Can a Diet High in Processed Fat and Sugar Cause Disc Degeneration?
Comments by James Iatridis, PhD and Deepak Vashishth, PhD
Researchers from Rensselaer Polytechnic Institute and the Icahn School of Medicine hypothesize that a diet high in processed fat and sugar leads to formation of advanced glycation endproducts (AGEs), which appear to speed up the process of age-accelerated spinal pathologies. Their newly launched study will explore exactly what role AGEs and type 2 diabetes play in the development of degenerative disc disease.
“Accumulation of AGEs is known to deteriorate biomechanical behaviors of spinal tissues and can also increase oxidative stress in the cells of the spine and the whole animal,” said coinvestigator Deepak Vashishth, PhD, Professor of Biomedical Engineering and Director of the Center for Biotechnology & Interdisciplinary Studies at Rensselaer Polytechnic Institute in Troy, NY. “We will focus on the role of these AGEs and their receptors as mechanisms for the hypothesized pathology observed.”
“Basic science studies on mice suggest a possible link between spinal degeneration, type 2 diabetes, and diets high in AGEs, yet no definitive link or causal mechanism has been demonstrated,” explained principal investigator James Iatridis, PhD, Professor and Vice Chair for Research in the Department of Orthopaedics at the Icahn School of Medicine at Mount Sinai in New York City.
Assessing the Systemic Effects of AGEs
In the first part of the project, researchers at Mount Sinai will help establish the systemic effects of AGEs on the body by raising mice fed a diet high in AGEs, similar to a fast food diet. The study will include both regular mice and knock-out mice that have been genetically modified to reduce the ability of their cells to bind to AGEs, accelerating AGE accumulation.
To separate the systemic effects of AGEs from local effects in specific tissues, researchers also will examine spinal bone and disc tissue from mice in vitro. In that research, bone and disc tissue from both normal and AGE knock-out mice fed on a regular diet will be bathed in a high AGE medium, accelerating the exposure of these specific tissues to AGEs. Selected tissue samples will be exposed to a drug that may be able to block AGEs in disc tissue, limiting exposure to bone and disc tissue.
Changes in indicators of disc and bone health, such as the activity of proinflammatory cytokines and AGE formation over time, will be examined. This research will separate the relative contribution of AGEs to tissue degeneration from systemic damage that may occur as a result of type 2 diabetes-associated hyperglycemia.
At Rensselaer, researchers will analyze how disc tissue in human cadavers and mice with and without disc degeneration differ, to help establish a link between AGEs and functional loss/deterioration in the biomechanical behaviors of spinal tissues, Dr. Vashishth said. In particular, researchers at Rensselaer will analyze proteins within the tissue samples, tracking the type and quantity of post-translational protein modifications. Similarities between mice and human tissue affected by disc degeneration would support a link between diet and disc degeneration.
Type 2 Diabetes May Accelerate Spinal Degeneration
“We are investigating type 2 diabetes since spinal degeneration is commonly an age-related disease and type 2 diabetes accelerates the aging process in many humans,” Dr. Iatridis told SpineUniverse. “There is also clinical research showing a relationship between diabetes and inferior surgical outcomes, motivating the need for minimally invasive interventions for spinal pathology subjects.”
“We will look for associations between diabetes and spinal degeneration in human autopsy tissues. However, because humans lead very complicated lifestyles with more differences than diabetes status, a definitive relationship is very hard to identify in humans,” Dr. Iatridis explained. “We, therefore, use a type 2 diabetes mouse model to investigate a causal relationship with spinal degeneration and also research how different diets result in spinal degeneration in mice.”
Potential Clinical Implications
“If we identify specific molecules important in this process, we can use this information to develop future treatments to slow or prevent these degeneration processes,” Dr. Vashishth explained.
“Future treatments might involve altered diet or drugs,” Dr. Vashishth told SpineUniverse. “If results are as hypothesized, there are many promising translational directions since AGE inhibition drugs are already approved for other diseases. However, this scientific investigation also holds promise to open new avenues for local or systemic therapies for painful spinal pathologies.”
The study is funded by the National Institutes of Health. Findings will be published periodically over 5 years with the study concluding in 2021.