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Have the fructose alarm bells rang too soon?

Fructose is both highly controversial and highly researched. Yet until this recent trial, it hadn’t been compared to other sugars for inflammation and intestinal impacts.

Study under review: No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial

Introduction

Consumption of sugar-sweetened beverages (SSBs) has been associated with increased risk of heart disease[1], type 2 diabetes, and metabolic syndrome[2]. These associations may be due to increased body fat, but have also been hypothesized to occur through mechanisms unrelated to body composition, such as chronic low-grade inflammation[3].

Table sugar is a disaccharide (two simple sugars linked chemically) made up of equal parts glucose and fructose. High-fructose corn syrup (HFCS) is just slightly different in composition compared to sugar, containing 55% fructose, 41% glucose, and 4% other saccharides. It’s been theorized that the fructose component may be disproportionately responsible for the associations seen between SSB intake and risk factors for chronic inflammation[4], abnormal blood lipid values[5], and decreased insulin sensitivity[6]. Metabolic comparisons to alcohol[7] consumption have also been made to fructose.

There are multiple mechanisms to explain why fructose might be more problematic compared to the consumption of an equivalent amount of glucose, some of which are summarized in Figure 1. Studies in mice have suggested that consumption of fructose can trigger hepatic and systemic inflammation via increased intestinal permeability and the translocation of endotoxin[8] from the gut and into circulation. An increase in de novo lipogenesis (the body’s synthesis of fatty acids) has also been observed[9] when substituting liquid fructose in place of solid carbohydrate foods, which can increase production of fetuin-A (a protein secreted by the liver and adipose tissue) and in turn lead to increased activity of inflammatory pathways[10] in adipose tissue.

Figure 1: The hypothetical mechanism that motivated this paper

To further examine the links between the types of carbohydrate consumed and their effects on inflammation and intestinal permeability, researchers set out to compare the effects of consuming beverages sweetened with fructose, HFCS, or glucose for eight days. This study warrants interest for a number of reasons: 1) researchers recruited human participants, 2) it is a randomized controlled trial rather than observational, 3) it attempted to keep bodyweight stable to determine whether fructose is inflammatory in the absence of major bodyweight changes, and 4) it looked specifically at adipose tissue inflammation, which is hypothesized to have a particularly important link with metabolic dysfunction.

Sugar-sweetened beverages are associated with chronic inflammation, which can be related to increased risks for diabetes and heart disease. Researchers compared the metabolic effects of beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose on markers of systemic and adipose tissue inflammation as well as intestinal permeability.

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