In many studies, exercise carbohydrate utilization in women is lower in the luteal (L) compared with the follicular (F) phase of the menstrual cycle. These data imply that free fatty acid (FFA) utilization is higher in L relative to F. PURPOSE: To directly compare FFA flux and total fat oxidation in both phases of the menstrual cycle and relate them to FFA availability. METHODS: 10 young, eumenorrheic women were studied during 45' of cycle ergometry at 52% VO2peak on the 10th day of both the F and L phases of their cycle. Ovarian hormone concentrations are shown in the Table. Dietary energy and macronutrient intake were strictly controlled for 2 weeks prior to testing. Rate of blood FFA disappearance (Rd) was measured by isotope dilution of infused [1-13Cpalmitate tracer. Total FFA oxidation was calculated from indirect calorimetry. RESULTS: Values at 30' and 45' of exercise were averaged and are shown in the Table (mean ± SEM). FFA concentrations were lower in L relative to F (p < .05). FFA Rd was not different between cycle phases and total fat oxidation was higher in L compared with F (p < .05). CONCLUSIONS: Despite lower blood FFA availability and no change in FFA Rd, total fat oxidation was considerably elevated in the luteal phase. These data suggest that the increase in FFA oxidation during L is ascribable to greater intramuscular, not blood-borne, oxidation of fat. Differentiating the independent actions of estrogen and progesterone in mediating this response is confounded by concurrent increases in both hormones during the luteal phase of the cycle. Supported by DOD contract# DAMD-17-95-C5110Table: No Caption Available

Interleukin-6 (IL-6), an important cytokine involved in a number of biological processes, is consistently elevated during periods of stress. The mechanisms responsible for the induction of IL-6 under these conditions remain uncertain. This study examined the effect of alpha-adrenergic blockade on the IL-6 response to acute and chronic high-altitude exposure in women both at rest and during exercise. Sixteen healthy, eumenorrheic women (aged 23.2 +/- 1.4 yr) participated in the study. Subjects received either alpha-adrenergic blockade (prazosin, 3 mg/day) or a placebo in a double-blinded, randomized fashion. Subjects participated in submaximal exercise tests at sea level and on days 1 and 12 at altitude (4,300 m). Resting plasma and 24-h urine samples were collected throughout the duration of the study. At sea level, no differences were found at rest for plasma IL-6 between groups (1.5 +/- 0.2 and 1.2 +/- 0.3 pg/ml for placebo and blocked groups, respectively). On acute ascent to altitude, IL-6 levels increased significantly in both groups compared with sea-level values (57 and 84% for placebo and blocked groups, respectively). After 12 days of acclimatization, IL-6 levels remained elevated for placebo subjects; however, they returned to sea-level values in the blocked group. alpha-Adrenergic blockade significantly lowered the IL-6 response to exercise both at sea level (46%) and at altitude (42%) compared with placebo. A significant correlation (P = 0.004) between resting IL-6 and urinary norepinephrine excretion rates was found over the course of time while at altitude. In conclusion, the results indicate a role for alpha-adrenergic regulation of the IL-6 response to the stress of both short-term moderate-intensity exercise and hypoxia.

814 We have previously documented the importance of the sympathetic nervous system in acclimatizing to high altitude in men. The purpose of this investigation was to determine: 1) the extent to which α-adrenergic blockade effects the sympathoadrenal responses to exercise during acute high altitude exposure, and 2) the extent to which menstrual cycle phase influences these responses. Twelve eumenorrheic women (24.7±1.3 yrs, 70.6±2.6 kgs) were studied at sea level and on day 2 of high altitude exposure (4,300 m - hypobaric chamber) either in their follicular or luteal phase. Subjects performed two graded-exercise tests at sea level (on separate days) on a bicycle ergometer after 3 days of taking either a placebo or an α-blocker (prazosin - 3 mg/day). Subjects also performed two similar exercise tests while at altitude. Effectiveness of blockade was determined by phenylephrine challenge. At sea level, plasma norepinephrine levels during exercise were 50% greater when subjects were α-blocked compared to their placebo trial. This difference was only 13% when subjects were studied at altitude. Plasma norepinephrine values were significantly elevated at altitude compared to sea level but to a greater extent for the placebo (↑ 49%) vs blocked (↑ 12%) trial. A more dramatic effect of both altitude (↑ 74 and 49% for placebo and blocked, respectively) and blockade (↑ 79% and 54% for sea level and altitude, respectively) was observed for plasma epinephrine levels during exercise. No phase differences were observed across any condition studied. It was concluded that α-adrenergic blockade: 1) resulted in a compensatory sympathoadrenal response during exercise at sea level and altitude; 2) this effect was more pronounced for plasma epinephrine, and; 3) cycle phase had little effect on these responses. Supported by Department of Defense contract #DAMD-17-95-C-5110

1030 Both exercise and hypoxia activate the adrenergic nervous system causing an increase in circulating catecholamines that may enhance the ventilatory response to exercise. Previous studies indicate that beta-adrenergic stimulation does not enhance the ventilatory response to exercise in normoxia or hypoxia. Weil et al. (JAP 33:1972), proposed that α-adrenergic vasoconstriction during exercise may decrease carotid body blood flow, hence augmenting chemosensitivity. Thus, blocking α1-adrenergic receptors should prevent vasoconstriction and attenuate carotid body stimulation of exercise hyperpnea. We examined the role of α-adrenergic activation during exercise in 12 women at sea level (SL) and during 40 h at simulated high altitude (HA: PB 445 mmHg) once on placebo and on an α1-adrenergic blocker (prazosin: 3mg/d). Subjects performed graded intensity cycle ergometry to exhaustion. Results ( ± S.D.): (Table)TableExercise ventilation increased (p<0.01) at HA vs. SL. However, α1-adrenergic blockade did not alter the ventilatory response to exercise in normoxic or hypoxic conditions. Thus, in humans α-adrenergic activation does not appear to augment exercise ventilation by vasoconstriction of the carotid body vasculature. Supported in part by DOD grant #DAMD 17-95-C5110

146 The purpose of the investigation was to examine the effect of growth hormone (GH) and/or insulin-like growth factor-I (IGF-I) on regional fat distribution in postmenopausal women undergoing a regimen of diet and exercise. Twenty seven healthy women aged 59-79 years, 20-40% above ideal body weight, underwent a 12 week exercise program consisting of strength training 3 d/wk and walking 2 d/wk, while consuming a diet that was 500 kcal/d less than that required for weight maintenance. Participants were randomly assigned in a double-blind fashion to receive GH (0.025 mg/kg body weight/d; n = 7), IGF-I (0.015 mg/kg body weight/d; n = 7), GH + IGF-I (n = 6), or placebo (PL; n = 7). The ratios of trunk fat-to-limb fat (TrF/LimbF), trunk fat-to-total fat (TrF/TotalFat), trunk fat-to-body weight (TrF/BW) and trunk fat % (Tr%) were determined by dual X-ray absorptiometry (DXA; Hologic QDR 2000). All groups experienced significant declines in body weight and total fat mass. However, differences among groups existed for each ratio of fat distribution. Percent change (ANOVA) was greater in GH than PL for TrF/LimbF, (GH, −13 ± 6; PL, −3 ± 4; IGF-I, −6 ± 10; GH + IGF-I, −9 ± 6; p = 0.05), and TrF/TotalF (GH, −8 ± 4; PL, −2 ± 2; IGF-I, −4 ± 5; GH + IGF-I, −6 ± 4; p < 0.05). For TrF/BW, the percent change was greater (p < 0.01) for GH and GH + IGF-I than PL (GH, −21 ± 8; PL, −7 ± 5; IGF-I, −13 ± 9; GH + IGF-I, −23 ± 10). Similarly for TrF%, the percent decline was greater for GH and GH + IGF-I than PL. There was no association between change in fat distribution and total cholesterol or triglycerides. These results suggest that administration of GH facilitates a decrease in central fat mass in older women undertaking a weight loss program that combines exercise and moderate caloric restriction.

1514 The rise in metabolic rate seen with acute altitude exposure has been shown to be blunted by blockade of the β-limb of the sympathetic nervous system(Moore, et al,, 1987). The hypothesis that metabolic rate measured by indirect calorimetry may be affected by blockade of the α-limb was tested in 13 women (24.73±4.57 yr, 169.2±7.34 cm, 70.63±9.26 kg,[mean±SD]) both with and without prazosin (3 mg/d) at sea level (SL) and at a simulated altitude of 4300m (HA). Women were tested in the environmental chamber at USARIEM at the same time during two menstrual cycles, once on placebo, and again on prazosin. During each admission, the women spent 72 hours at SL, were then taken within 30 min to a barometric pressure equivalent to 4300m (445 mmHg), where they were studied for 48 hours. Basal metabolic rate (BMR) was measured daily at 0600 hr before the subjects arose; resting metabolic rate (RMR) was determined while sitting quietly on a cycle ergometer before an exercise test on the last day of exposure to both SL and HA. When the women were on placebo, mean BMR was 1449±228 kcal/d after 62 hrs at SL, 1640±219 kcal/d after 14 hrs at HA. When the women were on prazosin, BMR was 1446±166 kcal/d at SL and 1717±172 kcal/d at HA. Similar results are seen when BMR was expressed per kg bd wt. RMR in the women when on placebo was 0.234±0.039 L/min at SL and 0.224±0.049 L/min at HA; when on drug 0.230±0.038 L/min at SL and 0.240±.020 L/min at HA. Thus, BMR rose significantly in response to acute exposure to HA, and α-blockade did not significantly affect that rise. However, RMR showed no significant difference between SL and HA in either the placebo or drug conditions. The mechanism for the discrepancy between the response of BMR and RMR to acute altitude exposure will require further study.

1515 We have previously documented an enhanced sympathoadrenal response during exercise to high altitude in men. The purpose of this investigation was to determine 1) if women respond in a similar manner as found previously in men, and 2) the extent to which menstrual cycle phase influences this response. Sixteen eumenorrheic women (23.6±1.2 yrs, 56.2±4.3 kgs) were studied at sea level and after 10 days of high altitude exposure (4,300 m) either in their follicular (F, n=11) or luteal (L, n=5) phase. While at sea level, subjects performed two 45 minute submaximal steady-state exercise tests(on separate days) on a bicycle ergometer at intensities which elicited 50& 65% VO2max. During day 10 of altitude exposure, an absolute exercise intensity similar to that of 50% sea level VO2max was chosen such that subjects were working at the same absolute VO2 which represented 65% of their VO2max at altitude. Compared to rest, plasma epinephrine levels increased 36% in response to exercise at 50% VO2max at sea level with no differences found between cycle phase. This increase was significantly greater (↑44%) during exercise at 65% VO2max. At altitude, the epinephrine response was identical to that found for 65% VO2max exercise at sea level (↑44%) with no differences found between phase assignments. The plasma norepinephrine response was similar to that found for epinephrine such that the increase with exercise at altitude(↑51%) was the same as 65% VO2max exercise at sea level (↑50%). Again, no phase differences were observed. It was concluded that the sympathoadrenal response to exercise: 1) did not differ between cycle phase across any condition; 2) was similar to that found previously in men and; 3) the relative exercise intensity is the primary factor responsible for the catecholamine response to exercise.

When humans ascend to high altitude (ALT) their plasma volume (PV) and total blood volume (BV) decrease during the first few days. With continued residence over several weeks, the hypoxia-induced stimulation of erythropoietin increases red cell production which tends to restore BV. Because hypoxia also activates the β-adrenergic system, which stimulates red blood cell production, we investigated the effect of adrenergic β-receptor inhibition with propranolol on fluid volumes and the polycythemic response in 11 healthy unacclimatized men (21–33 years old exposed to an ALT of 4300 m (barometric pressure 460 Torr) for 3 weeks on Pikes Peak, Colorado. PV was determined by the Evans blue dye method (PVEB), BV by the carbon monoxide method (BVCO), red cell volume (RCV) was calculated from hematocrit (Hct) and BVCO, and serum erythropoietin concentration ([EPO]) and reticulocyte count, were also determined. All determinations were made at sea level and after 9–11 (ALT-10) and 19–20 (ALT-20) days at ALT. At sea level and ALT, six men received propranolol (pro, 240 mg · day−1), and five received a placebo (pla). Effective β-blockade did not modify the mean (SE) maximal values of [EPO] [pla: 24.9 (3.5) vs pro: 24.5 (1.5) mU · ml−1] or reticulocyte count [pla: 2.7 (0.7) vs pro: 2.2 (0.5)%]; nor changes in PVEB [pla: −15.8 (3.8) vs pro: −19.9 (2.8)%], RCVCO [pla: +7.0 (6.7) vs pro: +10.1 (6.1)%], or BVCO [pla: −7.3 (2.3) vs pro: −7.1 (3.9)%]. In the absence of weight loss, a redistribution of body water with no net loss is implied. Hence, activation of the β-adrenergic system did not appear to affect the hypovolemic or polycythemic responses that occurred during 3 weeks at 4300 m ALT in these subjects.

GEORGE A. BROOKS, EUGENE E. WOLFEL, GAIL E. BUTTERFIELD, ALLEN CYMERMAN, AMY C. ROBERTS, ROBERT S. MAZZEO, AND JOHN T. REEVES Department of Integrative Biology, University of California, Berkeley, California 94720; Geriatric Research Educational Clinical Center, Palo Alto Veterans Affairs Medical Center, Palo Alto, California 94304; University of Colorado Health Sciences Center, Denver 80262; University of Colorado, Boulder, Colorado 80309; and United States Army Research Institute for Environmental Medicine, Natick, Massachusetts 01760

1282 Although Mabel Fitzgerald showed as early as 1913 that women do not respond to altitude as men do, their response has been understudied until now. Results of a multi-year, multi-disciplinary collaborative study of acclimatization to 4300 m in women will be presented. The hypotheses of the investigations included that women would acclimatize more rapidly during the luteal phase of the menstrual cycle than during the follicular, and that women would acclimatize more easily than men. Data to be presented include: 1) evaluation of the energy requirements for weight maintenance, 2) acute and chronic respiratory responses (hypercapnic and hypoxic ventilatory drive), 3) cardiovascular responses (blood pressure, heart rate and cardiac output), 4) evaluation of regulation of blood volume (volume regulatory hormones and plasma volume), and 5) fuel substrates used at rest and during moderate exercise. In all cases, comparisons will be made between responses during the follicular and luteal phases of the menstrual cycle, between sea level and altitude responses, and where possible, with responses in men studied under similar circumstances.

Whole body O2 uptake (VO2) during maximal and submaximal exercise has been shown to be preserved in the setting of beta-adrenergic blockade at high altitude, despite marked reductions in heart rate during exercise. An increase in stroke volume at high altitude has been suggested as the mechanism that preserves systemic O2 delivery (blood flow x arterial O2 content) and thereby maintains VO2 at sea-level values. To test this hypothesis, we studied the effects of nonselective beta-adrenergic blockade on submaximal exercise performance in 11 normal men (26 +/- 1 yr) at sea level and on arrival and after 21 days at 4,300 m. Six subjects received propranolol (240 mg/day), and five subjects received placebo. At sea level, during submaximal exercise, cardiac output and O2 delivery were significantly lower in propranolol- than in placebo-treated subjects. Increases in stroke volume and O2 extraction were responsible for the maintenance of VO2. At 4,300 m, beta-adrenergic blockade had no significant effect on VO2, ventilation, alveolar PO2, and arterial blood gases during submaximal exercise. Despite increases in stroke volume, cardiac output and thereby O2 delivery were still reduced in propranolol-treated subjects compared with subjects treated with placebo. Further reductions in already low levels of mixed venous O2 saturation were responsible for the maintenance of VO2 on arrival and after 21 days at 4,300 m in propranolol-treated subjects. Despite similar workloads and VO2, propranolol-treated subjects exercised at greater perceived intensity than subjects given placebo at 4,300 m. The values for mixed venous O2 saturation during submaximal exercise in propranolol-treated subjects at 4,300 m approached those reported at simulated altitudes >8,000 m. Thus beta-adrenergic blockade at 4,300 m results in significant reduction in O2 delivery during submaximal exercise due to incomplete compensation by stroke volume for the reduction in exercise heart rate. Total body VO2 is maintained at a constant level by an interaction between mixed venous O2 saturation, the arterial O2-carrying capacity, and hemodynamics during exercise with acute and chronic hypoxia.

1001 In men acclimatized to high altitude, blood glucose utilization is higher at rest and during submaximal exercise, compared with sea level (Brooks et al. 1991, Roberts et al. 1996). Altered metabolic regulation in the presence of ovarian hormones may cause women to respond to high altitude differently than men. 16 women (age=21.7±0.5 yr, ht=167±1 cm, wt=62.2±1.0 kg,) were studied 3 times at sea level (SL), and once at 4300 meters (HA). VO2peak was reduced from 42.0±5.4 at SL to 32.2±6.0 at HA. On day 10 of each 12-day study, blood glucose rate of appearance (Ra) was measured by isotope dilution with a [6,62H]glucose tracer at rest and during 45 minutes of steady-state cycle ergometry. Two SL trials were done at 52% SL-VO2peak (different menstrual cycle phases), with a 3rd trial at 65% SL-VO2peak. At HA, subjects cycled at 51% SL-VO2peak (same ABSOLUTE workload as SL trials 1,2) which was 66% HA-VO2peak (same RELATIVE workload as SL trial 3). Ra values were compared with a paired t-test. Results (x±SD) are shown below. TableTableCompared with SL, women acclimatized to HA: 1) used LESS blood glucose at rest, 2) had THE SAME blood glucose use during exercise when matched at the same absolute intensity, and LOWER glucose use at the same relative intensity. The effect of high altitude exposure on blood glucose utilization appears to be different in women than in men.

We evaluated the hypotheses that on acute exposure to hypobaric hypoxia, sympathetic stimulation leads to augmented muscle lactate production and circulating [lactate] through a β-adrenergic mechanism and that β-adrenergic adaptation to chronic hypoxia is responsible for the blunted exercise lactate response after acclimatization to altitude. Five control and 6 β-blocked men were studied during rest and exercise at sea level (SL), on acute exposure to 4,300 m (A1), and after a 3-wk sojourn at altitude (A2). Exercise was by leg cycling at 49% of SL peak O2 consumption (V˙o 2 peak) (65% of altitude V˙o 2 peak or 87 ± 2.6 W); β-blockade was by propranolol (80 mg 3× daily), femoral arterial and venous blood was sampled; leg blood flow (Q˙) was measured by thermodilution, leg lactate net release [L˙ = (2) (1-leg Q) venous-arterial concentrationL] was calculated, and vastus lateralis needle biopsies were obtained. Muscle [lactate] increased with exercise and acute altitude exposure but regressed to SL values with acclimatization; β-blockade had no effect on muscle [lactate]. Arterial [lactate] rose during exercise at SL (0.9 ± 0.1 to 1.5 ± 0.3 mM); exercise at A1 produced the greatest arterial [lactate] (4.4 ± 0.8 mM), and exercise at A2 an intermediate response (2.1 ± 0.6 mM). β-Blockade reduced circulating [lactate] ∼45% during exercise under all altitude conditions. L˙ increased transiently at exercise onset but then declined over time under all conditions. Blood and muscle "lactate paradoxes" occurred independent of β-adrenergic influences, and the hypotheses relating the blood lactate response at altitude to β-adrenergic mechanisms are rejected. During exercise at altitude, arterial [lactate] is determined by factors in addition to hypoxemia, circulating epinephrine, and net lactate release from active muscle beds.

High protein, low carbohydrate diets have been proposed for many years to accomplish rapid weight loss. Recent claims made for such diets include optimizing performance for athletesand generating the production of“good” eicosanoids which then positively impact recovery. This mini-symposium will evaluate the data available regarding weight loss with such diets including effects on body composition, blood lipids and blood glucose levels. The efficacy of low carbohydrate, high protein diets for athletic performance will then be evaluated in conjunction with an assessment of the resultant hormonal milieu. The possibility of a relationship between dietary intake, hormone levels, and eicosanoid production also will be discussed with an emphasis on the possibility of identifying“good” and “bad” eicosanoids. Case studies regarding athletes who have followed such diets and steps taken to improve performance with such athletes will be presented. A final recommendation as to the efficacy of such diets for weight loss and performance will be made.

After acclimatization to high altitude, weight-stable men use more carbohydrate as an exercise fuel compared with sea level (Roberts et al. 1996). The ovarian hormones estrogen (E) and progesterone (P) may cause women to acclimatize to high altitude differently than men, and variations in E and P in the follicular (F) and luteal (L) phases of the menstrual cycle may alter the response. Sixteen eumenorrheic women (age= 21.7 0.5 yrs, ht= 167 1 cm, wt= 62.2 1.0 kg, VO2peak= 42.0 5.4 ml/kg/min) were studied for 12 days in both F and L at sea level (SL), and either F or L at Pikes Peak (PP, 4300 m). Subjects ate a controlled diet adjusted to minimize weight changes. On Day 10 of each study period, 195' and 210' after a meal, oxygen consumption (VO2) and respiratory exchange ratio (R) were measured at rest by indirect calorimetry. Subjects then cycled at the same absolute workload in each condition (SL=52.1 0.8% VO2peak, PP=51.0.7% of SL VO2peak) with VO2 and R measured at 15, 30, and 45 minutes. Resting and exercise R, VO2, and grams carbohydrate oxidized/minute (gCHO) were almost identical between cycle phases at SL or PP. Resting R was significantly lower for PP-L (.846.072) relative to SL-L(.882.044)(p=0.47) but not in the F phase (p=.064). Exercise R was lower for PP-F (.919.021) relative to SL-F (.961.030) at 30 minutes (p=.004). Within a cycle phase, VO2 was the same between SL (1.404.481 L/min) and PP (1.372.432 L/min), but gCHO was significantly lower for PP (1.26.19 g/min) compared with SL (1.39.21 g/min). These data suggest that women oxidize less carbohydrate and more fat at 4300 meters relative to SL. These results await confirmation by analysis of substrate kinetics from isotopic tracer studies.

LEARNING OUTCOME: To list physiologic and performance differences following consumption of two preexercise meals of varying glycemic indices.