Title: Supplementing With Which Form of Creatine (Hydrochloride or Monohydrate) Alongside Resistance Training Can Have More Impacts on Anabolic/Catabolic Hormones, Strength and Body Composition?

PMID: 39545789 | Clinical Trial | Date: January 12, 2024 | PDF

Abbreviations

Creatine monohydrate (CrM) | Resistance training (RT) | Creatine hydrochloride (Cr-HCl) | CrM-loading phase (CrM-LP) | CrM-without loading phase (CrM-WLP) | body composition (percent body fat (PBF) | skeletal muscle mass (SMM) | muscular cross-sectional area (MCSA) | adrenocorticotropic hormone (ACTH) | growth hormone (GH) | insulin-like growth factor-1 (IGF-1)

Discussion

• This study attempted to determine the effects of RT alongside Cr-HCl or CrM supplementation on hormonal compatibility, muscle strength, muscle hypertrophy, and body composition and compare these two types of supplementation. Our findings showed that Cr-HCl did not provide any advantages over CrM.
• The results showed that RT Cr-HCl, RT CrMLP and RT CrM-WLP increased GH, IGF-1 levels and the follistatin/myostatin, testosterone/cortisol ratio and decreased cortisol and ACTH levels.
• Hormonal changes in the RT Cr-HCl group were insignificant compared to the RT CrM-LP and RT CrM-WLP groups.
• Changes in the GH, IGF-1, testosterone/cortisol, cortisol and ACTH levels in the RT Cr-HCl, RT CrM-LP and RT CrMWLP groups were significant compared to the RT PL group, but changes in the testosterone, follistatin, myostatin levels and the ratio of follistatin/myostatin were not significant.
• It seems that testosterone requires long-term intervention for meaningful changes.
• Cr-HCl supplementation (3 gr) for two weeks caused significant changes in soldiers' testosterone and cortisol levels.
• Supplementation (7 days) of Cr-HCl (3 gr) compared with CrM (3 gr) did not have a significant effect on the hormone levels of cortisol and testosterone
• CrM supplementation (4×5 gr.d-1) for more than five days along with RT (3×10 rep of 9 exercises, 75-85 % 1RM) was sufficient to increase testosterone concentration and decrease cortisol concentration
• A significant increase in intramuscular IGF-1 concentration in creatine receiving athletes (0.25 g. kg dry mass in 7 days and 0.06 g. kg dry mass in 49 days) after an 8-week RT program.
• the effects of RT on serum myostatin levels may explain the increased muscle mass induced by creatine supplementation.
• Creatine prevents or reverses myostatin-induced muscle fiber atrophy.
• Creatine may directly affect myostatin levels by increasing the expression of myostatin-related genes such as Akirin-1/Mighty, which negatively regulates myostatin.
• Anabolic and catabolic hormones affect muscle growth and strength. Two major signaling pathways control protein synthesis. One of pathways is the IGF1-Akt-mTOR, which acts as a positive regulator. The other major signaling pathway that controls skeletal muscle growth involves myostatin. Myostatin is produced by muscles and acts as a negative regulator of muscle growth.
• Muscle hypertrophy may also be induced by extracellular binding inhibitory proteins, such as follistatin, which have even greater effects than reducing myostatin.
• Androgens (steroid hormones) strongly stimulate muscle growth. The testosterone/cortisol ratio indicates an anabolic/catabolic environment due to their role in protein synthesis and protein degradation.
• Testosterone increases androgenic receptors in muscle cells and related myonucleoli and satellite cells.
• Testosterone also has an increasing effect on IGF-1 and GH and causes the promotion of anabolism by increasing protein synthesis and inhibiting protein degradation.
• The results of the present study showed no difference between the hormonal adaptations caused by supplementation with Cr-HCl and CrM. Cr-HCl has been marketed as a more bioavailable source of creatine than CrM.
• According to the research, if a bioavailable source of creatine is consumed in physiologically effective doses, it is not broken down during digestion. The creatine content of blood and tissue can be increased to physiologically significant amounts (20 to 40 %).
• It does not matter which form of creatine has better mixing properties and/or is more soluble.
• creatine salts with improved aqueous solubility and oral absorption characteristics can provide improvements over CM in therapeutic applications requiring high doses of creatine.
• Cr-HCl does not have a greater effect than CrM, and it seems that it only has better solubility.
• Creatine’s solubility depends on temperature and pH (the lower the pH, the more excellent the solubility).
• The common recommendation to dissolve creatine in acidic juice, such as orange juice, was made.
• CrM is the cheapest form of creatine. Therefore, according to the current research results and the effects of Cr-HCl compared to CrM, it is not economical to use and has no more effects.
• The results showed that HCl and CrM supplementation along with RT increased muscle strength (bench press, leg press), arm and thigh MCSA, SMM and reduced PBF, but the changes observed between Cr-HCl, RT CrM-LP and RT CrM-WLP were not significant.
• The dosage of creatine, supplementation period, training period and training intensity were the reasons for the different in some studies between HCl and CrM.
• Creatine supplementation (0.1 gr.kg-1) during six weeks of RT was a safe and effective strategy for increasing muscle strength in young active adults.
• Glycogen decreases during RT and creatine can affect muscle glycogen stores (glycogen increases ATP resynthesis during RT sessions).
• Creatine increases intramuscular PCr levels, which may accelerate ATP resynthesis and/or PCr recovery after each set; over time, these factors may help increase strength.
• Creatine supplementation increases calcium reabsorption into the sarcoplasmic reticulum, leading to faster actin-myosin cross-bridge cycling during repetitive muscle contractions and ultimately improving muscle strength.
• Creatine can increase glucose disposal and decrease glycogen stores during exercise sessions by increasing mobility and glucose transporter type 4 (GLUT-4) content in people who do RT.
• Creatine supplementation can stimulate signaling pathways including IGF-1 and predominantly phosphoinositide 3-kinase (PI3K)/Akt-PKB/mechanistic target of rapamycin complex (mTOR), which plays an important role in the regulation of muscle hypertrophy .
• The increase in lean mass following creatine supplementation has been attributed, at least in part, to water retention in muscle tissue.
• In general, studies on creatine supplementation have reported an increase in intracellular volume without changes in extracellular volume, possibly due to the high osmotic load associated with increased creatine and Na in the cytosol. Indeed, cell swelling has been characterized as an anabolic signal, which can trigger the activation of osmotic molecules as G protein-coupled receptors in the mitogen-activated protein kinase (MAPK) and sphingosine kinase 1 (SPHK1) pathways stimulate and create positive feedback.
• Regarding the effects of creatine on fat tissue, there is direct evidence that creatine affects certain aspects of fat and adipose tissue metabolism and triglyceride synthesis in cell types.
• Creatine stimulates mitochondrial ATP turnover in adipose tissue, increasing the metabolic rate of subcutaneous and brown adipose tissues.
• Creatine inhibited cytoplasmic triglyceride formation in adipogenic cell culture models in a dose-dependent manner.
• Creatine metabolism is important in fat bioenergetics, and creatine supplementation positively affects energy expenditure.
• Creatine increased lean tissue mass due to creatine supplementation, potentially increasing resting metabolic rate and total daily energy expenditure (through increased participation in physical activity), it can explain the decrease in fat mass and body fat percentage.
• Cr-HCl, like CrM, has an effect on hormonal compatibility, strength, hypertrophy and body composition and does not seem to have higher effects than CrM.
• CrM does not have a high solubility, but Cr-HCl has a high solubility; this is the only difference between the two supplements.
• According to the available information, solubility does not affect creatine's bioavailability; creatine monohydrate is 100 % bioavailable.

Study limitations

• The first limitation of the present study was the lack of measurement of muscle creatine content.
• The second limitation was the study of subjects' nutrition during the research period using a food recall questionnaire.
• In this study, with the guidance and recommendations made at the beginning of the study, the subjects tried to follow a similar dietary pattern to reduce the effects of nutrition on the desired variables. In addition, estimated body fat percentage and muscle mass were estimated using a multifrequency impedance body composition analyzer (Mediana, Seoul, South Korea) and the MSCA in this study was calculated based on formulas proposed by Heymsfield et al. and Knapik et al. for measuring the amount of hypertrophic changes in the arm (upper body) and thigh (lower body).

Conclusions

• In general, the results showed that supplementation with Cr-HCl and CrM increases GH, IGF-1 levels, the ratio of follistatin/myostatin, testosterone/cortisol, muscle strength (bench press, leg press), arm and thigh MCSA, SMM and significantly decreases cortisol, ACTH levels and PBF.
• Hormonal adaptations, strength and body composition in the RT Cr-HCl group were not significant compared to the RT CrM-LP and RT CrM-WLP groups and only changes in the supplementary groups were significant compared to the control group.
• The results showed the effects of Cr-HCl and CrM on hormonal compatibility, strength and hypertrophy, but Cr-HCl does not seem to have more effects than CrM. Despite claims of increased solubility, bioavailability, and superior absorption mechanisms, there is currently no evidence to support the use of Cr-HCl instead of CrM.
• Although Cr-HCl affects performance and hormonal indicators, due to its very high price compared to CrM, its use is not economical and it cannot replace CrM.
• Considering the very few studies in this regard, for more accurate conclusions, more studies are needed in different age groups and athletes of different fields, at different levels of sports and with longer supplementation period.