Methodological problems invalidate sugars differences

In a recent paper, Le et al. (1) reported finding differences between the two most commonly used sweeteners in the US, concluding that “compared with sucrose, HFCS [high fructose corn syrup] leads to greater fructose systemic exposure and significantly different acute metabolic effects.” Evidence in support of this conclusion was unconvincing, however, due to significant deficiencies in the experimental design.

First, this was not a comparison of HFCS and sucrose as advertised, but rather a comparison of HFCS and an inconsistent mix of sugars that ranged from 20% sucrose at the start of the study to 0% sucrose at the end (Table 1). Furthermore, the 16% and 12% loss of total sugars over the course of the study in the sucrose and HFCS soft drink variables, respectively, was both significant and not addressed by the authors (Table 1). This variability in sugars composition and concentration over the course of the study could well account for the reported differences in metabolic effects, and effectively nullifies the study conclusions.

Second, the experimental design did not reflect how humans typically consume soft drinks and sugars, and served to exaggerate any existing effects. Soft drinks were administered in large bolus form (24-oz; 300 kcal) to subjects fasted a minimum of 8-h overnight and given no other caloric intake over the course of the 6-h study. While soft drinks are occasionally consumed alone, they are frequently accompanied by foods containing nutrients that can appreciably influence human metabolism.

Third, despite these experimental irregularities, the fasting response parameters in Table 3 from HFCS and sucrose variables were all within the normal human range (2). The small differences observed were, therefore, of questionable clinical significance.

And fourth, the authors’ claim that the increasing frequency of a number of important health disorders is correlated with increased fructose use ignores current consumption trends. In fact, there has been no correlation for more than a decade, since use of HFCS (with sucrose, one of the major sources of added fructose) began to decline in 1999.

The methodological inconsistencies and irregularities in this study invalidate the authors’ conclusion about differences between HFCS and sucrose, and fail to challenge recent literature that supports metabolic similarities between HFCS and sucrose (3-5) and a rational role for fructose at typical human exposures (6-8).

1. Le MT, Frye RF, Rivard CJ, Cheng J, McFann KK, Segal MS, Johnson RJ, Johnson JA. Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects. Metabolism. 2011 Dec 5.
2. Merck Laboratories. The Merck manual of diagnosis and therapy. 19th ed. Whitehouse, N.J.: Merck Sharp & Dohme Corp.; 2011.
3. Soenen S, Westerterp-Plantenga MS. No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. Am J Clin Nutr. 2007 Dec;86:1586-94.
4. Melanson KJ, Zukley L, Lowndes J, Nguyen V, Angelopoulos TJ, Rippe JM. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Nutrition. 2007 Feb;23:103-12.
5. Stanhope KL, Griffen SC, Bair BR, Swarbrick MM, Keim NL, Havel PJ. Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am J Clin Nutr. 2008 May;87:1194-203.
6. Dolan LC, Potter SM, Burdock GA. Evidence-based review on the effect of normal dietary consumption of fructose on development of hyperlipidemia and obesity in healthy, normal weight individuals. Crit Rev Food Sci Nutr. 2010 Jan;50:53-84.
7. Dolan LC, Potter SM, Burdock GA. Evidence-based review on the effect of normal dietary consumption of fructose on blood lipids and body weight of overweight and obese individuals. Crit Rev Food Sci Nutr. 2010 Nov;50:889-918.
8. Livesey G. Fructose ingestion: dose-dependent responses in health research. J Nutr. 2009 Jun;139:1246S-52S.