Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Glucose production pathways by 2H and 13C NMR in patients with HIV-associated lipoatrophy.

Patients with HIV taking protease inhibitors were selected for the presence (five subjects) or absence (five subjects) of lipoatrophy. Following an overnight fast, subjects were given oral (2)H(2)O in divided doses (5 mL/kg body water), [U-(13)C(3)] propionate (10 mg/kg), and acetaminophen (1000 mg). Glucose (from plasma) or acetaminophen glucuronide (from urine) were converted to monoacetone glucose for (2)H NMR and (13)C NMR analysis. The fraction of plasma glucose derived from gluconeogenesis was not significantly different between groups. However, flux from glycerol into gluconeogenesis relative to glucose production was increased from 0.20 +/- 0.13 among subjects without lipoatrophy to 0.42 +/- 0.12 (P < 0.05) among subjects with lipoatrophy, and the TCA cycle contribution was reduced. Lipoatrophy was associated with an abnormal profile of glucose production as assessed by (13)C and (2)H NMR of plasma and urine.     

Quantification of hepatic transaldolase exchange activity and its effects on tracer measurements of indirect pathway flux in humans.

Exchange of hepatic glucose-6-phosphate (G6P) and glyceraldehyde-3-phosphate via transaldolase modifies hepatic G6P enrichment from glucose or gluconeogenic tracers. Transaldolase exchange was quantified in five healthy, fed subjects following an oral bolus of [1,2,3-(13)C(3)]glycerol (25-30 mg/kg) and paracetamol (10-12 mg/kg). (13)C Isotopomers of hepatic G6P were quantified by (13)C NMR spectroscopy of urinary glucuronide. [1,2,3-(13)C(3)]- and [4,5,6-(13)C(3)]glucuronide isotopomers, representing the conversion of [1,2,3-(13)C(3)]glycerol to G6P via dihydroxyacetone phosphate, were resolved from [1,2-(13)C(2)]- and [5,6-(13)C(2)]glucuronide (13)C-isotopomers, derived from metabolism of [1,2,3-(13)C(3)]glycerol via pyruvate and phosphoenolpyruvate. Enrichment of [1,2,3-(13)C(3)]glucuronide was significantly less than that of [4,5,6-(13)C(3)]glucuronide (1.30 +/- 0.57% versus 1.67 +/- 0.42%, P < 0.05). Also, [1,2-(13)C(2)]glucuronide enrichment was significantly less than that of [5,6-(13)C(2)]glucuronide (0.28 +/- 0.08% versus 0.36 +/- 0.03%, P < 0.05). Transaldolase and triose phosphate isomerase exchange activities were estimated by applying the (13)C-isotopomer data to a model of hepatic sugar phosphate metabolism. Triose phosphate isomerase exchange was approximately 99% complete and did not contribute significantly to the unequal (13)C-isotopomer distributions of the glucuronide triose halves. Instead, this was attributable to 25 +/- 23% of hepatic G6P flux undergoing transaldolase exchange. This results in substantial overestimates of indirect pathway contributions to hepatic glycogen synthesis with tracers such as [5-(3)H]glucose and (2)H(2)O.     

Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment

The contribution of gluconeogenesis to hepatic glucose production (GP) was quantified after ²H₂O ingestion by Bayesian analysis of the position 2 and 5 ²H‐NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx patients were lean and euglycemic (BMI = 24.3 ± 1.0 kg/m²; fasting glucose = 4.7 ± 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 ± 0.7 kg/m²; fasting glucose = 7.1 ± 0.5 mM). For the 16 spectra analyzed, the mean coefficient of variation for the gluconeogenesis contribution was 10% ± 5%. This uncertainty was associated with a mean signal‐to‐noise ratio (SNR) of 79:1 and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects, gluconeogenesis contributed 54% ± 7% of GP as determined by the mean and standard deviation (SD) of individual Bayesian analyses. For the lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% ± 7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a gluconeogenic contribution of 68% ± 3% (P < 0.005 vs. controls). These data suggest that in KTx patients, an increased gluconeogenic contribution to GP is strongly associated with obesity and hyperglycemia. Magn Reson Med 60:517–523, 2008. © 2008 Wiley‐Liss, Inc.     

Exercise and calcium supplementation: effects on calcium homeostasis in sportswomen

PURPOSE: Exercise-induced sweat calcium losses have been reported as substantial in male athletes. The first aim of the study was to quantify the increase in 24-h total dermal calcium losses and the net changes in calcium retention in active sportswomen after a 1-h strenuous exercise session. A second aim was to determine the effectiveness of calcium supplementation to offset any calcium loss. METHODS: Twenty-six premenopausal sportswomen completed three 8-d intervention phases in a randomized-order, crossover design. The three phases were placebo+no exercise (control), placebo+exercise, and 400 mg of calcium as calcium carbonate (TUMS Ultra) twice daily+exercise. The supervised exercise was 1 h.d(-1) cycling at 65-70% of heart rate reserve. A controlled diet of approximately 450 mg.d(-1) of calcium and 24-h pooled urine and fecal collections allowed determination of calcium balance on days 5-8 of each phase. Twenty-four-hour dermal collections were made at the end of each phase using a whole-body washdown procedure. RESULTS: Exercise increased (P<0.05) dermal calcium losses (means+/-SD, 92+/-49 vs 79+/-31 mg.d(-1) in the nonexercise intervention period), which was no longer significant (P=0.14) when calcium supplementation was provided (83+/-49 mg.d(-1)). Higher (P<0.01) urinary calcium excretion during calcium supplementation is suggestive of higher net calcium absorption. Exercise did not affect urinary calcium excretion indicating lack of compensation for dermal losses. Net calcium retention was positive only during the exercise+calcium supplementation intervention period. CONCLUSIONS: Calcium supplementation can correct for negative calcium balance attributable to low calcium dietary intake and additional dermal losses from exercise.     

Analysis of blood flow and glucose metabolism in mammary carcinomas and normal breast: a H2(15)O PET and 18F-FDG PET study

OBJECTIVE: To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of the tumour-specific micromilieu of breast cancer and compare them with corresponding values in normal breast tissue. METHODS: H2(15)O PET and 18F-FDG PET were performed on 10 patients with advanced invasive ductal carcinomas of the breast. Perfusion, distribution coefficient, and glucose metabolism and standardized uptake were quantified and analysed. RESULTS: Mean values based on the regions of interest were 59.2+/-43.9 ml x min(-1) x 100 g(-1) (perfusion), 0.58+/-0.26 ml x g(-1) (distribution coefficient), 7.76+/-6.10 (standardized uptake), and 5.4+/-2.5 mg x min(-1) x 100 g(-1) (glucose metabolism). The corresponding values for normal breast tissue were 22.1+/-13.2 ml x min x 100 g(-1) (perfusion), 0.16+/-0.05 ml x g(-1) (distribution coefficient), 0.33+/-0.07 (standardized uptake), and 0.18+/-0.08 mg x min x 100 g(-1) (glucose metabolism). For each tumour-normal tissue parameter pair, the mean values were significantly higher in tumours than normal breast tissue. Region-of-interest and pixel-wise correlation analysis revealed a positive association between glucose metabolism and distribution coefficient and glucose metabolism and perfusion for 7/10 tumours investigated. CONCLUSIONS: H2(15)O PET and 18F-FDG PET were able to differentiate breast cancer and normal breast tissue. The pixel-wise analysis revealed information about the heterogeneity of tumour fine structure in perfusion, distribution coefficient, and glucose metabolism, which may provide important guidelines for improving individual treatment.     

Quantitation of erythrocyte pentose pathway flux with [2-13C]glucose and 1H NMR analysis of the lactate methyl signal.

A simple and sensitive NMR method for quantifying excess (13)C-enrichment in positions 2 and 3 of lactate by (1)H NMR spectroscopy of the lactate methyl signal is described. The measurement requires neither signal calibrations nor the addition of a standard and accounts for natural abundance (13)C-contributions. As a demonstration, the measurement was applied to approximately 3 micromol of lactate generated by erythrocyte preparations incubated with [2-(13)C]glucose to determine the fraction of glucose metabolized by the pentose phosphate pathway (PP). PP fluxes were estimated from the ratio of excess (13)C-enrichment in lactate carbon 3 relative to carbon 2 in accordance with established metabolic models. Under baseline conditions, PP flux accounted for 7 +/- 2% of glucose consumption while in the presence of methylene blue, a classical activator of PP activity, its contribution increased to 27 +/- 10% of total glucose consumption (P < 0.01).     

Sources of plasma glucose by automated Bayesian analysis of 2H NMR spectra.

Sources of blood glucose can be determined after oral ingestion of (2)H(2)O followed by isolation of plasma glucose and measurement of the relative (2)H enrichments in select positions within the glucose molecule. Typically, (2)H enrichments are obtained by mass spectrometry but (2)H NMR offers an alternative. Here it is demonstrated that the entire analysis may be automated by Bayesian analysis of a (2)H free induction decay signal of monoacetone glucose to obtain a direct readout of the relative contributions of glycogenolysis, glycerol, and phosphoenol pyruvate to plasma glucose production. Furthermore, Markov Chain Monte Carlo (MCMC) simulations of the posterior probability density provide uncertainties in all metabolic parameters from a single patient, thereby allowing comparisons in glucose metabolism from one individual to another. The combined MCMC Bayesian methodology is operationally simple and requires little intervention from the operator.     

Quantitation of absolute 2H enrichment of plasma glucose by 2H NMR analysis of its monoacetone derivative.

A simple (2)H NMR method for quantifying absolute (2)H-enrichments in all seven aliphatic positions of glucose following its derivatization to monoacetone glucose is presented. The method is based on the addition of a small quantity of (2)H-enriched formate to the NMR sample. When the method was applied to [2-(2)H]monoacetone glucose samples prepared from [2-(2)H]glucose standards of known enrichments in the range of 0.2-2.5%, enrichment estimates derived by the NMR method were in good agreement with the real enrichment values of the [2-(2)H]glucose precursors. The measurement was also applied to monoacetone glucose derived from human plasma glucose samples following administration of (2)H(2)O and attainment of isotopic steady state, where glucose H2 and body water enrichment are equivalent. In these studies, the absolute H2 enrichment of plasma glucose estimated by the formate method was in good agreement with the (2)H-enrichment of body water measured by an independent method.     

Acetaminophen glucuronide and plasma glucose report identical estimates of gluconeogenesis and glycogenolysis for healthy and prediabetic subjects using the deuterated water method

Plasma glucose ²H‐enrichment in positions 5 (²H5) and 2 (²H2) from deuterated water (²H₂O) provides a measure of the gluconeogenic contribution to endogenous glucose production. Urinary glucuronide analysis can circumvent blood sampling but it is not known if glucuronide and glucose enrichments are equal. Thirteen subjects with impaired fasting glucose/impaired glucose tolerance and 11 subjects with normal fasting glucose and normal glucose tolerance ingested ²H₂O to ～0.5% body water and acetaminophen. Glucose and glucuronide ²H5 and ²H2 were measured by ²H NMR spectroscopy of monoacetone glucose. For normal fasting glucose/normal glucose tolerance, ²H5 was 0.23 ± 0.02% and 0.25 ± 0.02% for glucose and glucuronide, respectively, whereas ²H2 was 0.47 ± 0.01% and 0.49 ± 0.02%, respectively. For impaired fasting glucose/impaired glucose tolerance, ²H5 was 0.22 ± 0.01% and 0.26 ± 0.02% for glucose and glucuronide, respectively, whereas ²H2 was 0.46 ± 0.01% and 0.49 ± 0.02%, respectively. The gluconeogenic contribution to endogenous glucose production measured from glucose and glucuronide were identical for both normal fasting glucose/normal glucose tolerance (48 ± 4 vs. 51 ± 3%) and impaired fasting glucose/impaired glucose tolerance (48 ± 2 vs. 53 ± 3%). Magn Reson Med 70:315–319, 2013. © 2012 Wiley Periodicals, Inc.     

The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography

BACKGROUND: We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. METHODS: One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) > or =1.5 mg/dL (132.6 micromol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. RESULTS: The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 +/- 0.6 mg/dL (150.3 +/- 53.0 micromol/L) in the iomeprol-400 group and 1.7 +/- 0.7 mg/dL (150.3 +/- 61.9 micromol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 +/- 13.1 mL/Min in the iomeprol-400 group and 43.0 +/- 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72 patient receiving iodixanol-320 (6.9%) and none of the patients receiving iomeprol-400 showed an increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline [P = 0.025, 95% CI (-12.8%, -1.1%)]. The mean SCr change from baseline was significantly higher (P = 0.017 ANCOVA) after iodixanol-320 (0.06 +/- 0.27) than after iomeprol-400 (-0.04 +/- 0.19). CONCLUSIONS: The incidence of CIN was significantly higher after IV administration of iodixanol-320 than iomeprol-400. The mean rise in SCr from baseline was also higher in patients receiving iodixanol.     

The effect of glucose infusion on glucose kinetics during a 1-h time trial

PURPOSE AND METHODS: To investigate the effect of glucose infusion on glucose kinetics and performance, six endurance cyclists (VO2max = 61.7 +/- 2.0 (mean +/- SE) mL x kg(-1) x min(-1)) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible (991 +/- 41 kJ). Subjects were infused with either glucose (20% in saline; carbohydrate (CHO)) at a rate of 1 g x min(-1) or saline (0.9% saline; placebo (PLA)). It was hypothesized that time trial performance would be unaffected by the infusion of glucose, as endogenous stores of CHO would not be limiting in the PLA trial. RESULTS: Plasma glucose concentration increased from 4.8 +/- 0.1 mmol x L(-1) to 5.9 +/- 0.3 mmol x L(-1) during the PLA trial and from 4.9 +/- 0.1 mmol x L(-1) at rest to 12.4 +/- 1.1 mmol x L(-1) during the CHO trial. These values were significantly higher at all time points during the CHO trial compared with PLA (P < 0.001). In the final stages of the time trial, Rd in the PLA trial was 49 +/- 5 micromol x kg(-1) x min(-1) compared with 88 +/- 7 micromol x kg(-1) x min(-1) in the CHO trial (P < 0.05). Despite these differences, there was no difference in performance time between PLA and CHO (60.04 +/- 1.47 min, PLA, vs 59.90 +/- 1.49 min, CHO, respectively). Infused carbohydrate oxidation in the last 25% of the CHO trial was at least 675 +/- 120 micromol x kg(-1) and contributed 17 +/- 4% to total carbohydrate oxidation. CONCLUSION: The results demonstrate that glucose infusion had no effect on 1-h cycle time-trial performance, despite an increased availability of plasma glucose for oxidation and evidence of increased glucose uptake into the tissues.     

Vitamin E and immunity after the Kona Triathlon World Championship

PURPOSE: To measure the influence of vitamin E ingestion on oxidative stress and immune changes in response to the Triathlon World Championship in Kona, Hawaii. METHODS: Thirty-eight triathletes received vitamin E (VitE) (800 IU x d(-1) alpha-tocopherol) or placebo (Pla) capsules in randomized, double-blind fashion for 2 months before the race event. Blood, urine, and saliva samples were collected the day before the race, 5-10 min postrace, and 1.5 h postrace. RESULTS: Race times did not differ between VitE (N = 19, 721 +/- 24 min) and Pla groups (N = 17, 719 +/- 27 min, P = 0.959), and both groups maintained an intensity of approximately 80% maximum heart rate during the bike and run portions. Plasma alpha-tocopherol was approximately 75% higher in the VitE versus Pla group prerace (24.1 +/- 1.1 and 13.8 +/- 1.1 micromol x L(-1), P < 0.001, respectively) and postrace. Plasma F2-isoprostanes increased 181% versus 97% postrace in the VitE versus Pla groups (P = 0.044). IL-6 was 89% higher (166 +/- 28 and 88 +/- 13 pg x mL(-1), respectively, P = 0.016), IL-1ra was 107% higher (4848 +/- 1203 and 2341 +/- 790 pg x mL(-1), respectively, P = 0.057), and IL-8 was 41% higher postrace in the VitE versus Pla groups (26.0 +/- 3.6 and 18.4 +/- 2.4 pg x mL(-1), respectively, P = 0.094). CONCLUSION: These data indicate that vitamin E (800 IU x d(-1) for 2 months) compared with placebo ingestion before a competitive triathlon race event promotes lipid peroxidation and inflammation during exercise.     

Localized 1H NMR measurements of 2-pyrrolidinone in human brain in vivo.

Localized 1H NMR homonuclear J editing spectroscopy was used to measure the concentration of 2-pyrrolidinone (PRDN) in the human occipital lobe of five normal and six epileptic subjects taking vigabatrin. PRDN is a lactam cyclization product of gamma-aminobutyric acid (GABA). From a localized volume of 13.5 cm3 in the occipital cortex, the concentration of PRDN ranged from 0.2 to 0.3 micromol/g in normal subjects, whereas in epileptic subjects on vigabatrin PRDN was elevated to 0.6 +/- 0.1 micromol/g. The elevated PRDN in patients on vigabatrin was in accord with raised GABA levels compared with normals. 1H NMR measurements of PRDN will be important in assessment of the role of this metabolite for improved seizure control.     

Quantifying tracer levels of (2)H(2)O enrichment from microliter amounts of plasma and urine by (2)H NMR.

A simple and sensitive (2)H NMR measurement of (2)H(2)O enrichment from a 10 microl volume of body fluid is presented. The method allows (2)H-enrichment levels of 0.1% or above to be rapidly determined from 10 microl of plasma or urine. The measurement is insensitive to the presence of plasma protein, allowing direct analysis of (2)H(2)O enrichment from native plasma samples. Magn Reson Med 45:156-158, 2001.     

Effects of exercise and carbohydrate composition on gastric emptying

To examine the gastric emptying characteristics of selected test drinks varying in carbohydrate composition and concentration, twenty-five runners ingested 400 ml of a solution in one or more of a series of trials followed by either 15 min seated rest or 15 min running (50 to 70% VO2 max). The solutions tested at rest included water, 5.0% maltodextrin, 3.0% maltodextrin + 2% glucose (MG5.0), and 4.5% maltodextrin + 2.6% fructose (MF7.1). Solutions tested during running included water, MG5.0, MF7.1, 5.5% maltodextrin + 2% glucose, and 5.5% maltodextrin + 2% fructose. At rest and during running, water emptied significantly (P less than 0.5) faster than all other drinks. In the running trials, the volume of gastric residue of 5.5% maltodextrin + 2% fructose (221.7 +/- 11.0 ml) was significantly greater than water (103.4 +/- 19.0 ml), MG5.0 (153.3 +/- 16.8 ml), and MF7.1 (167.3 +/- 14.8), suggesting an inhibitory role of glucose on gastric emptying. Running resulted in a significantly lower volume of gastric residue of water, MG5.0, and MF7.1 (103.4 +/- 19.0, 153.3 +/- 16.8, and 167.3 +/- 14.8 ml, respectively) as compared to the corresponding drinks at rest (209.3 +/- 12.6, 287.7 +/- 16.0, and 271.0 +/- 17.8 ml, respectively). These results suggest a possible advantage for including maltodextrin and fructose as carbohydrate sources in athletic drinks. Furthermore, the rate of gastric emptying is enhanced while running, possibly due to increased mechanical movement of fluid within the stomach.     

The effect of ad libitum ingestion of a caffeinated carbohydrate-electrolyte solution on urinary caffeine concentration after 4 hours of endurance exercise

The purpose of the present study was to examine the effect of ad libitum ingestion of a carbohydrate-electrolyte solution (CES) with 150 mg x L (-1) caffeine (CAF) on urinary CAF concentration after 4 h of endurance exercise. Fifty-eight healthy and well-trained male subjects ingested ad libitum a 7 % CES with 150 mg x L (-1) CAF during 4 h cycling at 50 % of maximal work capacity. Total fluid consumption (mean +/- SE) was 2799 +/- 72 mL and CAF intake was 420 +/- 11 mg (5.7 +/- 0.2 mg x kg (-1) body weight). The post-exercise urinary CAF concentration (4.53 +/- 0.25 microg x mL (-1)) was below the doping level of the International Olympic Committee (12 microg x mL (-1)) in all subjects (range 1.20 - 10.84 microg x mL (-1)). A highly positive correlation was observed between CAF intake and post-exercise urinary CAF concentration (r = 0.68, p < 0.001). It is concluded that ad libitum ingestion of a CES with 150 mg x L (-1) CAF during 4 h cycling resulted in post-exercise urinary concentration below the doping level in all subjects.     

Reducing the dose of combined caffeine and ephedrine preserves the ergogenic effect

BACKGROUND: Ingestion of a combination of 5 mg x kg(-1) caffeine (C), and 1 mg x kg(-1) ephedrine (E) was reported to have an ergogenic effect on high intensity aerobic exercise performance, but 25% of the subjects experienced vomiting and nausea while engaging in hard exercise after the treatment. The present study was undertaken to investigate whether reduced levels of C+E would alleviate the problem and maintain the ergogenic effect. METHODS: Twelve healthy untrained male subjects completed four randomized and double-blind, cycle ergometer trials to exhaustion at a power output equivalent to approximately 85% Vo2peak 1.5-2 hours after ingesting a placebo (P) or a mixture of C+E in the following doses: 5 mg x kg(-1) of C plus 0.8 mg x kg(-1) of E (CLE); 4 mg x kg(-1) of C plus 1 mg x kg(-1) of E (LCE); or 4 mg x kg of C plus 0.8 mg x kg(-1) of E (LCLE). Trials were separated by 1 wk. Venous blood samples were obtained and analyzed for caffeine and ephedrine levels 1.5 h post-drug ingestion. Vo2, Vco2, VE, and RQ were measured every minute throughout the exhaustion ride. Heart rate and perceived exertion (RPE) were also recorded every 5 min and at the end of the exercise session. RESULTS: Plasma levels of C and E immediately before the exhaustion ride were (mean +/- SD): 38.7+/-5.2 micromol x L(-1) C, 1.285+/-0.275 micromol x L(-1) E in the CLE trial; 33.2+/-5.8 micromol x L(-1) C, 1.462+/-0.283 micromol x L(-1) E in the LCE trial; 33.0+/-2.9 micromol x L(-1) C, 1.229+/-0.202 micromol x L(-1) E in the LCLE trial. The times to exhaustion for the treatment trials (CLE = 27.5+/-12.4 min, LCE = 27.6+/-10.9 min, LCLE = 28.2+/-9.3 min) were similar and were significantly greater than placebo (p = 17.0+/-3.0 min). The drugs did not affect Vo2, Vco2, or VE. Heart rates were significantly higher for the drug trials while RPE was lower compared with P. No incidents of nausea or vomiting occurred with the lowest dose of the C+E, LCLE. CONCLUSIONS: A lower dose of C+E resulted in an ergogenic effect similar in magnitude to that reported previously with a higher dose, and with a reduced incidence of negative side effects.     

Pre-exercise carbohydrate status influences carbohydrate-mediated attenuation of post-exercise cytokine responses

Most studies investigating the effects of acute carbohydrate (CHO) ingestion on post-exercise cytokine responses have involved fasted athletes. This study characterised the effects of acute CHO beverage ingestion preceded by consumption of a CHO-containing pre-exercise meal. Sixteen highly-trained male cyclists/triathletes (age: 30.6 +/- 5.6 y; V O (2max): 64.8 +/- 4.7 ml . kg . min (-1) [mean +/- SD]) undertook two cycle ergometry trials involving randomised consumption of a 10 % CHO beverage (15 mL . kg (-1) . hr (-1)) or water (H (2)O). Trials were undertaken 2 h after a breakfast providing 2.1 g CHO . kg (-1) body mass (BM) (48 kJ . kg (-1) BM) and consisted of 100 min steady state cycle ergometry at 70 % V O (2max) followed by a time trial of approximately 30 min duration. Blood samples were collected pre-, post- and 1 h post-exercise for measurement of Interleukin (IL)-6, IL-8, IL-10 and IL-1ra. Time-trial performance was not substantially different between CHO and H (2)O trials (4.5 %, p = 0.42). Neither IL-6 nor IL-8 responses were substantially reduced in the CHO compared to the H (2)O trial. There was a substantial reduction in IL-10 (32 %, p = 0.05) and IL-1ra (43 %, p = 0.02) responses at 1 h post-exercise with CHO compared to H (2)O ingestion. In conclusion, the previously shown attenuating effects of CHO ingestion during exercise on cytokine responses appear reduced when athletes consume a CHO-containing pre-exercise meal.     

Hydroxylysine excretion does not indicate collagen damage with downhill running in young men

The purpose of this study was to determine whether urinary excretion of hydroxylysine (HO-Lys) is increased following prolonged, predominantly downhill running. Such an increase would be evidence of exercise-induced collagen damage. Each of ten young men performed a treadmill running test to determine VO2peak (an approximation of VO2max) followed by 60 min of intermittent running on -10% slope. Total urine excreted from 48 h pre-exercise to 96h post-exercise was collected in 8-h samples for measurement of HO-Lys. In addition, both urinary 3-methylhistidine (3-MeHis) excretion and serum creatine kinase (SCK) activity were measured as indicators of muscle tissue damage. In no sampling period was post-exercise HO-Lys excretion altered compared with pre-exercise (e.g., pre-exercise: 82.2 +/- 9.6 mumol.24 h-1, mean +/- SE; 51.0 +/- 3.7 mumol.g creatinine-1; post-exercise: 72.9 +/- 2.0 mumol.24 h-1; 47.0 +/- 1.5 mumol.g creatinine-1). SCK activity was increased (346%) 24 h post-exercise, but not immediately, 48 h, or 72 h post-exercise. 3-MeHis excretion was not altered following exercise. There were no strong associations between HO-Lys excretion and either of the markers of muscle damage. We concluded that no evidence of exercise-induced collagen damage was provided by urinary HO-Lys excretion.