Florida State University researchers have demonstrated that significantly increasing dietary folic acid in mice can prevent peripheral neuropathy, a condition commonly associated with diabetes and other health issues.
The research, published in the Proceedings of the National Academy of Sciences, PNAS, not only provides additional evidence that certain nutrients can help manage chronic health conditions, but also underscores the importance of considering higher levels of certain dietary components, called “special nutritional requirements,” for people with chronic health problems, including diabetes and obesity.
Folic acid is a synthetic form of folate, vitamin B9, and is required for DNA synthesis, which promotes nerve protection throughout the life span as new cells are constantly produced. Lower levels of folate are related to the risk of birth defects as well as the severity and incidence of peripheral neuropathy – nerve damage causing numbness, tingling, burning sensations and weakness, typically starting in the hands and feet. This type of neuropathy is commonly linked with diabetes but is related to many diseases and disorders; it can also be caused by infections, injuries, vitamin deficiencies and toxins.
Patrick Stover, a professor in the college’s Department of Biomedical Sciences, a founding director of FSU’s Institute for Connecting Nutrition and Health (ICON-Health) and a member of the National Academy of Sciences, was principal investigator on the project. He is an international research scholar in B-vitamins and their safe use in dietary fortification and supplements.
“Historically, the government’s Recommended Daily Allowances set the minimum amount of a nutrient you should have to maintain adequate nutrient status and function,” he said. “If the population is found to be deficient in a particular nutrient, then efforts are undertaken to fortify the food supply with that nutrient to avoid deficiencies.”
Common examples of food fortification are Vitamin D-fortified milk and yogurt, iodized salt and iron-fortified flour.
“Nutrient- and food-based dietary guidelines are derived with the assumption of a healthy population, and how much of each nutrient you need to stay healthy. The problem is that a lot of the population is not healthy,” Stover continued. “Many suffer from chronic diseases, often related to obesity, so guidance may need to be reconsidered in terms of impact on those who may have different requirements.”
This research, using a mouse model, indicates that a high-dose folic acid regimen prevented peripheral neuropathy among highly susceptible mice.
“This work is very exciting, and any nutritional strategies that can be leveraged to avoid disease risk and mitigate human suffering are critical,” said Regan Bailey, a co-author who is a professor in the college’s Department of Behavioral Sciences and Social Medicine, also a founding director of ICON-Health, and a member of the National Academy of Medicine.
Folic acid is an example of a fortification on an individual basis and is prescribed to prevent neural tube defects, called NTDs, in utero. NTDs are serious birth defects of the brain and spine that occur early in pregnancy, often before a pregnancy is known. Since folic acid is not necessarily needed by those who are not in early pregnancy, it’s recommended as a supplement and not added to the food supply.
The research also revealed that peripheral neuropathy and NTDs share a genetic etiology, a phenomenon where two or more conditions arise from the same underlying causes.
Robert J. Cousins, a University of Florida eminent scholar, Boston Family Professor Emeritus of Nutrition and founding director of the UF Center for Nutritional Sciences, said the connection between folic acid status and neurodevelopment was a major advance in nutrition science.
“Dr. Stover pioneered the development of mouse models that demonstrate, biochemically, the responsiveness of supplemental folate to correct developmental defects in the developing nervous system,” said Cousins, who was not involved in the research project.
The possibility of preventing and even curing peripheral neuropathy could be life-changing for millions of Americans.
In its National Diabetes Statistics Report issued in January, the Centers for Disease Control and Prevention estimates that as of 2023, there were 40.1 million people in the United States with diabetes – more than a quarter of them undiagnosed.
Furthermore, the Cleveland Clinic reports that 50% of people with diabetes experience peripheral neuropathy to some degree. Being able to prevent it would improve the quality of life for people with diabetes, as well as those with cancer.
According to the MD Anderson Cancer Center, 30-40% of the thousands of cancer patients each year experience peripheral neuropathy, either from the cancer itself or the toxins used to treat it with chemotherapy. The neuropathy sometimes is reversible once cancer treatment is concluded, but people with diabetes have no such exit door. Neuropathy treatment is generally focused on treating the symptoms, managing the underlying causes, and relieving pain to improve quality of life.
“Disease can affect nutrient needs by altering nutrient absorption, transport, or utilization,” said Martha Field, Ph.D., an associate professor of nutritional sciences at Cornell University who also worked on the project. “It is exciting to see here that meeting those needs also alters disease-related physiological outcomes in diabetic peripheral neuropathy.”
Stover and Bailey moved to FSU from Texas A&M last year and founded the Institute for Connecting Nutrition and Health as part of FSU Health.
Joydeep Chakraborty, lead author of the article, also moved from Texas A&M to FSU and is biomedical sciences research faculty at the College of Medicine. Other authors were Adhideb Ghosh of the University of Zurich; Eunice B. Awuah. of Cornell; and Sally P. Stabler of the University of Colorado.
The team plans to conduct clinical trials in Tallahassee, Stover said.
“If we see the same results in humans, which we believe we will, based on the literature that’s out there and what we’ve shown in this paper, that will change the standard of care,” he said. “This is exciting stuff.”