Misinterpretation and Mousetraps: Breaking Down the Latest Sugars Study

Highlights: 

•    Researchers' latest conclusions about added sugars come from mice. Mice are not humans.

•    Regardless of media quotes you may hear, the study did not assess the impact of different added sugars on gut bacteria.

•    Regardless of source of sugars, the study observed no difference in daily food intake or weight gain in male mice.

The latest study examining the health effects of sugars has dangled another piece of cheese in front of us. Will you bite?

This week, researchers at the University of Utah published a study in The Journal of Nutrition claiming that High-Fructose Corn Syrup (HFCS) is more “toxic” than sucrose. Many in the media have bitten, but we can avoid getting stuck in another mousetrap of misinterpreting scientific research findings. 

First let’s be clear, researchers completed this study in mice. Not humans—mice. Second, the study was not a randomized clinical control trial (the gold standard). It was a dietary intervention study.

The study examined the impact of having mice consume 25% of their total calories from added sugars. (They compared fructose and glucose monosaccharides versus sucrose—a disaccharide). This level of added sugars intake was selected because it was seen as being more relevant to humans; it reflects the amount of calories from added sugars for the 13–25% of Americans who consume them most heavily.

In the end, researchers observed higher mortality and lower levels of reproduction in female mice. These negative effects were only present in female mice. Researchers “found no differences in survival, reproduction or territoriality of male mice.” Yet the authors state in their press release that this “may be because both sugars are equally toxic to male mice.” 

Some media (and the press release) have devoted attention to the possibility of sugars’ effect on gut bacteria. The authors state, “So we speculate that the different sugars could favor different microbes in the guts of mice. Other research has shown differences in bacterial communities in the gut to be associated with metabolic diseases in rodents and in humans. It’s possible one form of sugar causes more bacteria to get across your gut than another.” (Emphasis added)

“It's always important to think critically when reading scientific studies in the popular press,” said Kris Sollid, RD, at the International Food Information Council (IFIC) and IFIC Foundation. “Does the piece you’re reading report the study accurately? The only way to know for sure is to read the study—and how many people take the time to do that?” he said.

Take this study, for example. Curiously, an assessment of whether sucrose or fructose or glucose monosaccharides are “equally toxic” to male mice is not undertaken. Neither are the potential differing effects of individual added sugars on gut bacteria. Yet, these are the statements and headlines that get put out for public consumption.

John Sievenpiper, MD, PhD, FRCPC, Associate Professor in the Department of Nutritional Sciences at the University of Toronto offered this take on the study: “It is yet another example of distortion by the media (and the authors through their press release) of low quality animal evidence,” he told us. “The highest level of evidence from randomized controlled trials consistently shows that there are no material differences between HFCS and sucrose in humans.”

A detailed review of the study comes from Megan Meyer, Microbiology and Immunology Doctoral Student at the University of North Carolina at Chapel Hill:

What’s in sugar? Recent study explores impact of added sugar on mouse health outcomes 

Nutrition experts have long debated whether increased added sugar intake contributes to obesity or chronic diseases. Further, many experts have investigated the similarities and differences between the various types of added sugars. The most common types of added sugars found in the American diet include sucrose (a fructose and glucose disaccharide) and high-fructose corn syrup (a fructose and glucose monosaccharide). For a comprehensive summary detailing the differences among added sugars, see the FoodInsight’s Q&A about Added Sugar and series on The Science of Sugars. 

Some speculate that the difference in sugar structure causes adverse health effects. Others hypothesize that the fructose component of added sugar negatively impacts health outcomes since fructose is predominately metabolized in the liver and does not need insulin for metabolism. As such, we need investigative studies to compare the effects of different added sugars on health outcomes. This most recent study has received attention from the media, but what is the verdict of the study? Was the research conducted in a scientifically sound manner? With the IFIC Foundation Study Evaluation Checklist, we've evaluated the hypothesis, design, methods, and analyses to help critically weigh the results and conclusions of the study.  
 

Q1. Do the title and abstract reflect the study?
Yes / No. View Results Skeptically.
A1. Yes. The title describes the main findings of the study, and the abstract succinctly details the background, objectives, methods, results, and conclusions. 
 
 

Q2. Is the study useful, novel, and/or relevant to humans?

Yes / No. View Results Skeptically.

A2. No. The study assessed the differences in survival and fitness in mice fed diets in which 25% of the calories were derived from an equal ratio of fructose/glucose (F/G) or an isocaloric amount of sucrose. Since Ruff et al. chose to use the sugar content for which, at most 25% Americans are exposed to, these findings are not relevant to at least three-fourths of Americans. Further, the authors cited a study that found that added sugars, such as fructose, only accounted for 10.2% of total caloric intake2. Other studies have found similar levels of added sugar consumption (14.6%)3 As such, the authors chose a much higher amount of added sugar to include in their study, which lowers the relevance of their findings. Finally, the authors utilized an animal model for their study, which greatly decreased the significance and application of their findings. In sum, these points significantly reduced the novelty and relevance of the study.

 

Q3. Is the hypothesis clearly stated?

Yes / No. View Results Skeptically.

A3. No. The paper never specifically stated a hypothesis.

 

Q4. Was the study methodology described in detail?

Yes / No

Do the authors cite a paper for the methods?
Yes / No. View Results Skeptically.

A4. Yes. The study methodology was detailed and referenced. For example, the study employed 160 mice in organismal performance assays (OPAs), which use seminatural conditions to examine physiologic performance of animals. OPAs allowed for the authors to quantify substantial health effects that can be missed with other laboratory methods. Additionally, the article used  many different statistical models, which were carefully described. Moreover, the authors explained their rationale for using each statistical model. 

 

Q5. Are the methods valid, accurate and reliable?

Yes / No. View Results Skeptically.

A5. No. The diets used in this study included F/G and sucrose diets, which comprised 25% of total calories. Also, the authors did not include control diets, which have lower amounts of fructose, glucose, and sucrose.  Further, when examining metabolic food intake and weight measures, the authors chose to only examine male animals since there was “an excess of male production in breeding cages”. However, examining the metabolic food intake and weight measures in the female animals is extremely important since only the female mice elicited a measurable response in their study. Similarly, when examining glucose clearance, the authors chose to assess only females because “previous work on this population has shown that male clearance rates are not affected by this level of added sugar consumption”. Taking measurements from one group or previous work and applying these findings to the other group is not an accurate or valid strategy when performing experimental research. 

 

Q6. Does the analysis of the results make sense?

Yes / No. View Results Skeptically.

A6. Yes. The authors found that there was no difference in weight gain or food intake between dietary treatments in male mice. Further, the investigators reported that female mice initially fed the F/G diet had death rates 1.87 times higher than female mice that had been on a sucrose diet. Interestingly, no effect on mortality was seen in the male mice fed either diet. Moreover, male competitive ability was not affected by diet. However, female reproduction was altered by diet, while male reproduction was unaltered. The female mice initially fed the F/G diet produced 26.4% fewer offspring than the female mice initially fed the sucrose diet. Finally, the authors found that glucose tolerance was not altered by diet in female mice. 

 

Q7. Are the conclusions supported by the data?

Yes / No. View Results Skeptically.

A7. Somewhat. The authors reported that female mice on the precompetition F/G diet were “dramatically outperformed by females initially fed sucrose,” as demonstrated by a two times greater death rate and 26% reduction in reproduction. While the investigators state that the mechanistic basis for enhanced mortality and decreased reproduction is not known, they speculate that their findings may be linked to fructose absorption, which was not measured in this article. Enhanced fructose levels has been previously shown by other to increase intestinal permeability and induce intestinal inflammation. Ruff et al. offered another explanation for their findings: They postulated that the different sugar diets induced alterations to the intestinal microbe community, termed the microbiome. Diet-induced changes to the microbiome has been shown to have severe health implications.4 Further, the microbiome has been shown to be depended on gender, which supports the findings of Ruff et al.5 

 

Q8. Are there conflicts of interest?
(personal, academic, financial, conflicts of commitment)

Yes/No

If yes, compare findings to the totality of evidence.

A8. No. The study was exclusively funded from government-funded agencies such as the NIH and the NSF

 

Q9. Does the study fit into the totality of evidence?

Yes / No. View Results Skeptically.

A9. No. There are few scientific studies that link fructose and glucose to deleterious health outcomes. The studies referenced in the Ruff et al. paper investigated the impact of high fructose corn syrup on metabolic disease in a correlative fashion rather than using randomized, placebo-controlled methods. Further, the authors referenced articles that employed animal models, which are difficult to apply and incorporate into the totality of evidence. However, the study does add to the growing body of literature that demonstrates the different effects of sucrose, glucose, and fructose on health outcomes using animal models. 

How did the study do on the checklist? As you can see, the article contained a large number of flaws and did not pass the guidelines for assessing a scientific study.

While the paper reported the effects of added sugars on health outcomes in mice, the findings have less significance to humans due to the use of animal models, incomplete and invalid methodologies, and lack of a control group.

The authors concluded by stating that their “study should not be seen as a vindication of sucrose.” Scientific experts and health care professionals share this important point and emphasize the importance of consuming a balanced diet that provides adequate calories and nutrients from a variety of sources. For some health care professionals, this means limiting individual intake of added sugars.

Most importantly, consumers and nutrition experts need to focus on improving overall diets to move toward positive health changes. Ultimately, the findings from Ruff et al. suggest that 25% of calories from fructose and glucose monosaccharides negatively affect female mouse survival and reproduction. While these results are interesting observations and the source of media fodder, whether we can apply these findings to human health remains to be seen. 

References

1.         Ruff, J.S. et al. Compared to Sucrose, Previous Consumption of Fructose and Glucose Monosaccharides Reduces Survival and Fitness of Female Mice. The Journal of Nutrition (2015).

2.         Vos, M.B., Kimmons, J.E., Gillespie, C., Welsh, J. & Blanck, H.M. Dietary fructose consumption among US children and adults: the Third National Health and Nutrition Examination Survey. Medscape journal of medicine 10, 160 (2008).

3.         Welsh, J.A., Sharma, A.J., Grellinger, L. & Vos, M.B. Consumption of added sugars is decreasing in the United States. Am J Clin Nutr 94, 726-734 (2011).

4.         Maukonen, J. & Saarela, M. Human gut microbiota: does diet matter? The Proceedings of the Nutrition Society, 1-14 (2014).

5.         Mueller, S. et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Applied and environmental microbiology 72, 1027-1033 (2006).

 

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