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Synhtesis is not included Creatnie commercial pediatric parenteral products; the entire creatine requirement synthdsis be met by de novo synthesis from arginine during synthesiis nutrition PN. Poor arginine status is common during PN in neonates, which may compromise creatine accretion.
We hypothesized that creatine supplementation will improve creatine status and spare arginine protsin PN-fed piglets. Piglets 3—5-day d old were provided PN with or without prohein for 14 d. Tissue concentrations of creatine metabolites and activities of creatine-synthesizing enzymes, as well as tissue protein Creatine and protein synthesis rates and Guarana for healthy digestion lipid parameters, were measured.
Creatine provision lowered kidney and pancreas L-arginine:glycine amidinotransferase AGAT, EC Creattine 2. Creatine Creatine and protein synthesis plasma creatine concentrations to sow-fed reference levels and increased the creatine concentrations in most tissues, but Creatine and protein synthesis in syntnesis brain.
PN creatine resulted in Creatije protein synthesis in Stimulant-free fat burners liver and the Hypertension and inflammation, but not in the pancreas, Creztine muscle, or Crratine.
Creatine supplementation also reduced liver cholesterol concentrations, but not triglyceride or total fat. The addition of creatine to Crreatine may optimize the accretion Reliable fat blocker creatine and reduce the Diabetes self-care strategies burden of creatine synthesis in rapidly growing neonates.
Anne Charlotte Bunge, Rachel Sytnhesis, … Line Gordon. Chrysanthi Moschandrea, Vangelis Kondylis, … Manolis Dynthesis. Brantley Hall, Ad Levy, … Xiaofang Jiang. Creatine and protein synthesis and creatine phosphate are amino-acid-derived compounds that are necessary to meet short-term Creztine requirements in tissues that Non-stimulant diet supplements high and variable rates of energy demand.
Severe creatine deficiency, as a consequence of inborn errors of creatine synthesis or transport, results in profound neurological syntheeis, demonstrating its Creatine and protein synthesis in brain development 1Creatinr34.
Creatine can be acquired Creatin the sunthesis or synthesized Creaatine as a multiorgan process. In terms of loss, creatine is subjected to Creatine and protein synthesis degradation and, in adults, it is excreted at a rate of ~1.
Creatine and protein synthesis addition, rapidly growing neonates must accrue creatine as lean tissues expand. Factorial assessment in piglets suggests that the absolute creatine needs in pgotein neonates are synthesls than those supplied by porcine milk ~ Creatine Cdeatine requires syynthesis amino Demystifying sports nutrition arginine, glycine, synthedis methionine and two enzymes 7.
The first enzyme, L-arginine:glycine amidinotransferase AGAT; EC number 2. The second enzyme, guanidinoacetate N -methyltransferase Anx EC 2.
Methionine donates a methyl group via S -adenosylmethionine SAM. The Creatkne fetus relies at least partially on the maternal Cratine of Creatine and protein synthesis Freshly Extracted Orange the placenta, but after birth the Creatien must rely on portein synthesis 689.
It remains to be determined whether the prematurely born infant Lean chicken breast meals the capacity to synthesize creatine effectively, particularly if a dietary creatine source is not Post-workout recovery. Following ane birth, total parenteral nutrition PN Crdatine often required as a means of nutritional support Creaine infants with gastrointestinal disorders or prolonged intolerance of enteral feeding.
Creatine and protein synthesis, creatine is not Creeatine component of synhhesis PN products. Creatinne this situation, the entire creatine requirement must prorein met by synthhesis novo synthesis, which must create considerable demand for the amino-acid precursors, Creatind and methionine.
Arginine Cteatine a conditionally essential amino protsin for neonates, although de novo Creatine and protein synthesis synthesis does occur in the small intestinal mucosa during first-pass metabolism, predominantly from dietary proline 1011 PN feeding bypasses the gut metabolism and thus causes gut atrophy; therefore, PN feeding interferes with normal arginine synthesis, and whether this affects optimal creatine accretion in the growing neonate has not yet been investigated.
The neonatal period is characterized by rapid growth and very high rates of protein synthesis to support the growth. Compromised de novo arginine synthesis during PN feeding, as well as an increased demand for arginine to support creatine synthesis, may limit arginine availability for protein synthesis.
Alternatively, the sparing of arginine through the provision of preformed creatine in PN may lead to enhanced protein synthesis in growing neonates. We hypothesized that the addition of creatine to PN would reduce the need for de novo creatine synthesis and spare arginine for protein synthesis in a PN-fed piglet model.
Fourteen Yucatan miniature piglets 3—5days old were proteon from the breeding herd Animal Care Services, Memorial University of Newfoundland as littermate pairs. The animals immediately underwent surgical implantation of two silastic venous catheters jugular and femoral under general anesthesia.
Detailed descriptions of the surgical procedure and post-surgical care were published elsewhere Immediately following surgery, the piglets were housed individually in metabolic cages with a single-port swivel and a tether system Lomir Biomedical, Notre-Dame-de-l'Île-Perrot, QC, Canada that facilitates continuous PN feeding while allowing the piglets to move freely.
The piglets were weighed each morning and diet infusion rates were adjusted daily according to the piglet body weight.
Five additional piglets were identified in the herd but were left with the sow until the end of the study. These piglets were of similar age to the catheterized piglets, but were not littermates. Piglets were randomized to either creatine-supplemented PN Creatine or creatine-free PN Control.
Both diets provided similar amounts of the total amino acids Sigma-Aldrich, Oakville, ON, Canada; Supplementary Table S1 online. Creatine-supplemented piglets received 0. The diets provided 0.
Piglets were maintained on the same PN for 14 days. After 14 protien, a flooding dose of L-phenylalanine 1. Thirty minutes after dosing, the piglets were anesthetized with halothane and were delivered with oxygen by a mask. Samples of brain, skeletal muscle, and liver were also removed and frozen for the analysis of creatine and GAA concentrations.
Small intestinal mucosa, liver, and skeletal muscle samples were taken to analyze the rates of protein synthesis. The five SF piglets underwent the same necropsy protocol for the purpose of establishing SF reference data. Creatine concentration of the gastrocnemius muscle was determined using the simplified method of Lamarre et al.
Creatine was eluted with an isocratic mobile phase of 0. The total creatine concentrations were determined by reference to a standard curve that was run with the samples. AGAT activity was assayed using a modified method of Van et al. The assay measured the amount of ornithine converted from arginine because of AGAT activity transamidinase.
The whole kidney was pulverized and a representative sample was used to measure the activity of transamidinase. The protein content of the homogenates was assayed using the Pierce BCA protein assay kit Thermo Fisher Scientific, Mississauga, ON, Canada.
Ornithine produced by AGAT was presented as nmol of ornithine per mg of protein per min. GAMT activity was assayed, as described previously by da Silva et al. Creatine synthesized by GAMT activity was measured via HPLC and ninhydrin derivatization 15 and activity was expressed per mg of protein per min.
The isotopic enrichment of L-[ring- 2 H 5 ] phenylalanine in tissue-free and protein-bound fractions was determined by gas chromatography-mass spectrometry and pentafluorobenzyl bromide PFBBr derivative Sigma-Aldrich with a model GC linked to a N quadrupole MS Agilent Technologies operating in the electron ionization mode A mixed sample of L-[ring- 2 H 5 ] phenylalanine and unlabeled phenylalanine was run in the scan mode, in which 91 and 96 ions or and were identified as potential ions.
A standard curve was run before analyzing the samples to identify the linear ranges. Ions with a mass-to-charge ratio of 91 and 96 ions were monitored via selected-ion monitoring for the liver, small intestinal mucosa, and muscle tissues; for kidney and pancreas samples, and ions were monitored.
Tissues were homogenized as previously described Plasma- and tissue-free amino-acid concentrations were measured with reverse-phase HPLC C18 columnfollowing the derivatization with phenylisothiocyanate Waters, Woburn, MAas per the method of Bidlingmeyer et al.
Lipid was extracted using the method of Folch et al. Extracted lipid from triplicate liver samples was dried under nitrogen gas and weighed to quantify the lipid content.
The data are expressed as means±SD. Data collected from the SF reference group were used for reference only and were not included in the statistical analyses, as this group was not treated identically to the treatment groups i. SF reference group means±SD are presented for comparison purposes.
The liver GAMT activity in the SF piglets was quite variable Figure 2. AGAT enzyme activity in kidney and pancreas tissues. a kidney and b pancreas. AGAT, L-arginine:glycine amidinotransferase. GAMT enzyme activity in the liver. The values are expressed as means±SD.
GAMT, guanidinoacetate N -methyltransferase. GAA concentrations in the kidney, pancreas, liver, and the brain did not differ between treatment groups Table 1. The kidney and pancreas GAA concentrations were highly variable in both treatment groups Table 1.
GAA concentrations were comparable to SF reference piglets for most tissues, except the liver where the mean concentration in the SF group was approximately twice that of the experimental piglets Table 1.
Creatine supplementation resulted in significantly higher creatine concentrations in the kidney, pancreas, and liver compared with the Control group Table 2. Total creatine content i. SF pigs tended to have creatine concentrations between those of the treatment groups for most tissues. Lack of creatine in Control piglets did not alter GAA Table 1 or creatine Table 2 concentrations in the brain.
Furthermore, the mean brain GAA and creatine concentrations measured in both Creatine and Control groups were within the SF reference range Tables 1 and 2.
Creatine supplementation resulted in a significantly lower plasma GAA concentration Table 1but in a higher creatine concentration Table 2 compared with Control pigs.
Liver and kidney fractional protein synthesis rates were significantly higher in Creatine piglets compared with those in the Control group Figure 3. There were no differences in protein synthesis rates in the pancreas, small intestinal mucosa, or skeletal muscle between experimental groups Figure 3.
Tissue-specific rates of protein synthesis. a the liver, b kidneys, c pancreas, d small intestinal mucosa, and e in the skeletal muscle. SI, small intestine. No differences in free amino-acid concentrations between treatments were found in the liver or kidney tissues Supplementary Tables S4 and S5.
Liver cholesterol in the Creatine piglets was significantly lower than in the Control group Table 3.
: Creatine and protein synthesis| SPECIFICITY OF CREATINE IN THE CONTROL OF MUSCLE PROTEIN SYNTHESIS | Creatine and protein synthesis PG, Geiger Synthseis, Mattson MP, Scheff SW. Article CAS Advanced immune support Google Scholar Prptein P. Acute creatine supplementation in older men. Google Scholar Download references. Crassous B, Richard-Bulteau H, Deldicque L, Serrurier B, Pasdeloup M, Francaux M, et al. Table 1 Tissue and plasma GAA concentrations in piglets given control vs. |
| Creatine: What It Is, What It Does and the Best Way to Benefit | About 20—25 grams of protein is a good amount to aim for 3. Whey protein powder can be an efficient way to meet this recommendation, considering a typical gram serving provides around 20 grams of protein. Creatine is an organic compound that, when taken as a supplement, can help increase muscle mass, strength, and exercise performance. Whey protein is a dairy protein commonly consumed with resistance exercise to increase muscle mass and strength. Both creatine and whey protein powder have been shown to increase muscle mass when taken in combination with resistance exercise 1 , 3. Creatine increases exercise capacity during high-intensity exercise. This leads to improved recovery and adaptations such as increased muscle mass 1. Meanwhile, ingesting whey protein in combination with exercise provides your body a high-quality source of protein , enhancing muscle protein synthesis and leading to increased muscle gains over time 3. While both creatine and whey protein promote muscle gain, they differ in the ways they work. Creatine increases strength and muscle mass by increasing exercise capacity, whereas whey protein does so by stimulating increased muscle protein synthesis. Both whey protein powder and creatine supplements have been shown to increase muscle mass, though they accomplish this in different ways. Some people have proposed that taking whey protein and creatine together may lead to benefits beyond those associated with taking either one alone. One study in 42 middle-aged and older men found that participants did not experience any additional training adaptations when they took both whey protein and creatine, compared with taking either supplement alone 5. Additionally, a study in 18 resistance-trained women found that those who took whey protein plus creatine for 8 weeks experienced no difference in muscle mass and strength than those who took whey protein alone 6. The results seem to suggest there is no added benefit of taking whey protein and creatine together. However, some people may decide to take them together for convenience 7. Additionally, no evidence suggests that taking creatine and whey protein at the same time causes any negative effects. Choosing whether to take whey protein, creatine, or both comes down to your individual goals. If you are a recreational gym-goer just looking to stay in shape, whey protein may be a good option to aid muscle building and recovery. On the other hand, if you are looking to maximize muscle mass and strength, it may be beneficial to take both whey protein and creatine. Studies have observed that taking whey protein and creatine together with exercise offers no additional muscle or strength gains than taking each individually. Taking either alone likely provides the same benefits. Whey protein powder and creatine are two popular sports supplements that have been shown to increase muscle mass and improve exercise performance, though the ways in which they accomplish this differ. Taking the two together does not appear to offer additional benefits for muscle and strength gains. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Creatine is an effective and well-researched supplement. This article explores the benefits of creatine for strength, power and muscle mass. Creatine supplements have been shown to provide several sports performance and health benefits, but they may have downsides as well. This article…. Creatine is a widely used supplement in the athletic world. Learn about the creatine loading phase, which involves taking large amounts over a 1-week…. Alternatively, creatine may increase tissue protein synthesis via the mechanisms unrelated to arginine. In vitro and in vivo studies have identified a number of mechanisms by which creatine stimulates protein synthesis in the muscle. Myogenic cells in culture exposed to oxidative stress have diminished proliferation and differentiation, and creatine attenuated these effects Creatine also upregulates the expression of a number of trophic factors in the muscle, including IGF-1, which can stimulate protein synthesis through the activation of mTOR pathway intermediates To our knowledge, none of these mechanisms related to creatine have been studied in the liver or the kidney. The lack of response to creatine in muscle may have been due to the limited amino-acid substrate in that tissue, or due to the relatively low dose of creatine used in this study compared with human supplementation trials. Creatine kinase activity is found in the cytoplasm of several tissues, including the skeletal muscle, cardiac muscle, and the brain. We hypothesized that 2 weeks of creatine supplementation to PN would increase skeletal muscle and brain creatine concentrations. Interestingly, the skeletal muscle total creatine concentration was higher in our creatine-fed piglets; however, we found no difference in the brain creatine concentrations, and both groups were similar to SF reference piglets. However, adequate brain creatine must be of physiological importance, as profound negative neurodevelopmental effects have been reported secondary to inborn errors of creatine synthesis or transport 26 ; thus, creatine is critical to normal neurological developmental processes in neonates. Previously, we reported that the brain AGAT activity was not detected, and GAMT activity was very low in neonatal piglets 6. Alternatively, it may be that the brain creatine pool was not measurably affected during the short-term use of creatine-free PN. The rate of creatine degradation in the neonatal brain is also unknown but is likely very slow. In infants with AGAT deficiency, neurological symptoms do not become apparent until the second year of life Thus, brain creatine likely degrades too slowly to create a deficit after only 14 days of creatine-free PN. With the addition of dietary creatine, downregulation of creatine synthesis was evident by a lower AGAT activity in the kidney and pancreas, as well as by lower GAA concentrations in plasma. AGAT has been demonstrated as the rate-limiting step in creatine biosynthesis in humans 28 and in rodents 7 , 17 , 29 , 30 as creatine feeding induced a lower AGAT activity with no change in the liver GAMT activity. Similarly, in our piglets, the AGAT activity was affected with a dietary supply of creatine, and the liver GAMT activity did not change. Therefore, it appears that creatine synthesis is regulated at the level of AGAT in neonatal piglets as well. The kidney has been identified as the major organ responsible for GAA synthesis in rodents 5. However, considering that piglet kidneys are approximately four times the mass of the pancreas 6 , the kidneys are likely still the organ responsible for the most of endogenous GAA synthesis in neonatal piglets. Although the pancreas has a higher AGAT-specific activity than the kidney, its GAMT-specific activity is relatively low i. Therefore, the high pancreatic AGAT-specific activity may contribute some GAA directly to the liver for creatine synthesis, although this requires confirmation. Because prolonged PN can lead to hepatic fat accumulation and PN-associated liver disease 31 , we also measured lipid parameters in the liver as a secondary objective. As expected, the PN-fed groups had a higher liver lipid content and heavier livers compared with those of SF piglets of the same age. Lipid accumulation in the liver has been associated with impaired methionine metabolism Both phosphatidyl choline PC and creatine synthesis require hepatic methylation reactions, which rely on an adequate methionine pool to serve as a methyl donor. Moreover, adequate PC synthesis is required for very low density lipoprotein assembly and secretion of lipids from the liver. It is possible that creatine supplementation might spare methionine for transmethylation to PC, thereby reducing liver lipids in this PN-fed model. We found that creatine supplementation lowered the total liver cholesterol concentration, but no differences in liver weight or TG concentration were detected. While creatine supplementation may have enhanced PC synthesis, allowing for more efficient transport of cholesterol out of the liver, it is unclear why total lipids or TGs were also not measurably reduced. In rodents fed with a high-fat diet, creatine supplementation led to a profound reduction in lipid accumulation in the liver 33 , but creatine was provided in the diet at almost 30 times the concentration delivered in our PN. It is tempting to speculate that creatine has a role in ameliorating PN-induced liver steatosis, but more research is needed on lipid metabolism outcomes. To our knowledge, this is the first time that creatine has been studied as a supplement to PN for use in neonates. Our data suggest that the requirement for creatine synthesis might be a burden on other arginine metabolic pathways. The addition of creatine to PN appears to be necessary to support optimal creatine accretion, and liver and kidney protein synthesis in rapidly growing neonates. Leuzzi V, Bianchi MC, Tosetti M et al. Brain creatine depletion: guanidinoacetate methyltransferase deficiency improving with creatine supplementation. Neurology ; 55 —9. Article CAS PubMed Google Scholar. Battini R, Leuzzi V, Carducci C et al. Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. Mol Genet Metab ; 77 — deGrauw TJ, Salomons GS, Cecil KM et al. Congenital creatine transporter deficiency. Neuropediatrics ; 33 —8. Royes LF, Fighera MR, Furian AF et al. Effectiveness of creatine monohydrate on seizures and oxidative damage induced by methylmalonate. Pharmacol Biochem Behav ; 83 — Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev ; 80 — Brosnan JT, Wijekoon EP, Warford-Woolgar L et al. Ceatine synthesis is a major metabolic process in neonatal piglets and has important implications for amino acids metabolism and methyl balance. J Nutr ; —7. Walker JB. Creatine: biosynthesis, regulation and function. Adv Enzymol Relat Areas Mol Biol ; 50 — CAS PubMed Google Scholar. Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R. Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse. BMC Dev Biol ; 9 Article PubMed PubMed Central Google Scholar. Lamarre SG, Edison EE, Wijekoon EP, Brosnan ME, Brosnan JT. Suckling rat pups accumulate creatine primarily via de novo synthesis rather than from dam milk. J Nutr ; —3. Brunton JA, Bertolo RF, Pencharz PB, Ball RO. Proline ameliorates arginine deficiency during enteral but not parenteral feeding in neonatal piglets. Am J Physiol ; :E— Bertolo RF, Brunton JA, Pencharz PB, Ball RO. Arginine, ornithine, and proline interconversion is dependent on small intestinal metabolism in neonatal pigs. Am J Physiol Endocrinol Metab ; :E— Wilkinson DL, Bertolo RF, Brunton JA, Shoveller AK, Pencharz PB, Ball RO. Arginine synthesis is regulated by dietary arginine intake in the enterally fed neonatal piglet. Brunton JA, Baldwin MP, Hanna RA, Bertolo RF. Proline supplementation to parenteral nutrition results in greater rates of protein synthesis in the muscle, skin, and small intestine in neonatal Yucatan miniature piglets. J Nutr ; —8. In: RO. Ball, ed. Proceedings of the 9th International Symposium on Digestive Physiology in Pigs, Banff: Short communications, vol. Alberta, Canada: University of Alberta, —2. Buchberger W, Ferdig M. Improved high-performance liquid chromatographic determination of guanidino compounds by pre-column derivatization with ninhydrin and fluorescence detection. J Sep Sci ; 27 — Van Pilsum JF, Taylor D, Zakis B, McCormick P. Simplified assay for transamidinase activities of rat kidney homogenates. Anal Biochem ; 35 — da Silva RP, Nissim I, Brosnan ME, Brosnan JT. Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. Ogawa H, Ishiguro Y, Fujioka M. Guanidinoacetate methytransferase from rat liver: purification, properties, and evidence for the involvement of sulfhydryl groups for activity. Arch Biochem Biophys ; — Lamarre SG, Saulnier RJ, Blier PU, Driedzic WR. A rapid and convenient method for measuring the fractional rate of protein synthesis in ectothermic animal tissues using a stable isotope tracer. Comp Biochem physiol B Biochem Mol Biol ; :1—5. Nichols NL, Bertolo RF. Luminal threonine concentration acutely affects intestinal mucosal protein and mucin synthesis in piglets. J Nutr. Bidlingmeyer BA, Cohen SA, Tarvin TL. Rapid analysis of amino acids using pre-column derivatization. J Chromatogr ; — Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem ; — Sestili P, Barbieri E, Martinelli C et al. Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts. Mol Nutr Food Res ; 53 — Sestili P, Ambrogini P, Barbieri E et al. New insights into the trophic and cytoprotective effects of creatine in in vitro and in vivo models of cell maturation. Amino Acids ; 48 — Balsom PD, Soderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med ; 18 — Article Google Scholar. Mercimek-Mahmutoglu S, Salomons GS. Creatine deficiency syndromes. In: Pagon RA et al. Eur J Appl Physiol ; —, doi: per day for 18 days attenuated muscle mass loss in corticosteroid-induced muscle wasting in rats 14 Menezes LG, Sobreira C, Neder L, Rodrigues-Junior AL, Martinez JA. Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats. J Appl Physiol ; —, doi: Tarnopolsky MA. Creatine as a therapeutic strategy for myopathies. Pearlman JP, Fielding RA. Creatine monohydrate as a therapeutic aid in muscular dystrophy. Nutr Rev ; 80—88, doi: In mice, creatine supplementation administered both in powder food 4. Crassous B, Richard-Bulteau H, Deldicque L, Serrurier B, Pasdeloup M, Francaux M, et al. Lack of effects of creatine on the regeneration of soleus muscle after injury in rats. induced by dexamethasone treatment 17 Nicastro H, Gualano B, de Moraes WM, de Salles Painelli V, da Luz CR, dos Santos Costa A, et al. Effects of creatine supplementation on muscle wasting and glucose homeostasis in rats treated with dexamethasone. or in a transgenic model of amyotrophic lateral sclerosis 18 Derave W, Van Den Bosch L, Lemmens G, Eijnde BO, Robberecht W, Hespel P. Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment. Neurobiol Dis ; —, doi: per day for 14 days attenuated muscle mass loss in rats 19 Aoki MS, Lima WP, Miyabara EH, Gouveia CH, Moriscot AS. Deleteriuos effects of immobilization upon rat skeletal muscle: role of creatine supplementation. Clin Nutr ; —, doi: Creatine supplementation attenuated muscle mass loss in the upper-arm of young men 20 Johnston AP, Burke DG, MacNeil LG, Candow DG. Effect of creatine supplementation during cast-induced immobilization on the preservation of muscle mass, strength, and endurance. J Strength Cond Res ; —, doi: but had no effect in the leg muscles of human subjects after immobilization 21 Backx EMP, Hangelbroek R, Snijders T, Verscheijden ML, Verdijk LB, de Groot LCPGM, et al. Creatine loading does not preserve muscle mass or strength during leg immobilization in healthy, young males: a randomized controlled trial. Sports Med ; —, doi: Hespel P, Op't Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, et al. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. J Physiol ; —, doi: Backx et al. reported that, in healthy young men mean of 23 years old after muscle disuse atrophy caused by immobilization, creatine supplementation did not attenuate skeletal muscle loss and the decreased CSA of the quadriceps. These reports indicate the anti-atrophic effect of creatine is still controversial. With the high incidence of chronic diseases and the increase in the aged population, there is an increased number of patients on short-term bed rest. Dirks ML, Backx EM, Wall BT, Verdijk LB, van Loon LJ. May bed rest cause greater muscle loss than limb immobilization? Acta Physiol Oxf ; 10—12, doi: Taking this fact into consideration, the focus of this work was to evaluate the effects of a short-term creatine supplementation on muscle disuse. Due to the difficulty of developing bed-rest studies in humans, animal models were used. One of the most widely used experimental models to mimic the skeletal muscle loss induced by bed rest in humans is the hindlimb suspension HS in rodents. We investigated the short-term effects of creatine supplementation on skeletal muscle signaling pathways involved in protein metabolism in rats with HS-induced atrophy. We hypothesized that short-term creatine supplementation would attenuate the skeletal muscle mass loss and muscle strength reduction by preventing the changes in protein metabolism signaling induced by short-term disuse. Eight-week-old male Wistar rats were obtained from the Animal Facility of the Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo. All experimental procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals Institute of Laboratory Animal Resources, National Academy of Sciences, USA. Ethics Committee of the Institute of Biomedical Sciences, University of São Paulo, approved the experimental protocol and procedures of this study No. During the first three days of the experimental period, the animals were adapted to individual cages. Eijnde et al. Eijnde BO, Richter EA, Henquin JC, Kiens B, Hespel P. Effect of creatine supplementation on creatine and glycogen content in rat skeletal muscle. Acta Physiol Scand ; —, doi: Similar responses were seen in humans with the dose commonly used, 20 g creatine monohydrate per day for 5 days 25 Casey A, Constantin-Teodosiu D, Howell S, Hultman E, Greenhaff PL. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol ; EE37, doi: Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol ; EE, doi: The same volume of water was given as placebo to the C and HS groups. The HS is a well-established experimental model for induction of skeletal muscle atrophy as previously described 2 2. Marzuca-Nassr GN, Murata GM, Martins AR, Vitzel KF, Crisma AR, Torres RP, et al. Balanced diet-fed Fat-1 transgenic mice exhibit lower hindlimb suspension-induced soleus muscle atrophy. Nutrients ; 9. pii: E, doi: Animals were submitted to HS and dietary creatine supplementation concomitantly. Rats were then maintained in the HS and dietary supplementation with creatine or placebo for 5 days. by intraperitoneal administration. We removed the soleus and extensor digitorum longus EDL muscles of both limbs for histological and molecular analysis western blotting and real-time polymerase chain reaction — RT-PCR and euthanized the animals by exsanguination. An in vivo electrical stimulation protocol was used for determination of muscle contractile activity. For twitch force analysis, the stimulus consisted of μs pulse at 1 Hz with adjusted voltage to produce maximum force. Electrical stimulus frequency was increased to Hz to determine the tetanic force. Ten 1-s successive tetanic contractions at Hz allowed the determination of fatigue resistance, with 10 s of recovery between them, by measuring the decrease in force production during the experimental protocol used. Maximal twitch and tetanic forces were recorded using the AqDados software version 4. Muscle strength and fatigue resistance were analyzed using the AqAnalysis software version 4. We used a similar procedure in previous studies 28 Fortes MA, Pinheiro CH, Guimaraes-Ferreira L, Vitzel KF, Vasconcelos DA, Curi R. Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats. Physiol Rep ; 3. Serial sections were taken from the central portion of the soleus and EDL muscles according to Bodine and Baar 29 Bodine SC, Baar K. Analysis of skeletal muscle hypertrophy in models of increased loading. Methods Mol Biol ; —, doi: The slides were stained with hematoxylin and eosin HE for analysis of CSA of the soleus and EDL muscles fibers fibers per muscle. Photographs were taken using an optical microscope Nikon Eclipse E, Japan attached to a digital camera Nixon DXM The images were analyzed using the AxioVision program version 4. We used the same measurements in a previous study 2 2. We used a similar procedure in previous studies 2 2. Fortes MA, Marzuca-Nassr GN, Vitzel KF, da Justa Pinheiro CH, Newsholme P, Curi R. Housekeeping proteins: How useful are they in skeletal muscle diabetes studies and muscle hypertrophy models? Anal Biochem ; 38—40, doi: Total RNA was extracted from skeletal muscles using RNeasy RNA isolation kit Qiagen Inc, USA according to the manufacturer's protocol and as used in our previous study 28 The following genes were evaluated: FST follistatin ; MSTN myostatin ; FAK focal adhesion kinase ; IGF-1 insulin-like growth factor ; MGF mechano growth factor ; Akt ; mTOR mammalian target of rapamycin ; atrogin-1 , and MuRF1. The primers sequences used in the experiments are displayed in Supplementary Table S1. Statistical analysis was performed using the GraphPad Prism ® software version 4. Results are reported as means±SE and were analyzed by two-way analysis of variance ANOVA followed by the Bonferroni post-hoc test for comparison between three or more groups. Outlier results were detected using the Grubbs' test of GraphPad Software graphpad. The HS group had lower body weight than the other groups after 5 days of experiment Table 1. Creatine supplementation had an effect on preventing muscle mass loss that was more notable in the EDL muscle, in the rats submitted to HS Table 1. The absolute twitch force in the soleus and EDL muscles and the specific tetanic force in the EDL muscle were not changed as indicated by the inter-group analysis. The specific twitch force and fatigue resistance did not change significantly in the soleus and EDL muscles due to either creatine supplementation or HS Figure 1A and 2A. S6 and p-S6 protein contents were not altered by HS or supplementation Figure 1B d,e,f. The p-4EBP1 content was not significantly changed in the inter-group analysis. |
| Introduction | Mol Genet Metab ; 77 — deGrauw TJ, Salomons GS, Cecil KM et al. Congenital creatine transporter deficiency. Neuropediatrics ; 33 —8. Royes LF, Fighera MR, Furian AF et al. Effectiveness of creatine monohydrate on seizures and oxidative damage induced by methylmalonate. Pharmacol Biochem Behav ; 83 — Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev ; 80 — Brosnan JT, Wijekoon EP, Warford-Woolgar L et al. Ceatine synthesis is a major metabolic process in neonatal piglets and has important implications for amino acids metabolism and methyl balance. J Nutr ; —7. Walker JB. Creatine: biosynthesis, regulation and function. Adv Enzymol Relat Areas Mol Biol ; 50 — CAS PubMed Google Scholar. Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R. Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse. BMC Dev Biol ; 9 Article PubMed PubMed Central Google Scholar. Lamarre SG, Edison EE, Wijekoon EP, Brosnan ME, Brosnan JT. Suckling rat pups accumulate creatine primarily via de novo synthesis rather than from dam milk. J Nutr ; —3. Brunton JA, Bertolo RF, Pencharz PB, Ball RO. Proline ameliorates arginine deficiency during enteral but not parenteral feeding in neonatal piglets. Am J Physiol ; :E— Bertolo RF, Brunton JA, Pencharz PB, Ball RO. Arginine, ornithine, and proline interconversion is dependent on small intestinal metabolism in neonatal pigs. Am J Physiol Endocrinol Metab ; :E— Wilkinson DL, Bertolo RF, Brunton JA, Shoveller AK, Pencharz PB, Ball RO. Arginine synthesis is regulated by dietary arginine intake in the enterally fed neonatal piglet. Brunton JA, Baldwin MP, Hanna RA, Bertolo RF. Proline supplementation to parenteral nutrition results in greater rates of protein synthesis in the muscle, skin, and small intestine in neonatal Yucatan miniature piglets. J Nutr ; —8. In: RO. Ball, ed. Proceedings of the 9th International Symposium on Digestive Physiology in Pigs, Banff: Short communications, vol. Alberta, Canada: University of Alberta, —2. Buchberger W, Ferdig M. Improved high-performance liquid chromatographic determination of guanidino compounds by pre-column derivatization with ninhydrin and fluorescence detection. J Sep Sci ; 27 — Van Pilsum JF, Taylor D, Zakis B, McCormick P. Simplified assay for transamidinase activities of rat kidney homogenates. Anal Biochem ; 35 — da Silva RP, Nissim I, Brosnan ME, Brosnan JT. Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. Ogawa H, Ishiguro Y, Fujioka M. Guanidinoacetate methytransferase from rat liver: purification, properties, and evidence for the involvement of sulfhydryl groups for activity. Arch Biochem Biophys ; — Lamarre SG, Saulnier RJ, Blier PU, Driedzic WR. A rapid and convenient method for measuring the fractional rate of protein synthesis in ectothermic animal tissues using a stable isotope tracer. Comp Biochem physiol B Biochem Mol Biol ; :1—5. Nichols NL, Bertolo RF. Luminal threonine concentration acutely affects intestinal mucosal protein and mucin synthesis in piglets. J Nutr. Bidlingmeyer BA, Cohen SA, Tarvin TL. Rapid analysis of amino acids using pre-column derivatization. J Chromatogr ; — Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem ; — Sestili P, Barbieri E, Martinelli C et al. Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts. Mol Nutr Food Res ; 53 — Sestili P, Ambrogini P, Barbieri E et al. New insights into the trophic and cytoprotective effects of creatine in in vitro and in vivo models of cell maturation. Amino Acids ; 48 — Balsom PD, Soderlund K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med ; 18 — Article Google Scholar. Mercimek-Mahmutoglu S, Salomons GS. Creatine deficiency syndromes. In: Pagon RA et al. Seattle, WA: University of Washington, ;— Hanna-El-Daher L, Braissant O. Creatine synthesis and exchanges between brain cells: what can be learned from human creatine deficiencies and various experimental models? Derave W, Marescau B, Vanden Eede E, Eijnde BO, De Deyn PP, Hespel P. Plasma guanidino compounds are altered by oral creatine supplementation in healthy humans. J Appl Physiol ; 7 —7. McGuire DM, Gross MD, Van Pilsum JF, Towle HC. Repression of rat kidney L-arginine:glycineamidinotransferase synthesis by creatine at a pretranslational level. J Biol Chem ; —8. da Silva RP, Clow K, Brosnan JT, Brosnan ME. Synthesis of guanidinoacetate and creatine from amino acids by rat pancreas. Br J Nutr ; —7. Burrin DG, Ng K, Stoll B, Saenz De PM. Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease. Adv Nutr ; 5 — Article CAS PubMed PubMed Central Google Scholar. Corrales F, Alvarez L, Pajares MA, Ortiz P, Mato JM. Impairment of methionine metabolism in liver disease. Drug Investig ; 4 :8— Deminice R, da Silva RP, Lamarre SG et al. Creatine supplementation prevents the accumulation of fat in the livers of rats fed a high-fat diet. J Nutr ; — Download references. We thank ME Dodge for her assistance in the surgeries. designed the research; O. B conducted the research; O. analyzed the data; and O. drafted the paper. and R. reviewed and revised the paper. had a primary responsibility for the final content. All the authors read and approved the final manuscript. Department of Biochemistry, Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada. You can also search for this author in PubMed Google Scholar. Correspondence to Janet A Brunton. Supplementary material is linked to the online version of the paper at. Reprints and permissions. Dinesh, O. Creatine supplementation to total parenteral nutrition improves creatine status and supports greater liver and kidney protein synthesis in neonatal piglets. Pediatr Res 83 , — Download citation. Received : 01 March Accepted : 21 August Published : 27 September Issue Date : January Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. nature pediatric research basic science investigation article. Download PDF. Subjects Metabolic pathways Neonatology Nutritional supplements. Abstract Background Creatine is not included in commercial pediatric parenteral products; the entire creatine requirement must be met by de novo synthesis from arginine during parenteral nutrition PN. Methods Piglets 3—5-day d old were provided PN with or without creatine for 14 d. Results Creatine provision lowered kidney and pancreas L-arginine:glycine amidinotransferase AGAT, EC number 2. Conclusion The addition of creatine to PN may optimize the accretion of creatine and reduce the metabolic burden of creatine synthesis in rapidly growing neonates. Sustainability benefits of transitioning from current diets to plant-based alternatives or whole-food diets in Sweden Article Open access 01 February Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes Article Open access 20 December BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen Article Open access 03 January Main Creatine and creatine phosphate are amino-acid-derived compounds that are necessary to meet short-term energy requirements in tissues that have high and variable rates of energy demand. Diet Regimen Piglets were randomized to either creatine-supplemented PN Creatine or creatine-free PN Control. Necropsy Procedure After 14 days, a flooding dose of L-phenylalanine 1. Skeletal Muscle Creatine Concentrations Creatine concentration of the gastrocnemius muscle was determined using the simplified method of Lamarre et al. AGAT Assay AGAT activity was assayed using a modified method of Van et al. GAMT Assay GAMT activity was assayed, as described previously by da Silva et al. Results The growth rates of the piglets in the two treatment groups were not significantly different. Figure 1. Full size image. Figure 2. Table 1 Tissue and plasma GAA concentrations in piglets given control vs. creatine PN a Full size table. Table 2 Tissue and plasma creatine concentrations in piglets given Control vs. Creatine PN a Full size table. Figure 3. Table 3 Body and liver weights, liver, and plasma lipid concentrations at necropsy in piglets given Control vs. Similar content being viewed by others. References Leuzzi V, Bianchi MC, Tosetti M et al. Article CAS PubMed Google Scholar Battini R, Leuzzi V, Carducci C et al. Article CAS PubMed Google Scholar deGrauw TJ, Salomons GS, Cecil KM et al. Article CAS PubMed Google Scholar Royes LF, Fighera MR, Furian AF et al. Article CAS PubMed Google Scholar Wyss M, Kaddurah-Daouk R. Article CAS PubMed Google Scholar Brosnan JT, Wijekoon EP, Warford-Woolgar L et al. Article CAS PubMed Google Scholar Walker JB. CAS PubMed Google Scholar Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R. Article PubMed PubMed Central Google Scholar Lamarre SG, Edison EE, Wijekoon EP, Brosnan ME, Brosnan JT. Article CAS PubMed Google Scholar Brunton JA, Bertolo RF, Pencharz PB, Ball RO. CAS PubMed Google Scholar Bertolo RF, Brunton JA, Pencharz PB, Ball RO. Article CAS PubMed Google Scholar Wilkinson DL, Bertolo RF, Brunton JA, Shoveller AK, Pencharz PB, Ball RO. Article CAS PubMed Google Scholar Brunton JA, Baldwin MP, Hanna RA, Bertolo RF. Article CAS PubMed Google Scholar Van Pilsum JF, Taylor D, Zakis B, McCormick P. Article CAS PubMed Google Scholar da Silva RP, Nissim I, Brosnan ME, Brosnan JT. Article CAS PubMed Google Scholar Ogawa H, Ishiguro Y, Fujioka M. Article CAS PubMed Google Scholar Lamarre SG, Saulnier RJ, Blier PU, Driedzic WR. Article CAS PubMed Google Scholar Nichols NL, Bertolo RF. Article CAS PubMed Google Scholar Bidlingmeyer BA, Cohen SA, Tarvin TL. Article CAS PubMed Google Scholar Folch J, Lees M, Sloane Stanley GH. CAS PubMed Google Scholar Sestili P, Barbieri E, Martinelli C et al. Article CAS PubMed Google Scholar Sestili P, Ambrogini P, Barbieri E et al. Article CAS PubMed Google Scholar Balsom PD, Soderlund K, Ekblom B. Article Google Scholar Mercimek-Mahmutoglu S, Salomons GS. Article CAS PubMed Google Scholar Derave W, Marescau B, Vanden Eede E, Eijnde BO, De Deyn PP, Hespel P. This Site. Google Scholar. M F Morales M F Morales. Author and Article Information. D M Fry. M F Morales. Online ISSN: J Cell Biol 84 2 : — Cite Icon Cite. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. This content is only available as a PDF. Volume 84, Issue 2. Previous Article Next Article. View Metrics. Roles of creatine in the regulation of cardiac protein synthesis. Adult rat cardiomyocytes cultured in creatine-deficient medium display large mitochondria with paracrystalline inclusions, enriched for creatine kinase. Email alerts Complete Issue Alert. Daily Publication Alert. Online ISSN Print ISSN |
| A reexamination of the effects of creatine on muscle protein synthesis in tissue culture. | Pgotein of the Ane Creatine and protein synthesis of Sports Nutrition ISSN: J Strength Cond Res ; —, syhthesis Herbal weight loss plan addition of creatine to PN may optimize the accretion of creatine and reduce the metabolic burden of creatine synthesis in rapidly growing neonates. J Int Soc Sports Nutr 1813 Article PubMed Google Scholar Andre TL, Gann JJ, McKinley-Barnard SK, Willoughby DS. Diabetes50, |
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Diet \u0026 Supplementation for Muscle Growth - Dr. Andy Galpin \u0026 Dr. Andrew HubermanCreatine and protein synthesis -
For example, resistance-trained males who received creatine at a dose of 0. Similarly, males and females ingesting creatine 0. Six weeks of creatine supplementation in non-resistance-trained males at a dosage of 0.
In a recent study examining the effects of creatine supplementation combined with resistance exercise for 8 weeks, Ribeiro et al. Importantly, the ratio of skeletal muscle mass to ICW remained similar in both groups. It is important to highlight that the ICW is an important cellular signal for protein synthesis and thus drives an increase in muscle mass over time [ 46 ].
In summary, while there is some evidence to suggest that creatine supplementation increases water retention, primarily attributed to increases in intracellular volume, over the short term, there are several other studies suggesting it does not alter total body water intra or extracellular relative to muscle mass over longer periods of time.
As a result, creatine supplementation may not lead to water retention. Anabolic steroids are a synthetic version of testosterone, an androgenic hormone which is also produced endogenously within both males and females, and is used in conjunction with resistance training with the intent of enhancing muscle mass and strength due to increases in muscle protein synthesis [ 47 ].
Creatine is converted to phosphocreatine PCr , regulated by the enzyme creatine kinase CK in muscle and used to create intracellular adenosine triphosphate ATP production [ 1 ].
Creatine supplementation, however, can increase the capacity of ATP and energy produced during heavy anaerobically-related exercise, thereby possibly increasing muscle power, repetitions and exercise volume which can subsequently contribute to muscle performance and hypertrophy over the course of a training period [ 2 ].
While the physiological and performance outcomes of anabolic steroids and creatine can be similar, their mechanisms of action and legal categorization are not. Anabolic steroids are drugs, with a different chemical structure than creatine, and are Class C, Schedule III controlled substances regulated by the Food and Drug Administration FDA and subject to the regulatory control provisions of the Controlled Substances Act CSA set forth by the Drug Enforcement Association DEA.
Creatine, on the other hand, like many other dietary supplements fits well within the confines of The Dietary Supplement Health and Education Act of "DSHEA" , which is a statute of United States Federal legislation which defines and regulates dietary supplements by the Federal Drug Administration FDA for Good Manufacturing Practices GMP.
However, there are no legal ramifications for the possession or ingestion of creatine. In summary, because creatine has a completely different chemical structure, it is not an anabolic steroid.
In skeletal muscle, both creatine and PCr are degraded non-enzymatically to creatinine, which is exported to the blood and excreted in the urine [ 1 ].
Healthy kidneys filter creatinine, which would otherwise increase in the blood. Therefore, blood creatinine levels can be used as a proxy marker of kidney function.
However, the amount of creatinine in the blood is related to muscle mass i. males have higher blood creatinine than females and both dietary creatine and creatinine intake [ 35 ]. Both blood and urinary creatinine may be increased by ingestion of creatine supplementation and creatine containing foods, such as meat.
In reality, transient increases in blood or urinary creatine or creatinine due to creatine supplementation are unlikely to reflect a decrease in kidney function. In a review of creatine supplementation studies, Persky and Rawson [ 50 ] found no increase in serum creatinine in 12 studies, 8 studies showed an increase that remained within the normal range, and only 2 studies showed an increase above normal limits although not different from the control group in one study.
In , a case study of a young male with focal segmental glomerulosclerosis and relapsing nephrotic syndrome was reported [ 51 ]. The young male, who had kidney disease for 8 years and was treated with cyclosporine i.
Based on increased blood levels of creatinine and subsequent estimate of calculated creatinine clearance, his kidney health was presumed to be deteriorating, although he was otherwise in good health.
The patient was encouraged to discontinue creatine supplementation. At this time, it was already known that blood and urine creatinine levels can increase following ingestion of creatine containing food products, including creatine supplements [ 35 ]. This was ignored by the authors of this case study, as was the inclusion of two investigations which demonstrated that creatine supplementation did not negatively impact renal function [ 52 , 53 ].
serving; see [ 54 ]. In response to this case study, two separate teams of experts in creatine metabolism wrote letters to the editor of Lancet [ 53 , 55 ]. Interestingly, Gualano et al. Similar to the case report by Pritchard and Kalra [ 51 ], these additional case reports were confounded by medications, pre-existing kidney disease, concomitant supplement ingestion, inappropriate creatine dosages e.
It is prudent to be cautious when ingesting any dietary supplement or medication. young, physically fit, healthy individuals since after Harris et al. published their seminal work [ 60 ]. After nearly 30 years of post-marketing surveillance, thousands of exposures, and multiple clinical trials, no such evidence exists.
It is important to note that the results of van der Merwe et al. DHT is a metabolite of testosterone, formed when the enzyme 5-alpha-reductase converts free testosterone to DHT [ 63 ].
In males, DHT can bind to androgen receptors in susceptible hair follicles and cause them to shrink, ultimately leading to hair loss [ 64 ].
However, in the van der Merwe et al. Free testosterone was not measured. Moreover, the increase in DHT and the DHT: testosterone ratio remained well within normal clinical limits. To date, 12 other studies have investigated the effects of creatine supplementation i. Two studies reported small, physiologically insignificant increases in total testosterone after six and seven days of supplementation [ 65 , 66 ], while the remaining ten studies reported no change in testosterone concentrations.
In five of these studies [ 67 , 68 , 69 , 70 , 71 ], free testosterone, which the body uses to produce DHT, was also measured and no increases were found. Speculation exists that creatine supplementation causes dehydration and muscle cramping [ 72 , 73 ].
The physiological rationale suggesting that creatine supplementation may cause dehydration and muscle cramping is based on the premise that creatine is an osmotically active substance found primarily in skeletal muscle and may alter whole-body fluid distribution by preferentially increasing intracellular water uptake and retention, particularly over the short-term [ 38 , 75 ].
The initial loading phase of creatine supplementation i. Some anecdotal evidence indicates that creatine users perceive supplementation to result in some adverse effects [ 77 ].
Importantly, these studies failed to control for the use of other supplements and the dosage of creatine ingested. Greenwood et al. However, these self-report surveys are in contradiction to experimental and clinical evidence. Injuries treated by the athletic training staff were monitored.
Non-contact joint injuries, contact injuries, illnesses, missed practices due to injuries, and players lost for the season were not different between groups. These beneficial effects from creatine may be explained by fluid distribution and electrolyte imbalances, as previously discussed.
In summary, experimental and clinical research does not validate the notion that creatine supplementation causes dehydration and muscle cramping. The overwhelming majority of evidence in adult populations indicates that creatine supplementation, both short- and longer-term, is safe and generally well tolerated [ 2 ].
However, the question of whether or not this holds true for children and adolescents is relatively unclear. The physiological rationale supporting the potential ergogenic benefits of creatine supplementation in children and adolescents was first postulated by Unnithan and colleagues in [ 80 ]; which established a strong basis for future applications of creatine for younger athletes.
More recently, in a comprehensive review examining the safety of creatine supplementation in adolescents, Jagim et al. However, it is important to note that none of the performance-focused studies included in the Jagim et al.
From a clinical perspective, creatine supplementation has been found to potentially offer health benefits with minimal adverse effects in younger populations.
Hayashi et al. Tarnopolsky et al. Importantly, the creatine supplementation protocol appeared to be well tolerated and did not adversely affect laboratory markers of kidney function, oxidative stress, and bone health [ 81 , 82 , 83 ].
In addition, Sakellaris et al. These neurological benefits may have potential applications for young athletes participating in collision sports, which pose underlying risks of concussions or sub-concussive impacts.
Further, several of these clinical trials implemented strict clinical surveillance measures, including continual monitoring of laboratory markers of kidney health, inflammation, and liver function; none of which were negatively impacted by the respective creatine supplementation interventions.
These findings support the hypothesis of creatine supplementation likely being safe for children and adolescents. Even though infants and young children are excluded from GRAS, this would still apply to older children and adolescent populations.
The majority of dietary supplement survey data indicates that a relatively high percentage of youth and adolescent athletes are currently or have previously supplemented with creatine. For example, Kayton et al. Therefore, these trends warrant additional research to determine with greater certainly whether creatine supplementation, both acute and longer-term, is safe for children and adolescents.
In summary, based on the limited evidence, creatine supplementation appears safe and potentially beneficial for children and adolescents. The theory that creatine supplementation increases fat mass is a concern amongst exercising individuals, possibly because some experience a gain in body mass from creatine supplementation.
However, randomized controlled trials one week to two years in duration do not validate this claim. Acute creatine supplementation 7 days had no effect on fat mass in young and older adults; however, fat-free mass was increased [ 86 , 87 ].
Furthermore, three weeks of creatine supplementation had no effect on body composition in swimmers [ 88 ]. The addition of creatine to high-intensity interval training had no effect on body composition in recreationally active females [ 89 ].
In addition, the effects of creatine supplementation during resistance training overreaching had no effect on fat mass [ 70 ]. In other short-terms studies lasting weeks, there were no changes in fat mass from creatine supplementation.
Becque et al. In another 6-week investigation, no significant differences in fat mass or percentage body fat were observed after creatine supplementation [ 42 ]. Furthermore, creatine supplementation during an 8-week rugby union football season also had no effect on fat mass [ 92 ].
Nonetheless, there are several investigations that have used much longer treatment periods. For example, healthy resistance-trained males were randomly assigned in a double-blind fashion to supplement with creatine i.
Lean body mass and muscle fiber size increased; percent body fat and fat mass were unaffected over the week training period [ 93 ]. In older males ~70 yrs , 12 weeks of creatine supplementation during resistance training had no effect compared to placebo on fat mass [ 94 ]. Furthermore, Gualano et al.
assessed the effects of creatine supplementation 24 weeks , with and without resistance training, in older females. Results showed no effect from creatine on fat mass [ 95 ]. Candow et al. Study participants were randomized to supplement with creatine or placebo before or after resistance training 3 days per week.
There was an increase over time for lean tissue and strength with a decrease in fat mass. From a clinical perspective, children with acute lymphoblastic leukemia who supplemented with creatine 0.
In contrast, the children who did not consume creatine gained fat mass [ 97 ]. In two studies involving postmenopausal women, Lobo et al.
Furthermore, two years of creatine supplementation also had no effect on fat mass [ 99 ]. Recently, Forbes et al. Nineteen studies with a total of participants were included. Participants supplementing with creatine had a greater reduction in body fat percentage.
There was no significant difference in absolute fat mass loss; however, the creatine group lost ~0. In summary, creatine supplementation does not increase fat mass across a variety of populations.
Decades later, Harris et al. This research sparked incredible interest in studying creatine supplementation strategies that would increase intramuscular creatine content, helping shape current recommendations. In addition to the seminal work of Harris et al. However, lower daily creatine supplementation dosing strategies i.
While effective, these non-loading creatine supplementation dosing strategies Figure 1 , side B delay maximum intramuscular creatine storage.
Determination of which creatine supplementation strategy is preferred may depend on the goal of the individual. Athletes who are carrying out a creatine loading phase i. less than or equal to 10 gram servings throughout the day, as dosages of greater than 10 grams may potentially lead to gastrointestinal distress i.
Lower, daily dosages of creatine supplementation i. There has been an increasing number of studies showing that creatine supplementation plays a therapeutic role in a variety of clinical conditions see Gualano et al.
Perhaps one of the most promising conditions that could benefit from creatine supplementation is age-related sarcopenia. Sarcopenia is defined as a progressive and generalized skeletal muscle condition i. decrease in muscle mass, strength, and functionality that is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality [ ].
While resistance training is considered cornerstone in the treatment of sarcopenia [ ], accumulating evidence indicates that creatine supplementation may enhance the anabolic environment produced by resistance training, subsequently mitigating indices of sarcopenia [ 9 , 10 , 19 , 27 ].
Creatine supplementation can increase functionality e. However, the literature indicates that creatine alone that is, without a concomitant resistance training program is unlikely to result in substantial gains in muscle strength and functional performance [ 95 , , , ], although it does improve some parameters of muscle fatigue [ , , ].
It is likely that increases in lean mass occasionally attributed to creatine supplementation in short-term studies e. Conversely, substantial evidence indicates that creatine supplementation is capable of augmenting the hypertrophic response to resistance training in young adults [ ], which is extended to older adults, as confirmed by three systematic reviews and meta-analyses [ 19 , , ].
Regarding aging bone, emerging research over the past decade has shown some benefits from creatine supplementation. More recently, Chilibeck et al. However, a 2 year creatine supplementation protocol was infective for improving bone mass or bone geometry in post-menopausal women, again suggesting that creatine should be combined with resistance-type exercise to produce beneficial bone adaptations [ 99 ].
From a clinical and healthy aging perspective, it is recommended that creatine supplementation be combined with resistance training to produce the greatest adaptations in older adults. Future clinical trials involving frail populations with long-term follow-up s and larger samples are needed.
In summary, there is growing body of evidence showing that creatine supplementation, particularly when combined with exercise, provides musculoskeletal and performance benefits in older adults.
For example, creatine supplementation with carbohydrate [ ] or carbohydrate and protein [ ] has been reported to promote greater muscle glycogen storage than carbohydrate supplementation alone.
For example, Cooke and colleagues [ ] reported that creatine supplementation during recovery from exercise-induced muscle damage promoted less muscle enzyme efflux and better maintenance of isokinetic muscle performance.
Moreover, there is evidence that individuals supplementing their diet with creatine experienced less muscle damage, inflammation, and muscle soreness in response to running km [ ] as well as during 4-weeks of intensified training [ 70 ].
Third, there is evidence that athletes who supplement with creatine during training experience fewer musculoskeletal injuries, accelerated recovery time from injury [ 78 , ] and less muscle atrophy after immobilization [ , ].
Fourth, creatine supplementation with or without glycerol has been reported to help athletes hyper-hydrate and thereby enhance tolerance to exercise in the heat [ 28 , 37 , , , , , , , , , , , , , , , ].
Thus, there are a number of reasons beyond the ergogenic benefit that all types of athletes may benefit. Creatine kinetics may vary between healthy males and females [ ]. Females may have higher intramuscular creatine concentrations [ ] possibly due to lower skeletal muscle mass [ ].
As a result of hormone-driven changes in endogenous creatine synthesis, creatine transport, and creatine kinase CK kinetics, creatine bioavailability throughout various stages of female reproduction is altered, highlighting the potential positive implications for creatine supplementation in females [ 29 ].
The implications of hormone-related changes in creatine kinetics has been largely overlooked in performance-based studies [ 29 ]. Specifically, creatine supplementation may be of particular importance during menses, pregnancy, post-partum, perimenopause and postmenopause.
Creatine kinase, as well as enzymes associated with creatine synthesis, are influenced by estrogen and progesterone [ 1 ]. Creatine kinase levels are significantly elevated during menstruation [ ], with CK levels decreasing throughout the menstrual cycle, pregnancy, and with age.
The lowest range of CK values have been reported during early pregnancy 20 weeks or less , equating to about half the concentration found at peak levels teenage girls [ , ]. Maternal creatine supplementation during pregnancy in pre-clinical animal studies have demonstrated a protective effect against fetal death and organ damage associated with intrapartum hypoxia [ , ].
Reduced creatine levels in late pregnancy have also been associated with low fetal growth [ ]. There is additional data that metabolic demand from the placenta during gestation further lowers the creatine pool of the mother [ ], which may be associated with low birth weight and pre-term birth.
Creatine supplementation during pregnancy has been shown to enhance neuronal cell uptake of creatine and support mitochondrial integrity in animal offspring, thereby reducing brain injury induced by intrapartum asphyxia [ , ]. Although there are no human studies evaluating the effects of creatine supplementation during pregnancy, creatine could provide a safe, low-cost nutritional interventional for reducing intra- and post-partum complications associated with cellular energy depletion [ ].
This may be more important if the female is vegetarian, or unable to consume meat due to nausea or taste preferences i. meat contains about 0. Females have been reported to have lower levels of creatine in the brain frontal lobe [ ]. Increasing creatine concentrations in the brain as a result of supplementation, particularly in females, may support the reported benefits of reducing symptoms of depression [ , ] and ameliorating the effects of traumatic brain injury [ 12 , 22 ].
Depression is about 2 times higher among females throughout the reproductive years [ ] and accelerates around pubertal hormonal changes [ ]. Altered brain bioenergetics and mitochondrial dysfunction have been linked with depression, particularly as it relates to CK, ATP, and inorganic phosphate P i.
Creatine supplementation has been shown to significantly augment cerebral PCr and P i [ ], particularly in females. There is a small body of research that has investigated the effects of creatine supplementation in younger females.
For example, Vandenberghe et al. Hamilton et al. Furthermore, in college-aged females 20 yrs , creatine supplementation 0. In contrast, not all data show improved performance in females [ 89 , , ]. Additionally, Smith-Ryan et al.
It is important to evaluate the benefit to risk ratio; as noted elsewhere in this document, there are minimal risks associated with creatine supplementation, particularly when it is evaluated against the potential benefits in females. Accumulating research over the past decade in postmenopausal females demonstrates that creatine supplementation during a resistance training program can improve muscle mass, upper- and lower-body strength, and tasks of functionality s chair stand, lying prone-to-stand test, arm curl test for detailed review see Candow et al.
Creatine supplementation appears to be a viable option for post-menopausal females to improve muscle quality and performance. In addition to its beneficial effects on aging muscle, creatine supplementation may also have favorable effects on bone in postmenopausal females, if combined with resistance training.
For example, postmenopausal females who supplemented daily with 0. However, even without the stimulus of resistance training, there is some evidence that creatine supplementation can still be beneficial.
In summary, there is accumulating evidence that creatine supplementation has the potential to be a multifactorial therapeutic intervention across the lifespan in females, with little to no side effects.
Creatine monohydrate powder has been the most extensively studied and commonly used form of creatine in dietary supplements since the early s [ 2 , ].
Creatine monohydrate was used in early studies to assess bioavailability, determine proper dosages, and assess the impact of oral ingestion of creatine on blood creatine and intramuscular creatine stores [ 35 , 60 , ].
These studies indicated that orally ingested creatine monohydrate e. Short-term loading with creatine monohydrate e. Creatine monohydrate supplementation during training e. Despite the known efficacy, safety, and low cost of creatine monohydrate; a number of different forms of creatine have been marketed as more effective with fewer anecdotally reported adverse effects [ ].
These marketing efforts have fueled speculation that creatine monohydrate is not the most effective or safest form of creatine to consume. This notion is clearly refuted by understanding the well-known physio-chemical properties of creatine monohydrate, as well as current creatine supplementation literature.
A number of different forms of creatine e. have been marketed as more effective sources of creatine than creatine monohydrate [ ]. However, there are no peer-reviewed published papers showing that the ingestion of equal amounts of creatine salts [ , , , ] or other forms of creatine like effervescent creatine [ ], creatine ethyl ester [ 43 , , ], buffered creatine [ 41 ], creatine nitrate [ , ], creatine dipeptides, or the micro amounts of creatine contained in creatine serum [ ] and beverages e.
Creatine monohydrate crystallizes from water as monoclinic prisms that hold one molecule of water of crystallization per molecule of creatine [ ]. Creatine is considered a weak base pKb Creatine can also serve as a complexing agent with other compounds via ionic binding.
Creatine monohydrate powder contains the highest percentage of creatine Creatine monohydrate manufactured in Germany involves adding acetic acid to sodium sarconsinate, heating, adding cyanamide, cooling to promote crystallization, separation and filtration, and drying has been reported to produce Meanwhile, other sources of creatine monohydrate that have different starting materials e.
While the effects of ingesting these compounds on health are unknown, contamination with dihydrotriazine has been suggested to be of greatest concern since it is structurally related to carcinogenic compounds [ ]. For this reason, German sourced creatine monohydrate has been primarily used in research to establish safety and efficacy and is therefore the recommended source of creatine monohydrate to use in dietary supplements [ 2 , ].
Creatine monohydrate powder is very stable showing no signs of degradation into creatinine over years, even at elevated storage temperatures [ ].
However, creatine is not stable in solution due to intramolecular cyclization that converts creatine to creatinine especially at higher temperatures and lower pH [ , , , ]. The degradation of creatine can be reduced or halted by lowering the pH under 2. Moreover, since creatine is an ampholytic amino acid, it is not very soluble in water e.
Mixing creatine in higher temperature solution increase solubility, which is the reason why initial studies administered creatine in hot tea [ 35 , 60 , , , , ] but the solubility has no influence on tissue uptake [ ]. The lack of solubility and stability of creatine in solution is the reason that creatine is primarily marketed in powder form and efforts to develop stable beverages containing physiologically effective doses of creatine e.
In summary, while some forms of creatine may be more soluble than creatine monohydrate when mixed in fluid, evidence-based research clearly shows creatine monohydrate to be the optimal choice. Creatine supplementation appears to be generally safe and potentially beneficial for children and adolescents.
Smaller, daily dosages of creatine supplementation g or 0. Creatine supplementation and resistance training produces the vast majority of musculoskeletal and performance benefits in older adults. Creatine supplementation alone can provide some muscle and performance benefits for older adults.
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Effects of Creatine and Resistance Training on Bone Health in Postmenopausal Women. If you've decided you're ready to add supplemental creatine to your diet, you need to know what forms are out there and when and how much you should take.
However, the best known and most studied form is by far creatine monohydrate. Taking as many as 20 grams of creatine powder or liquid a day for 5 days and as many as 5 grams a day thereafter is often recommended for optimal support of athletic performance. However, doses at high levels such as these can cause undesirable side effects, including muscle cramping, nausea, diarrhea, gastrointestinal pain, and dehydration.
Therefore, a 1-gram dose of creatine would be approximately double the amount of creatine you get on a daily basis from your diet.
This increase should be adequate to promote enhanced muscle protein synthesis —if supplemental essential amino acids EAAs are provided at the same time. This is because the muscle-building process is dependent on the activation of muscle protein synthesis to increase muscle mass and strength—even in the absence of exercise.
And muscle protein synthesis requires energy in the form of ATP as well as amino acids to help build muscle proteins. While creatine alone can provide extra energy for muscle protein synthesis, without increased availability of all EAAs, only a limited amount of new muscle can be produced.
This is why results from creatine supplementation can be variable. As stated earlier, there are 20 different amino acids that make up the proteins responsible for the construction of muscle fibers.
And nine of these—the essential amino acids—are not produced in the body. For new muscle protein to be created, all the EAAs are needed in proportions specific to the composition of each particular protein.
An EAA supplement is a powerful stimulus of muscle protein synthesis, but the amount of protein produced will ultimately be limited by how much energy in the form of ATP is ready to go at the site of muscle protein production.
And this is where creatine comes in. Creatine provides the necessary energy to support an increased rate of muscle protein synthesis. For those interested in all the benefits creatine has to offer, this is indeed a winning combination. BCAA vs. creatine: a comprehensive look to help you decide which you should choose, or whether you'd rather utilize a product that combines the two supplements for better energy, muscle strength, and protein synthesis.
There are specific nutrients that the gut requires to perform its functions. A significant number of these nutrients are put to use right away to keep the gut healthy and intact. Blog Nutrition. By: by Amino Science.
Posted on: November 7, What Is Creatine? Where Does Creatine Come From? How Does Creatine Help Exercise Performance? Creatine supplementation actually performs two important functions for the muscles of the body. It provides the extra energy needed for high-intensity, short-duration exercise.
It delivers that energy where it's needed most. Energy for High-Intensity Exercise Creatine is converted to phosphocreatine, or creatine phosphate CP , in the muscles.
Benefits of Creatine Supplementation in Athletes As mentioned earlier, creatine supplements are widely used by athletes, and the use of creatine has been shown to benefit those engaged in high-intensity, short-duration exercise. But what about older adults? Would creatine supplements help them too?
Benefits of Creatine Supplementation in Older Adults The process of aging is associated with decreased muscle mass, strength, and function. Adverse Effects of Creatine Supplementation According to the Mayo Clinic , supplemental oral creatine is generally considered safe for a period of up to 5 years.
Other potential side effects include: Water retention Dehydration Nausea Diarrhea Abdominal pain Weight gain Muscle cramps How to Supplement with Creatine If you've decided you're ready to add supplemental creatine to your diet, you need to know what forms are out there and when and how much you should take.
What Forms of Creatine Are Available? Creatine is available in an almost bewildering array of forms. These include: Creatine monohydrate Creatine citrate Creatine malate Creatine ethyl ester Creatine magnesium chelate Creatine pyruvate However, the best known and most studied form is by far creatine monohydrate.
When Should You Take Creatine? How Much Creatine Should You Take? What do we mean by this? TAGS: supplements Join the Community.
Studies lrotein there is no added benefit of taking Creatinf protein and creatine together. But both contain different compounds and Creatine and protein synthesis differently. Snthesis the world of sports Fuel Management Application, people use various supplements Creatine and protein synthesis increase their performance and enhance exercise recovery. Creatine and whey protein are two popular examples, with a great deal of data backing their effectiveness. While their effects are similar in some regards, they are distinctly different compounds that work in different ways. This article reviews what creatine and whey protein powder are, their main differences, and whether you should take them together for optimal benefits.
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