Abstract
Whether dietary fructose (as sucrose or high fructose corn syrup) has unique effects separate from its role as carbohydrate, or, in fact, whether it can be considered inherently harmful, even a toxin, has assumed prominence in nutrition. Much of the popular and scientific media have already decided against fructose and calls for regulation and taxation come from many quarters. There are conflicting data, however. Outcomes attributed to fructose — obesity, high triglycerides and other features of metabolic syndrome — are not found in every experimental test and may be more reliably caused by increased total carbohydrate. In this review, we try to put fructose in perspective by looking at the basic metabolic reactions. We conclude that fructose is best understood as part of carbohydrate metabolism. The pathways of fructose and glucose metabolism converge at the level of the triose-phosphates and, therefore, any downstream effects also occur with glucose. In addition, a substantial part of ingested fructose is turned to glucose. Regulation of fructose metabolism per se, is at the level of substrate control — the lower Km of fructokinase compared to glucokinase will affect the population of triose-phosphates. Generally deleterious effects of administering fructose alone suggest that fructose metabolism is normally controlled in part by glucose. Because the mechanisms of fructose effects are largely those of a carbohydrate, one has to ask what the proper control should be for experiments that compare fructose to glucose. In fact, there is a large literature showing benefits in replacing total carbohydrate with other nutrients, usually fat, and such experiments sensibly constitute the proper control for comparisons of the two sugars. In terms of public health, a rush to judgement analogous to the fat-cholesterol-heart story, is likely to have unpredictable outcome and unintended consequences. Popular opinion cannot be ignored in this problem and comparing fructose to ethanol, for example, is without biochemical correlates. Also, nothing in the biochemistry suggests that sugar is a toxin. Dietary carbohydrate restriction remains the best strategy for obesity, diabetes and metabolic syndrome. The specific contribution of the removal of fructose or sucrose to this effect remains unknown.
Highlights
Fructose (as sucrose or high fructose corn syrup (HFCS)) has become an obsession in nutrition
From a public health standpoint, the scarcity of studies showing significant improvement of metabolic abnormalities by specific reduction in dietary sucrose or fructose is of concern since that is being recommended for the population at large
There are clearly specific effects of fructose but we emphasize that these must be rationalized in the face of the continuum between fructose and glucose metabolism
Summary
Fructose (as sucrose or high fructose corn syrup (HFCS)) has become an obsession in nutrition. The results conformed to an operational definition of insulin resistance, Dirlewanger, et al [31] provided an explanation of the results which seems like a normal response to the experimental conditions and which would be consistent with the mechanism in Figure 1: the effective hepatic glucose concentration is very much higher in the fructose group due to the extensive gluconeogenesis This will lead to enhanced total glucose output despite the high insulin concentration, an insulin concentration that was able to repress output in the glucose-alone controls. Of 18 relevant studies, she considered that only 8 met the criteria of 1) sufficient dietary and experimental control, 2) glucose or starch for comparison; and 3) had limited heterogeneity present in the study population Of these 8, half showed no change in plasma TAG while one found no change in a normal group but an increase in Figure 6 Comparative effects of fructose-sweetened (red) and glucose-sweetened beverages (blue). The presence of fructose tends to increase the levels of plasma lactate but, generally, differences between dietary glucose vs. fructose + glucose tends to become smaller and, as in other conditions, fructose alone is not desirable [43]
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