Andrew R. Coggan

Carbohydrate ingestion during prolonged exercise: effects on metabolism and performance.

It is well recognized that energy from CHO oxidation is required to perform prolonged strenuous (greater than 60% VO2 max) exercise. During the past 25 years, the concept has developed that muscle glycogen is the predominant source of CHO energy for strenuous exercise; as a result, the potential energy contribution of blood glucose has been somewhat overlooked. Although during the first hour of exercise at 70-75% VO2max, most of the CHO energy is derived from muscle glycogen, it is clear that the contribution of muscle glycogen decreases over time as muscle glycogen stores become depleted, and that blood glucose uptake and oxidation increase progressively to maintain CHO oxidation (Fig. 1.7). We theorize that over the course of several hours of strenuous exercise (i.e., 3-4 h), blood glucose and muscle glycogen contribute equal amounts of CHO energy, making blood glucose at least as important as muscle glycogen as a CHO source. During the latter stages of exercise, blood glucose can potentially provide all of the CHO energy needed to support exercise at 70-75% VO2max if blood glucose availability is maintained. During prolonged exercise in the fasted state, however, blood glucose concentration often decreases owing to depletion of liver glycogen stores. This relative hypoglycemia, although only occasionally severe enough to result in fatigue from neuroglucopenia, causes fatigue by limiting blood glucose (and therefore total CHO) oxidation. The primary purpose of CHO ingestion during continuous strenuous exercise is to maintain blood glucose concentration and thus CHO oxidation and exercise tolerance during the latter stages of prolonged exercise. CHO feeding throughout continuous exercise does not alter muscle glycogen use. It appears that blood glucose must be supplemented at a rate of approximately 1 g/min late in exercise. Feeding sufficient amounts of CHO 30 minutes before fatigue is as effective as ingesting CHO throughout exercise in maintaining blood glucose availability and CHO oxidation late in exercise. Most persons should not wait, however, until they are fatigued before ingesting CHO, because it appears that glucose entry into the blood does not occur rapidly enough at this time. It also may be advantageous to ingest CHO throughout intermittent or low-intensity exercise rather than toward the end of exercise because of the potential for glycogen synthesis in resting muscle fibers. Finally, CHO ingestion during prolonged strenuous exercise delays by approximately 45 minutes but does not prevent fatigue, suggesting that factors other than CHO availability eventually cause fatigue.

Metabolism and performance following carbohydrate ingestion late in exercise

To determine whether a single carbohydrate feeding could rapidly restore and maintain plasma glucose availability late in exercise, six trained cyclists were studied on two occasions during exercise to fatigue at 70 +/- 1% of VO2max. After 135 min of exercise, the men were fed either an artificially sweetened placebo or glucose polymers (3 g.kg-1 in a 50% solution). Prolonged exercise led to a decline in plasma glucose from 4.6 +/- 0.1 mM at rest to 3.9 +/- 0.2 mM after 135 min (P less than 0.05). Plasma glucose decreased further (P less than 0.05) to 3.2 +/- 2.0 mM at fatigue following placebo ingestion but increased (P less than 0.05) and was then maintained at 4.5-4.9 mM following carbohydrate ingestion. Respiratory exchange ratio (R) fell gradually during the placebo trial from 0.88 +/- 0.01 after 10 min of exercise to 0.81 +/- 0.01 at fatigue (P less than 0.01). R also reached a minimum of 0.81-0.82 in each subject after 135-180 min of exercise during the carbohydrate feeding trial but increased again to 0.84-0.86 as plasma glucose rose following the carbohydrate feeding. Exercise time to fatigue was 21% longer (205 +/- 17 vs 169 +/- 12 min; P less than 0.01) during the carbohydrate ingestion trial. Plasma insulin did not increase significantly, whereas plasma free fatty acids and blood glycerol plateaued following carbohydrate ingestion. These data indicate that a single carbohydrate feeding late in exercise can supply sufficient carbohydrate to restore euglycemia and increase carbohydrate oxidation, thereby delaying fatigue.

Plasma Glucose Metabolism During Exercise in Humans

SummaryPlasma glucose is an important energy source in exercising humans, supplying between 20 and 50% of the total oxidative energy production and between 25 and 100% of the total carbohydrate oxidised during submaximal exercise. Plasma glucose utilisation increases with the intensity of exercise, due to an increase in glucose utilisation by each active muscle fibre, an increase in the number of active muscle fibres, or both. Plasma glucose utilisation also increases with the duration of exercise, thereby partially compensating for the progressive decrease in muscle glycogen concentration. When compared at the same absolute exercise intensity (i.e. the same V̇O2), reliance on plasma glucose is also greater during exercise performed with a small muscle mass, i.e. with the arms or just 1 leg. This may be due to differences in the relative exercise intensity (i.e. the %V̇O2peak), or due to differences between the arms and legs in their fitness for aerobic activity.The rate of plasma glucose utilisation is decreased when plasma free fatty acid or muscle glycogen concentrations are very high, effects which are probably mediated by increases in muscle glucose-6-phosphate concentration. However, glucose utilisation is also reduced during exercise following a low carbohydrate diet, despite the fact that muscle glycogen is also often lower.When exercise is performed at the same absolute intensity before and after endurance training, plasma glucose utilisation is lower in the trained state. During exercise performed at the same relative intensity, however, glucose utilisation may be lower, the same, or actually higher in trained than in untrained subjects, because of the greater absolute V̇O2 and demand for substrate in trained subjects during exercise at a given relative exercise intensity.Although both hyperglycaemia and hypoglycaemia may occur during exercise, plasma glucose concentration usually remains relatively constant. Factors which increase or decrease the reliance of peripheral tissues on plasma glucose during exercise are therefore generally accompanied by quantitatively similar increases or decreases in glucose production. These changes in total glucose production are mediated by changes in both hepatic glycogenolysis and hepatic gluconeogenesis. Glycogenolysis dominates under most conditions, and is greatest early in exercise, during high intensity exercise, or when dietary carbohydrate intake is high. The rate of gluconeogenesis is increased when exercise is prolonged, preceded by a restricted carbohydrate intake, or performed with the arms. Both glycogenolysis and gluconeogenesis appear to be decreased by endurance exercise training. These effects are due to changes in both the hormonal milieu and in the availability of hepatic glycogen and gluconeogenic precursors.Hepatic glucose production during exercise is stimulated by glucagon and the catecholamines and suppressed by insulin or an increase in plasma glucose concentration. In contrast to earlier suggestions, it appears that a decrease in insulin and an increase in glucagon are both required for hepatic glucose production to increase normally during moderate intensity, moderate duration (40 to 60 minutes) exercise. Changes in the catecholamines. however, may still prove to be important, especially during more intense or more prolonged exercise.

Effectiveness of Carbohydrate Feeding in Delaying Fatigue during Prolonged Exercise

SummaryProlonged exercise in the fasted state frequently results in a lowering of blood glucose concentration, and when the intensity is moderate (i.e. 60–80% of V̇O2max), muscle often becomes depleted of glycogen. The extent to which carbohydrate feedings contribute to energy production, and their effectiveness for improving endurance during prolonged exercise, are reviewed in this article.Prolonged exercise (i.e. > 2 hours) results in a failure of hepatic glucose output to keep pace with muscle glucose uptake. As a result, blood glucose concentration frequently declines below 2.5 mmol/L. Despite this hypoglycaemia, fewer than 25% of subjects display symptoms suggestive of central nervous system dysfunction. Since fatigue rarely results from hypoglycaemia alone, the effectiveness of carbohydrate feeding should be judged by its potential for muscle glycogen sparing.Carbohydrate feeding during moderate intensity exercise postpones the development of fatigue by approximately 15 to 30 minutes, yet it does not prevent fatigue. This observation agrees with data suggesting that carbohydrate supplementation reduces muscle glycogen depletion. It is not certain whether carbohydrate feeding increases muscle glucose uptake throughout moderate exercise or if glucose uptake is higher only during the latter stages of exercise.In contrast to moderate intensity exercise, carbohydrate feeding during low intensity exercise (i.e. < 45% of V̇O2max) results in hyperinsulinaemia. Consequently, muscle glucose uptake and total carbohydrate oxidation are increased by approximately the same amount. The amount of ingested glucose which is oxidised is greater than the increase in total carbohydrate oxidation and therefore endogenous carbohydrate is spared. The majority of sparing appears to occur in the liver, which is reasonable since muscle glycogen is not utilised to a large extent during mild exercise.Although carbohydrate feedings prevent hypoglycaemia and are readily used for energy during mild exercise, there is little data indicating that feedings improve endurance during low intensity exercise. When the reliance on carbohydrate for fuel is greater, as during moderate intensity exercise, carbohydrate feedings delay fatigue by apparently slowing the depletion of muscle glycogen.

Training-induced alterations in fat and carbohydrate metabolism during exercise in elderly subjects

Compared with young adults, fat oxidation is lower in elderly persons during endurance exercise performed at either the same absolute or relative intensity. We evaluated the effect of 16 wk of endurance training on fat and glucose metabolism during 60 min of moderate intensity exercise [50% of pretraining peak oxygen consumption (VO2peak)] in six elderly men and women (74 +/- 2 yr). Training caused a 21% increase in mean VO2peak. The average rate of fat oxidation during exercise was greater after (221 +/- 28 mumol/min) than before (166 +/- 17 mumol/min) training (P = 0.002), and the average rate of carbohydrate oxidation during exercise was lower after (3,180 +/- 461 mumol/min) than before (3,937 +/- 483 mumol/min) training (P = 0.003). Training did not cause a significant change in glycerol rate of appearance (Ra), free fatty acid (FFA) Ra, and FFA rate of disappearance during exercise. However, glucose Ra during exercise was lower after (1,027 +/- 95 mumol/min) than before (1,157 +/- 69 mumol/min) training (P = 0.01). These results demonstrate that a 16-wk period of endurance training increases fat oxidation without a significant change in lipolysis (glycerol Ra) or FFA availability (FFA Ra) during exercise in elderly subjects. Therefore, the training-induced increase in fat oxidation during exercise is likely related to alterations in skeletal muscle fatty acid metabolism.Compared with young adults, fat oxidation is lower in elderly persons during endurance exercise performed at either the same absolute or relative intensity. We evaluated the effect of 16 wk of endurance training on fat and glucose metabolism during 60 min of moderate intensity exercise [50% of pretraining peak oxygen consumption (V˙o 2 peak)] in six elderly men and women (74 ± 2 yr). Training caused a 21% increase in meanV˙o 2 peak. The average rate of fat oxidation during exercise was greater after (221 ± 28 μmol/min) than before (166 ± 17 μmol/min) training ( P = 0.002), and the average rate of carbohydrate oxidation during exercise was lower after (3,180 ± 461 μmol/min) than before (3,937 ± 483 μmol/min) training ( P = 0.003). Training did not cause a significant change in glycerol rate of appearance (Ra), free fatty acid (FFA) Ra, and FFA rate of disappearance during exercise. However, glucose Ra during exercise was lower after (1,027 ± 95 μmol/min) than before (1,157 ± 69 μmol/min) training ( P = 0.01). These results demonstrate that a 16-wk period of endurance training increases fat oxidation without a significant change in lipolysis (glycerol Ra) or FFA availability (FFA Ra) during exercise in elderly subjects. Therefore, the training-induced increase in fat oxidation during exercise is likely related to alterations in skeletal muscle fatty acid metabolism.

Nutritional manipulations before and during endurance exercise: effects on performance.

1) Ingesting CHO during prolonged, moderate-intensity (60-85% VO2max) exercise can improve performance by maintaining plasma glucose availability and oxidation during the later stages of exercise. 2) Plasma glucose may be oxidized at rates in excess of 1 g.min-1 late in exercise. Athletes therefore need to ingest sufficient quantities of CHO in order to meet this demand. This can be accomplished by ingesting CHO at 40-75 g.h-1 throughout exercise or by ingesting approximately 200 g of CHO late in exercise. Ingesting CHO after fatigue has already occurred, however, is generally ineffective in restoring and maintaining plasma glucose availability, CHO oxidation, and/or exercise tolerance. 3) No apparent differences exist between glucose, sucrose, or maltodextrins in their ability to improve performance. Ingesting fructose during exercise, however, does not improve performance and may cause gastrointestinal distress. 4) The form of CHO (i.e., solid vs liquid) ingested during exercise is unlikely to be important provided that sufficient water is also consumed when ingesting CHO in solid form. 5) Ingesting 50-200 g of CHO 30-60 min before exercise results in transient hypoglycemia early in exercise, but this does not affect the rate of muscle glycogen utilization or, in most people, cause overt symptoms of neuroglucopenia. Whether performance is impaired, unaffected, or enhanced by such pre-exercise CHO feedings remains equivocal. 6) Ingesting 200-350 g of CHO 3-6 h before exercise appears to improve performance, possibly by maximizing muscle and/or liver glycogen stores or by supplying CHO from the small intestine during exercise itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex and type 2 diabetes: obesity-independent effects on left ventricular substrate metabolism and relaxation in humans.

Patients with type 2 diabetes (T2DM), particularly women, are at risk for heart failure. Myocardial substrate metabolism derangements contribute to cardiac dysfunction in diabetic animal models. The purpose of this study was to determine the effects of diabetes and sex on myocardial metabolism and diastolic function in humans, separate from those of obesity. Thirty‐six diabetic subjects (22 women) and 36 nondiabetic, BMI‐matched subjects (21 women) underwent positron emission tomography (myocardial metabolism) and echocardiography (structure, function). Myocardial blood flow and oxygen consumption (MVO2) were higher in women than men (P = 0.003 and <0.0001, respectively). Plasma fatty acid (FA) levels were higher in diabetics (vs. obese, P < 0.003) and sex and diabetes status interacted in its prediction (P = 0.03). Myocardial FA utilization, oxidation, and esterification were higher and percent FA oxidation lower in diabetics (vs. obese, P = 0.0004, P = 0.007, P = 0.002, P = 0.02). FA utilization and esterification were higher and percent FA oxidation lower in women (vs. men, P = 0.03, P = 0.01, P = 0.03). Diabetes and sex did not affect myocardial glucose utilization, but myocardial glucose uptake/plasma insulin was lower in the diabetics (P = 0.04). Left ventricular relaxation was lower in diabetics (P < 0.0001) and in men (P = 0.001), and diabetes and sex interacted in its prediction (P = 0.03). Sex, T2DM, or their interaction affect myocardial blood flow, MVO2, FA metabolism, and relaxation separate from obesitys effects. Sexually dimorphic myocardial metabolic and relaxation responses to diabetes may play a role in the known cardiovascular differences between men and women with diabetes.

Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women.

Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3(-)) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3(-) intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(-). After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3(-) intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3(-) intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3(-) intake increases whole-body NO production and muscle speed and power in healthy men and women.

Impact of sex on the heart's metabolic and functional responses to diabetic therapies

Increased myocardial lipid delivery is a determinant of myocardial substrate metabolism and function in animal models of type 2 diabetes (T2DM). Sex also has major effects on myocardial metabolism in the human heart. Our aims were to determine whether 1) sex affects the myocardial metabolic response to lipid lowering in T2DM, 2) altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM. To this end, we studied 78 T2DM patients (43 women) with positron emission tomography, echocardiography, and whole body tracer studies before and 3 mo after randomization to metformin (MET), metformin + rosiglitazone (ROSI), or metformin + Lovaza (LOV). No treatment main effects were found for myocardial substrate metabolism, partly because men and women often had different responses to a given treatment. In men, MET decreased FA clearance, which was linked to increased plasma FA levels, myocardial FA utilization and oxidation, and lower myocardial glucose utilization. In women, ROSI increased FA clearance, thereby decreasing plasma FA levels and myocardial FA utilization. Although LOV did not change triglyceride levels, it improved diastolic function, particularly in men. Group and sex also interacted in determining myocardial glucose uptake. Thus, in T2DM, different therapeutic regimens impact myocardial metabolism and diastolic function in a sex-specific manner. This suggests that sex should be taken into account when designing a patients diabetes treatment.

PET Measurements of Myocardial Glucose Metabolism with 1-11C-Glucose and Kinetic Modeling

The aim of this study was to investigate whether compartmental modeling of 1-11C-glucose PET kinetics can be used for noninvasive measurements of myocardial glucose metabolism beyond its initial extraction. Methods: 1-11C-Glucose and U-13C-glucose were injected simultaneously into 22 mongrel dogs under a wide range of metabolic states; this was followed by 1 h of PET data acquisition. Heart tissue samples were analyzed for 13C-glycogen content (nmol/g). Arterial and coronary sinus blood samples (ART/CS) were analyzed for glucose (μmol/mL), 11C-glucose, 11CO2, and 11C-total acidic metabolites (11C-lactate [LA] + 11CO2) (counts/min/mL) and were used to calculate myocardial fractions of (a) glucose and 1-11C-glucose extractions, EF(GLU) and EF(11C-GLU); (b) 11C-GLU and 11C-LA oxidation, OF(11C-GLU) and OF(11C-LA); (c) 11C-glycolsysis, GCF(11C-GLU); and (d) 11C-glycogen content, GNF(11C-GLU). On the basis of these measurements, a compartmental model (M) that accounts for the contribution of exogenous 11C-LA to myocardial 11C activity was implemented to measure M-EF(GLU), M-GCF(GLU), M-OF(GLU), M-GNF(GLU), and the fraction of myocardial glucose stored as glycogen M-GNF(GLU)/M-EF(GLU)). Results: ART/CS data showed the following: (a) A strong correlation was found between EF(11C-GLU) and EF(GLU) (r = 0.92, P < 0.0001; slope = 0.95, P = not significantly different from 1). (b) In interventions with high glucose extraction and oxidation, the contribution of OF(11C-GLU) to total oxidation was higher than that of OF(11C-LA) (P < 0.01). In contrast, in interventions in which glucose uptake and oxidation were inhibited, OF(11C-LA) was higher than OF(11C-GLU) (P < 0.05). (c) A strong correlation was found between GNF(11C-GLU)/EF(GLU) and direct measurements of fractional 13C-glycogen content, (r = 0.96, P < 0.0001). Model-derived PET measurements of M-EF(GLU), M-GCF(GLU), and M-OF(GLU) strongly correlated with EF(GLU) (slope = 0.92, r = 0.95, P < 0.0001), GCF(11C-GLU) (slope = 0.79, r = 0.97, P < 0.0001), and OF(11C-GLU) (slope = 0.70, r = 0.96, P < 0.0001), respectively. M-GNF(GLU)/M-EF(GLU) strongly correlated with fractional 13C-content (r = 0.92, P < 0.0001). Conclusion: Under nonischemic conditions, it is feasible to measure myocardial glucose metabolism noninvasively beyond its initial extraction with PET using 1-11C-glucose and a compartmental modeling approach that takes into account uptake and oxidation of secondarily labeled exogenous 11C-lactate.