Cyclic hypobaric hypoxia improves markers of glucose metabolism in middle-aged men.

UNLABELLED: Chronic hypoxia increases dependence on glucose in men and increases insulin sensitivity in men and women. Cyclic Variations in Altitude Conditioning (CVAC) is a novel technology that provides exposure to rapidly fluctuating cyclic hypobaric hypoxia (CHH). PURPOSE: To test the hypothesis that markers of glucose metabolism would change with CVAC CHH, two groups of middle-aged men were exposed to 10 weeks (40 min/day, 3 day/week) of either CHH or sham (SH) sessions. METHODS: CHH subjects (age: 48 ± 6, weight: 86 ± 12 kg, BMI: 27.1 ± 3, n=11) experienced cyclic pressures simulating altitudes ranging from sea level to 3048 m (week 1) and progressing to 6096 m (by week 5 through week 10). SH subjects (age: 50 ± 4, weight: 89 ± 15 kg, BMI: 27.5 ± 3, n=10) were exposed to slowly-fluctuating pressures up to 607 m (all subjects blinded to elevation). Physical function and blood markers of glucose metabolism were measured at baseline, 3, 6, and 10 weeks. RESULTS: Two CHH subjects were dropped from analysis for failure to progress past 3048 m (CHH: n=9). Weight and physical activity remained stable for both groups. There was a group-by-time interaction in fasting glucose (CHH: 96 ± 9 to 91 ± 7 mg/dL, SH: 94 ± 7 to 97 ± 9 mg/dL, p<0.05). Reduction in plasma glucose response to oral glucose tolerance test [area under the curve] was greater in CHH compared to SH after 10 weeks of exposure (p<0.03). Neither group experienced changes in fasting insulin, insulin response during the OGTT, or changes in a timed walk test. CONCLUSION: Ten weeks of CVAC CHH exposure improves markers of glucose metabolism in middle-aged men at risk for metabolic syndrome.

Sildenafil has little influence on cardiovascular hemodynamics or 6-km time trial performance in trained men and women at simulated high altitude.

UNLABELLED: Sildenafil improves maximal exercise capacity at high altitudes (∼4350-5800 m) by reducing pulmonary arterial pressure and enhancing oxygen delivery, but the effects on exercise performance at less severe altitudes are less clear. PURPOSE: To determine the effects of sildenafil on cardiovascular hemodynamics (heart rate, stroke volume, and cardiac output), arterial oxygen saturation (SaO2), and 6-km time-trial performance of endurance-trained men and women at a simulated altitude of ∼3900 m. METHODS: Twenty men and 15 women, endurance-trained, completed one experimental exercise trial (30 min at 55% of altitude-specific capacity +6-km time trial) at sea level (SL) and two trials at simulated high altitude (HA) while breathing hypoxic gas (12.8% FIo2) after ingestion of either placebo or 50 mg sildenafil in double-blind, randomized, and counterbalanced fashion. RESULTS: Maximal exercise capacity and SaO2 were significantly reduced at HA compared to SL (18%-23%), but sildenafil did not significantly improve cardiovascular hemodynamics or time-trial performance in either men or women compared to placebo and only improved SaO2 in women (4%). One male subject (5% of male subjects, 2.8% of all subjects) exhibited a meaningful 36-s improvement in time-trial performance with sildenafil compared to placebo. CONCLUSIONS: In this group of endurance trained men and women, sildenafil had very little influence on cardiovascular hemodynamics, SaO2, and 6-km time-trial performance at a simulated altitude of ∼3900 m. It appears that a very small percentage of endurance-trained men and women derive meaningful improvements in aerobic performance from sildenafil at a simulated altitude of ∼3900 m.

Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women.

Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (≥ 4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO(2)), peak exercise capacity (W (peak)), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; ~2,100 m, 16.2% F(I)O(2)) and high (HA; ~3,900 m, 12.8% F(I)O(2)) altitudes. Eleven men and ten women completed two HA W (peak) trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitude-specific W (peak) + 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO(2) values (+3%, p < 0.05) compared to placebo during steady state and time trial exercise at HA. W (peak) at HA was 19% lower than SL (p < 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p < 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.

Substantial working muscle glycerol turnover during two-legged cycle ergometry.

We combined tracer and arteriovenous (a-v) balance techniques to evaluate the effects of exercise and endurance training on leg triacylglyceride turnover as assessed by glycerol exchange. Measurements on an exercising leg were taken to be a surrogate for working skeletal muscle. Eight men completed 9 wk of endurance training [5 days/wk, 1 h/day, 75% peak oxygen consumption (Vo(2peak))], with leg glycerol turnover determined during two pretraining trials [45 and 65% Vo(2peak) (45% Pre and 65% Pre, respectively)] and two posttraining trials [65% of pretraining Vo(2peak) (ABT) and 65% of posttraining Vo(2peak) (RLT)] using [(2)H(5)]glycerol infusion, femoral a-v sampling, and measurement of leg blood flow. Endurance training increased Vo(2peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 mlxkg(-1)xmin(-1), P < 0.05). At rest, there was tracer-measured leg glycerol uptake (41 +/- 8 and 52 +/- 15 micromol/min for pre- and posttraining, respectively) even in the presence of small, but significant, net leg glycerol release (-68 +/- 19 and -50 +/- 13 micromol/min, respectively; P < 0.05 vs. zero). Furthermore, while there was no significant net leg glycerol exchange during any of the exercise bouts, there was substantial tracer-measured leg glycerol turnover during exercise (i.e., simultaneous leg muscle uptake and leg release) (uptake, release: 45% Pre, 194 +/- 41, 214 +/- 33; 65% Pre, 217 +/- 79, 201 +/- 84; ABT, 275 +/- 76, 312 +/- 87; RLT, 282 +/- 83, 424 +/- 75 micromol/min; all P < 0.05 vs. corresponding rest). Leg glycerol turnover was unaffected by exercise intensity or endurance training. In summary, simultaneous leg glycerol uptake and release (indicative of leg triacylglyceride turnover) occurs despite small or negligible net leg glycerol exchange, and furthermore, leg glycerol turnover can be substantially augmented during exercise.

Effects of growth hormone and pioglitazone in viscerally obese adults with impaired glucose tolerance: a factorial clinical trial.

OBJECTIVE: Recombinant human growth hormone (GH) and pioglitazone (PIO) in abdominally obese adults with impaired glucose tolerance were evaluated under the hypothesis that the combination attenuates GH-induced increases in glucose concentrations, reduces visceral adipose tissue (VAT), and improves insulin sensitivity over time. DESIGN: Randomized, double-blind, placebo-controlled, 2 x 2 factorial design. SETTING: Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States. PARTICIPANTS: 62 abdominally obese adults aged 40-75 with impaired glucose tolerance. INTERVENTIONS: GH (8 microg/kg/d, or placebo) and pioglitazone (30 mg/d, or placebo) for 40 wk. OUTCOME MEASURES: Baseline and after 40 wk of treatment, VAT content was quantified by CT scan, glucose tolerance was assessed using a 75-g oral glucose tolerance test, and insulin sensitivity was measured using steady-state plasma glucose levels obtained during insulin suppression test. RESULTS: BASELINE: body mass index (BMI), plasma glucose, and visceral fat content were similar. 40 wk: visceral fat area declined 23.9 +/- 7.4 cm(2) in GH group, mean difference from placebo: -28.1 cm(2) (95% CI -49.9 to -6.3 cm(2); p = 0.02). Insulin resistance declined 52 +/- 11.8 mg/dl with PIO, mean difference from placebo of -58.8 mg/dl (95% CI -99.7 to -18.0 mg/dl; p = 0.01). VAT and SSPG declined with GH and PIO combined, mean differences from placebo of -31.4 cm(2) (95% CI -56.5 cm(2) to -6.3 cm(2); p = 0.02) and -55.3 mg/dl (95% CI -103.9 to -6.7 mg/dl; p = 0.02), respectively. Fasting plasma glucose increased transiently in GH group. No significant changes in BMI were observed. CONCLUSIONS: Addition of PIO to GH attenuated the short-term diabetogenic effect of GH; the drug combination reduced VAT and insulin resistance over time. GH plus PIO may have added benefit on body composition and insulin sensitivity in the metabolic syndrome.

Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women.

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72.2 (SD 6.4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0.05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0.05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0.05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0.887 +/- 0.102 v. 1.104 +/- 0.121 g/cm2; P < 0.01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training.

To evaluate the contribution of working muscle to whole body lipid oxidation, we examined the effects of exercise intensity and endurance training (9 wk, 5 days/wk, 1 h, 75% Vo(2 peak)) on whole body and leg free fatty acid (FFA) kinetics in eight male subjects (26 +/- 1 yr, means +/- SE). Two pretraining trials [45 and 65% Vo(2 max) (45UT, 65UT)] and two posttraining trials [65% of pretraining Vo(2 peak) (ABT), and 65% of posttraining Vo(2 peak) (RLT)] were performed using [1-(13)C]palmitate infusion and femoral arteriovenous sampling. Training increased Vo(2 peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 ml.kg(-1).min(-1), P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX) compared with rest regardless of workload or training status ( approximately 20 vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest ( approximately -36 micromol/min) to net uptake during EX for 45UT (179 +/- 75), ABT (236 +/- 63), and RLT (136 +/- 110) (P < 0.05), but not 65UT (51 +/- 127). Leg FFA tracer measured uptake was higher during EX than rest for all trials and greater during posttraining in RLT (716 +/- 173 micromol/min) compared with pretraining (45UT 450 +/- 80, 65UT 461 +/- 72, P < 0.05). Leg muscle lipid oxidation increased with training in ABT (730 +/- 163 micromol/min) vs. 65UT (187 +/- 94, P < 0.05). Leg muscle lipid oxidation represented approximately 62 and 30% of whole body lipid oxidation at lower and higher relative intensities, respectively. In summary, training can increase working muscle tracer measured FFA uptake and lipid oxidation for a given power output, but both before and after training the association between whole body and leg lipid metabolism is reduced as exercise intensity increases.

Changes in ventilatory threshold at high altitude: effect of antioxidants.

PURPOSE: To investigate the effects of prolonged hypoxia and antioxidant supplementation on ventilatory threshold (VT) during high-altitude (HA) exposure (4300 m). METHODS: Sixteen physically fit males (25 +/- 5 yr; 77.8 +/- 8.5 kg) performed an incremental test to maximal exertion on a cycle ergometer at sea level (SL). Subjects were then matched on VO2peak, ventilatory chemosensitivity, and body mass and assigned to either a placebo (PL) or antioxidant (AO) supplement group in a randomized, double-blind manner. PL or AO (12 mg of beta-carotene, 180 mg of alpha-tocopherol acetate, 500 mg of ascorbic acid, 100 mug of selenium, and 30 mg of zinc daily) were taken 21 d prior to and for 14 d at HA. During HA, subjects participated in an exercise program designed to achieve an energy deficit of approximately 1400 kcal.d(-1). VT was reassessed on the second and ninth days at HA (HA2, HA9). RESULTS: Peak power output (Wpeak) and VO2peak decreased (28%) in both groups upon acute altitude exposure (HA2) and were unchanged with acclimatization and exercise (HA9). Power output at VT (WVT) decreased from SL to HA2 by 41% in PL, but only 32% in AO (P < 0.05). WVT increased in PL only during acclimatization (P < 0.05) and matched AO at HA9. Similar results were found when VT was expressed in terms of % Wpeak and % VO2peak. CONCLUSIONS: VT decreases upon acute HA exposure but improves with acclimatization. Prior AO supplementation improves VT upon acute, but not chronic altitude exposure.

Endurance training has little effect on active muscle free fatty acid, lipoprotein cholesterol, or triglyceride net balances.

We evaluated the hypothesis that net leg total FFA, LDL-C, and TG uptake and HDL-C release during moderate-intensity cycling exercise would be increased following endurance training. Eight sedentary men (26 +/- 1 yr, 77.4 +/- 3.7 kg) were studied in the postprandial state during 90 min of rest and 60 min of exercise twice before (45% and 65% V(O2 peak)) and twice after 9 wk of endurance training (55% and 65% posttraining V(O2 peak)). Measurements across an exercising leg were taken to be a surrogate for active skeletal muscle. To determine limb lipid exchange, femoral arterial and venous blood samples drawn simultaneously at rest and during exercise were analyzed for total and individual FFA (e.g., palmitate, oleate), LDL-C, HDL-C, and TG concentrations, and limb blood flow was determined by thermodilution. The transition from rest to exercise resulted in a shift from net leg total FFA release (-44 +/- 16 micromol/min) to uptake (193 +/- 49 micromol/min) that was unaffected by either exercise intensity or endurance training. The relative net leg release and uptake of individual FFA closely resembled their relative abundances in the plasma with approximately 21 and 41% of net leg total FFA uptake during exercise accounted for by palmitate and oleate, respectively. Endurance training resulted in significant changes in arterial concentrations of HDL-C (49 +/- 5 vs. 52 +/- 5 mg/dl, pre vs. post) and LDL-C (82 +/- 9 vs. 76 +/- 9 mg/dl, pre vs. post), but there was no net TG or LDL-C uptake or HDL-C release across the resting or active leg before or after endurance training. In conclusion, endurance training favorably affects blood lipoprotein profiles, even in young, healthy normolipidemic men, but muscle contractions per se have little effect on net leg LDL-C, or TG uptake or HDL-C release during moderate-intensity cycling exercise. Therefore, the favorable effects of physical activity on the lipid profiles of young, healthy normolipidemic men in the postprandial state are not attributable to changes in HDL-C or LDL-C exchange across active skeletal muscle.

Visceral obesity, impaired glucose tolerance, metabolic syndrome, and growth hormone therapy.

Overweight adults with impaired glucose tolerance have a 5-10% risk of developing diabetes per year, and insulin resistance is an important cause of progression to diabetes in these individuals. Weight loss has been shown to improve insulin sensitivity and prevent or delay progression to diabetes. According to recent studies, the improvement in insulin sensitivity that occurs with weight loss is closely linked to the reduction of visceral adipose tissue (VAT), the collection of intra-abdominal adipose depots that includes omental and intrahepatic fat. After controlling for BMI, whole body fat, and subcutaneous fat, only VAT is an independent predictor of endogenous insulin sensitivity and glucose tolerance before or after weight loss. This, in turn, suggests that reducing VAT is crucial to improving insulin sensitivity and preventing diabetes in high-risk individuals. Recombinant human growth hormone (GH) is a lipolytic drug that reduces total body, abdominal, and visceral fat in growth hormone-deficient (GHD) adults. Several studies have reported substantial reductions in VAT following GH treatment in this population. Like GHD adults, abdominally obese individuals have increased VAT, insulin resistance, and growth hormone levels that are below normal during continuous 24-h monitoring. These similarities have prompted a number of recent investigations in abdominally obese adults that reported significant reductions in truncal and visceral fat and an improvement in insulin sensitivity following prolonged GH administration. However, other studies have shown that insulin resistance and glucose concentrations transiently worsen during the first few weeks of GH treatment and that these deleterious effects can persist even after VAT reduction has occurred. Prior studies involving GH treatment were generally limited to adults who were normoglycemic at baseline. Less is known about the effects of GH in adults with impaired glucose tolerance or diabetes. The effects of GH used in conjunction with insulin sensitizers on glycemic control and VAT in patients with impaired glucose tolerance will be reviewed.

Cytokine responses at high altitude: effects of exercise and antioxidants at 4300 m.

PURPOSE: This study tested the hypothesis that antioxidant supplementation would attenuate plasma cytokine (IL-6, tumor necrosis factor (TNF)-alpha), and C-reactive protein (CRP) concentrations at rest and in response to exercise at 4300-m elevation. METHODS: A total of 17 recreationally trained men were matched and assigned to an antioxidant (N = 9) or placebo (N = 8) group in a double-blinded fashion. At sea level (SL), energy expenditure was controlled and subjects were weight stable. Then, 3 wk before and throughout high altitude (HA), an antioxidant supplement (10,000 IU beta-carotene, 200 IU alpha-tocopherol acetate, 250 mg ascorbic acid, 50 microg selenium, 15 mg zinc) or placebo was given twice daily. At HA, energy expenditure increased approximately 750 kcal.d(-1) and energy intake decreased approximately 550 kcal.d, resulting in a caloric deficit of approximately 1200-1500 kcal.d(-1). At SL and HA day 1 (HA1) and day HA13, subjects exercised at 55% of VO2peak until they expended approximately 1500 kcal. Blood samples were taken at rest, end of exercise, and 2, 4, and 20 h after exercise. RESULTS: No differences were seen between groups in plasma IL-6, CRP, or TNF-alpha at rest or in response to exercise. For both groups, plasma IL-6 concentration was significantly higher at the end of exercise, 2, 4, and 20 h after exercise at HA1 compared with SL and HA13. Plasma CRP concentration was significantly elevated 20 h postexercise for both groups on HA1 compared to SL and HA13. TNF-alpha did not differ at rest or in response to exercise. CONCLUSION: Plasma IL-6 and CRP concentrations were elevated following exercise at high altitude on day 1, and antioxidant supplementation did not attenuate the rise in plasma IL-6 and CRP concentrations associated with hypoxia, exercise, and caloric deficit.

Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia.

Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals.

Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction.

High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

Saccadic velocity and pupillary reflexes during acclimatization to altitude (4300 m).

INTRODUCTION: Oculometrics have been shown to be responsive to acute hypoxemia. We investigated whether oculometrics could be used as an objective index of a hypoxic effect on the central nervous system (CNS) during altitude acclimatization. We hypothesized that oculomotor reflexes [pupil diameter (PD), constriction amplitude (CA), constriction latency (CL), and saccadic velocity (SV)] changed in concert with a select number of accepted acclimatization variables and that these changes correlated with the severity of acute mountain sickness (AMS). METHODS: After sea-level, baseline (SLB) measurements were obtained, 18 men (19-33 yr) were transported to Pikes Peak, CO (4300 m), where they remained for 14 d. Periodic measurements (days 1-4, 6, 7, 9, 10, and 12) were made of PD, CA, CL, and SV in addition to heart rate (HR), pulse oximetry (SpO2), end-tidal PO2 and PCO2, 24-h urinary catecholamine concentrations, and AMS severity (environmental symptoms questionnaire, ESQ). RESULTS: PD and CL decreased from SLB on days 1-4 and subsequently returned toward SLB; these changes paralleled changes in ventilatory and circulatory variables. CA decreased on days 1 and 2 and remained decreased for 12 d. SV increased over days 1-6 then returned toward SLB with continued exposure, similar to changes in urinary catecholamines. With acclimatization, CL correlated with HR and SpO2; SV correlated with PCO2, HR, and SpO2. AMS severity peaked during days 2-4, returned toward SLB over the next 10 d, and correlated only with CL (p = 0.045). CONCLUSIONS: Oculometrics can be used as an indicator of CNS hypoxia and altitude acclimatization, although there was no strong correlation with AMS severity.

Three weeks of caloric restriction alters protein metabolism in normal-weight, young men.

The effects of prolonged caloric restriction (CR) on protein kinetics in lean subjects has not been investigated previously. The purpose of this study was to test the hypotheses that 21 days of CR in lean subjects would 1) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation and 2) negatively impact exercise performance. Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1). Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool model in the postabsorptive state during rest and 50 min of exercise (EX) at 50% of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise performance were measured throughout the intervention. At rest, leucine flux (approximately 131 micromol.kg(-1).h(-1)) and oxidation (R(ox); approximately 19 micromol.kg(-1).h(-1)) did not differ pre- and post-CR. During EX, leucine flux (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR than they were pre-CR. Nitrogen balance was negative throughout the intervention ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric restriction reduced leucine flux and R(ox) during exercise in normal-weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.

Effects of heat removal through the hand on metabolism and performance during cycling exercise in the heat.

OBJECTIVE: This two-part study tested the hypotheses that the use of a new cooling device, purported to extract heat from the body core through the palm of the hand, would (a) attenuate core temperature rise during submaximal exercise in the heat, thereby suppressing exercise-associated metabolic changes, and (b) facilitate a higher sustained workload, thus shortening the completion time of a time-trial performance test. METHODS: In Study 1, 8 male triathletes (age 27.9 +/- 2.0 yrs, mass 77.2 +/- 3.1 kg, VO2peak 59.0 +/- 4.1 ml x min(-1) x kg(-1)) cycled for 1 hr at the same absolute workload (approximately 60% VO2peak) in a heated room (31.9 +/- 0.1 degrees C, 24 +/- 1% humidity) on two occasions counterbalanced for cooling (C) or noncooling (NC). In Study 2, 8 similar subjects (age 26.9 +/- 2.0 yrs, mass 75.2 +/- 3.7 kg, VO2peak 54.1 +/- 3.1 ml x min(-1) x kg(-1)) performed two 30-km cycling time-trial performance tests under the same conditions (C(T), NC(T)). RESULTS: In Study 1, cooling attenuated the rise in tympanic temperature (T(TY)) (1.2 +/- 0.2 vs. 1.8 +/- 0.2 degrees C; p < 0.01) and lowered mean oxygen consumption (VO2, 2.4 +/- 0.1 vs. 2.7 +/- 0.1 L x min(-1); p < 0.05) and blood lactate (1.7 +/- 0.2 vs. 2.2 +/- 0.2 mmol x L(-1); p < 0.01) during exercise. There were no significant differences in respiratory exchange ratio (RER), blood glucose, heart rate (HR), face temperature (T(F)), or back temperature (T(B)) between NC and C. In Study 2, time to complete 30 km was 6 +/- 1% less with cooling than without cooling (60.9 +/- 2.0 vs. 64.9 +/- 2.6 min; p < 0.01). During the last 20% of C(T), subjects sustained a workload that was 14 +/- 5% (p = 0.06) higher than NC(T) at the same T(TY) and HR. CONCLUSIONS: Heat extraction through the hand during cycle ergometer exercise in the heat can (a) lower T(TY), lactate concentration, and VO2 during a submaximal set-workload test and (b) reduce the time it takes to complete a 30-km time-trial test.

Antioxidant supplementation does not attenuate oxidative stress at high altitude.

INTRODUCTION: Hypobaric hypoxia and heightened metabolic rate increase free radical production. PURPOSE: We tested the hypothesis that antioxidant supplementation would reduce oxidative stress associated with increased energy expenditure (negative energy balance) at high altitude (HA 4300 m). METHODS: For 12 d at sea level (SL), 18 active men were fed a weight-stabilizing diet. Testing included fasting blood and 24-h urine samples to assess antioxidant status [plasma alpha-tocopherol, beta-carotene, lipid hydroperoxides (LPO), and urinary 8-hydroxydeoxyguanosine (8-OHdG)] and a prolonged submaximal (55% Vo2peak) oxidative stress index test (OSI) to evaluate exercise-induced oxidative stress (plasma LPO, whole blood reduced and oxidized glutathione, glutathione peroxidase, and urinary 8-OHdG). Subjects were then matched and randomly assigned to either a placebo or antioxidant supplement group for a double-blinded trial. Supplementation (20,000 IU of beta-carotene, 400 IU alpha-tocopherol acetate, 500 mg ascorbic acid, 100 microg selenium, and 30 mg zinc, or placebo) was begun 3 wk prior to and throughout a 14-d HA intervention. At HA, subjects' daily energy intake and expenditure were adjusted to achieve a caloric deficit of approximately 1400 kcal. Fasting blood and 24-h urine samples were collected throughout HA and the OSI test was repeated on HA day 1 and day 13. RESULTS: Resting LPO concentrations increased and urinary 8-OHdG concentrations decreased over HA with no effect of supplementation. Prolonged submaximal exercise was not associated with increased concentrations of oxidative stress markers at SL or HA. CONCLUSIONS: Antioxidant supplementation did not significantly affect markers of oxidative stress associated with increased energy expenditure at HA.

Foot cooling reduces exercise-induced hyperthermia in men with spinal cord injury.

UNLABELLED: The number of individuals with spinal cord injury (SCI) participating in sports at recreational and elite levels is on the rise. However, loss of autonomic nervous system function below the lesion can compromise thermoregulatory capacity and increase the risk of heat stress relative to able-bodied (AB) individuals. PURPOSE: To test the hypotheses that exercise in a heated environment would increase tympanic temperature (TTY) more in individuals with SCI than AB individuals, and that foot cooling using a new device would attenuate the rise in TTY during exercise in both groups. METHODS: Six subjects with SCI (lesions C5-T5) and six AB controls were tested in a heated environment (means +/- SEM, temperature = 31.8 +/- 0.2 degrees C, humidity = 26 +/- 1%) for 45 min at 66% +/- 5 of arm cranking VO2peak and 30 min of recovery on two separate occasions with foot cooling (FC) or no foot cooling (NC) in randomized order. RESULTS: During exercise and recovery in both trials, SCI TTY was elevated above baseline (P < 0.001) but more so in the NC versus FC trial (1.6 +/- 0.2 degrees C vs 1.0 +/- 0.2 degrees C, respectively, P < 0.005). Within the AB group, TTY was elevated above baseline for both trials (P < 0.001) with peak increases of 0.5 +/- 0.2 degrees C and 0.3 +/- 0.2 degrees C for NC and FC, respectively. TTY, face, and back temperature were higher in both SCI trials compared with AB trials (P < 0.05). Heart rate during exercise and recovery was lower in the SCI FC versus SCI NC (P < 0.05). CONCLUSION: These results suggest that extraction of heat through the foot may provide an effective way to manipulate tympanic temperature in individuals with SCI, especially during exercise in the heat.

Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women.

Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.