***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: This study examined the effect of vegetarianism on skeletal muscle total creatine ( TCr ) content and creatine transporter ( CreaT ) gene expression , prior to and during 5 d of Cr supplementation ( CrS ) . In a double-blind , crossover design , 7 vegetarians ( VEG ) and nonvegetarians ( NVEG ) were assigned Cr or placebo supplements for 5 d and after 5 wk , received the alternative treatment . Muscle sampling occurred before , and after 1 and 5 d of treatment ingestion . Basal muscle TCr content was lower ( P < 0.05 ) in VEG compared with NVEG . Muscle TCr increased ( P < 0.05 ) throughout the Cr trial in both groups but was greater ( P < 0.05 ) in VEG compared with NVEG , at days 1 and 5 . CreaT gene expression was not different between VEG and NVEG . The results indicate that VEG have a lower muscle TCr content and an increased capacity to load Cr into muscle following CrS.  Muscle CreaT gene expression does not appear to be affected by vegetarianism Abstract Background Human ageing is a process characterized by loss of muscle mass , strength , and bone mass . We aim ed to examine the efficacy of low‐dose creatine supplementation associated with resistance training on lean mass , strength , and bone mass in the elderly . Methods This was a 12‐week , parallel‐group , double‐blind , r and omized , placebo‐controlled trial . The individuals were r and omly allocated into one of the following groups : placebo plus resistance training ( PL + RT ) and creatine supplementation plus resistance training ( CR + RT ) . The participants were assessed at baseline and after 12 weeks . The primary outcomes were lean mass and strength , assessed by dual energy X‐ray absorptiometry ( DXA ) and ten‐repetition maximal tests ( 10 RM ) , respectively . Secondary outcomes included the lumbar spine , right and left femoral neck , both femur and whole body bone mineral density ( BMD ) , and whole body bone mineral content ( BMC ) , assessed by DXA . Results The CR + RT group had superior gains in lean mass when compared with the PL + RT group ( P = 0.02 ) . Changes in the 10 RM tests in bench press and leg press exercises , body composition , BMD , and BMC of all assessed sites did not significantly differ between the groups ( P > 0.05 ) . Conclusions Twelve weeks of low‐dose creatine supplementation associated with resistance training result ed in increases in lean mass in the elderly Summary .Recent findings have indicated that creatine supplementation may affect glucose metabolism . This study aim ed to examine the effects of creatine supplementation , combined with aerobic training , on glucose tolerance in sedentary healthy male . Subjects ( n = 22 ) were r and omly divided in two groups and were allocated to receive treatment with either creatine ( CT ) ( ∼10 g · day over three months ) or placebo ( PT ) ( dextrose ) . Administration of treatments was double blind . Both groups underwent moderate aerobic training . An oral glucose tolerance test ( OGTT ) was performed and both fasting plasma insulin and the homeostasis model assessment ( HOMA ) index were assessed at the start , and after four , eight and twelve weeks . CT demonstrated significant decrease in OGTT area under the curve compared to PT ( P = 0.034 ) . There were no differences between groups or over time in fasting insulin or HOMA . The results suggest that creatine supplementation , combined with aerobic training , can improve glucose tolerance but does not affect insulin sensitivity , and may warrant further investigation with diabetic subjects Creatine monohydrate ( CrM ) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling . Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle . In a r and omized , placebo-controlled , crossover , double-blind design , 12 young , healthy , nonobese men were supplemented with either a placebo ( PL ) or CrM ( loading phase , 20 g/day x 3 days ; maintenance phase , 5 g/day x 7 days ) for 10 days . Following a 28-day washout period , subjects were put on the alternate supplementation for 10 days . Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression ( cDNA microarrays + real-time PCR ) and protein content ( Kinetworks KPKS 1.0 Protein Kinase screen ) . CrM supplementation significantly increased fat-free mass , total body water , and body weight of the participants ( P < 0.05 ) . Also , CrM supplementation significantly upregulated ( 1.3- to 5.0-fold ) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction , cytoskeleton remodeling , protein and glycogen synthesis regulation , satellite cell proliferation and differentiation , DNA replication and repair , RNA transcription control , and cell survival . We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation , a response that suggests changes in cellular osmolarity PURPOSE This study investigated whether acute ( 5 d ) and /or short-term ( 28 d ) creatine ( Cr ) ingestion altered glucose tolerance or insulin action in healthy , untrained men ( aged 26.9 + /- 5.7 yr ; SD ) . METHODS Subjects were r and omly allocated to either a Cr ( N= 8) or placebo group ( N = 9 ) and were tested in the control condition ( presupplementation ) , and after 5 and a further 28 d of supplementation . The Cr group ingested 20 g and 3 g.d ( -1 ) of Cr for the first 5 and following 28 d , respectively . The placebo group ingested similar amounts of glucose over the same time period . During each testing period , subjects underwent an oral glucose tolerance test ( OGTT ) to determine insulin sensitivity , and six subjects from each group underwent a muscle biopsy before each OGTT . RESULTS Cr supplementation result ed in an increased ( P < 0.05 ) muscle TCr content after both the acute and short-term loading phase compared with placebo . Neither acute nor short-term Cr supplementation influenced skeletal muscle glycogen content , glucose tolerance , or measures of insulin sensitivity . CONCLUSIONS These findings demonstrated that acute Cr supplementation ( 20 g.d(-1 ) for 5 d ) followed by short-term Cr supplementation ( 3 g.d(-1 ) for 28 d ) did not alter insulin action in healthy , active untrained men UNLABELLED Creatine supplementation improves glucose tolerance in healthy subjects . PURPOSE S The aim was to investigate whether creatine supplementation has a beneficial effect on glycemic control of type 2 diabetic patients undergoing exercise training . METHODS A 12-wk r and omized , double-blind , placebo-controlled trial was performed . The patients were allocated to receive either creatine ( CR ) ( 5 g·d ) or placebo ( PL ) and were enrolled in an exercise training program . The primary outcome was glycosylated hemoglobin ( HbA1c ) . Secondary outcomes included the area under the curve of glucose , insulin , and C-peptide and insulin sensitivity indexes . Physical capacity , lipid profile , and GLUT-4 protein expression and translocation were also assessed . RESULTS Twenty-five subjects were analyzed ( CR : n=13 ; PL : n=12 ) . HbA1c was significantly reduced in the creatine group when compared with the placebo group ( CR : PRE=7.4 ± 0.7 , POST=6.4 ± 0.4 ; PL : PRE=7.5 ± 0.6 , POST=7.6 ± 0.7 ; P=0.004 ; difference=-1.1 % , 95 % confidence interval=-1.9 % to -0.4 % ) . The delta area under the curve of glucose concentration was significantly lower in the CR group than in the PL group ( CR=-7790 ± 4600 , PL=2008 ± 7614 ; P=0.05 ) . The CR group also presented decreased glycemia at times 0 , 30 , and 60 min during a meal tolerance test and increased GLUT-4 translocation . Insulin and C-peptide concentrations , surrogates of insulin sensitivity , physical capacity , lipid profile , and adverse effects were comparable between the groups . CONCLUSIONS Creatine supplementation combined with an  exercise program improves glycemic control in type 2 diabetic patients . The underlying mechanism seems to be related to an increase in GLUT-4 recruitment to the sarcolemma 1 . The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed , and if continued result ed in an increase in the total creatine pool in muscle . An additional effect of exercise upon uptake into muscle was also investigated . 2 . Low doses ( 1 g of creatine monohydrate or less in water ) produced only a modest rise in the plasma creatine concentration , whereas 5 g result ed in a mean peak after 1h of 795 ( SD 104 ) mumol/l in three subjects weighing 76 - 87 kg . Repeated dosing with 5 g every 2h sustained the plasma concentration at around 1000 mumol/l . A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh , uncooked steak . 3 . Supplementation with 5 g of creatine monohydrate , four or six times a day for 2 or more days result ed in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects . This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range . In some the increase was as much as 50 % . 4 . Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32 % of the dose administered in three subjects receiving 6 x 5 g of creatine monohydrate/day . In these subjects renal excretion was 40 , 61 and 68 % of the creatine dose over the first 3 days . Approximately 20 % or more of the creatine taken up was measured as phosphocreatine . No changes were apparent in the muscle ATP content . ( ABSTRACT TRUNCATED AT 250 WORDS The present study was undertaken to explore the effects of creatine and creatine plus protein supplementation on GLUT-4 and glycogen content of human skeletal muscle . This was investigated in muscles undergoing a decrease ( immobilization ) and subsequent increase ( resistance training ) in activity level , compared with muscles with unaltered activity pattern . A double-blind , placebo-controlled trial was performed by 33 young healthy subjects . The subjects ' right legs were immobilized with a cast for 2 wk , followed by a 6-wk resistance training program for the right knee extensor muscles . The participants were supplemented throughout the study with either placebo ( Pl group ) or creatine ( Cr group ) or with creatine during immobilization and creatine plus protein during retraining ( Cr+P group ) . Needle biopsies were bilaterally taken from the vastus lateralis . GLUT-4 protein expression was reduced by the immobilization in all groups ( P < 0.05 ) . During retraining , GLUT-4 content increased ( P < 0.05 ) in both Cr ( + 24 % ) and Cr+P ( + 33 % ) , which result ed in higher posttraining GLUT-4 expression compared with Pl ( P < 0.05 ) . Compared with Pl , muscle glycogen content was higher ( P < 0.05 ) in the trained leg in both Cr and Cr+P. Supplements had no effect on GLUT-4 expression or glycogen content in contralateral control legs . Area under the glucose curve during the oral glucose tolerance test was decreased from 232 + /- 23 mmol . l(-1 ) . min(-1 ) at baseline to 170 + /- 23 mmol . l(-1 ) . min(-1 ) at the end of the retraining period in Cr+P ( P < 0.05 ) , but it did not change in Cr or Pl . We conclude that creatine intake stimulates GLUT-4 and glycogen content in human muscle only when combined with changes in habitual activity level . Furthermore , combined protein and creatine supplementation improved oral glucose tolerance , which is supposedly unrelated to the changes in muscle GLUT-4 expression We aim ed to investigate the possible role of creatine ( CR ) supplementation in counteracting dexamethasone-induced muscle wasting and insulin resistance in rats . Also , we examined whether CR intake would modulate molecular pathways involved in muscle remodeling and insulin signaling . Animals were r and omly divided into four groups : ( 1 ) dexamethasone ( DEX ) ; ( 2 ) control pair-fed ( CON-PF ) ; ( 3 ) dexamethasone plus CR ( DEX-CR ) ; and ( 4 ) CR pair-fed ( CR-PF ) . Dexamethasone ( 5 mg/kg/day ) and CR ( 5 g/kg/day ) were given via drinking water for 7 days . Plantaris and extensor digitorum longus ( EDL ) muscles were removed for analysis . Plantaris and EDL muscle mass were 
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Regarding human studies , considering the sample s characteristics , the findings can not be extrapolated to patients who have poorer glycemic control , are older , are on a different pharmacological treatment ( e.g. , exogenous insulin therapy ) or are physically inactive .
Thus , creatine supplementation is a possible nutritional therapy adjuvant with hypoglycemic effects , particularly when used in conjunction with exercise