figures are not stated in the passages of our copy found for this claim. (LLM, conf=0.83)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationGalvan and colleagues found that 7 days of creatine loading (12 g/day of CrM and CrN) significantly increased muscle creatine content in the CrM and CrN-High groups, but no difference versus placebo was observed with 4 × 1.5 g/day CrN for 7 days or after 28 days of 1.5 or 3 g/day CrN.
“Results revealed that 7 days of creatine loading (12 g/day of CrM and CrN) significantly increased muscle creatine content in the CrM (7.1 mmol/kg DW) and CrN-High (4.6 mmol/kg DW). However, no difference was seen compared to placebo was observed when ingesting 4 × 1.5 g/day of CrN for 7 days or after 28 days of taking 1.5 or 3 g/day of CrN.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] Galvan, 2016, Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance, J. Int. Soc. Sports Nutr. source
May combine two claims.
PremisecitationDalton et al. reported that ingestion of up to 6 g of creatine nitrate for 6 days does not negatively affect resting hemodynamics, response to a postural challenge, the ability to perform high-intensity exercise, or clinical chemistry profiles.
“Dalton et al. [36] reported that ingestion of up to 6 g of CrN for 6 days does not negatively affect resting hemodynamics, response to a postural challenge, the ability to perform high-intensity exercise, or clinical chemistry profiles.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [36] Dalton, R.L., Sowinski, R.J., Grubic, T.J., Collins, P.B., Coletta, A.M., Reyes, A.G., Sanchez, B., Koozehchian, M., Jung, Y.P., and Rasmussen, C. (2017). Hematological and Hemodynamic Responses to Acute and Short-Term Creatine Nitrate Supplementation. Nutrients, 9. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCEE converts to creatinine in a linear manner as pH levels drop below 8.0 and is mostly stable at a pH of 1.0.
“Gufford et al. [194] reported that CEE converted to creatinine in a linear manner as pH levels dropped below 8.0 and that CEE was mostly stable at a pH of 1.0.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [194] Gufford, 2013, pH-dependent stability of creatine ethyl ester: Relevance to oral absorption, J. Diet. Suppl. source
The Results (pH-Dependent CEE Stability) report a linear relationship between pH and the logarithm of the conversion rate constant only from pH 2.5 to 8.0, not at all pH levels below 8.0. The same section says CEE was most stable at pH 1.0, where it primarily hydrolyzed to creatine rather than cyclizing to creatinine. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
Premisecitationda Silva found that rats fed creatine monohydrate experienced significant increases in creatine concentrations in arterial plasma, portal vein plasma, and muscle creatine content, and tended to increase brain creatine content compared to controls.
“As shown in Figure 16, rats fed CrM experienced significant increases in creatine concentrations in arterial plasma (+7-fold), portal vein plasma (+10-fold), muscle creatine content (+1.63-fold from control, and +1.53-fold from CLL) while tending to increase brain creatine content (p = 0.052) compared to controls.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [221] da Silva, R.P. (2022). The Dietary Supplement Creatyl-l-Leucine Does Not Bioaccumulate in Muscle, Brain or Plasma and Is Not a Significant Bioavailable Source of Creatine. Nutrients, 14. source
May combine two claims.
InterpretationcitationCLL is poorly absorbed by the intestine and is not a bioavailable source of creatine.
“The researcher concluded that provision of large doses of CLL to rats did not increase creatine bioaccumulation indicating that CLL is poorly absorbed by the intestine and is not a bioavailable source of creatine.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [221] da Silva, R.P. (2022). The Dietary Supplement Creatyl-l-Leucine Does Not Bioaccumulate in Muscle, Brain or Plasma and Is Not a Significant Bioavailable Source of Creatine. Nutrients, 14. source
May combine two claims.
InterpretationcitationHigher than recommended doses of CEE can positively affect training adaptations, but the study did not assess the effects of CEE on blood or muscle creatine content or compare CEE to CrM.
“While this study indicates that higher than recommended doses of CEE can positively affect training adaptations, this study did not assess the effects of CEE supplementation on blood or muscle creatine content or compare the efficacy of CEE supplementation to CrM.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [197] Arazi, 2019, Effect of creatine ethyl ester supplementation and resistance training on hormonal changes, body composition and muscle strength in underweight non-athlete men, Biomed. Hum. Kinet. source
May combine two claims.
FindingcitationCEE supplementation increased muscle total creatine content after 27 days compared to placebo, but CrM produced significantly greater increases than placebo and CEE.
“while CEE supplementation promoted a significant increase in muscle total creatine content after 27 days of supplementation compared to those ingesting a placebo, those taking CrM observed significantly greater increases compared to the placebo and CEE groups (Figure 10C).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] Spillane, 2009, The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels, J. Int. Soc. Sports Nutr. source
The Results (Muscle creatine, Figure 2; page not provided) report higher total muscle creatine in both CEE and CRT than in placebo, and an increase in CEE at day 27. The Discussion (Serum and Muscle Creatine; page not provided) explicitly says CRT was not significantly greater than CEE in total muscle creatine, contrary to the claim's final comparison. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn the United States, DSHEA placed dietary supplements in a special category of foods under the jurisdiction of the FDA.
“In the United States (US), congress enacted the Dietary Supplement Health and Education Act (DSHEA) of 1994 that placed dietary supplements in a special category of foods under the jurisdiction of the FDA.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [14] Kerksick, 2018, ISSN exercise & sports nutrition review update: Research & recommendations, J. Int. Soc. Sports Nutr. source
- cites [234] (2020, October 26). New Dietary Ingredients in Dietary Supplements-Background for Industry, Available online: https://www.fda.gov/food/new-dietary-ingredients-ndi-notification-process/new-dietary-ingredients-dietary-supplements-background-industry.
Not checked in the free run.
May combine two claims.
PremisecitationPhosphate loading has been found to increase myocardial ejection fraction during exercise and maximal aerobic capacity and is considered an ergogenic aid for endurance athletes.
“Phosphate loading has been found to increase myocardial ejection fraction during exercise and maximal aerobic capacity [231,232] and is considered an ergogenic aid for endurance athletes [14].”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites [231] Kreider, 1990, Effects of phosphate loading on oxygen uptake, ventilatory anaerobic threshold, and run performance, Med. Sci. Sports Exerc.
- cites [232] Kreider, 1992, Effects of phosphate loading on metabolic and myocardial responses to maximal and endurance exercise, Int. J. Sport Nutr. source
- cites [14] Kerksick, 2018, ISSN exercise & sports nutrition review update: Research & recommendations, J. Int. Soc. Sports Nutr. source
May combine two claims.
FindingcitationFasting serum creatine levels significantly increased only in the CrM group, and CEE supplementation had no effect on fasting serum creatine levels compared to placebo.
“As seen in Figure 10A, fasting serum creatine levels significantly increased only in the CrM group.”
- Also stated in: § 9.3. Creatine Ethyl Ester · plain
“CEE supplementation had no effect on fasting serum creatine levels compared to a placebo.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [27] Spillane, 2009, The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels, J. Int. Soc. Sports Nutr. source
- Also stated in: § 9.3. Creatine Ethyl Ester · plain
May combine two claims.
PremisecitationJagim and colleagues found some evidence that higher doses of CrM-Alk increased muscle creatine content after 28 days, but these values were less than observed with creatine monohydrate.
“There was some evidence that ingesting higher doses of CrM-Alk increased muscle creatine content after 28 days (6.2 ± 29.2; 27.3 ± 49.1%, respectively), but these values were less than observed with CrM (23.5 ± 49.0; 50.4 ± 44.8%, respectively).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [28] Jagim, 2012, A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate, J. Int. Soc. Sports Nutr. source
May combine two claims.
PremisecitationDietary nitrates, typically ingested as beet root juice or nitrate powder, can improve endurance and explosive exercise capacity.
“A number of studies have indicated that dietary nitrates, typically ingested in the form of beet root juice or nitrate powder, can improve endurance [203] and explosive exercise capacity [204].”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [203] Hlinský, T., Kumstát, M., and Vajda, P. (2020). Effects of Dietary Nitrates on Time Trial Performance in Athletes with Different Training Status: Systematic Review. Nutrients, 12. source
- cites [204] Tan, R., Cano, L., Lago-Rodríguez, Á., and Domínguez, R. (2022). The Effects of Dietary Nitrate Supplementation on Explosive Exercise Performance: A Systematic Review. Int. J. Environ. Res. Public Health, 19. source
May combine two claims.
PremisecitationGalvan and colleagues found that plasma creatine AUC over 5 h for creatine monohydrate was significantly greater than placebo, CrN-Low, and CrN-High, with no differences between the CrN dosages.
“Results revealed that the plasma creatine AUC over a 5 h period for CrM (5634.4 ± 1949.8 μmol/L) was significantly greater than the placebo (1012.4 ± 1882.2 μmol/L), CrN-Low (2342.0 ± 3133.3 μmol/L, p = 0.004), and CrN-High (1761.7 ± 3408.8 μmol/L, p = 0.007) treatments with no differences seen between the CrN dosages.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] Galvan, 2016, Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance, J. Int. Soc. Sports Nutr. source
May combine two claims.
InterpretationcitationGiven the health benefits of creatine, availability of ineffective sources of creatine or recommendations to take less creatine than needed to increase creatine stores in the muscle and/or brain can limit the benefits these populations may derive from creatine supplementation.
“Given the health benefits of creatine, availability of ineffective sources of creatine or recommendations to take less creatine than needed to increase creatine stores in the muscle and/or brain can limit the benefits theses populations may derive from creatine supplementation [5].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] Kreider, R.B., and Stout, J.R. (2021). Creatine in Health and Disease. Nutrients, 13. source
Section 3 (Metabolic Role; page unavailable) gives doses used to increase muscle creatine and notes that some clinical populations need higher doses to increase brain creatine. Sections 4 and 6.1 describe potential health benefits, but the copy does not establish that ineffective creatine sources are available or directly assess whether such sources limit those benefits. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingnone givenTo date, no study has evaluated the effects of CC or CPY on muscle or brain creatine content.
“To date, we are unaware of any study that has evaluated the effects of CC or CPY on muscle or brain creatine content.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingreasoningThere is substantial evidence to support the safety and efficacy of CrM supplementation, and CrM is classified as having strong evidence from pharmacokinetic and tissue bioavailability studies, numerous randomized and controlled clinical trials, and a long history of safety.
“Thus, there is substantial evidence to support the safety and efficacy of CrM supplementation (see Table 2).”
- Also stated in: § Creatine Monohydrate · boosted
“CrM is classified as having strong evidence from pharmacokinetic and tissue bioavailability studies, numerous randomized and controlled clinical trials, and a long-history of safety assessed in clinical trials and historical widespread use supporting bioavailability, efficacy, and safety.”
Quote in the paperSubstantial claim- Also stated in: § Creatine Monohydrate · boosted
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
FindingreasoningMagnesium creatine chelate (MgCr-C) contains about 84.4% of creatine by molecular weight and could theoretically serve as a good source of creatine if creatine easily dissociates from MgCr-C and equimolar amounts of creatine were consumed compared to CrM.
“Since MgCr-C contains about 84.4% of creatine by molecular weight (see Table 1), it could theoretically serve as a good source of creatine if creatine easily dissociates from MgCr-C and equimolar amounts of creatine were consumed compared to CrM.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationCrM and MgCr-C were both effective in increasing performance with no differences observed between types of creatine ingested.
“Results revealed that CrM and MgCr-C were both effective in increasing performance with no differences observed between types of creatine ingested.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [190] Selsby, 2004, Mg2+-creatine chelate and a low-dose creatine supplementation regimen improve exercise performance, J. Strength Cond. Res. source
May combine two claims.
FindingreasoningThere are no studies indicating that CC is more bioavailable, more effective, or a safer source of creatine than CrM, and CC is categorized as having limited evidence to support bioavailability, efficacy, and safety.
“Therefore, there are no studies indicating that CC is more bioavailable, more effective, or a safer source of creatine than CrM. Given this, CC is categorized as having limited evidence to support bioavailability, efficacy, and safety.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationBody water increased with MgCr-C but not CrM, while torque and power increased similarly with CrM and MgCr-C.
“Results revealed that body water increased with MgCr-C, but not CrM while torque and power increased similarly with CrM and MgCr-C.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [189] Brilla, 2003, Magnesium-creatine supplementation effects on body water, Metabolism source
May combine two claims.
Findingnone givenThere are no data showing that MgCr-C increases blood creatine levels or promotes greater creatine retention in skeletal muscle, and no data supporting that MgCr-C is more bioavailable to tissue than CrM.
“We are aware of no data showing that MgCr-C increases blood creatine levels or promotes greater creatine retention in skeletal muscle. Thus, there are no data supporting that MgCr-C is more bioavailable to tissue than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
FindingreasoningThere is no data showing that MgCr-C increases blood or muscle creatine, only limited data showing potential ergogenic effect, and no evidence that MgCr-C is more bioavailable, efficacious, and/or a safer source of creatine than CrM.
“Consequently, there is no data showing that MgCr-C increases blood or muscle creatine and there is only limited data showing potential ergogenic effect. There is also no evidence that MgCr-C is more bioavailable, efficacious, and/or a safer source of creatine than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone givenAs of this writing, no PubMed indexed articles have been published on Cr-HCl and muscle creatine retention or performance, but several articles have been published in non-indexed journals from Brazil that have been cited in marketing materials.
“As of this writing, no PubMed indexed articles have been published on Cr-HCl and muscle creatine retention or performance. However, several articles have been published in non-indexed journals from Brazil that have been cited in marketing materials.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
FindingcitationGains in fat-free mass were greatest in the CrM group (+1.7 kg), but supposedly not significantly different than 5 g/day of Cr-HCl (+1.6 kg), which were reported to be significantly different than controls (+1.1 kg) and those ingesting 1.5 g/day of Cr-HCl (+1.1 kg).
“gains in fat-free mass were greatest in the CrM group (+1.7 kg), but supposedly not significantly different than observed with 5 g/day of Cr-HCL (+1.6 kg) that were reported to be significantly different than controls (+1.1 kg) and those ingesting 1.5 g/day of Cr-HCl (+1.1 kg).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [65] Avelar, 2015, Creatine HCl and Creatine Monohydrate Improve Strength but Only Creatine HCl Induced Changes on Body Composition in Recreational Weightlifters, Food Nutr. Sci.
Not checked in the free run.
May combine two claims.
FindingcitationCrM was assessed at a saturation pH of 8.6 while Cr-HCl was measured at a saturation pH of 0.3.
“CrM was assessed at a saturation pH of 8.6 while Cr-HCL was measured at a saturation pH of 0.3.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [179] Gufford, 2010, Physicochemical characterization of creatine N-methylguanidinium salts, J. Diet. Suppl. source
May combine two claims.
FindingreasoningThere is no evidence that ingesting recommended doses of CEE is effective or that ingesting typical CrM loading and maintenance doses of CEE is more effective than CrM.
“there is no evidence that ingesting recommended doses of CEE is effective or that ingesting typical CrM loading, and maintenance doses of CEE is more effective than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationThere is no evidence that Cr-HCl is absorbed more effectively than CrM in humans, that Cr-HCl promotes greater muscle creatine retention than CrM at equivalent doses, or that lower doses of Cr-HCl are as effective as standard supplementation protocols with CrM.
“there is no evidence that Cr-HCl is absorbed more effectively than CrM in humans; Cr-HCl promotes greater muscle creatine retention than CrM at equivalent doses; or, that lower doses of Cr-HCl are as effective as standard supplementation protocols with CrM.”
Quote in the paperSubstantial claimMay combine two claims.
FindingreasoningNo alternative form of creatine has shown superior bioavailability, efficacy, or safety compared to CrM; there is no evidence that other forms are more bioavailable, effective, or safer than CrM.
“No alternative form of creatine has shown superior bioavailability, efficacy or safety compared to CrM.”
- Also stated in: § 12. Summary · plain
“However, there is no evidence that other “forms” of creatine are more bioavailable, effective, or safer forms of creatine compared to CrM.”
Quote in the paperSubstantial claim- Also stated in: § 12. Summary · plain
May combine two claims.
Findingnone givenCreatine monohydrate can be legally sold throughout the world, although some countries limit the amount of CrM that can be included per dose (e.g., no more than 3-5 g/serving).
“Creatine monohydrate can be legally sold throughout the world although some countries limit the amount to of CrM that can be included per dose (e.g., no more than 3–5 g/serving).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Findingnone givenStudies published in 2003 clearly showed that creatine serum was not a bioavailable source of creatine, yet it continues to be sold as a creatine-containing product.
“For example, studies published in 2003 clearly showed that creatine serum was not a bioavailable source of creatine, yet it continues to be sold as a creatine-containing product.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingreasoningThe bioavailability, efficacy, safety, and regulatory status of other purported sources of creatine are less clear, with only a few having some data supporting efficacy compared to placebo.
“The bioavailability, efficacy, safety, and regulatory status of other purported sources of creatine are less clear, with only a few having some data supporting efficacy compared to placebo (see Table 7).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Findingnone givenAlternative forms of creatine are typically more expensive than CrM.
“While alternative forms of creatine are unlikely to pose a health risk, they are typically more expensive than CrM.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenSince the last review in 2011, more data is available about several forms of creatine, and several now have data providing some support as to efficacy and safety while others do not.
“Since our last review in 2011, more data is available about several forms of creatine and several now have data providing some support as to efficacy and safety while others do not.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Findingnone givenAlternatives to CrM continue to be prevalent in the marketplace, including several that do not appear to meet regulatory requirements in several countries.
“Alternatives to CrM continue to be prevalent in the marketplace, including several that do not appear to meet regulatory requirements in several countries.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenCrM is approved for use in the EU and Australia.
“Pure CrM is the only source of creatine with strong evidence of bioavailability, efficacy, and safety and considered as GRAS by the FDA, approved for use in the EU and Australia, and evaluated for safety by Health Canada.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenCrM has been extensively reviewed and approved by Health Canada.
“CrM remains the only source of creatine that has substantial evidence of bioavailability, efficacy and safety and is considered GRAS by the U.S. FDA, is approved for use with accompanying health claims in the EU, has been extensively reviewed and approved by Health Canada, and is approved to be sold in major global markets.”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone givenThe FDA initially rejected some of the IND notification applications, yet the forms were sold for years before finally submitting an acceptable IND notification application or Self-Affirming GRAS.
“Of these, the FDA initially rejected some of the IND notification applications, yet the forms were sold for years before finally submitting an acceptable IND notification application or Self-Affirming GRAS.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
InterpretationreasoningTo be comparatively effective, a creatine salt must deliver physiologically effective doses of creatine (3-5 g per serving) to blood and tissue in an equivalent manner as CrM.
“To do so, the creatine salt must deliver physiologically effective doses of creatine (i.e., 3–5 g per serving) to the blood and tissue in an equivalent manner as CrM to be comparatively effective.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThere is consensus among professional organizations that CrM is an effective nutritional ergogenic aid that may benefit athletes involved in numerous sports and individuals initiating exercise training to promote health and fitness.
“Thus, there is consensus among professional organizations that CrM is an effective nutritional ergogenic aid that may benefit athletes involved in numerous sports and individuals initiating exercise training to promote health and fitness.”
Quote in the paperSubstantial claimMay combine two claims.
Premisenone givenCrM powder is not highly soluble; when mixing CrM in solution, some CrM residue remains at the bottom of the glass.
“One of the limitations in terms of developing consumer products containing CrM is that CrM powder is not highly soluble. For example, when mixing CrM in solution, some CrM residue remains at the bottom of the glass requiring consumers to add more fluid, swirl, and quickly ingest to ensure they consumed all the creatine.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationCPY can serve as an effective source of creatine to increase blood creatine content, and a few short-term studies suggest there may be some ergogenic value.
“These studies indicate that CPY can serve as effective source of creatine to increase blood creatine content and a few short-term studies suggest there may be some ergogenic values.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenThis paper was conducted as a systematic review of the literature related to sources of creatine marketed as ingredients for dietary supplements or found in dietary supplements, food products, and/or beverages marketed as containing creatine.
“This paper was conducted as a systematic review of the literature related to sources of creatine marketed as ingredients for dietary supplements or found in dietary supplements, food products, and/or beverages marketed as containing creatine.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationA dose of orally ingested creatine should ideally increase plasma creatine levels to greater than 500 μmol/L (75 μg/mL) to optimize tissue uptake.
“In support of this contention, classic experiments by Harris et al. [12] indicated that a dose of orally ingested creatine should ideally increase plasma creatine levels to greater than 500 µmol/L (75 µg/mL) to optimize tissue uptake.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
May combine two claims.
PremisecitationIngestion of one oral dose of 5 g of CrM resulted in plasma creatine levels of about 800 μmol/L (120 μg/mL) after 1 h of ingestion and sustained plasma creatine above 200 μmol/L (30 μg/mL) for over 4-5 h.
“However, ingestion of one oral dose of 5 g of CrM (equivalent to about 1.1 kg of uncooked beef) resulted in plasma creatine levels of about 800 µmol/L (120 µg/mL) after 1 h of ingestion. It sustained plasma creatine above 200 µmol/L (30 µg/mL) for over 4–5 h (see Figure 2A).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Harris, 1992, Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation, Clin. Sci. source
May combine two claims.
InterpretationcitationCC can serve as a viable source of creatine by increasing blood creatine level in a similar manner as CrM, and there is some data supporting an ergogenic benefit compared to placebo.
“While these studies provide evidence that CC can serve as a viable source of creatine by increasing blood creatine level in a similar manner as CrM and there is some data supporting the ergogenic benefit compared to placebo”
Quote in the paperSubstantial claimMay combine two claims.
Premisenone givenCrM contains 87.9% creatine whereas creatine citrate (40.6%), di-creatine citrate (57.7%), creatine pyruvate (59.8%), and creatine HCl (78.2%) contain less creatine by weight compared to CrM.
“In this regard, CrM contains 87.9% creatine whereas creatine citrate (40.6%), di-creatine citrate (57.7%), creatine pyruvate (59.8%), and creatine HCl (78.2%) contain less creatine by weight compared to CrM.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationCo-ingesting CrM with carbohydrates and carbohydrate and protein promotes more consistent and greater creatine retention.
“Co-ingesting CrM with carbohydrates [20,21,22] and carbohydrate and protein [23] promotes more consistent and greater creatine retention.”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [20] Green, 1996, Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans, Am. J. Physiol. source
- cites [21] Green, 1996, Carbohydrate ingestion augments creatine retention during creatine feeding in humans, Acta Physiol. Scand. source
- cites [22] Greenwood, 2003, Differences in creatine retention among three nutritional formulations of oral creatine supplements, J. Exerc. Physiol. Online
Not checked in the free run.
- cites [23] Steenge, 2000, Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans, J. Appl. Physiol. source
Classified as probably not a substantial claim.
InterpretationreasoningPurported sources of creatine that increase blood levels of creatine but do not increase tissue levels of creatine in physiologically effective amounts (i.e., 20-40% in muscle and 10-20% in brain) are not bioavailable sources of creatine.
“Purported sources of creatine that increase blood levels of creatine but do not increase tissue levels of creatine in physiologically effective amounts (i.e., 20–40% in muscle and 10–20% in brain) are not bioavailable sources of creatine.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Premisenone givenCompanies continue to market new forms of creatine that are purportedly more stable, bioavailable, and/or effective than CrM.
“Despite this clear scientific evidence, guidance from professional organizations, and regulatory challenges of selling other forms of creatine in the global marketplace, companies continue to market “new forms” of creatine that are purportedly more stable, bioavailable, and/or effective than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningSome of the creatine in CEE converts to creatinine during digestion and therefore CEE is less bioavailable than CrM.
“some of the creatine in CEE converts to creatinine during digestion and therefore it is less bioavailable than CrM.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThe optimal single dose of CrM to increase plasma creatine levels is 5 g, but ingesting 2-3 g will increase plasma creatine to sufficient levels to promote creatine uptake to tissue.
“(2) the optimal single dose of CrM to increase plasma creatine levels is 5 g, but that ingesting 2–3 g will increase plasma creatine to sufficient levels to promote creatine uptake to tissue;”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationConsuming 4 × 5 g of CrM per day for 6-days significantly increased muscle free creatine content by 33% and returned to baseline within 4-weeks after supplementation.
“(1) consuming 4 × 5 g of CrM per day for 6-days (i.e., creatine loading strategy) significantly increased muscle free creatine content by 33% and returned to baseline within 4-weeks after supplementation;”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Hultman, 1996, Muscle creatine loading in men, J. Appl. Physiol. source
May combine two claims.
Premisenone givenCrM is recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.
“Additionally, CrM is the source of creatine recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningThe source of creatine must be transported into tissues by creatine-specific transporters and increase tissue levels of creatine in physiologically significant amounts (i.e., 20-40%) to affect creatine-related metabolism.
“Ultimately, the source of creatine must be transported into tissues by creatine-specific transporters and increase tissue levels of creatine in physiologically significant amounts to affect creatine-related metabolism (i.e., 20–40%).”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningCreatine serum is classified in the no-evidence-to-support category, and there is no evidence that creatine serum outperforms creatine monohydrate.
“Therefore, it is classified in the no evidence to support category, and there is no evidence that CS outperforms CrM.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationReports submitted in ongoing lawsuits provide data showing that CLL is not degraded into creatine upon oral ingestion, does not increase blood creatine content, and does not increase muscle or brain creatine content even at doses much higher than found in marketed products containing CLL in humans.
“These reports provide additional data showing CLL is not degraded into creatine upon oral ingestion [222,223,226], CLL does not increase blood creatine content [222,223,226], and CLL does not increase muscle [224,225] or brain creatine content [224] even when administered at doses much higher than found in marketed products containing CLL in humans [222,223,224,225,226].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [222] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-46. C.D. Cal. Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [223] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-53. C.D. Cal. Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [226] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-133 (C.D. Cal.). Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [224] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-50 (C.D. Cal.). Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [225] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-51. (C.D. Cal.). Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
May combine two claims.
InterpretationreasoningAvailable evidence indicates that CLL is not creatine, is not a bioavailable source of creatine, and is not 'super creatine' compared to creatine monohydrate.
“Thus, available evidence indicates that CLL is not creatine, CLL is not a bioavailable source of creatine, and CLL is not “super creatine” compared to CrM.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationCreatine serum does not contain creatine and has no bioavailability in the blood.
“Consequently, this study shows that CS does not contain creatine and has no bioavailability in the blood [38].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] Harris, 2004, The creatine content of Creatine Serum and the change in the plasma concentration with ingestion of a single dose, J. Sports Sci. source
May combine two claims.
Interpretationnone givenThere are limited published data on these purported sources of creatine, and the available evidence indicates that they are not bioavailable sources of creatine.
“As can be seen, there are limited published data on these purported sources of creatine, and the available evidence indicates that they are not bioavailable sources of creatine.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThese findings directly refute claims that CEE is a more bioavailable source of creatine than CrM and that CEE promotes greater training adaptations than CrM.
“These findings directly refute claims that CEE is more bioavailable source of creatine than CrM and that CEE promotes greater training adaptations than CrM.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
InterpretationreasoningBecause salts are relatively weak bonds, it is likely that these creatine salts would increase creatine in the blood at equimolar doses about 1.3-1.6 times greater than creatine monohydrate.
“Since salts are relatively weak bonds, it is likely that these creatine salts would increase creatine in the blood at equimolar doses that are generally about 1.3–1.6 times greater than CrM.”
Quote in the paperNot a substantial claim- Rests on an assumption: Salts are relatively weak bonds.
Classified as probably not a substantial claim.
Interpretationnone givenWe are not aware of any pharmacokinetic or exercise-related studies to test the creatine ascorbate hypothesis.
“However, we are not aware of any pharmacokinetic or exercise related studies to test this hypothesis and benefits would seemingly be similar and more effectively dosed by co-ingestion of CrM and vitamin C.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationCreatinol in the form of creatinol-O-phosphate is not creatine, nor was it intended to increase muscle creatine content.
“Creatinol in the form of COP is not creatine, nor was it intended to increase muscle creatine content.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationMelloni and colleagues found that creatinol-O-phosphate administration increased blood phosphate levels as well as urinary excretion of phosphate and creatinine.
“The researchers found that COP administration increased blood phosphate levels as well as urinary excretion of phosphate and creatinine.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [228] Melloni, 1979, Acute clinical tolerance of creatinol-O-phosphate, Arzneimittelforschung
Not checked in the free run.
May combine two claims.
PremisereasoningCEE is a chemical alteration of creatine and is not actually creatine.
“Thus, CEE is a chemical alteration of creatine and is not actually creatine.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationCEE rapidly degrades to creatinine when exposed to stomach acid; under physiological conditions, CEE non-enzymatically converts to creatinine with no measurable conversion to creatine; and the half-life of CEE is about one minute, suggesting it may hydrolyze too quickly to reach muscle cells in its ester form.
“Childs and Tallon reported that CEE rapidly degrades to creatinine when exposed to stomach acid [34].”
- Also stated in: § 9.3. Creatine Ethyl Ester · plain
“Giese et al. [35,192] reported that under physiological conditions, CEE non-enzymatically converted to creatinine with no measurable conversion to creatine (see Figure 9).”
- Also stated in: § 9.3. Creatine Ethyl Ester · hedged
“Katseres and colleagues [193] reported that the half-life of CEE was in the order of one minute suggesting CEE may hydrolyze too quickly to reach muscle cells in its ester form.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [34] Child, R., and Tallon, M.J. (2007, January 12). Creatine ethyl ester rapidly degrades to creatinine in stomach acid. Proceedings of the International Society of Sports Nutrition 4th Annual Meeting, Las Vegas, NV, USA.
Not checked in the free run.
- cites [35] Giese, 2009, Non-enzymatic cyclization of creatine ethyl ester to creatinine, Biochem. Biophys. Res. Commun. source
- cites [192] Giese, 2009, Qualitative in vitro NMR analysis of creatine ethyl ester pronutrient in human plasma, Int. J. Sports Med. source
- cites [193] Katseres, 2009, Non-enzymatic hydrolysis of creatine ethyl ester, Biochem. Biophys. Res. Commun. source
- Also stated in: § 9.3. Creatine Ethyl Ester · plain
May combine two claims.
InterpretationreasoningCr-HCl is classified in the some evidence category to support efficacy compared to placebo, but claims that Cr-HCl is more bioavailable, effective, and/or a safer source of creatine than CrM are not supported.
“Given this analysis, Cr-HCl is classified in some evidence category to support efficacy compared to placebo. However, claims that Cr-HCl is more bioavailable, effective, and/or a safer source of creatine than CrM are not supported.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPharmacokinetic studies indicated that absorption of creatinol-O-phosphate was complete when administered intramuscularly and distributed primarily to the kidney, liver, and heart, and that COP could cross myocardial cell membranes.
“However, pharmacokinetic studies indicated that absorption of COP was complete when administered intramuscularly and distributed primarily to the kidney, liver, and heart and that COP could cross myocardial cell membranes [230].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [230] Marzo, 1979, Pharmacological and toxicological properties of creatinol O-phosphate. A review, Arzneimittelforschung
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
InterpretationreasoningBenefits of creatine ascorbate would seemingly be similar and more effectively dosed by co-ingestion of creatine monohydrate and vitamin C.
“However, we are not aware of any pharmacokinetic or exercise related studies to test this hypothesis and benefits would seemingly be similar and more effectively dosed by co-ingestion of CrM and vitamin C.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningAdding hydrochloric acid to creatine would be expected to decrease pH and improve solubility.
“Like other creatine salts, adding hydrochloric acid to creatine would be expected to decrease pH and improve solubility.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThe de França study reported some benefits of Cr-HCl and CrM supplementation on leg press and skinfold-determined body composition, but the use of skinfold calipers and statistical analysis methods make it difficult to draw any conclusions.
“The researchers reported some benefits of Cr-HCl and CrM supplementation on leg press and skinfold determine body composition. However, the use of skinfold calipers to estimate body composition and statistical analysis methods employed make it difficult to draw any conclusions.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [65] Avelar, 2015, Creatine HCl and Creatine Monohydrate Improve Strength but Only Creatine HCl Induced Changes on Body Composition in Recreational Weightlifters, Food Nutr. Sci.
Not checked in the free run.
May combine two claims.
InterpretationreasoningBecause the pre-workout supplement contained caffeine and other ergogenic nutrients, the benefits cannot be attributed to creatine nitrate.
“However, since the supplement contained caffeine and other ergogenic nutrients, the benefits cannot be attributed to CrN.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationKreider and colleagues found that creatine monohydrate loading significantly increased total muscle creatine (+31%) and phosphocreatine (+16%).
“Results revealed that CrM loading significantly increased total muscle creatine (+31%) and phosphocreatine (+16%) (see Figure 13).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Kreider, 2003, Effects of serum creatine supplementation on muscle creatine content, J. Exerc. Physiol. Online
Not checked in the free run.
May combine two claims.
InterpretationreasoningMost studies have used higher than recommended doses of creatine nitrate, and those studies show that creatine nitrate is not more effective than creatine monohydrate supplementation.
“However, most studies have used higher than recommended doses, and those studies show that CrN is not more effective than CrM supplementation.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningClaims that oral creatinol-O-phosphate is a source of creatine and/or is more bioavailable than creatine monohydrate are not supported.
“Claims that oral COP is a source of creatine and/or is more bioavailable than CrM are not supported.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningWhile mixing creatine in acidic solutions may improve solubility when mixed in water, it would have no effect on bioavailability.
“While mixing creatine in acidic solutions may improve solubility when mixed in water, as noted above, it would have no effect on bioavailability.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningSince there is some evidence that ingesting high doses of CEE can increase muscle creatine content and performance compared to placebo, CEE is categorized in the some evidence category.
“since there is some evidence that ingesting high doses of CEE can increase muscle creatine content and performance compared to placebo, we have categorized CEE in some evidence category.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningBecause amide bonds are generally very strong, pharmacokinetic data would need to show that CLL breaks down into creatine, increases creatine in the blood, and increases tissue creatine content to establish that CLL is a bioavailable source of creatine.
“Additionally, amide bonds are generally very strong, so pharmacokinetic data would need to show that CLL breaks down into creatine, increases creatine in the blood, and increases tissue creatine content to establish that CLL is a bioavailable source of creatine.”
Quote in the paperSubstantial claim- Rests on an assumption: Amide bonds are generally very strong.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCr-HCl contains about 78% creatine by molecular weight and was 37.9 times more soluble in water than CrM at 25 °C.
“They reported that Cr-HCl contains about 78% creatine by molecular weight and that Cr-HCl was 37.9 times more soluble in water than CrM at 25 °C.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [179] Gufford, 2010, Physicochemical characterization of creatine N-methylguanidinium salts, J. Diet. Suppl. source
May combine two claims.
InterpretationcitationThere is no evidence that CrM-Alk is up to 10 times more bioavailable than creatine monohydrate and/or that recommended doses are efficacious.
“Thus, while high doses of CrM-Alk may increase muscle creatine content to some degree over time, there is no evidence that CrM-Alk is up to 10 times more bioavailable than CrM and/or recommended doses are efficacious.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThese creatine salts are classified in the no-evidence-to-support bioavailability, efficacy, and safety category and cannot be considered more effective than creatine monohydrate.
“Based on this analysis, these creatine salts are classified in the no evidence to support bioavailability, efficacy, and safety category. Therefore, they cannot be considered more effective than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningSince stomach acidity generally ranges from 1.5 to 3.5, it is likely that some CEE is degraded into creatinine during normal digestion while delivering some level of creatine to blood.
“Since acidity in the stomach generally ranges from 1.5 to 3.5, it is likely that some CEE is degraded into creatinine during normal digestion while delivering some level of creatine to blood.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThere are species-specific differences in creatine metabolism and storage, so results from mice or rat data cannot be directly extrapolated to human creatine oral dosing studies.
“it is well-known that there are species specific differences in creatine metabolism and storage [200]. Therefore, you cannot directly extrapolate results from mice or rat data to human creatine oral dosing studies.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [200] Kreider, 2003, Species-specific responses to creatine supplementation, Am. J. Physiol. Regul. Integr. Comp. Physiol. source
May combine two claims.
PremisecitationSeveral studies reported that ingesting equivalent doses of creatine monohydrate promoted significantly greater increases in blood and tissue creatine content than ingesting CLL, and CLL ingestion was no different than placebo controls.
“Additionally, several of these studies reported that ingesting equivalent doses of CrM promoted significantly greater increases in blood [222,223,226] and tissue creatine content [225] than those ingesting CLL and CLL ingestion was no different than placebo controls [225,226].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [222] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-46. C.D. Cal. Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [223] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-53. C.D. Cal. Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [226] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-133 (C.D. Cal.). Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
- cites [225] Monster Energy Co., v. Vital Pharmaceuticals, Inc. et al. (2022, January 15). Case No. 5:18-cv-1882-JGB-SHK, Dkt. 434-51. (C.D. Cal.). Available online: https://www.law360.com/cases/5b8f06c4a5fd16342f7dd1b6.
Not checked in the free run.
May combine two claims.
PremisecitationOne 5 mL oral dose of creatine serum purportedly providing 2.5 g of creatine had no effect on plasma creatine levels, whereas ingestion of 2.5 g of creatine monohydrate increased plasma creatine levels to about 300 μmol/L after one hour and declining over the next 8 h.
“Additionally, they found that one 5 mL oral dose of CS purportedly providing 2.5 g of creatine had no effect on plasma creatine levels (same as water) whereas ingestion of 2.5 g of CrM increased plasma creatine levels to about 300 µmol/L after one hour of ingestion and declining in a classical manner throughout the next 8 h (see Figure 14A) [38].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] Harris, 2004, The creatine content of Creatine Serum and the change in the plasma concentration with ingestion of a single dose, J. Sports Sci. source
May combine two claims.
InterpretationreasoningCreatine orotate does not seem to be a good alternative for creatine monohydrate in dietary supplements, particularly when co-ingestion of effective doses of creatine monohydrate and beta alanine would seemingly be more effective.
“Therefore, CO does not seem to be a good alternative for CrM in dietary supplements particularly when co-ingestion of effective doses of CrM and beta alanine would seeming be more effective.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningA large amount of CEE is converted to creatinine, and CEE is less effective in increasing muscle creatine content than CrM.
“These findings suggest a large amount of CEE is converted to creatinine and CEE is less effective in increasing muscle creatine content than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationGavan and colleagues found some ergogenic benefit of creatine nitrate supplementation on muscular endurance, but it was unrelated to changes in muscle creatine content, suggesting the benefit was primarily due to nitrate and not creatine at the dosages studied.
“In terms of performance, Gavan and colleagues found some ergogenic benefit of CrN supplementation on muscular endurance, but they were unrelated to changes in muscle creatine content, suggesting the ergogenic benefit was primarily due to providing ergogenic levels of nitrate and not creatine at the dosages studied.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningBuffered creatine monohydrate is classified in the some-evidence-to-support bioavailability, efficacy, and safety category, but there is no evidence that buffered creatine is better.
“Therefore, buffered creatine monohydrate is classified in some evidence to the support bioavailability, efficacy, and safety categories, but there is no evidence that buffered creatine is better.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationCreatine serum is not a bioavailable source of creatine and therefore can have no creatine-related efficacy.
“Collectively, these studies show that CS is not a bioavailable source of creatine, and therefore can have no creatine-related efficacy.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationnone givenThere are no data indicating that these creatine salts increase blood creatine content, increase tissue creatine content, have ergogenic value, are safe for long-term supplementation, or are more effective sources of creatine than creatine monohydrate.
“However, there are no data indicating that these creatine salts increase blood creatine content, increase tissue creatine content, have any ergogenic value, are safe for long-term supplementation, or are more effective sources of creatine than CrM.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationDietary ingredients sold in the U.S. prior to October 15, 1994 were considered grandfathered and not NDIs subject to these requirements, including creatine monohydrate since it was introduced into the U.S. market in 1993.
“Dietary ingredients that were sold in the U.S. prior to October 15, 1994, were considered “grandfathered,” and therefore not NDIs subject to these requirements. This included CrM since it was introduced into the U.S. market in 1993 [236].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [236] (2020). U.S. Food and Drug Administation (Standard No. GRN, No. 931 Creatine Monohydrate).
Not checked in the free run.
May combine two claims.
Study design and conductcitationA limitation of the Ostojic et al. study is that only a 7-day washout period was observed, and it takes about 4 weeks for muscle creatine to return to normal after creatine supplementation, so testing order may have confounded results.
“However, a limitation to this study is that only a 7-day washout period was observed between treatments. It is well known that it takes about 4 weeks for muscle creatine to return to normal after creatine supplementation [47]. Thus, it is possible that the testing order may have confounded results.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] Vandenberghe, 1997, Long-term creatine intake is beneficial to muscle performance during resistance training, J. Appl. Physiol. source
May combine two claims.
InterpretationcitationThere was no evidence that CrM-Alk promoted greater training adaptations than creatine monohydrate or that participants taking CrM-Alk experienced fewer side effects than those taking creatine monohydrate.
“Additionally, was no evidence that CrM-Alk promoted greater training adaptations than those taking CrM or that participants taking CrM-Alk experienced fewer side effects than those taking CrM.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenResearch on CrM has served as the basis to establish professional guidelines, recommendations, and regulation.
“Research on CrM has served as the basis to establish professional guidelines, recommendations, and establish regulation.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationAlzChem Trostberg GmbH voluntarily submitted a GRAS application to the FDA that was not acted upon, meaning it could claim that creatine monohydrate has FDA-approved GRAS status.
“Since then, AlzChem Trostberg GmbH (the Germany manufacturer of CrM) voluntary submitted a GRAS application to the FDA that was not acted upon, meaning it could claim that CrM has FDA approved GRAS status [237,238].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [237] Carlson, S.J. (2021). GRAS Notice No. GRN 000931, Center for Food Safety and Applied Nutrition.
Not checked in the free run.
- cites [238] U.S. Food & Drug Administration (2022, January 05). GRAS Notices, Available online: https://www.cfsanappsexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&sort=GRN_No&order=DESC&startrow=1&type=basic&search=CLL.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Premisenone givenWhile FDA GRAS notifications are published and accessible to the public, self-affirmed GRAS files are not published, which makes them difficult to search and to validate their content.
“While FDA GRAS notifications are published and are accessible to the public, self-affirmed GRAS files are not published, which makes them difficult to search and to validate its content.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenAlteration of the chemical structure of creatine may negate any benefit of creatine supplementation.
“Alteration of the chemical structure of creatine in any way is assumed to change the chemical activity and biological function and may negate any benefit of creatine supplementation.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: Alteration of the chemical structure of creatine in any way changes the chemical activity and biological function of creatine.
May combine two claims.
PremisereasoningOnce an ingredient is self-affirmed as GRAS, it can be introduced into the food supply and is then not required to submit an NDI Notification to the FDA to be included in a dietary supplement under the present-in-the-food-supply exemption.
“Once an ingredient is self-affirmed as GRAS, it can be introduced into the food supply, and is then not required to submit an NDI Notification to FDA to be included in dietary supplement under the “present in the food supply” exemption noted above.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisenone givenAn NDI Notification only indicates that the FDA considers the NDI reasonably safe for human consumption; it does not affirm efficacy and/or validate any claims made about the NDI.
“However, it is important to understand that an NDI Notification only indicates that the FDA considers the NDI to be reasonably be considered as safe for human consumption. It does not affirm efficacy and/or validate any claims made about the NDI.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThe legal and regulatory status of creatine monohydrate in dietary supplements is indisputable because it appeared on the U.S. market in 1993 and there was a large body of evidence showing it was reasonably expected to be safe.
“The legal and regulatory status of CrM in dietary supplements is indisputable because it appeared on the US market in 1993 [236], and there was a large body of evidence showing it was reasonably expected to be safe.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [236] (2020). U.S. Food and Drug Administation (Standard No. GRN, No. 931 Creatine Monohydrate).
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).
InterpretationreasoningThe reason why alternate marketed forms of creatine are in the marketplace without pre-market IND notification is likely due to confusion over legal definitions of dietary supplements, natural health products, and/or food additives in different countries as well as what is meant by chemical alteration in a nutrient.
“The reason why alternate marketed forms of creatine are in the marketplace without pre-market IND notification is likely due to confusion over legal definitions of dietary supplements, natural health products, and/or food additives in different countries as well as what is meant by chemical alteration in a nutrient.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningCreatine pyruvate at doses of 5-10 g/day and creatine nitrate at 750 mg per day have not been objected to by the FDA and can be sold as dietary ingredients.
“However, creatine pyruvate at doses of 5–10 g/day and creatine nitrate at 750 mg per day have not been objected to by the FDA and can be sold as dietary ingredients.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenBinding creatine to other compounds may prevent creatine from being liberated in vivo, thereby making the form of creatine non-bioavailable or less bioavailable.
“Additionally, binding creatine to other compounds may prevent creatine from being liberated in vivo, thereby making the form of creatine non-bioavailable or less bioavailable source of creatine.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisereasoningAfter a dietary supplement is entered into the U.S. market, the FDA can restrict or ban its sale if it is deemed adulterated, and the FTC has jurisdiction over marketing claims that companies make about dietary supplements in advertising.
“After a dietary supplement is entered into the U.S. market, the FDA can restrict or ban its sale if it is deemed adulterated (e.g., unsafe). The FDA works with the Federal Trade Commission (FTC), who has jurisdiction over marketing claims that companies make about dietary supplements in advertising to regulate the dietary supplement industry.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenAlternative forms of creatine are unlikely to pose a health risk.
“While alternative forms of creatine are unlikely to pose a health risk, they are typically more expensive than CrM.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based). May combine two claims.
InterpretationreasoningConfusion over laws regulating dietary supplements combined with inadequate enforcement by regulators has created an environment where there are often little consequences of non-compliance.
“Regardless, confusion of over laws regulating dietary supplements combined with inadequate enforcement by regulators has created an environment where there are often little consequences of non-compliance.”
Quote in the paperNot a substantial claim
The authors state this as an assumption.
A full creatine molecule is contained in each creatine-related compound and would be liberated as creatine in circulation.
“assuming that a full creatine molecule is contained in the compound and would be liberated as creatine in circulation.”
The authors state this as an assumption.
Creatine citrate would have similar bioavailability to CrM.
“if it had similar bioavailability.”
The authors state this as an assumption.
The other creatine-related sources would be bioavailable.
“if the other sources were indeed bioavailable.”
The paper relies on this without support.
Nitrates may lower blood pressure.
“In terms of safety, since nitrates may lower blood pressure, there has been some concern that CrN may promote hypotension, particularly around intense exercise and/or if individuals take higher than recommended doses.”
The paper relies on this without support.
Salts are relatively weak bonds.
“Since salts are relatively weak bonds, it is likely that these creatine salts would increase creatine in the blood at equimolar doses that are generally about 1.3–1.6 times greater than CrM.”
The paper relies on this without support.
Amide bonds are generally very strong.
“Additionally, amide bonds are generally very strong, so pharmacokinetic data would need to show that CLL breaks down into creatine, increases creatine in the blood, and increases tissue creatine content to establish that CLL is a bioavailable source of creatine.”
The authors state this as an assumption.
Any change in the chemical structure of an ingredient alters the biological activity of the ingredient, thereby requiring toxicology studies to establish that the NDI is reasonably expected to be safe as altered and that the biological behavior is comparable to the native ingredient.
“Any change in the chemical structure of an ingredient is assumed to alter the biological activity of the ingredient thereby requiring toxicology studies to establish that the NDI is reasonably expected to be safe as altered and that the biological behavior is comparable to the native ingredient.”
The authors state this as an assumption.
Alteration of the chemical structure of creatine in any way changes the chemical activity and biological function of creatine.
“Alteration of the chemical structure of creatine in any way is assumed to change the chemical activity and biological function and may negate any benefit of creatine supplementation.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
To date, hundreds of clinical trials have been conducted in humans on healthy and medically managed populations with no adverse events reported and relatively few, if any, side effects noted.
“To date, hundreds of clinical trials have been conducted in humans on healthy and medically managed populations with no adverse events reported and relatively few, if any, side effects noted [2,4,12,50].”
From Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports (2025) · cites this paper as [2]
Section 8 (Creatine Monohydrate; page not provided) describes numerous controlled clinical trials, studies in healthy and clinical populations, and no reported side effects other than desired weight gain. It does not establish the specific count of hundreds of trials or explicitly say that no adverse events were reported. Its safety conclusion concerns creatine monohydrate, not all forms of creatine. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAnecdotally reported side effects and claims that creatine monohydrate is not as effective as other forms of creatine continue to permeate the Internet.
“Nevertheless, anecdotally reported side effects and claims that CrM is not as effective as other “forms” of creatine continue to permeate the Internet [2,50].”
From Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports (2025) · cites this paper as [2]
Section 8 (Creatine Monohydrate; page unavailable) describes anecdotal side-effect claims and says companies have used such claims in marketing. The Introduction (page unavailable) describes marketing claims that other forms are more effective than CrM. The Methods say the authors reviewed company websites, but the cited passages do not establish that these claims continue to permeate the Internet. (LLM, conf=0.79)
Experimental — accuracy not yet measuredCreatine monohydrate is considered Generally Recognized as Safe (GRAS) by the FDA in the United States and is the only form of creatine approved for sale in the United States, Canada, Europe, Australia, Japan, the Republic of Korea, and China.
“CrM is considered Generally Recognized as Safe (GRAS) by the Food and Drug Administration (FDA) in the United States [51] and is the only form of creatine approved for sale in the United States, Canada, Europe, Australia, Japan, the Republic of Korea, and China [2].”
From Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports (2025) · cites this paper as [2]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredMuch of the misinformation about creatine comes from companies and influencers who promote different types of creatine as more effective than CrM with fewer side effects.
“Much of the misinformation about creatine comes from companies and influencers who are promoting different types of creatine as more effective than CrM with fewer “side effects” [2].”
From Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports (2025) · cites this paper as [2]
The Introduction (section 1; page unavailable) says companies market alternative forms of creatine as more effective than CrM and describes marketing claims that they have fewer side effects, despite little or no supporting evidence. The paper does not identify influencers as promoters or establish that these claims account for much of the misinformation about creatine. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe most effective and clinically assessed source of creatine for dietary supplements is creatine monohydrate.
“The most effective and clinically assessed source of creatine for dietary supplements is creatine monohydrate (CrM) [2].”
From Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports (2025) · cites this paper as [2]
Most studies show that creatine supplementation can benefit healthy active populations as they age and provide therapeutic benefits in some clinical populations.
“Most studies show that creatine supplementation can benefit healthy active populations as they age and provide therapeutic benefits in some clinical populations [2,4].”
From Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports (2025) · cites this paper as [2]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Creatine-salt dose multipliers are too low
MajorTo deliver the same amount of creatine, the required mass ratio is CrM's creatine percentage divided by the salt's percentage. Creatine citrate therefore requires about 2.17 times as much by weight, not 1.54 times; the stated multipliers for di-creatine citrate and creatine pyruvate are also too low.
Reported 1.54 · recomputed 2.165025
“In this regard, CrM contains 87.9% creatine whereas creatine citrate (40.6%), di-creatine citrate (57.7%), creatine pyruvate (59.8%), and creatine HCl (78.2%) contain less creatine by weight compared to CrM. Therefore, one would need to mix 1.54, 1.34, 1.32, and 1.11 times more of these forms of creatine in solution to deliver the same amount of creatine than CrM.”
Citation [55] does not identify a Harris study
MinorThe text attributes a solution-stability result to Harris and coworkers [55], but reference 55 lists Kreider and coworkers and a study on body composition, strength, and sprint performance.
“Harris and coworkers [55] reported that creatine is relatively stable for 3 days in solution at neutral pH (6.5 to 7.5)”
“55. Kreider R.B. Ferreira M. Wilson M. Grindstaff P. Plisk S. Reinardy J. Cantler E. Almada A.L. Effects of creatine supplementation on body composition, strength, and sprint performance Med. Sci. Sports Exerc. 1998 30 73 82 10.1097/00005768-199801000-00011 9475647”
The creatine-pyruvate dose differs for the same cited study
MinorTwo descriptions citing study [63] give its creatine-pyruvate dose as 7.7 g and 7.3 g, respectively.
“Jäger et al. [63] compared the effects of oral ingestion of 5 g of CrM to 6.7 g of tri-creatine citrate (CC) and 7.7 g of creatine pyruvate (CPY) that provided equimolar amounts of creatine.”
“As seen in Figure 7, ingestion of 7.3 g of CPY promoted significant increases in plasma creatine levels in a similar manner as ingesting 5 g of CrM [63].”
Plasma-creatine guidance switches from μg/mL to μg/L
MinorThe guidance pairs essentially the same 200-500 μmol/L range with μg/L, whereas the earlier threshold uses μg/mL. Those mass-concentration units differ by a factor of 1000.
“Pharmacokinetic studies must be performed to show that the novel form of creatine is degraded into creatine and increases blood creatine levels to physiological levels necessary to promote creatine uptake into tissue (e.g., >200–500 µmol/L or 25–65 µg/L).”
“Viable sources of creatine in dietary supplements should increase plasma creatine levels above 200–500 µmol/L (30–75 µg/mL) within the first hour of oral ingestion”
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Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation
Harris, R. C., Söderlund, K., & Hultman, E. (1992) · Clinical Science · doi:10.1042/cs0830367 · Cited by 1,141 · cited 10× · see citing works
“In the case of creatine, individuals who consume meat and fish in their diet typically have a plasma creatine level of around 25 µmol/L (about 3.75 µg/mL), and a muscle creatine content of about 120 mmol/kg dry muscle mass (DMM) [11,12,19,20].”
BackgroundMethodInfluentialIOC Consensus Statement: Dietary Supplements and the High-performance Athlete
Maughan, R. J., Burke, L. M., Dvorak, J., Larson-Meyer, D. E., Peeling, P., Phillips, S. M., Rawson, E. S., Walsh, N. P., Garthe, I., Geyer, H., et al. (2018) · British Journal of Sports Medicine · doi:10.1136/bjsports-2018-099027 · Cited by 1,004 · see citing works
ISSN exercise & sports nutrition review update: research & recommendations
Kerksick, C. M., Wilborn, C. D., Roberts, M. D., Smith-Ryan, A., Kleiner, S. M., Jäger, R., Collins, R., Cooke, M., Davis, J. N., Galvan, E., et al. (2018) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-018-0242-y · Cited by 945 · cited 8× · see citing works
“Given the metabolic and ergogenic properties of CrM [7,14,15,24], there has also been interest in assessing the effects of CrM supplementation in various clinical populations that may benefit from increasing high-energy phosphate availability and/or increasing strength and muscle mass [5].”
BackgroundInfluentialSelf-citation(2009) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2009.01.005 · Cited by 912 · see citing works
Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-017-0173-z · Cited by 854 · cited 13× · see citing works
“R = randomized; DB = double-blind; p = placebo; SB = single blind; C = crossover; yrs = years; PLA = placebo, CHO = carbohydrate; PRO = protein; Cr = creatine; CrM = creatine monohydrate; CC = creatine citrate; CPY = creatine pyruvate; caPYR = calcium pyruvate, MgCr-C = magnesium creatine chelate, CEE = creatine ethyl…”
BackgroundInfluentialSelf-citationMuscle creatine loading in men
Hultman, E., Soderlund, K., Timmons, J. A., Cederblad, G., & Greenhaff, P. L. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.81.1.232 · Cited by 822 · see citing works
The creatine kinase system and pleiotropic effects of creatine
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- Authors
- Kreider, R. B., Jäger, R., & Purpura, M.
- Affiliations
- Texas A&M University (US)
- Increnovo LLC (United States) (US)
- Corresponding author
- Kreider, Richard B.
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2022-02-28
- Volume
- 14
- Issue
- 5
- Pages
- 1035
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC8912867
- OpenAlex
- W4214502989
- Cited by
- 103
- References
- 208
- Citations by year
- 2026: 27 · 2025: 30 · 2024: 35 · 2023: 7 · 2022: 4
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutrition and Health Studies
- Health Sciences › Medicine › Physiology › Biochemical effects in animals
- Keywords
- creatine monohydrate, bioavailability, supplement efficacy, supplement safety, regulatory status, dietary supplements, supplement marketing claims, comparative effectiveness trials
- MeSH terms
- Biological Availability, Creatine, Food Additives, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-01.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-01.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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