Authors of blog post: Stefania E. Kapsetaki & Anthony J. Basile

Our research journey started with a simple question: could there be a link between diet, plasma sugar (glucose) levels, and cancer prevalence across vertebrate species? What began as a chance encounter at a virtual conference during the Covid-19 pandemic blossomed into a fascinating investigation, revealing interesting patterns and raising even more questions.

Serendipity strikes at a virtual conference

This project came about rather unpredictably. Anthony Basile, at the time an evolutionary biology PhD student at Arizona State University, was presenting a poster on “The effect of an evolutionary mismatch narrative on veteran diet quality: Methodology” at the July 2021 ISEMPH virtual conference. Stefania Kapsetaki, at the time a post-doc, was in the virtual audience. When Anthony finished presenting, Stefania sent an email to Anthony, and within 10 minutes, Anthony replied.

After then, Stefania and Anthony started discussing potential projects over several zoom calls. Anthony and his supervisor, Karen Sweazea, an assistant professor at ASU, had experience working on diet and glucose levels. The Arizona Cancer & Evolution team had data on cancer prevalence across vertebrate species and Stefania was in the process of finding factors that might correlate with cancer prevalence. If we could find species’ glucose level data, perhaps we could test for correlations of glucose levels with cancer prevalence. The known high glucose levels in the blood of birds versus mammals, reptiles, amphibia, and fish, together with the known lower cancer prevalence in birds relative to mammals and reptiles, made us think that it would be interesting to perform correlations on glucose levels and cancer prevalence across vertebrates and within vertebrate groups. Then, thinking of mechanistic links between diet, glucose, and cancer, we thought of also including diet in the analyses. We made the first blood glucose concentration ~ cancer prevalence figures on the 31^st of August 2021. Our study also included gastrointestinal and non-gastrointestinal cancer and neoplasia (including benign or malignant tumors) prevalence data across vertebrate species, as we aimed to investigate whether the relationship between diet and cancer prevalence is specific to certain tissue types.

What did we discover?

Vertebrate species vary in their diet, plasma glucose concentrations, neoplasia prevalence, cancer prevalence, gastrointestinal neoplasia and cancer prevalence, as well as non-gastrointestinal neoplasia and cancer prevalence. This diversity is key to uncovering potential relationships between diet, plasma glucose concentrations, and neoplasia prevalence across vertebrates.

Plasma glucose concentration is relatively higher in birds than reptiles and mammals. Cancer and neoplasia prevalence is relatively lower in birds than reptiles and mammals. Therefore, we saw a negative correlation between plasma glucose concentrations and cancer prevalence, gastrointestinal cancer prevalence, gastrointestinal neoplasia prevalence, non-gastrointestinal cancer prevalence, and non-gastrointestinal neoplasia prevalence in analyses where all the groups (birds, reptiles, mammals) were included. However, these correlations did not remain when we controlled the analyses for birds, reptiles, and mammals. The correlations also did not remain within birds, within reptiles, or within mammals.

Ultimately, there were no statistically significant correlations between diet and plasma glucose concentrations across vertebrates. Neoplasia prevalence across tissues, but not gastrointestinal or non-gastrointestinal neoplasia prevalence, was statistically higher in primary carnivores than herbivores when controlling for species’ domestication.

There are some potential explanations for the relatively higher plasma glucose concentrations in birds, such as the loss of some genes encoding proteins responsible for glucose import inside bird cells. Production of fewer reactive oxygen species inside bird cells possibly partly explain the lower neoplasia and cancer prevalence in birds relative to reptiles and mammals.

There are many molecular pathways yet to be explored between diet, plasma glucose concentrations, and neoplasia prevalence across all the examined vertebrate species. Finding cancer-preventing genes and pathways may also help cancer prevention strategies in humans. There are many uncovered areas in the fields of diet, plasma glucose concentration, and cancer that remain to be addressed across vertebrates for improving veterinary and human health.

A musical note on the title

While listening to music during this project, one song was important in some moments of the project: “A Spoonful of Sugar”. The duo of a human and a bird singing “A spoonful of sugar helps the medicine go down” resonated somewhat with the project. Both Anthony and Stefania are musicians and could hardly resist calling the article “A Spoonful of Sugar Helps the Cancer Go Down: The Relationship Between Diet, Plasma Glucose, and Cancer Prevalence Across Vertebrates” based on the observation that birds have relatively higher plasma glucose levels and lower cancer prevalence than reptiles and mammals. At the end though we decided to choose the more scientifically accurate title of “Relationship Between Diet, Plasma Glucose, and Cancer Prevalence Across Vertebrates”.

The publication process: perseverance pays off

In August 2023, we uploaded the manuscript “The Relationship Between Diet, Plasma Glucose, and Cancer Prevalence Across Vertebrates” to bioRxiv. We then submitted the manuscript to a Springer Nature journal, then another Springer Nature journal, then a National Academy of Sciences journal, and then an AACR journal. The manuscript was not sent for peer review in any of those journals. This process lasted 2 months in 2023. Then, we submitted the manuscript to the Spring Nature journal Nature communications and it was sent for peer review. After peer review, it was unfortunately rejected. However, we thought we could address the comments, and therefore early in 2024 we resubmitted the amended manuscript to the same journal. A year later, the manuscript is published in Nature communications.

A collaborative effort

This project was a collaborative effort involving researchers from different backgrounds and institutions. During the four years of this project, Stefania navigated three different postdoc positions across two continents. Anthony graduated from Arizona State University and is now an Assistant Professor at the State University of New York Oneonta. Zachary Compton also graduated from Arizona State University and is now a postdoc at the University of Arizona. Carlo Maley has become a full Professor at Arizona State University. We are grateful to our research team and the journal team for their support, and of course, to the non-human vertebrates from which the data shown in this article originate.

We hope you enjoy this article!

Read the full paper here: https://www.nature.com/articles/s41467-025-57344-1