Consumption of added sugar has increased over recent decades and is correlated with numerous diseases. Rodent models have elucidated mechanisms of toxicity, but only at concentrations beyond typical human exposure. Here we show that comparatively low levels of added sugar consumption have substantial negative effects on mouse survival, competitive ability, and reproduction. Using Organismal Performance Assays (OPAs) – in which mice fed human-relevant concentrations of added sugar (25% Kcal from a mixture of fructose and glucose [F/G]) and control mice compete in seminatural enclosures for territories, resources and mates – we demonstrate that F/G-fed females experience a two-fold increase in mortality while F/G-fed males control 26% fewer territories and produce 25% less offspring. These findings represent the lowest level of sugar consumption shown to adversely affect mammalian health. Clinical defects of F/G-fed mice were decreased glucose clearance and increased fasting cholesterol. Our data highlight that physiological adversity can exist when clinical disruptions are minor, and suggest that OPAs represent a promising technique for unmasking negative effects of toxicants.

This study provides experimental evidence that the consumption of human-relevant levels of F/G is more deleterious than an isocaloric amount of sucrose for key organism-level health measures in female mice.

The ultimate function of an organism’s physiology is the performance of complex behaviors that facilitate reproduction. Here we use Organismal Performance Assays (OPAs) to quantify declines in Darwinian fitness of house mice due to experimental exposures. OPAs are sensitive phenotyping approaches that use semi‐natural conditions to challenge the physiology of differentially treated animals in direct competition with each other. Using OPAs we demonstrated that consumption of human‐relevant levels of added sugar (25% kcal) decreases reproduction of male mice by 25% while doubling the mortality rate of females relative to starch‐fed controls. Furthermore, we showed that many clinical measures associated with proximate effects of added sugar consumption were not predictive of organismal‐level effects. We expand upon these studies by using OPAs to test for differential health consequences of the two most common forms of added sugar. We report that females fed a diet containing an equal ratio of fructose and glucose monosaccharides (modeling high fructose corn syrup; HFCS) experienced a mortality rate 1.9 times higher and produced 26% fewer offspring than those fed sucrose (fructose‐glucose disaccharide). This experiment provides evidence that fructose and glucose monosaccharides (HFCS) are more deleterious to mammalian health than isocaloric sucrose. Grant Funding Source: Supported by NIH and NSF

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