Of all the things I learned about at the national meeting of the Society for Toxicology last week in San Diego, there was one phrase that really hit home. One simple phrase, uttered by Dr. Andrew Gerwitz of Georgia State University during his talk: “What doesn’t kill you makes you fatter”. Recently published in Nature, Dr. Gerwitz’s research focuses on the interactions between the microbiome (the collection of germs found naturally in our gut), low-grade inflammation (a subtle, long-term activation of the immune system), and the metabolic syndrome (a term that describes obesity-like symptoms). Specifically, he is interested in how emulsifiers from our food influence these three parameters.
What are emulsifiers exactly? Emulsifiers are food additives that help mix together two things that don’t normally mix. Take a vinaigrette salad dressing for example. Every time you go to an Italian restaurant there’s always a bottle of it on the table, and more often than not, it has separated into its constituent oil and vinegar layers. Any time you shake that bottle of vinaigrette, you combine these layers and create an emulsion. However, this emulsion is not stable, and so by the time the next reservation is seated, it usually has separated once again. By adding an emulsifier, such as soy lecithin, you can help stabilize the mixture, allowing it to stay emulsified for a longer period of time. Examples of common emulsifiers used in the food industry include polysorbates and carboxymethylcellulose. But enough about emulsifiers, let’s get back that quote.
“What doesn’t kill you makes you fatter.” The first thing that really hit me about the phrase was the implication that as toxicologists, we may have been completely missing something this whole time. In a nutshell, the field of toxicology seeks to identify the adverse effects of chemicals on living creatures. Now, what do we consider to be adverse effects? Ask someone today and you’ll get answers like nausea and vomiting, severe pain, cancer, or death. Of course, these are all quite reasonable answers, and are great examples of the types of endpoints that have been, and are still used today to determine the safety of a drug. Obviously no one wants to be ingesting a chemical that might harm them in any way. But times are changing, and perhaps safe drugs can no longer be defined as chemicals that simply don’t kill us.
The diseases that haunt us today are not the same as the diseases that have haunted our past. Perhaps the most defining epidemic of our times is obesity and diabetes, neither of which are standalone diseases. In fact, both of them have links to numerous other diseases, ones that are also characteristic of our times, including cancer and cardiovascular disease. The combination of these complex and intricately connected diseases is often fatal over the long-term. So perhaps the time has come to rethink how we define the safety of a chemical. Maybe it’s not enough anymore to say a drug is safe, just because it doesn’t kill you right there and then. Maybe we need to take into account additional factors that occur over the long term.
Which brings us to Dr. Gerwitz’s research. According to his results, what doesn’t kill us, might actually makes us fatter. And it might not have anything to do with direct interactions between chemicals and our bodies either. Using mice as their model, these researchers found that treatment with relatively low concentrations of two commonly used emulsifiers in processed food, polysorbate-80 (PS80) and carboxymethylcellulose (CMC), result in obesity-type symptoms and “low-grade inflammation”. In other words, the emulsifier-treated mice gained more body weight and more fat mass then the non-treated mice, while also exhibiting a mild activation of the immune system in their gut. But the interesting part about their data is that those changes may have nothing to do with the direct interactions between the human gut and the emulsifiers. Instead, the issue at hand seems to be interactions between the emulsifiers and the bacteria in our gut. For example, obesity-type symptoms didn’t occur in emulsifier-treated mice that had a sterile, germ-free intestine. Yet, when they transferred the gut bacteria from a normal emulsifier-treated mouse into those germ-free mice, all of a sudden these germ-free mice began to develop obesity-type symptoms. Importantly, this occurred despite the fact that the germ-free mice never ingested any emulsifiers to begin with! Thus, it appears that some interaction between the bacteria and the emulsifiers is causing the body to get fatter.
So what is alarming then, is that maybe the chemicals we thought were safe are not so safe anymore. PS80 was approved for use in food during the 1960’s, while MCM is classified by the FDA as “generally regarded as safe” (GRAS). However, the impact of these chemicals on the gut bacteria, up until now, was not really known, and was not an issue really able to be researched until recently. Thus, Dr. Gerwitz’s research begs us to ask, are there other GRAS chemicals that might not be as safe as we thought? All this being said, I certainly do not wish to set an alarmist tone. After all, we know these chemicals at least won’t kill us with normal use. Yet, “what doesn’t kill us makes us fatter”, which also isn’t good.
Ultimately, I believe we should re-evaluate drug safety as it stands today, and maybe alter our approach to it. This of course, is much easier said than done. These kinds of things take years to develop. And I mean let’s face it, my name carries no weight in the field of toxicology, not to mention I don’t even have a PhD degree (yet). So let’s consider this an open letter to the scientific community.