On 2013 Dec 02, Kenneth N Litwak commented:

This study, by Ruff et al, attempted to demonstrate negative effects of excess sugar consumption on mouse survival, competitive ability, and reproduction, as a means of demonstrating the utility of Organismal Performance Assays (OPAs) in quantifying toxicities. However, there are multiple methodological issues in the article affecting its value.<br> 1. In the discussion, the authors state that the diet was “analogous to human subjects consuming a healthy diet plus the equivalent of ~3 cans of soda per day”. This statement does not correctly reflect the study diet vs. control diet, as the two diets were isocaloric. Adding 3 cans of soda to the diet would add additional calories to a diet, not replace a source of carbohydrates.<br> 2. The authors correctly noted that this experiment would have ideally maintained the different groups on their original diets for duration of the study; however, all mice were given the F/G diet once they entered the OPA enclosures at 26 weeks of age and for the next 7 – 8 months. This change in diet is a major confounding point of the entire experiment. It might be reasonably assumed that initial outcomes in the OPA enclosures would be due to different diets, but the authors do not provide any data to support this premise, for initial or long-term outcomes.<br> 3. Mouse pups were only counted every six week to determine reproductive success (Methods). The long duration between counts would likely result in an under-count of reproductive success, as cannibalism and early pup death would be difficult to determine. Further, the duration between counts was sufficient to allow multiple litters to be born to founder mice and to F1 mice.<br> 4. The confounding effects of the OPA enclosures and their locations (Supplementary Figure S3) are potentially significant. Each enclosure was immediately adjacent to others. However, some enclosures were only bounded by two enclosures, while some were bounded on three sides by other enclosures. Stress associated with territorial boundaries has been repeatedly documented in mice. Due to the small size of this study, the potential space interaction could have had significant effects on the outcomes.

On 2013 Dec 02, Kenneth N Litwak commented:

This study, by Ruff et al, attempted to demonstrate negative effects of excess sugar consumption on mouse survival, competitive ability, and reproduction, as a means of demonstrating the utility of Organismal Performance Assays (OPAs) in quantifying toxicities. However, there are multiple methodological issues in the article affecting its value.<br> 1. In the discussion, the authors state that the diet was “analogous to human subjects consuming a healthy diet plus the equivalent of ~3 cans of soda per day”. This statement does not correctly reflect the study diet vs. control diet, as the two diets were isocaloric. Adding 3 cans of soda to the diet would add additional calories to a diet, not replace a source of carbohydrates.<br> 2. The authors correctly noted that this experiment would have ideally maintained the different groups on their original diets for duration of the study; however, all mice were given the F/G diet once they entered the OPA enclosures at 26 weeks of age and for the next 7 – 8 months. This change in diet is a major confounding point of the entire experiment. It might be reasonably assumed that initial outcomes in the OPA enclosures would be due to different diets, but the authors do not provide any data to support this premise, for initial or long-term outcomes.<br> 3. Mouse pups were only counted every six week to determine reproductive success (Methods). The long duration between counts would likely result in an under-count of reproductive success, as cannibalism and early pup death would be difficult to determine. Further, the duration between counts was sufficient to allow multiple litters to be born to founder mice and to F1 mice.<br> 4. The confounding effects of the OPA enclosures and their locations (Supplementary Figure S3) are potentially significant. Each enclosure was immediately adjacent to others. However, some enclosures were only bounded by two enclosures, while some were bounded on three sides by other enclosures. Stress associated with territorial boundaries has been repeatedly documented in mice. Due to the small size of this study, the potential space interaction could have had significant effects on the outcomes.