Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth

Alraddadi, Eman A.; Ryan, L.; Vennerstrom, Jonathan L.; Lakowski, Ted M.; Miller, Donald W.

doi:10.3390/pharmaceutics10010031

Cited by 16 publications

(14 citation statements)

References 47 publications

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“…Creatine (methyl guanidine-acetic acid) is derived and synthesized from reactions involving the amino acids arginine, glycine, and methionine in the kidneys and liver or can be ingested exogenously primarily from animal-based foods (i.e., red meat, seafood) or through dietary supplements (8)(9)(10)(11). Ninety-five percent of creatine is found in skeletal muscle with the remaining 5% dispersed across the brain, liver, kidney, and testes (8,12).…”

Section: Discussion Creatine Metabolism and Energy Supplymentioning

confidence: 99%

“…The average amount of total creatine stored in the body is ~120 g (for a 70 kg human) and the rate of creatine degradation to creatinine is ~1.7% of the total body creatine pool per day (13,14). To compensate for this daily turnover, the average person requires ~2 g creatine per day, with about half of this daily requirement (1 g) synthesized endogenously and the remainder coming from dietary sources (10,12,15).…”

Section: Discussion Creatine Metabolism and Energy Supplymentioning

confidence: 99%

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The Potential and Challenges of Creatine Supplementation for Cognition/Memory in Older Adults

Machado¹,

Pereira²

2023

ejgg

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The following databases were searched: PubMed, PsychInfo, EBSCO, Medline, BioMed central, and Science Direct. Inclusion criteria specified peer-reviewed studies investigating creatine metabolism and/or creatine supplementation, and assessing cognition, and memory in old adults, and published between January, 2000 to September, 2022. Each author searched for articles separately based on the descriptors "creatine supplementation", "old people", "elderly", and "aging". After removing duplicate articles and abstracts that did not meet the inclusion criteria, only common articles selected by the authors were adopted.

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Section: Discussion Creatine Metabolism and Energy Supplymentioning

confidence: 99%

Section: Discussion Creatine Metabolism and Energy Supplymentioning

confidence: 99%

The Potential and Challenges of Creatine Supplementation for Cognition/Memory in Older Adults

Machado¹,

Pereira²

2023

ejgg

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“…While mixing creatine in acidic solutions may improve solubility when mixed in water, as noted above, it would have no effect on bioavailability. These claims are also apparently based on a report from Alraddadi et al [199] who conducted a bioavailability study in rats with labeled creatine (creatine-13 C) at a low (10 mg/kg) and high (70 mg/kg) oral doses. They then assessed the amount of creatine-13 C incorporated into plasma, muscle and brain tissue and used a simulated prediction model to estimate how Cr-HCl would theoretically affect tissue creatine retention based on differences in solubility.…”

Section: Creatine Hclmentioning

confidence: 99%

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review

Kreider

Jäger²,

Purpura³

2022

Nutrients

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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.

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“…Although CRM has been validated in many studies for its value and safety, its use seems to be somewhat limited due to several technical or performance constraints, including its solubility in water, stability, bioavailability, and/or performance in specific conditions (Alraddadi, Lillico, Vennerstrom, Lakowski, & Miller, 2018;Kieburtz et al, 2015).…”

Section: Cn-crn Performancementioning

confidence: 99%

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

Ostojić

Štajer

Ostojić

2019

Food Science & Nutrition

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A novel creatine blend (creatine nitrate mixed with creatinine, CN‐CRN) has been anecdotally suggested to be superior to traditional creatine formulations for bioavailability and performance. However, does CN‐CRN supremely affects creatine levels in the blood and skeletal muscle of healthy humans remain currently unknown. This randomized, controlled, double‐blind, crossover trial evaluated the acute effects of single‐dose CN‐CRN on serum creatine levels, and 5‐days intervention with CN‐CRN on skeletal muscle creatine and safety biomarkers in healthy men. Ten healthy young men (23.6 ± 2.9 years) were allocated to receive either CN‐CRN (3 grams of creatine nitrate mixed with 3 grams of creatinine), pure creatine nitrate (3 grams, CN), or regular creatine monohydrate (3 grams, CRM) by oral administration. We found that CN‐CRN resulted in a more powerful rise in serum creatine levels comparing to either CN or CRM after a single‐dose intervention, as evaluated with the area under the concentration–time curve calculation (701.1 ± 62.1 (µmol/L) × min versus 622.7 ± 62.9 (µmol/L) × min versus 466.3 ± 47.9 (µmol/L) × min; p < .001). The peak serum creatine levels at 60‐min sampling interval were significantly higher in CN‐CRN group (183.7 ± 15.5 µmol/L), as compared to CN group (163.8 ± 12.9 µmol/L) and CRM group (118.6 ± 12.9 µmol/L) (p < .001). This was accompanied by a significantly superior increase in muscle creatine levels after CN‐CRN administration at 5‐days follow‐up, as compared to CN and CRM, respectively (9.6% versus 8.0% versus 2.1%; p = .01). While 2 out of 10 participants were found to be nonresponsive to CN intervention (20.0%) (e.g., no amplification in muscle creatine levels found at 5‐days follow‐up), and 3 participants out of 10 were nonresponsive in CRM trial (30%), no nonresponders were found after CN‐CRN administration, with individual upswing in total muscle creatine varied in this group from 2.0% (lowest increment) to 16.8% (highest increment). Supplemental CN‐CRN significantly decreased estimated glomerular filtration rate (eGFR) at 5‐days follow‐up, as compared to other interventions (p = .004), with the average reduction was 14.8 ± 7.7% (95% confidence interval; from 9.3 to 20.3). Nevertheless, no single participant experienced a clinically relevant reduction in eGFR (< 60 ml/min/1.73 m2) throughout the course of the trial. Liver enzymes remained in reference ranges throughout the study, with no participant experienced high liver blood tests (e.g., AST > 40 units per L or ALT >56 units per L). Besides, no participant reported any major side effects during the trial, while the odors of CN‐CRN and CN formulations were considered somewhat unpleasant in 8 out of 10 participants (80.0%). Our results suggest that CN‐CRN is a preferred and relatively safe alternative to traditional creatine formulations for improved creatine bioavailability in the blood and skeletal muscle after single‐dose and 5‐days interventions.

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Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth

Cited by 16 publications

References 47 publications

The Potential and Challenges of Creatine Supplementation for Cognition/Memory in Older Adults

The Potential and Challenges of Creatine Supplementation for Cognition/Memory in Older Adults

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review

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

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