Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women

Abstract

Objective

Fructose has been implicated in obesity, partly due to lack of insulin-mediated leptin stimulation and ghrelin suppression. Most work has examined effects of pure fructose, rather than high-fructose corn syrup (HFCS), the most commonly consumed form of fructose. This study examined effects of beverages sweetened with HFCS or sucrose (Suc), when consumed with mixed meals, on blood glucose, insulin, leptin, ghrelin, and appetite.

Methods

Thirty lean women were studied on two randomized 2-d visits during which HFCS- and Suc-sweetened beverages were consumed as 30% of energy on isocaloric diets during day 1 while blood was sampled. On day 2, food was eaten ad libitum. Subjects rated appetite at designated times throughout visits.

Results

No significant differences between the two sweeteners were seen in fasting plasma glucose, insulin, leptin, and ghrelin (P > 0.05). The within-day variation in all four items was not different between the two visits (P > 0.05). Net areas under the curve were similar for glucose, insulin, and leptin (P > 0.05). There were no differences in energy or macronutrient intake on day 2. The only appetite variable that differed between sweeteners was desire to eat, which had a higher area under the curve the day after Suc compared with HFCS.

Conclusion

These short-term results suggest that, when fructose is consumed in the form of HFCS, the measured metabolic responses do not differ from Suc in lean women. Further research is required to examine appetite responses and to determine if these findings hold true for obese individuals, males, or longer periods.

Introduction

The consumption of total sugars has increased significantly in the past 30 y in the United States, with shifts in the sources of sweeteners [1], [2]. Before the mid-1960s carbonated soft drinks (CSDs) were largely sweetened with sucrose (Suc; 50% glucose and 50% fructose), but currently the leading source of fructose in the diet in the United States is high-fructose corn syrup (HFCS). HFCS-55 used in CSDs contains 55% fructose and 42% glucose [2]. It has been argued that increased consumption of fructose in the diet may be a contributing factor to the dramatic increase in obesity in the United States and other developed countries, because fructose does not stimulate the production and secretion of insulin [3], [4].

A role for insulin in the regulation of energy balance and adiposity was postulated in the early 1970s [5], and since this time considerable evidence has supported this hypothesis. Insulin may influence energy balance through direct actions on the central nervous system that regulate energy intake [6], [7] and through its influence on leptin. Insulin-mediated glucose uptake and metabolism in adipose tissue plays a key regulatory role in leptin concentrations [8], [9]. Leptin, whose diurnal patterns have been shown to be regulated by insulin [10], is recognized as a medium- to long-term regulator of energy balance through its effects on reducing energy intake and stimulating energy expenditure [11]. Deficits in leptin production have been demonstrated to be associated with increased body adiposity in humans [10], [12].

Blood glucose, insulin, and leptin tend to be inversely related to circulating ghrelin in the fasting [13] and fed [14], [15], [16] states. Ghrelin, an orexigenic hormone secreted from the enteroendocrine cells of the stomach, is implicated in short-term hunger, food intake, and body weight [17], [18], [19], [20]. Ghrelin administration in rodents leads to increased food intake and body weight, and in humans it has been shown to increase food intake [17], [21]. Circulating ghrelin is highest in humans in the fasting state, shows premeal increases that are associated with hunger and meal initiation, and is suppressed upon food ingestion [18], [21], [22]. Carbohydrate-rich meals have been shown to suppress ghrelin and associated subjective hunger more so than fat-rich meals [22], [23], which is likely due to effects on glycemia and possibly insulinemia [10], [15].

Fructose, unlike glucose, does not stimulate insulin secretion from the pancreatic B cells [24], [25]. In a recent study, fructose, consumed with mixed meals, was shown to result in decreased circulating insulin and leptin and to attenuate postprandial suppression of ghrelin in women as compared with dietary glucose [16]. It was concluded that the differential effect of fructose on energy regulatory systems compared with glucose might contribute to increased caloric intake and ultimately contribute to weight gain and obesity during long-term consumption of a diet high in fructose [16]. However, pure fructose and glucose are not commonly consumed, as are Suc and HFCS. Based on these findings [16] and the fact that Suc has been replaced by HFCS to a large extent over the past 40 y, the primary objective of the present study was to compare the effects of HFCS with the effects of Suc on endocrine systems associated with energy balance, including insulin, leptin, and ghrelin, and with appetite through subjective ratings and ad libitum consumption. The aim was to investigate whether HFCS may have more deleterious effects on measured indicators of energy balance control as compared with Suc.