Conventional energy-restricted diets have very poor long-term outcomes with regard to weight loss (4
), possibly because these diets elicit changes in hunger and metabolism that promote weight regain (5
). The results of the present study suggest that dietary composition can modify the physiologic adaptations to energy restriction, which might have relevance to the design of novel dietary treatments for obesity.
Weight loss did not differ significantly between the high-GI diet and the low-GI diet, as would be expected from the identical energy contents of the diets. However, serum leptin decreased to a greater extent with the low-GI diet. This difference may be explained by the lower insulin concentrations associated with this diet, because insulin is a leptin secretagogue (31
), or by decreased adipocyte glucose metabolism (33
). This observation is consistent with that of Jenkins et al (34
), who showed a positive association between carbohydrate consumption and leptin concentration during energy restriction. Interestingly, the lower leptin concentration with the low-GI diet occurred without evidence of increased hunger (ad libitum food intake was actually lower with this diet), suggesting a functional improvement in the leptin resistance associated with obesity (35
). Further investigation into the significance of this phenomenon is warranted.
REE decreased to a lesser extent with the low-GI than with the high-GI diet. Consistent with this finding, Whitehead et al (37
) showed that sleeping metabolic rate fell less rapidly with a high-protein than a low-protein energy-restricted diet. In the present study, the low-GI diet did contain more protein than did the high-GI diet. We note, however, that the present results were not caused by the increased thermic effect of protein relative to that of the other macronutrients because metabolic rate was measured 10 h after the last meal. The preservation of REE during energy restriction with the low-GI diet, together with the differences in voluntary food intake and satiety shown by us and others (21
), suggests that low-GI diets may be better tolerated than high-GI diets.
Although both diets were protein sufficient (the average subject received 56 or 100 g protein/d), analysis of nitrogen balance suggested that fat tissue was oxidized to a lesser degree, and muscle to a greater degree, with the high-GI than the low-GI diet. This finding is consistent with that of Pasquali et al (38
), who observed a more negative nitrogen balance with an isoenergetic, very-low-energy diet with a high carbohydrate-to-protein ratio than with a diet with a low carbohydrate-to-protein ratio. The possible adverse effects of the high-GI diet on body composition can be explained by hormonal responses to meals with different GIs (26
). Consumption of a high-GI meal results in relatively high insulin concentrations and low glucagon concentrations. This hormonal response tends to promote uptake of glucose and triacylglycerol in the liver and adipose tissue, limit glycogenolysis and lipolysis, and, therefore, suppress concentrations of glucose and fatty acids in the postabsorptive period. The low circulating concentrations of these major metabolic fuels elicit marked increases in the counterregulatory hormones, some of which have proteolytic actions (39
). Thus, decreased mobilization of the primary metabolic fuels with high-GI, energy-restricted diets may induce a series of physiologic events that favor catabolism of lean body tissue.
Two methodologic issues should be discussed. First, although the formula used for calculating nitrogen balance was validated across a variety of dietary conditions (30
), the possibility remains that greater delivery of nutrients to the lower digestive tract with the low-GI than with the high-GI diet led to increased nitrogen trapping by colonic bacteria. If this were the case, we may have overestimated nitrogen balance with the low-GI diet. This possibility should be addressed in future studies. Second, previous studies by us and others sought to examine the hormonal and metabolic effects of dietary GI while controlling for other potentially confounding variables, such as macronutrient composition (21
). However, GI is a complex dietary component that is affected by other factors, including protein and fat (15
). Thus, one cannot simultaneously obtain maximum differences in GI and control for confounding variables. We chose to maximize differences between treatment groups because of the relative inaccuracy and imprecision of measuring metabolic rate compared with measuring hormone concentration. We believed that it would be difficult to show significant differences in resting metabolic rate in a relatively brief study using a small number of subjects without varying macronutrients. Therefore, our results cannot be definitively attributed solely to GI. Nevertheless, these results do suggest that the adaptations to energy restriction can be modified by dietary composition. Moreover, the findings are consistent with the possibility that the increased availability of metabolic fuels with a low-GI diet (26
) improves tolerance to energy restriction.
In summary, this study showed beneficial effects of a low-GI, medium-fat diet compared with a high-GI, low-fat diet that accorded with current nutritional recommendations. This finding suggests that the hormonal and metabolic responses to energy restriction—involving leptin concentrations, energy expenditure, voluntary food intake, and nitrogen balance—can be affected by dietary composition. Additional research is needed to confirm these results in other populations and over a longer period, to determine which specific dietary factors mediate these physiologic events, and to examine the long-term effects of GI on the regulation of body weight.