Fructose and glucose ingestion glycogen use during submaximal

Transcription

1 Fructose and glucose ingestion glycogen use during submaximal and muscle exercise L. LEVNE, W. J. EVANS, B. S. CADARETTE, E. C. FSHER, AND B. A. BULLEN Department of Health Sciences, Boston University, Boston, Massachusetts LEVNE, L., W. J. EVANS, B. S. CADARETTE, E. C. FSHER, AND B. A. BULLEN. Fructose and glucose ingestion and muscle glycogen use during submaximal exercise. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 55(6): , Substrate utilization after fructose, glucose, or water ingestion was examined in four male and four female subjects during three treadmill runs at -75% of maximal O2 uptake. Each test was preceded by three days of a carbohydrate-rich diet. The runs were 0 min long and were spaced at least 1 wk apart. Exercise began 45 min after ingestion of 00 ml of randomly assigned 75 g fructose (F), 75 g glucose (G), or control (C). Muscle glycogen depletion determined by pre- and postexercise biopsies (gastrocnemius muscle) was significantly (P < 0.05) less during the F trial than during C or G. Venous blood samples revealed a significant increase in serum glucose (P < 0.05) and insulin (P < 0.01) within 45 min after the G drink, followed by a decrease (P < 0.05) in serum glucose during the first 15 min of exercise, changes not observed in the C or F trials. Respiratory exchange ratio was higher (P < 0.05) during the G than C or F trials for the first 5 min of exercise and lower (P c 0.05) during the C trial compared with G or F for the last 15 min of exercise. These data suggest that fructose ingested before 0 min of submaximal exercise maintains stable blood glucose and insulin concentrations, which may lead to the observed sparing of muscle glycogen. sugar ingestion ; carbohyd insulin; muscle biopsy rate metabolism; treadmill exercise; THE RELATONSHP BETWEEN glycogen depletion and performance decrements during prolonged exercise has been previously reported (4, 19, 20, 24). To delay muscle glycogen depletion, athletes have sought dietary manipulations that could spare glycogen stores. n an attempt to provide carbohydrates to contracting muscles, it has been observed that glucose ingestion before exercise results in increased insulin secretion. This hyperinsulinemia is followed by an exercise-induced rapid decrease in blood glucose concentration and greater depletion of muscle- glycogen (8, 19, 29). Several studies that have compared fructose ingestion with that of glucose or sucrose have noted significantly lower elevations in plasma glucose and little or no elevation in insulin after fructose ingestion. The normal hypoglycemic effect after glucose ingestion is also avoided with fructose (5, 10; 17). Previous studies indicate that there is less glucose and insulin fluctuation after fructose compared with glucose ingestion (5, 10, 17) an.d greater reliance on glycogen stores with glucose compared with water ingestion (8). Therefore, fructose ingestion before submaximal exercise (in the fed state) could have a glycogen sparing effect. To our knowledge muscle glycogen depletion after fructose ingestion has not previously been investigated. The purpose of this investigation was to study the depletion of glycogen in contracting muscle after subjects had ingested fructose, glucose, or a control drink to determine whether, in fact, there was significant glycogen sparing with fructose. Circulating levels of blood glucose and insulin, as well as triglycerides and glycerol, were measured to investigate the relationship of these substrate levels to any alterations in glycogen metabolism which may have occurred. METHODS Subjects. Four male and four female subjects, after giving their informed consent, were selected for participation on the basis of screening tests for maximal O2 consumption (VO 2max) and normal glucose tolerance. The subjects mean (ME) age, height, weight, and VOW max, respectively, are as follows: males, 25.0 t 2. yr, t 2.5 cm, 70.4 t 4.2 kg, and 57.9 t 0.9 ml-kg- omin- ; females, 20.0 t 0.4 yr, t 2.9 cm, 55.8 t 1.1 kg, and 47.4 t 1.6 ml. kg-. min-. Procedure. A continuous treadmill test (9) was used t.o determine VOW max. Heart rate was determined from an electrocardiographic recording throughout the test. Expired air was collected each minute via the Wilmore- Costill semiautomated system for gas sampling (1). Gases were analyzed with a previously calibrated (25) Applied Electrochemistry S-A 02 analyzer and a Beckman LB-2 COZ analyzer. nspired ventilatory volumes were determined with a Parkinson-Cowan gasometer calibrated against a tissot spirometer. Acceptable fitness levels were set at the high category according to the guidelines of Astrand (2) to help ensure completion of the submaximal exercise bouts. Standard oral glucose tolerance tests were administered and each subject was classified according to the guidelines suggested by the National Diabetes Data Group (18). To enhance liver and muscle glycogen stores, each of three 0-min sub- maximal (w 75% VO, max) treadmill runs was preceded by days of limited exercise and a carbohydrate (CHO)- rich diet consisting of -45 kcal. kg-. day- containing 70% CHO, 15% fat, and 15% protein. Four hours before each trial, subjects ate a light CHO-rich meal (-40 kcal, ~80 g CHO). Exercise began 45 min after subjects 1767 Downloaded from by on September 16, 2016

2 1768 LEVNE ET AL. ingested either 00 ml of refrigerated distilled water as the control drink (C), 00 ml of a refrigerated 25% fructose (F), or glucose (G) solution containing 75 g of sugar. The order of the three trials was randomly assigned with at least 1 wk between each trial. Blood S6 samples (12 ml) were taken from an antecubital vein 5 before the drink (base line), pre-, mid-, and postexercise. g The samples were allowed to clot, centrifuge, and then s the serum was frozen for later determination of glucose $5 (16), insulin (26), glycerol (0), and triglycerides (28). z Pre- and postexercise muscle biopsies were obtained from $ the lateral aspect of the gastrocnemius muscle according to the method of Bergstrom () as modified by Evans et 4 al. (11). The muscle specimens (~75 mg each) were cleaned of connective tissue, divided into pieces of 45 0 mg each, and immediately frozen in liquid N2 for later determination of muscle glycogen (2). Heart rate was monitored and expired gases analyzed as has been described for the Vozmax testing. n addition, subjects were asked to rate their perception of exertion (RPE), using the Borg scale (6) at 5-min intervals during exercise. Statistical treatment. A mixed factorial analysis of variance with repeated measures was used to assess differences with each subject receiving all combinations of factors (dose and time); subjects were divided into groups by gender. When significance was observed, the Student Newman-Keuls test was used to locate differences and a probability level of 0.05 was chosen as the criterion for acceptance of statistical significance. No significant differences between the male and female groups were observed for any of the parameters measured in this study. All values reported are means t SE for the combined groups. RESULTS As illustrated in Fig. 1, serum glucose concentrations increased 67% (P < 0.05) from base line to preexercise values during the G trial. The midexercise value declined ~0% (P c 0.05) from the preexercise value and did not differ significantly from base line. A significant rise (P < 0.05) from mid- to postexercise values ensued. During the C and F trials, glucose levels were not different between trials (P > 0.05) and increased during exercise with greater mid- and postexercise values (P c 0.05) than values at base line. During C, mid- and postexercise values were greater than preexercise values (P < 0.05) and appeared to plateau by the end of exercise. Serum glucose for the G run was significantly (P < 0.05) greater than C or F preexercise, was less (P < 0.05) at midexercise, and did not differ significantly (P > 0.05) at postexercise. A corresponding rise in the preexercise insulin concentration (Fig. 2) during the G trial was 6.5- and - fold (P < 0.01) higher than preexercise values during the C and F trials, respectively. nsulin concentrations were not different among trials (P > 0.05) for base-line, midand postexercise values. Serum triglyceride (Fig. ) concentrations were not significantly different among trials (P > 0.05). Overall triglycerides rose slightly (P < 0.05) during the first 15 min of exercise compared with base-line values. Postexercise concentrations were not different from base line - b CONTROL =---- GLUCOSE h SE b...- FRUCTOSE J ) DRNK EXERCSE 1 TME (min) FG. 1. Mean values (GE) for serum glucose are illustrated during each trial at base line (-45), pre- (0), mid-(15), and postexercise (0; n = 8). * Significant difference between 1 trial and other trials, P c = E 20 Z 2 20 s z % 10 OL - CONTROL )-mm -we A FRUCTOSE 0 0, 0...y... a f DRNK EXERCSE TME (min) FG. 2. Mean values (HE) for serum insulin during each of trials at base line (-45), pre-(o), mid-(15), and postexercise (0; n = 8). * Significant difference between 1 trial and other trials, P c n ) DRNK 0 CONTROL 7 m ---- GLUCOSE x+se A-...- FRUCTOSE TME EXERCSE (min) FG.. Mean values (GE) for serum triglycerides with time as in Figs. 1 and 2 (n = 8). Downloaded from by on September 16, 2016

3 FRUCTOSE AND GLUCOSE NGESTON AND MUSCLE GLYCOGEN USE 1769 (P > 0.05). On the other hand, glycerol concentrations (Fig. 4) increased throughout exercise during each trial; midexercise values during the C trial were 2 and 1.6 times greater (p < 0.05) than during the G and F trials, respectively. Postexercise values during C were 1.6 and 1.4 times greater (P < 0.05) than G or F. Muscle glycogen analysis (Fig. 5) revealed a pre- to postexercise depletion of approximately 20% for C and G compared with about 9% for F. When compared with preexercise glycogen values, which were not significantly different among trials, depletion during F was 12.5% and 10.9% less than during G or C, respectively (P c 0.05). Respiratory exchange ratios (R) during exercise for the three trials are shown in Fig. 6. These R values were significantly greater (P < 0.05) during the G run than during the C or F runs in the first 5 min of exercise CONTROL c GLUCOSE kse &...- FRUCTOSE T * P d s t DRNK EXERCSE J TME(min) FG. 4. Mean values (&SE) for serum glycerol for each trial with time as in Figs. 1 and 2 (n = 8). * Significant difference between 1 trial and other trials, P < A = 27.6 A = 0.7 A = 1.0*.0 PRE POST PRE POST PRE POST CONTROL GLUCOSE FRUCTOSE FG. 5. Bars illustrate mean (&SE) muscle glycogen concentration pre-(cross hatched) and postexercise (diagonal shading) for each of trials. Glycogen depletion for each trial is indicated above bars by A (n = 8). * Significant difference between 1 trial and other trials, P < GLUCOSE SE EXERCSE TME (min) FG. 6. Respiratory exchange ratios are presented with each value representing mean &SE of 5 min of exercise. Break after 15th min represents 1-2 min stop for blood sampling. VCO~, CO* production; VO2, 02 consumption. * Significant difference between 1 trial and other trials, P c During the last 15 min of exercise, R values for C were significantly lower (P < 0.05) than for F or G. Heart rate (HR) and % Tjozmax were not different among the three trials. The overall mean values were t 1. beats min- and 75.6 t 0.6% for HR and vozmax, respectively. There were significant increases (P < 0.05) during exercise; HR increased from t 1.4 to 181. t 2. beats min-l and % Vozrnax increased from 70.7 t 0.7 to 78.2 t 1.1% for the first 5 and last 5 min, respectively. RPE also rose significantly during exercise. Additionally, during the last 10 min of exercise, RPE values for the F trial were significantly higher (P < 0.05) than C or G ( , 12.8 k 0.9, and 12.6 t 1.2 during min 0 for F,C, and G, respectively). DSCUSSON The prominent finding of this study was the significantly reduced muscle glycogen depletion during the 0- min exercise period after fructose ingestion compared with the C and G tests. This glycogen sparing during the F trial occurred while similar levels of CHO oxidation appeared to occur in both F and G, as evident from R values. Whereas lower R values were observed during the last 15 min of exercise during the C trial, indicating greater reliance on lipid oxidation, muscle glycogen depletion was not significantly less than during the G trial. The glycogen data from the glucose and control trials in the present investigation are similar to those reported by Costill et al. (8). Those authors, however, observed a significant difference in glycogen depletion between a glucose ingestion trial and control trial during exercise of similar duration and intensity to that of the present study. n their study, 15% less glycogen depletion occurred in the control compared with the glucose trial (4.1 and 9.9,umoLg wet wt-, respectively), which approximates the 10% less glycogen depletion in C when compared with G in the present study. The absence of statistical significance in the present study may have Downloaded from by on September 16, 2016

4 1770 LEVNE ET AL. been related to the training status of our subjects, indi- F trial may be somewhat elevated due to diminished vidual variability of the subjects, or to the sample size. clearance by the liver. The flattened serum glucose and insu.lin response The higher RPE values during the final minutes of the curves after fru.ctose i.ngestion confi rm observations F trial were likely due to the perceptions of two subjects made by other investigators (5, 10, 17). The hypoglyce- who complained of intestinal distress during that trial. mia seen in many subjects that occurs when exercise Because of its slower absorption from the intestine, it is follows glucose ingestion (8, 17) was not evident in our not uncommon for osmotic diarrhea to occur after ingessubjects. n the present study, the high CHO diet and tion of fructose in loads as large as used n the present limited exercise for days before testing and the CHO study (7). Before an athletic event, sugar supplementameal 4 h before each trial may have been important tion would likely be less than that employed experimenfactors in maintaining glucose homeostasis. Often sub- tally. jects have been tested after an overnight fast (17) when Although epinephrine was not measured in this study, somewhat depleted hepatic glycogen stores may have it is possible that responses of this hormone to different contributed to the occurrence of hypoglycemia; that we levels of serum glucose may have affected glycogen deobserved no decline in insulin concentration during the pletion in the three trials. n studies by Galbo et al. (14, control trial probab ly reflects this diet manipulation as 15), a close relationship was noted between the rate of well as the relatively short duration of the exercise. decline in plasma glucose concentrations and the rate of Absorption of fructose from the gut occurs more slowly increase in epinephrine concentrations during prolonged than does that of glucose and, in healthy humans, 70- exercise and,&adrenergic blockade. Since epinephrine is 90% of ingested fructose enters the portal circulation as a major stimulant of muscle glycogenolysis (15), the fructose. n the fasted state most of the glucose formed implications of these findings may offer support for the in the liver is converted to glycogen and subsequently greater glycogen depletion we observed during the gluthere is no significant rise in plasma glucose or insulin case trials in the present study. levels (5, 7, 10, 19, 22, 27). Because of the antecedent n summary, the findings of this study indicate that diet in this study, hepati.c glycogen stores may be as- when fructose is ingested before submaximal exercise, sumed to be full, and the ingested sugars m ay not have serum glucose and insulin concentrations do not flucbeen retained for glycogen synthesis. That the fructose tuate as dramatically as they do after glucose ingesti.on. was delivered to the liver more slowly and was possibly These flattened response curves during the F trial are released as glucose more slowly when compared with the also associated with a significant sparing of muscle glyingested glucose may account for the steady increase in cogen during 0 min of exercise. The mechanisms for the serum glucose concentrations during the F trial com- observed glycogen sparing, as well as the extent to which pared with G. The similar increase in serum glucose this sparing would continue during more prolonged (2 to during C may have been provided by hepatic glycogeno- 4 h) exercise (when glycogen reserves become critical), lysis and gluconeogenesis. deserve further investigation. Triglyceride concentrations were generally stable throughout exercise and similar among trials. On the other-hand, evidence of increased fat oxidation during the C trial as observed in the R data is supported by significantly elevated serum glycerol concentrations when that trial is compared with G and F. The large increase in insulin after glucose ingestion and the trend toward higher than base-line insulin values during the F trial suggest an antilypolytic effect on fat stores 7 an effect that occurs at lower insulin concentrations tha.n are required to stimulate glucose uptake (20). nsulin is known to inhibit hepatic clearance of gluconeogenic precursors such as lactate, alanine, and glycerol, and it appears that exercise does not overcome this inhibition (1, 12, 20, 29). Glycerol values observed during the first part of exercise in the G trial and to some extent in the Great appreciation is extended to the US Army Research nstitute of Environmental Medicine for the generous use of their facility. The authors would also like to acknowledge the cooperation of the test subjects, the assistance of Nancy Pimental, Michael Sawka, and Kent Pandolf in the editing, Ella Munro and William Holden in the statistical analysis, and Julie Cyphers in the preparation of this manuscript. This study was made possible by a grant provided by the Hoffmann- LaRoche Co. and was supported in part by the Dudley Allen Sargent Fund of Boston University. Present addresses: L. Levine and B. S. Cadarette, US Army Research nstitute of Environmental Medicine, Natick, MA W. J. Evans and E. C. Fisher, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA Address for reprint requests: L. Levine, US Army Research nstitute of Environmental Medicine, Natick, MA Received 25 October 1982; accepted in final form 26 July 198. Downloaded from by on September 16, 2016 REFERENCES 1. AHLBORG, G., AND P. FELG. Substrate utilization during prolonged exercise preceded by ingestion of glucose. Am. J. Physiol. 2 (Endocrinol. Metab. Gastrointest. Physiol. 2): El@&-E194, ASTRAND,. Aerobic work capacity in men and women with special reference to age. Acta Physiol. Stand. 49, Suppl. 169: 29, BERGSTROM, J. Muscle electrolytes in man. Stand. J. Clin. Lab. nvest. Suppl. 68: l-110, BERGSTROM, J., AND E. HULTMAN. A study of the glycogen metabolism during exercise in man. Stand. J. CLin. Lab. nvest. 19: , BOHANNON, N. V., J. H. KARAM, AND P. H. FORSHAM. Endocrine responses to sugar ingestion in man. J. Am. Diet. Assoc. 2: ,198O. 6. BORG, G. Perceived exertion as an indicator of somatic stress. Stand. J. Rehabil. Med. 2: 92-98, CHEN, M., AND R. L. WHSTLER. Metabolism of D-Fructose. Adv. Carbohydr. Chem. B&hem. 4: 285-4, COSTLL, D. L., E. COYLE, G. DALSKY, W. EVANS, W. FNK, AND D. HOOPES. Effects of elevated plasma FFA and insulin on muscle glycogen usage during exercise. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 4: , COSTLL, D. L., W. J. FNK, L. H. GETCHELL, J. L. VY, AND F. A.

5 FRUCTOSE AND GLUCOSE NGESTON AND MUSCLE GLYCOGEN USE 1771 WTZMANN. Lipid metabolism in skeletal muscle of endurancetrained males and females. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: , CRAPO, P., 0. G. KOLTERMAN, AND J. M. OLEFSKY. Effects of oral fructose in normal, diabetic and impaired glucose tolerance subjects. Diabetes Care : , EVANS, W. J., S. D. PHNNEY, AND V. R. YOUNG. Suction applied to a muscle biopsy maximizes sample size. Med. Sci. Sports Exercise 14: , FELG, P., AND J. WAHREN. Fuel homeostasis in exercise. N. Engl. J. Med. 29: , FOSTER, C., D. L. COSTLL, AND W. J. FNK. Effects of pre-exercise feedings on endurance performance. Med. Sci. Sports 11: l-5, GALBO, H., N. J. CHRSTENSEN, AND J. J. HOLST. Glucose-induced decrease in glucagon and epinephrine responses to exercise in man. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: , GALBO, H., J. J. HOLST, N. J. CHRSTENSEN, AND J. HLSTED. Glucagon and plasma catecholamines during beta-receptor blockade in exercising man. J. Appl. Physiol. 40: , HYVARNEN, A., AND E. NKKLA. Specific determination of blood glucose with o-toluidine. Clin. Chin. Acta. 7: 140, KOVSTO, V. A., S.-L. KARONEN, AND E. A. NKKLA. Carbohydrate ingestion before exercise: comparison of glucose, fructose, and sweet placebo. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: , National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: , NEWSHOLME, E. A. The control of fuel utilization by muscle during exercise and starvation. Diabetes 28, Suppl. 1: l-7, NEWSHOLME, E. A., AND C. STUART. Regulation in Metabolism. Chichester, New York: Wiley, NLSSON, L., AND E. HULTMAN. Liver and muscle glycogen in man after glucose and fructose infusion. Stand. J. Clin. Lab. nvest. : 5-10, OLEFSKY, J. M., AND P. CRAPO. Fructose, xylitol and sorbitol. Diabetes Care : 90-9, PASSONEAU, J. V., AND V. R. LAUDERDALE. A comparison of three methods of glycogen measurement in tissues. Anal. Biochem. 60: , PERNOW, B., AND B. SALTN. Availability of substrates and capacity for prolonged heavy exercise in man. J. Appl. Physiol. 1: ,197l. 25. SCHOLANDER, P. F. Analyzer for accurate estimation of respiratory gases in 0.5 cc sample. J. Biol. Chem. 167: , Serono Laboratories. Polyethylene glycol method. nsulin RA Kit. Braintree, MA: Serono Laboratories, SESTOFT, L. Fructose and the dietary therapy of Diabetes Mellitus. Diabetologia 17: l-, SOLON, F. G. Simplified manual micromethod for determination of serum triglycerides. Clin. Chem. 17: , WAHREN, J. Glucose turnover during exercise in healthy man and in patients with diabetes mellitus. Diabetes 28, Suppl. 1: 82-88, WELAND, 0. Glycerol; U-V method. n: Methods of Enzymatic Analysis, edited by H. U. Bergmeyer. New York: Academic, 1974, vol., p WLMORE, J. H., AND D. L. COSTLL. Semiautomated systems approach to the assessment of oxygen uptake during exercise. J. Appl. Physiol. 6: , Downloaded from by on September 16, 2016