Acute fuel selection in response to high-sucrose and high-starch meals in healthy men

¹ From the Human Nutrition Research Centre, the Department of Biological and Nutritional Sciences, the Human Diabetes and Metabolism Research Centre, and the Department of Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.

² Supported by the Ministry of Agriculture, Fisheries, and Food (contract no. AN0309); the British Diabetic Association; and Novo Nordisk Industries.

³ Address reprint requests to ME Daly, Human Nutrition Research Centre, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP United Kingdom. E-mail: m.e.daly{at}ncl.ac.uk.

ABSTRACT  
Background: Despite considerable controversy over the inclusion of sucrose in the diets of people with diabetes, the acute metabolism of sucrose is not completely understood.

Objective: Our objective was to investigate the metabolism of the monomeric constituents of sucrose after a high-sucrose meal.

Design: Three test meals were consumed in a randomized, crossover design by 7 healthy male volunteers. Two of the meals were high in sucrose; one was supplemented with 200 mg uniformly labeled [¹³C]fructose and one was supplemented with 200 mg [¹³C]glucose. The other meal was high in starch, supplemented with 200 mg [¹³C]glucose. Fifty percent of energy was supplied as sucrose in the high-sucrose meals and as starch in the high-starch meal. Breath ¹³CO₂ enrichment was measured at 15-min intervals and indirect calorimetry was performed for five 20-min sessions immediately before and during a 6-h postprandial period.

Results: Carbohydrate oxidation rates rose much faster after the high-sucrose meals than after the high-starch meal. Breath ¹³CO₂ enrichment rose faster and peaked earlier and at a higher value when [¹³C]fructose rather than [¹³C]glucose was given with the high-sucrose test meal. Values for breath ¹³CO₂ enrichment from [¹³C]glucose after the high-starch meal were intermediate.

Conclusions: These results show that fructose is preferentially oxidized compared with glucose after a high-sucrose meal and that glucose is oxidized more slowly after a high-sucrose meal than after a high-starch meal.

Key Words: Sucrose • fructose • starch • fuel selection • metabolic isotopes • diabetes • sucrose metabolism • carbohydrate oxidation • glucose oxidation • fructose oxidation • indirect calorimetry

INTRODUCTION  
The metabolic effects of high-sucrose and high-fructose diets have been the subject of intense study for the past 25 y. The effects of such diets in laboratory animals are well characterized, but there is controversy about responses in humans. Diets that are very high in sucrose or fructose can induce insulin resistance or hypertriglyceridemia in animals (1–10), particularly rats. Evidence indicates that certain groups of humans, possibly those who are initially hypertriglyceridemic or insulin-resistant, are more susceptible to the effects of such diets (11, 12; see 13 for a recent review). These studies (11, 12) included individuals who were deemed to be insulin resistant on the basis of exaggerated postprandial hyperinsulinemia but who did not have diabetes. Other authors have argued that a review of the literature suggests that people with diabetes may be protected from this susceptibility to hyperlipidemia by chronic consumption of high-sucrose diets (14). The liver is the main site of fructose metabolism (15–17), and studies have shown that oral ingestion of fructose or sucrose increases the carbohydrate oxidation rate and thermogenesis more than does ingestion of glucose (18–20). However, it is less clear how the monosaccharides glucose and fructose are metabolized when consumed together as the disaccharide sucrose and also in comparison with other sources of commonly consumed carbohydrates, such as starch.

Understanding the metabolic consequences of sucrose intake is important, because this sugar makes a substantial contribution to habitual diets in many countries; eg, in the United Kingdom sucrose contributes 16% of total dietary energy (21). Current recommendations to lower fat intake with the intention of reducing cardiovascular disease risk are matched by recommendations to increase total carbohydrate intake, especially intake of complex carbohydrates (22). Previous studies have shown a tendency for individuals to increase their intake of sugars when they reduce fat intake (23), which may lead to a further increase in sucrose consumption. In the present study, we investigated the acute metabolism of the monosaccharide components of sucrose in the resting postprandial state to test the hypothesis that there is differential fuel selection between glucose and fructose when they are consumed as part of a sucrose-rich meal. Comparisons were made with a high-starch test meal.

SUBJECTS AND METHODS  
Subjects
Seven healthy, weight-stable male volunteers were recruited from the students and staff of the University of Newcastle upon Tyne and the staff of the Royal Victoria Infirmary, Newcastle upon Tyne. None had diabetes mellitus (or a first-degree relative with diabetes), ischemic heart disease, hypertension, or any other disease associated with altered insulin sensitivity. None were taking any drugs known to alter insulin sensitivity or affect carbohydrate or lipid metabolism. All were nonsmokers and had a habitual alcohol intake of <21 units/wk (1 unit = 8 g alcohol; 24).

The experimental protocol was approved by the Joint Ethics Committees of the Newcastle and North Tyneside Health Authorities, the University of Newcastle upon Tyne, and the University of Northumbria at Newcastle. Each subject gave informed, written consent. All studies were conducted in the Human Diabetes and Metabolism Research Centre, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.

Experimental protocol
Each subject took part in 3 experimental sessions according to a randomized, crossover design. Subjects were admitted at 0700 after they had fasted since 2200 the previous evening. Alcohol and strenuous exercise were avoided for 24 h before each experimental session. Subjects consumed high-sucrose test meals on 2 occasions and a high-starch test meal on 1 occasion. A combination of techniques that involved stable isotopes and indirect calorimetry was used to determine fuel selection and substrate oxidation. Concentrations of blood glucose, serum insulin, plasma fatty acids, serum triacylglycerols, and other blood metabolites (pyruvate, lactate, glycerol, and hydroxybutyrate) were measured frequently. Subjects recorded their food intake for the 24-h period before the first experiment and were asked to repeat that food intake pattern for the 24 h before each subsequent experiment. Each study period was separated from the next by 1 wk of washout.

Anthropometry
Percentage body fat was calculated with the equations of Siri (25) by using estimates of body density. These estimates were derived from skinfold-thickness measurements (Holtain/Tanner-Whitehouse skinfold caliper; Holtain, Crosswell, United Kingdom) taken at 4 separate sites (26).

Assessment of fuel selection
Indirect calorimetry
Carbon dioxide production (O₂) were measured with a Deltatrac Indirect Calorimeter (Datex Instrumentarium Corporation, Helsinki) that had a ventilated, transparent hood system. Five measurements (1 basal and 4 postprandial), each of 20 min duration, were made during each experimental period. Urine was also collected during each 6-h experimental period, and urinary nitrogen excretion was measured by the Kjeldahl method (Kjeltec Analyzer; Perstorp Analytic Ltd, Perstorp, Sweden). Carbohydrate and lipid oxidation rates were calculated by using de Weir's equations (27) as follows:

RESULTS  
Subject characteristics
Our subjects were a group of healthy men with a wide age range (22–68 y). Their mean BMI (in kg/m²) was within the normal range, but their mean percentage body fat (21%) was relatively high (Table 3). The habitual dietary intake data suggested that mean consumption of carbohydrates was higher and that of fats was lower (Table 4) than intakes reported for the adult population of the United Kingdom (21).

View this table:
TABLE 3.. Characteristics of the volunteers¹  

View this table:
TABLE 4.. Habitual daily energy and nutrient intakes of the volunteers¹  
Fuel selection
The carbohydrate and lipid oxidation rates estimated from indirect calorimetry after the test meals are summarized in Figures 1 and 2, respectively. To obtain the high-sucrose-meal values, we used the means of the values for the 2 high-sucrose meals. After the high-sucrose meals were consumed, there was a marked increase in carbohydrate oxidation, with a corresponding decline in lipid oxidation; the latter remained suppressed until 150 min after the meal. Thereafter, both the lipid and the carbohydrate oxidation rates returned to fasting values. After the high-starch meal, there was a smaller and more delayed increase in the carbohydrate oxidation rate, mirrored by a smaller and more delayed decrease in the lipid oxidation rate.

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FIGURE 1. . Mean (±SEM) total carbohydrate oxidation rate assessed by indirect calorimetry data. n = 7.

 

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FIGURE 2. . Mean (±SEM) total lipid oxidation rate assessed by indirect calorimetry data. n = 7.

 
The enrichment of breath carbon dioxide increased much more rapidly and to a higher peak after the [¹³C]fructose-labeled high-sucrose meal than after the other test meals (Figure 3). ¹³C labeling of breath carbon dioxide was slower and peaked much later when the labeled glucose accompanied the sucrose-rich meal than when it accompanied the starch-rich meal. In all cases, breath carbon dioxide enrichment remained substantially elevated above background levels 6 h after the test meals, a time when rates of oxidation for carbohydrate and lipids had returned to fasting values. In comparisons of the enrichment of carbon dioxide from the labeled glucose after the high-starch and high-sucrose meals, note that the 200 mg of tracer was in a larger pool of glucose with the high-starch meal than with the high-sucrose meal. This effect is accounted for in Figure 4, in which we showed the rate of carbohydrate oxidation derived from the stable-isotope measurements. These values were calculated from the enrichment values of breath carbon dioxide in atoms percent excess, the CO₂ data, the quantity of isotope administered, and the carbohydrate contents of the meals. Separate oxidation rates for the fructose and glucose moieties and for total carbohydrate (glucose plus fructose) in the high-sucrose test meals are shown in Figure 4, as is the glucose oxidation rate after the high-starch meal. Fructose was oxidized much more rapidly than glucose after the high-sucrose meals. The curve representing glucose oxidation after the high-starch meal was higher than that for the individual monosaccharides in the high-sucrose meals, which was expected given the greater quantity of glucose supplied by the high-starch meal. However, the overall carbohydrate oxidation rate after the high-sucrose meals was higher than the glucose oxidation rate after the high-starch meal, which is consistent with the indirect calorimetry data (Figure 1
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FIGURE 3. . Mean (±SEM) breath ¹³CO₂ enrichment after consumption of the test meals. n = 7.

 

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FIGURE 4. . Mean (±SEM) oxidation rate of exogenously supplied carbohydrate after consumption of the test meals. n = 7.

 
Metabolic profiles
The glycemic profiles for the 2 test meals were quite different (Figure 5). There was a more rapid rise in blood glucose concentration after the high-sucrose meal than after the high-starch meal, to a slightly higher (NS) peak value. Blood glucose concentrations dropped more rapidly to a lower value after the high-sucrose meal than after the high-starch meal. Postprandial blood glucose concentrations after the first 75 min were maintained at higher values after the high-starch meal than after the high-sucrose meal. Similarly, after the high-sucrose meal there was a higher (NS) peak in serum insulin concentration, which then tended to be lower during the final 3 h of the experimental period.

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FIGURE 5. . Mean (±SEM) plasma glucose and serum insulin concentrations after consumption of the test meals. n = 7.

 
Plasma fatty acid concentrations fell rapidly after both meals (Figure 6) and remained below fasting concentrations throughout the postprandial period after the high-starch meal. In contrast, after the high-sucrose meal, plasma fatty acid concentrations began to rise at 150 min and returned to premeal values by the end of the measurement period. Pyruvate and lactate concentrations in whole blood rose more rapidly and to much higher peaks after the high-sucrose meal than after the high-starch meal (Figure 7). After both test meals, concentrations of both metabolites returned to fasting values by the end of the study.

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FIGURE 6. . Mean (±SEM) plasma fatty acid concentrations after consumption of the test meals. n = 7.

 

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FIGURE 7. . Mean (±SEM) pyruvate and lactate concentrations in whole blood after consumption of the test meals. n = 7.

 

DISCUSSION  
The health effects of fructose and sucrose are of considerable interest for several reasons. It is thought that the fructose component causes most of the characteristic metabolic effects of high-sucrose diets (ie, those not shared by high-starch diets), whether these effects occur acutely after consumption of a meal or with longer-term exposure to a sucrose-rich diet (13). However, there has been a paucity of research on the effects of dietary sucrose on tissue fuel selection and on how the 2 constituent monosaccharides (glucose and fructose) are metabolized relative to each other. The main purpose of this study was to compare the metabolism of glucose and fructose after a high-sucrose meal, with the metabolism of glucose after a starch-rich meal as a reference point.

Clearly, under these conditions, fructose is oxidized more rapidly than is glucose (Figure 3). This is not unexpected given what is understood about its metabolic fate. Only small amounts of fructose are found in the peripheral blood after sucrose or fructose ingestion because absorbed fructose is predominantly taken up by the liver. The rapid metabolism of fructose may be explained in part by the fact that it bypasses one of the key regulatory enzymes in glycolysis, 6-phosphofructokinase. Fructose enters glycolysis after phosphorylation to fructose-1-phosphate, a reaction that is mediated by hepatic fructokinase. Fructose-1-phosphate stimulates pyruvate kinase, which explains the high concentrations of pyruvate and consequently lactate after fructose ingestion; research by Brundin and Wahren (17) supports this. They found much greater lactate and pyruvate concentrations after human volunteers consumed a 75-g fructose load than after they consumed a 75-g glucose load. Our use of [¹³C]glucose and [¹³C]fructose in separate but otherwise identical high-sucrose test meals enabled us to investigate both constituents of sucrose. Despite the rapid increase in carbohydrate oxidation rate after the high-sucrose test meals, glucose was oxidized much more slowly than was fructose and was also oxidized more slowly than was the labeled glucose in the high-starch test meal (Figures 3 and 4).

Quantitative interpretation of the isotopic-tracer studies is based on several assumptions. The first assumption is that the amount of ¹³C in breath carbon dioxide above fasting amounts was derived from the oxidation of the administered dose of [¹³C]glucose or [¹³C]fructose. Our gas chromatography–IRMS measurements showed that the other constituents of the test meals contributed <3% of the excess ¹³C. The second assumption is that the enrichment of breath carbon dioxide in the fasting period (before the test meal) is a reliable estimate of the enrichment of carbon from oxidation of exogenous materials throughout the study. In theory, this assumption might present a problem if the enrichments of body stores of fat and carbohydrate were markedly different and if there was a major shift in the proportion of each that was oxidized in response to the test meal. However, background enrichments are relatively low in European subjects, so this potential problem is likely to have little or no effect (35).

The third assumption is that oxidation of [¹³C]carbohydrate can be quantified on the basis of enrichment of breath ¹³CO₂. Carbon dioxide produced as the end product of oxidation reactions is in equilibrium with the body's bicarbonate pool and a considerable proportion (50%) of label administered as bicarbonate (36) can be sequestered in the body during the time course of a study. Provided that the size of the bicarbonate pool was similar for all treatments, such sequestration would not be expected to alter the conclusions drawn about differences among the treatments in our study. This assumption would be true for both sucrose-rich meals, and therefore the comparison of oxidation rates for the glucose and fructose moieties of this disaccharide is not affected.

The greater rise in blood lactate concentrations after the high-sucrose meal than after the high-starch meal requires further consideration. An increase in blood lactate concentration tends to lower the pH. This in turn tends to decrease both the size of the bicarbonate pool and the amount of ¹³CO₂ being sequestered. This would lead to a higher estimate of carbohydrate oxidation. If this was quantitatively important in the present study, it would mean that the actual rate of glucose oxidation for glucose derived from sucrose would be even lower with respect to the rate of glucose oxidation for glucose derived from starch than is apparent from Figures 3 and 4 for the early and mid-postprandial phases.

In conclusion, this study showed that the fructose component of sucrose is oxidized much more rapidly than is the glucose component after a high-sucrose meal and that glucose is oxidized more rapidly after a high-starch meal than after a high-sucrose meal. Thus, fructose may have a sparing effect on oxidation of exogenously supplied glucose. These differences in fuel selection help explain the metabolic changes that accompany consumption of these 2 major dietary carbohydrates.

ACKNOWLEDGMENTS  
We are grateful to Lesley Morrison and Linda Ashworth for their hard work in the laboratory and to Sister Mavis Brown for her nursing assistance.

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