Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men

OBJECTIVE: We evaluated the pharmacokinetics, safety, and efficacy of l-arginine alpha-ketoglutarate (AAKG) in trained adult men. METHODS: Subjects participated in two studies that employed a randomized, double-blind, controlled design. In study 1, 10 healthy men (30-50 y old) fasted for 8 h and then ingested 4 g of time-released or non-timed-released AAKG. Blood samples were taken for 8 h after AAKG ingestion to assess the pharmacokinetic profile of l-arginine. After 1 wk the alternative supplement was ingested. In study 2, which was placebo controlled, 35 resistance-trained adult men (30-50 y old) were randomly assigned to ingest 4 g of AAKG (three times a day, i.e., 12 g daily, n = 20) or placebo (n = 15). Participants performed 4 d of periodized resistance training per week for 8 wk. At 0, 4, and 8 wk of supplementation the following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. Data were analyzed by repeated measures analysis of variance. RESULTS: In study 1, significant differences were observed in plasma arginine levels in subjects taking non-timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group (P < 0.05) for 1RM bench press, Wingate peak power, blood glucose, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity. CONCLUSION: AAKG supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. AAKG did not influence body composition or aerobic capacity.     

Dietary protein to support anabolism with resistance exercise in young men

Resistance exercise is fundamentally anabolic and as such stimulates the process of skeletal muscle protein synthesis (MPS) in an absolute sense and relative to skeletal muscle protein breakdown (MPB). However, the net effect of resistance exercise is to shift net protein balance (NPB = MPS - MPB) to a more positive value; however, in the absence of feeding NPB remains negative. Feeding stimulates MPS to an extent where NPB becomes positive, for a transient time. When combined, resistance exercise and feeding synergistically interact to result in NPB being greater than with feeding alone. This feeding- and exercise-induced stimulation of NPB is what, albeit slowly, results in muscle hypertrophy. With this rudimentary knowledge we are now at the point where we can manipulate variables within the system to see what impact these interventions have on the processes of MPS, MPB, and NPB and ultimately and perhaps most importantly, muscle hypertrophy and strength. We used established models of skeletal muscle amino acid turnover to examine how protein source (milk versus soy) acutely affects the processes of MPS and MPB after resistance exercise. Our findings revealed that even when balanced quantities of total protein and energy are consumed that milk proteins are more effective in stimulating amino acid uptake and net protein deposition in skeletal muscle after resistance exercise than are hydrolyzed soy proteins. Importantly, the finding of increased amino acid uptake would be independent of the differences in amino acid composition of the two proteins. We propose that the improved net protein deposition with milk protein consumption is also not due to differences in amino acid composition, but is due to a different pattern of amino acid delivery associated with milk versus hydrolyzed soy proteins. If our acute findings are accurate then we hypothesized that chronically the greater net protein deposition associated with milk protein consumption post-resistance exercise would eventually lead to greater net protein accretion (i.e., muscle fiber hypertrophy), over a longer time period. In young men completing 12 weeks of resistance training (5d/wk) we observed a tendency (P = 0.11) for greater gains in whole body lean mass and whole as greater muscle fiber hypertrophy with consumption of milk. While strength gains were not different between the soy and milk-supplemented groups we would argue that the true significance of a greater increase in lean mass that we observed with milk consumption may be more important in groups of persons with lower initial lean mass and strength such as the elderly.     

Plasma antioxidants and lipid oxidation after submaximal resistance exercise in men

Summary.Background: An increased generation of reactive oxygen species occurs during exercise.The aim of the study: We investigated whether changes in plasma antioxidants and lipid oxidation products after submaximal resistance exercise are detectable, and whether training status has any effect on changes.Methods: Seven resistance trained (RT, 31.3 ± 10.2 yrs) and ten non-resistance trained male subjects (NRT, 28.2 ± 3.9 yrs) performed a submaximal resistance exercise circuit (10 different exercises, 75% of 1-repetition maximum, 18.6 ± 1.1 minutes). Blood samples were taken before and immediately after exercise. Plasma antioxidants (AO), lipid oxidation products malondialdehyde (MDA) and conjugated dienes (CD) were measured using HPLC and/or photometric detection. Groups were compared using the Mann-Whitney U test, the exercise effect was tested using the Wilcoxon signed ranks test. P < 0.05 was regarded as significant.Results: -Tocopherol, -tocopherol, -carotene, lycopene, ascorbic acid,MDA and CD concentrations did not differ between groups at rest. There was a similar increase of fat soluble plasma AO in both groups after exercise, but not ascorbic acid. MDA increased also in both groups after exercise, but CD increased only in NRT.Conclusion: There is no difference in plasma AO and lipid oxidation products in RT and NRT at rest. After short time resistance exercise there is a mobilization of fat soluble AO. Despite mobilization of AO, oxidative stress occurs during submaximal resistance exercise, which is indicated by increased MDA and CD concentrations. As exercise induced an increase of CD only in NRT, it seems that regular resistance training partly prevents lipid peroxidation during exercise.     

The effects of antioxidant vitamin supplementation on resistance exercise induced lipid peroxidation in trained and untrained participants

Background  

The theoretical benefits of using antioxidant vitamin supplements to quench oxygen free radicals appear large. High intensity aerobic-type exercise produces oxygen free radicals that can cause damage to lipid membranes (lipid peroxidation) that may lead to many problems such as the inactivation of cell membrane enzymes, the progression of degenerative diseases (cardiovascular disease and cancer) and lessening of the effectiveness of the immune system. The major function of vitamin E is to work as a chain-breaking antioxidant in a fat soluble environment. Little research has examined lipid peroxidation associated with high intensity resistance exercise or possible protective effects of antioxidant supplementation or the effects of training state.     

Effect of meal timing after resistance exercise on hindlimb muscle mass and fat accumulation in trained rats

To study the effect of meal timing after exercise on body composition, 20 male rats were assigned to either a group fed a meal right after exercise (R) or a group fed a meal 4 h after exercise (L). Resistance exercise (squatting) was conducted from 6:00 to 7:00, 3 d/wk for 10 wk. Meals were consumed from 7:00 to 8:00 and from 19:00 to 20:00 for R, and from 11:00 to 12:00 and from 19:00 to 20:00 for L. The room was lighted from 7:00 to 19:00. After 10 wk, the body weight was comparable between the groups. The hindlimb muscle weight was higher in R than in L by 6% (p < 0.05), whereas the sum of the weight of perirenal, epididymal, and mesenteric adipose tissues was lower in R than in L by 24% (p < 0.01). The soleus lipoprotein lipase (LPL) activity was higher in R than in L by 70% (p < 0.01), and the activity negatively correlated with the adipose tissue weight (r = -0.49, p < 0.05). These results suggest the possibility that ingesting a meal right after resistance exercise may contribute to an increase in the muscle mass and to a decrease in the adipose tissue compared to ingesting a meal several hours later.     

Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men

This investigation evaluated the effects of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation on training responses in resistance-trained male athletes who were randomly administered HMB in standard encapsulation (SH), HMB in time release capsule (TRH), or placebo (P) in a double-blind fashion. Subjects ingested 3 g x day(-1) of HMB or placebo for 6 weeks. Tests were conducted pre-supplementation and following 3 and 6 weeks of supplementation. The testing battery assessed body mass, body composition (using dual energy x-ray absorptiometry), and 3-repetition maximum isoinertial strength, plus biochemical parameters, including markers of muscle damage and muscle protein turnover. While the training and dietary intervention of the investigation resulted in significant strength gains (p < .001) and an increase in total lean mass (p = .01), HMB administration had no influence on these variables. Likewise, biochemical markers of muscle protein turnover and muscle damage were also unaffected by HMB supplementation. The data indicate that 6 weeks of HMB supplementation in either SH or TRH form does not influence changes in strength and body composition in response to resistance training in strength-trained athletes.     

Protein ingestion further augments S6K1 phosphorylation in skeletal muscle following resistance type exercise in males

Our objective was to determine the impact of carbohydrate and/or protein ingestion before and after exercise on ribosomal protein S6 kinase (S6K1) and S6 phosphorylation status in human skeletal muscle tissue. Seven healthy, untrained men (22.5 +/- 0.9 y) were randomly assigned to 2 cross-over experiments. Before, immediately after, and 1 h after a single bout of resistance exercise, subjects consumed 0.3 g x kg(-1) carbohydrate with or without 0.3 g x kg(-1) protein hydrolysate (CHO+PRO and CHO, respectively). Muscle biopsies were taken before and immediately after exercise and after 1 and 4 h of postexercise recovery to determine 4E-BP1, S6K1 (both T(421)/S(424) and T(389)), and S6 phosphorylation status. Following resistance exercise, 4E-BP1 phosphorylation was reduced to a greater extent in the CHO treatment (-48 +/- 7%) than in the CHO+PRO treatment (-15 +/- 14%, P < 0.01). During recovery, 4E-BP1 phosphorylation increased in both experiments (P < 0.01), and tended to be higher in the CHO+PRO test (P = 0.08). S6K1 phosphorylation at T(421)/S(424) substantially increased following exercise and remained elevated during recovery with no differences between treatments. In contrast to the CHO treatment (-4 +/- 2%), S6K1 phosphorylation at T(389) was higher following exercise in the CHO+PRO treatment only (+78 +/- 2%, P < 0.01). During recovery, S6K1 phosphorylation at T(389) remained higher in CHO+PRO than in CHO (P < 0.05). S6 phosphorylation was substantially higher following exercise in the CHO+PRO (1.69 +/- 0.35) than in the CHO experiment (0.45 +/- 0.07, P < 0.01) and remained elevated during recovery (P < 0.05). We conclude that the availability of dietary protein further enhances phosphorylation of S6K1 during recovery from resistance type exercise.     

Creatine and glycerol hyperhydration in trained subjects before exercise in the heat

The authors examined the effects of combined creatine (Cr) and glycerol (Gly) supplementation on responses to exercise in the heat. Subjects (N=24) were matched for body mass and assigned to either a Cr or placebo (Pl) group. Twice daily during two 7-d supplementation regimens, the Cr group received 11.4 g of Cr x H2O and the Pl group received 11.4 g of glucose. Subjects in both groups also ingested 1 g of Gly/kg body mass (twice daily) in either the first or the second supplementation regimen. This design allowed 4 possible combinations of supplements to be examined (Pl/Pl, Pl/Gly, Cr/Pl, and Cr/Gly). Exercise trials were conducted pre- and postsupplementation at 30 degrees C and 70% relative humidity. In the Pl group, total body water (TBW) increased by 0.50 +/- 0.28 L after Gly and in the Cr group by 0.63 +/- 0.33 L after Pl and by 0.87 +/- 0.21 L after Gly. Both Cr/Pl and Cr/Gly resulted in significantly attenuated heart rate, rectal temperature, and perceived effort during exercise, although no regimen had any effect on performance. The addition of Gly to Cr significantly increased TBW more than Cr alone (P=0.02) but did not further enhance the attenuation in HR, Tre, and RPE during exercise. These data suggest that combined Cr and Gly is an effective method of hyperhydration capable of reducing thermal and cardiovascular responses.     

游泳运动对胰岛素抵抗大鼠脂肪组织中MEK/ERK1磷酸化水平的影响

目的 探究慢性和急性游泳运动对肥胖诱导的胰岛素抵抗大鼠脂肪组织中丝裂原活化细胞外信号调节激酶(MEK)和细胞外信号调节激酶(ERK1)磷酸化水平的影响。方法 100只清洁级雄性SD大鼠随机分为对照组(10只,普通饲料喂养)和高脂组(90只,高脂饲料喂养)。喂养8周后,从高脂组中筛选出体重上游1/3大鼠(30只)并随机分为3组:高脂安静组、高脂慢性运动组和高脂急性运动组,每组10只,高脂饲料再喂养8周,并根据运动方案进行运动干预;对照组继续喂食普通饲料8周。运动干预后,取内脏脂肪组织,Western Blot方法检测MEK和ERK1的磷酸化水平。结果 慢性运动干预显著降低了胰岛素抵抗大鼠的体重、内脏脂肪质量和脂体比(P<0.01),急性运动对大鼠体重、内脏脂肪质量和脂体比影响无统计学意义。两种运动干预均显著改善了机体胰岛素敏感性(P<0.05),降低了脂肪组织MEK和ERK1的磷酸化水平(P<0.01)。结论 运动改善肥胖诱导的胰岛素抵抗可能与抑制脂肪组织中MEK和ERK1的磷酸化有关。     

Diet and short term plasma lipoprotein-lipid changes after exercise in trained Men

To test the effect of diet on the short-term lipid response to exercise, fourteen moderately trained (VO2max: 50.2 +/- 6.7 ml/kg/min), healthy men (mean age: 28 +/- 4 years) were alternately fed a high fat (60 +/- 6.7% fat) and a high carbohydrate (63 +/- 3.2% carbohydrate) isoenergetic diet for 2 weeks in a randomized crossover design. During the last 4 days of the treatments, fasting total cholesterol, triglyceride, HDL-cholesterol, and HDL3-cholesterol were measured the day before, and again immediately, 24 hr, and 48 hr after exercise (4190 kJ, 70% VO2max). LDL-cholesterol and HDL2-cholesterol were calculated. Lipid concentrations were adjusted for plasma volume changes after exercise. A 2 (diet) x 4 (time) ANOVA with repeated measures revealed no significant interaction between the diet and exercise treatments. Furthermore, diet alone did not influence lipid concentrations in these trained men. Exercise resulted in an increase in HDL-C (10.7%) and HDL3-C (8.5%) concentrations and a concomitant fall in triglyceride (-25%) and total cholesterol (-3.5%). Thus, we conclude that diet composition does not affect the short-term changes in blood lipids and lipoproteins that accompany a single session of aerobic exercise in moderately trained men.     

Antioxidant supplementation enhances neutrophil oxidative burst in trained runners following prolonged exercise

The influence of an antioxidant vitamin supplement on immune cell response to prolonged exercise was determined using a randomized, double-blind, placebo-controlled, cross-over study. Twelve healthy endurance subjects (n = 6 male, n = 6 female; mean +/- SD for age, 30.1 +/- 6.2 yr; height, 1.76 +/- 7 m; body mass, 72.2 +/- 10.2 kg; VO2max, 63.7 +/- 12 ml x kg(-1) x min(-1)) participated in the study. Following a 3-week period during which subjects ingested a multivitamin and -mineral complex sufficient to meet the recommended daily allowance, they took either a placebo or an antioxidant vitamin supplement (containing 18 mg beta-carotene, 900 mg vitamin C, and 90 mg vitamin E) for 7 days prior to a 2-h treadmill run at 65% VO2max. Blood samples were drawn prior to and immediately following exercise. These were analyzed for neutrophil oxidative burst activity, cortisol and glucose concentrations, and white blood cell counts, as well as serum anti-oxidant vitamin concentrations. Plasma vitamin C, vitamin E, and beta-carotene concentrations significantly increased following 7-day supplementation (p < .05). In comparison to the placebo group, neutrophil oxidative burst was significantly higher following exercise (p < .05), but no differences were found in any other parameter following the 7-day supplementation period. Although the impact of exercise on neutrophil function is multifactorial, our data suggest that antioxidant supplementation may be of benefit to endurance athletes for the maintenance of this particular function of the innate immune system following the 7-day supplementation period.     

Effects of upper-body resistance exercise training on serum nesfatin-1 level,insulin resistance,and body composition in obese paraplegic men

Background

As a recently discovered adipokine, nesfatin-1 is conducive to insulin sensitivity, lipid profile, energy balance, and probably obesity.

Whey protein ingestion activates mTOR-dependent signalling after resistance exercise in young men: a double-blinded randomized controlled trial

The effect of resistance exercise with the ingestion of supplementary protein on the activation of the mTOR cascade, in human skeletal muscle has not been fully elucidated. In this study, the impact of a single bout of resistance exercise, immediately followed by a single dose of whey protein isolate (WPI) or placebo supplement, on the activation of mTOR signalling was analyzed. Young untrained men completed a maximal single-legged knee extension exercise bout and were randomized to ingest either WPI supplement (n = 7) or the placebo (n = 7). Muscle biopsies were taken from the vastus lateralis before, and 2, 4 and 24 h post-exercise. WPI or placebo ingestion consumed immediately post-exercise had no impact on the phosphorylation of Akt (Ser473). However, WPI significantly enhanced phosphorylation of mTOR (Ser2448), 4E-BP1 (Thr(37/46)) and p70(S6K) (Thr389) at 2 h post-exercise. This study demonstrates that a single dose of WPI, when consumed in modest quantities, taken immediately after resistance exercise elicits an acute and transient activation of translation initiation within the exercised skeletal muscle.     

Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men

ABSTRACT: BACKGROUND: Increased amino acid availability stimulates muscle protein synthesis, however, aged muscle appears less responsive to the anabolic effects of amino acids when compared to the young. We aimed to compare changes in myofibrillar protein synthesis (MPS) in elderly men at rest and after resistance exercise following ingestion of different doses of soy protein and compare the responses to those we previously observed with ingestion of whey protein isolate. METHODS: Thirty elderly men (age 71 +/- 5 y) completed a bout of unilateral knee-extensor resistance exercise prior to ingesting no protein (0 g), or either 20 g or 40 g of soy protein isolate (0, S20, and S40 respectively). We compared these responses to previous responses from similar aged men who had ingested 20 g and 40 g of whey protein isolate (W20 and W40). A primed constant infusion of L-[1-13C]leucine and L-[ring-13C6]phenylalanine and skeletal muscle biopsies were used to measure whole-body leucine oxidation and MPS over 4 h post-protein consumption in both exercised and non-exercised legs. RESULTS: Whole-body leucine oxidation increased with protein ingestion and was significantly greater for S20 vs. W20 (P = 0.003). Rates of MPS for S20 were less than W20 (P = 0.02) and not different from 0 g (P = 0.41) in both exercised and non-exercised leg muscles. For S40, MPS was also reduced compared with W40 under both rested and post-exercise conditions (both P < 0.005); however S40 increased MPS greater than 0 g under post-exercise conditions (P = 0.04). CONCLUSIONS: The relationship between protein intake and MPS is both dose and protein source-dependent, with isolated soy showing a reduced ability, as compared to isolated whey protein, to stimulate MPS under both rested and post-exercise conditions. These differences may relate to the lower postprandial leucinemia and greater rates of amino acid oxidation following ingestion of soy versus whey protein.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Enhanced amino acid sensitivity of myofibrillar protein synthesis persists for up to 24 h after resistance exercise in young men

We aimed to determine whether an exercise-mediated enhancement of muscle protein synthesis to feeding persisted 24 h after resistance exercise. We also determined the impact of different exercise intensities (90% or 30% maximal strength) or contraction volume (work-matched or to failure) on the response at 24 h of recovery. Fifteen men (21 ± 1 y, BMI = 24.1 ± 0.8 kg · m(-2)) received a primed, constant infusion of l-[ring-(13)C(6)]phenylalanine to measure muscle protein synthesis after protein feeding at rest (FED; 15 g whey protein) and 24 h after resistance exercise (EX-FED). Participants performed unilateral leg exercises: 1) 4 sets at 90% of maximal strength to failure (90FAIL); 2) 30% work-matched to 90FAIL (30WM); or 3) 30% to failure (30FAIL). Regardless of condition, rates of mixed muscle protein and sarcoplasmic protein synthesis were similarly stimulated at FED and EX-FED. In contrast, protein ingestion stimulated rates of myofibrillar protein synthesis above fasting rates by 0.016 ± 0.002%/h and the response was enhanced 24 h after resistance exercise, but only in the 90FAIL and 30FAIL conditions, by 0.038 ± 0.012 and 0.041 ± 0.010, respectively. Phosphorylation of protein kinase B on Ser473 was greater than FED at EX-FED only in 90FAIL, whereas phosphorylation of mammalian target of rapamycin on Ser2448 was significantly increased at EX-FED above FED only in the 30FAIL condition. Our results suggest that resistance exercise performed until failure confers a sensitizing effect on human skeletal muscle for at least 24 h that is specific to the myofibrillar protein fraction.     

Bolus arginine supplementation affects neither muscle blood flow nor muscle protein synthesis in young men at rest or after resistance exercise

The aim of this study was to investigate the ergogenic potential of arginine on NO synthesis, muscle blood flow, and skeletal muscle protein synthesis (MPS). Eight healthy young men (22.1 ± 2.6 y, 1.79 ± 0.06 m, 76.6 ± 6.2 kg; mean ± SD) participated in 2 trials where they performed a bout of unilateral leg resistance exercise and ingested a drink containing either 10 g essential amino acids with 10 g l-arginine (ARG) or an isonitrogenous control (CON). Femoral artery blood flow of both the nonexercised and exercised leg was measured continuously using pulsed-wave Doppler ultrasound, while rates of mixed and myofibrillar MPS were determined using a primed continuous infusion of L-[ring-(13)C(6)] or L-[ring-(2)H(5)]phenylalanine. The plasma arginine concentration increased 300% during the ARG trial but not during the CON trial (P < 0.001). Plasma nitrate, nitrite, and endothelin-1, all markers of NO synthesis, did not change during either the ARG or CON trial. Plasma growth hormone increased to a greater degree after exercise in the ARG trial than CON trial (P < 0.05). Femoral artery blood flow increased 270% above basal in the exercised leg (P < 0.001) but not in the nonexercised leg, with no differences between the ARG and CON trials. Mixed and myofibrillar MPS were both greater in the exercised leg compared with the nonexercised leg (P < 0.001), but did not differ between the ARG and CON treatments. We conclude that an oral bolus (10 g) of arginine does not increase NO synthesis or muscle blood flow. Furthermore, arginine does not enhance mixed or myofibrillar MPS either at rest or after resistance exercise beyond that achieved by feeding alone.     

Short-term high-fat diet alters substrate utilization during exercise but not glucose tolerance in highly trained athletes

We determined the effect of a high-fat diet and carbohydrate (CHO) restoration on substrate oxidation and glucose tolerance in 7 competitive ultra-endurance athletes (peak oxygen uptake [VO(2peak)] 68 +/- 1 ml x kg(-1) x min(-1); mean +/- SEM). For 6 days, subjects consumed a random order of a high-fat (69% fat; FAT-adapt) or a high-CHO (70% CHO; HCHO) diet, each followed by 1 day of a high-CHO diet. Treatments were separated by an 18-day wash out. Substrate oxidation was determined during submaximal cycling (20 min at 65% VO(2peak)) prior to and following the 6 day dietary interventions. Fat oxidation at baseline was not different between treatments (17.4 +/- 2.1 vs. 16.1 +/- 1.3 g x 20 min(-1) for FAT-adapt and HCHO, respectively) but increased 34% after 6 days of FAT-adapt (to 23.3 +/- 0.9 g x 20 min(-1), p < .05) and decreased 30% after HCHO (to 11.3 +/- 1.4 g x 20 min(-1), p < .05). Glucose tolerance, determined by the area under the plasma [glucose] versus time curve during an oral glucose tolerance (OGTT) test, was similar at baseline (545 +/- 21 vs. 520 +/- 28 mmol x L(-1) x 90 min(-1)), after 5-d of dietary intervention (563 +/- 26 vs. 520 +/-18 mmol x L(-1) x 90 min(-1)) and after 1 d of high-CHO (491 +/- 28 vs. 489 +/- 22 mmol x L(-1) x 90 min(-1) for FAT- adapt and HCHO, respectively). An index of whole-body insulin sensitivity ( S(I), 10000/divided by fasting [glucose] x fasting [insulin] x mean [glucose] during OGTT x mean [insulin] during OGTT) was similar at baseline (15 +/- 2 vs. 17 +/- 5 arbitrary units), after 5-d of dietary intervention (15 +/- 2 vs. 15 +/- 2) and after 24 h of CHO loading (17 +/- 3 vs. 18 +/- 2 for FAT- adapt and HCHO, respectively). We conclude that despite marked changes in the pattern of substrate oxidation during submaximal exercise, short-term adaptation to a high-fat diet does not alter whole-body glucose tolerance or an index of insulin sensitivity in highly-trained individuals.