Comparison of new forms of creatine in raising plasma creatine levels
Open accessAbstract
BACKGROUND: Previous research has shown that plasma creatine levels are influenced by extracellular concentrations of insulin and glucose as well as by the intracellular creatine concentration. However, the form of creatine administered does not appear to have any effect although specific data on this is lacking. This study examined whether the administration of three different forms of creatine had different effects on plasma creatine concentrations and pharmacokinetics. METHODS: Six healthy subjects (three female and three male subjects) participated in the study. Each subject was assigned to ingest a single dose of isomolar amounts of creatine (4.4 g) in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr) using a balanced cross-over design. Plasma concentration curves, determined over eight hours after ingestion, were subject to pharmacokinetic analysis and primary derived data were analyzed by repeated measures ANOVA. RESULTS: Mean peak concentrations and area under the curve (AUC) were significantly higher with CrPyr (17 and 14%, respectively) in comparison to CrM and CrC. Mean peak concentration and AUC were not significantly different between CrM and CrC. Despite the higher peak concentration with CrPyr there was no difference between the estimated velocity constants of absorption (ka) or elimination (kel) between the three treatments. There was no effect of treatment with CrPyr on the plasma pyruvate concentration. CONCLUSION: The findings suggest that different forms of creatine result in slightly altered kinetics of plasma creatine absorption following ingestion of isomolar (with respect to creatine) doses of CrM, CrC and CrPyr although differences in ka could not be detected due to the small number of blood samples taken during the absorption phase. Characteristically this resulted in higher plasma concentrations of creatine with CrPyr. Differences in bioavailability are thought to be unlikely since absorption of CrM is already close to 100%. The small differences in kinetics are unlikely to have any effect on muscle creatine elevation during periods of creatine loading.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Peak 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).”
From Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review (2022) · cites this paper as [63]
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 measuredSome 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].”
From Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review (2022) · cites this paper as [63]
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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 4× · see citing works
“All treatments at all doses resulted in substantial increases in plasma creatine which if repeated could be expected to lead to enhancement of the creatine content in muscle [1,2].”
BackgroundInfluentialSelf-citationPharmacokinetics of the Dietary Supplement Creatine
Persky, A. M., Brazeau, G. A., & Hochhaus, G. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342060-00005 · Cited by 132 · see citing works
Rawson, E. S., Clarkson, P. M., Price, T. B., & Miles, M. P. (2002) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2002.00924.x · Cited by 94 · see citing works
Flagged first, then by citations
Research works printed but not linked: 15
- Terjung RL Clarkson P Eichner ER Greenhaff PL Hespel PJ Israel RG Kraemer WJ Meyer RA Spriet LL Tarnopolsky MA Wagenmakers AJM Williams MH The American College of Sports Medicine Roundtable on the physiological and health effects of oral creatine supplementation Med Sci Sports Exerc 2000 32 706 717 10731017 10.1097/00005768-200003000-00024 · DOI
- Deldicque L Décombaz J Zbinden Foncea H Vuichoud J Poortmans JR Francaux M Kinetics of creatine ingested as a food ingredient Eur J Appl Physiol 2008 102 133 143 17851680 10.1007/s00421-007-0558-9 · DOI · Paper page
- Stanko RT Robertson RJ Galbreath RW Reilly JJ Jr Greenawalt KD Goss FL Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate J Appl Physiol 1990 69 1651 1656 2272957
- Stanko RT Robertson RJ Spina RJ Reilly JJ Jr Greenawalt KD Goss FL Enhancement of arm exercise endurance capacity with dihydroxyacetone and pyruvate J Appl Physiol 1990 68 119 124 2312449
- Kalman D Colker CM Wilers I Routs JB Antonio J The effects of pyruvate supplementation on body composition in overweight individuals Nutrition 1999 15 337 340 10355844 10.1016/S0899-9007(99)00034-9 · DOI
- Stone MH Sanborn K Smith LL O'Bryant HS Hoke T Utter AC Johnson RL Boros R Hruby J Pierce KC Stone ME Garner B Effects of in-season (5 weeks) creatine and pyruvate supplementation on aerobic performance and body composition in American football players Int J Sport Nutr 1999 9 146 165 10362452
- Koh-Banerjee PK Ferrerira MP Greenwood M Bowden RG Cowen PN Almada AL Kreider RB Effects of Calcium Pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise Nutrition 2005 21 312 319 15797672 10.1016/j.nut.2004.06.026 · DOI
- Morrison MA Spriet LL Dyck DJ Pyruvate ingestion for 7-days does not improve aerobic performance in well-trained individuals J Appl Physiol 2000 89 549 556 10926637
- Van Schuylenbergh R Van Leemputte M Hespel P Effects of oral creatine-pyruvate supplementation in cycling performance Int J Sports Med 2003 24 144 150 12669262 10.1055/s-2003-38400 · DOI · Paper page
- Harris RC Hultman E Nordesjö LO Glycogen, glycolytic intermediates and high energy phosphates in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values Scand J Clin Lab Invest 1974 33 109 120 4852173 10.3109/00365517409082477 · DOI
- Fitch CD Sinton DW A Study of Creatine Metabolism in Diseases Causing Muscle Wasting J Clin Invest 1964 43 444 452 14135495 PMC441937
- Green AL Hultman E Macdonald IA Sewell DA Greenhaff PL Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans Am J Physiol 1996 271 E821 826 8944667
- Schedel JM Tanaka H Kiyonaga A Shindo M Schutz Y Acute creatine ingestion in human: consequences on serum creatine and creatinine concentrations Life Sci 1999 65 2463 2470 10622230 10.1016/S0024-3205(99)00512-3 · DOI · Paper page
- Vanakoski J Kosunen V Meririnne E Seppala T Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations Int J Clin Pharmacol Ther 1998 36 258 262 9629989
- Persky AM Müller M Derendorf H Grant M Brazeau GA Hochhaus G Single- and multiple-dose pharmacokinetics of oral creatine J Clin Pharmacol 2003 43 29 37 12520625 10.1177/0091270002239703 · DOI
Cited by
Sorted by citations
Creatine supplementation with specific view to exercise/sports performance: An update
Cooper, R., Naclerio, F., Allgrove, J., & Jimenez, A. (2012) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-9-33 · Cited by 306 · see citing works
Creatine biosynthesis and transport in health and disease
Joncquel-Chevalier Curt, M., Voicu, P.-M., Fontaine, M., Dessein, A.-F., Porchet, N., Mention-Mulliez, K., Dobbelaere, D., Soto-Ares, G., Cheillan, D., & Vamecq, J. (2015) · Biochimie · doi:10.1016/j.biochi.2015.10.022 · Cited by 238 · see citing works
Analysis of the efficacy, safety, and regulatory status of novel forms of creatine
Jäger, R., Purpura, M., Shao, A., Inoue, T., & Kreider, R. B. (2011) · Amino Acids · doi:10.1007/s00726-011-0874-6 · Cited by 181 · see citing works
Self-citationKreider, R. B., Jäger, R., & Purpura, M. (2022) · Nutrients · doi:10.3390/nu14051035 · Cited by 103 · see citing works
Self-citationCreatine supplementation in women's health: a lifespan perspective
Smith-Ryan, A. E., Cabre, H. E., Eckerson, J. M., & Candow, D. G. (2021) · Nutrients · doi:10.3390/nu13030877 · Cited by 92 · see citing works
Cooke, M. B., Brabham, B., Buford, T. W., Shelmadine, B. D., McPheeters, M., Hudson, G. M., Stathis, C., Greenwood, M., Kreider, R., & Willoughby, D. S. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-014-2866-1 · Cited by 58 · see citing works
Effect of creatine, creatinine, and creatine ethyl ester on TLR expression in macrophages
Leland, K. M., McDonald, T. L., & Drescher, K. M. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.04.018 · Cited by 37 · see citing works
Vallet, J. L., Miles, J. R., & Rempel, L. A. (2013) · Journal of Animal Science · doi:10.2527/jas.2012-5610 · Cited by 33 · see citing works
Fazio, C., Elder, C. L., & Harris, M. M. (2022) · Journal of Strength & Conditioning Research · doi:10.1519/jsc.0000000000003873 · Cited by 20 · see citing works
- Authors
- Jäger, R., Harris, R. C., Purpura, M., & Francaux, M.
- Affiliations
- Increnovo LLC (United States) (US)
- University of Chichester (GB)
- UCLouvain (BE)
- Corresponding author
- Jäger, Ralf
- Venue
- Journal of the International Society of Sports Nutrition
- Publisher
- Informa UK Limited
- Published
- 2007-07-13
- Volume
- 4
- Issue
- 1
- Pages
- 17-17
- ISSN
- 1550-2783 (ISSN-L)
- PMC
- PMC2206055
- OpenAlex
- W1980508398
- Cited by
- 47
- References
- 3
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the International Society of Sports Nutrition (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Biochemical effects in animals
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Keywords
- creatine, creatine monohydrate, plasma creatine, bioavailability, creatine loading, muscle creatine, pyruvate
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
