The New F-Word and its Diabetes Connection

March 13, 2018 — For decades, scientists have been working to understand not only the cause of diabetes but why the disease is increasing at an alarming rate. Surprisingly, a possible answer may lie right inside your pantry.

Folic acid, or vitamin B9, has been used to enrich bread, cereal, flour, cornmeal, pasta, rice and other grain products since the mid-1990s, when the U.S. Food and Drug Administration (FDA) required it as part of the Flour Fortification Initiative. A vital nutrient that supports many functions in the body, folic acid was added to help prevent birth defects in infants worldwide.

However, in populations where folic acid is readily available along with vitamin supplements, the additive might not be necessary and may actually be detrimental to people with particular genetic predispositions, according to published findings by Diabetes Research Institute scientists. In fact, excess consumption of folic acid may result in adverse health conditions and even cause the onset of autoimmune conditions, like type 1 diabetes (T1D), the study shows. 

U.S. incidence of diabetes over the past 50 years (type 1 and type 2) expressed as a % of total population. The red arrow depicts the initial point of mandatory fortification of flour products with folic acid. The green bars are measurements of serum folate levels from NHANES subjects of the corresponding years. 

“What was striking to us was the sudden uptick in the incidence of diabetes, nearly threefold the rate, in a few years following the mandatory fortification of flour in this country,” said Dr. Chris Fraker, research assistant professor of surgery and cell transplantation and co-author of the study published in Frontiers in Endocrinology. “Additionally, the serum levels of folate (metabolized folic acid) and non-metabolized folic acid measured in the blood of NHANES (National Health and Nutrition Examination Survey/Centers for Disease Control) study subjects were significantly increased.”

Folic Acid, Viruses and T1D: A Possible Connection?

Folic acid’s role as a possible trigger for the onset of type 1 diabetes became a target of increasing interest as Dr. Fraker, together with Dr. Allison Bayer, research assistant professor of microbiology and immunology and study co-author, furthered their ongoing research into natural killer (NK) cells, critical cells of the immune system that serve as the first line of defense against viruses and other harmful invaders.
Scientists throughout the diabetes field have established that viruses are a likely role player in the development of T1D. Viruses are known to cause problems in the immune system that lead to unchecked inflammation which, in turn, launches an improper response against “self” tissues, like insulin-producing cells.

Different viruses are prevalent in a large percentage of the population. They are passed down from generation to generation and go through cycles of activation and latency over one’s lifetime. Typically, the viruses do not pose a threat in the majority of people; if they did, they would be eliminated by the immune system.

But research has shown that in some people, like those at risk for autoimmune conditions, the viruses are able to gain a foothold in cells, escaping destruction and causing problems in the host immune system.

Drs. Fraker and Bayer have observed in their work, and supported by other studies, that NK cells are defective in people with type  

1 diabetes and, as a result, viruses are capable of manipulating the immune response in their favor so as not to be destroyed. Getting to the bottom of how and why this happens led the researchers to some unexpected findings.

The Evidence Stacks Up

In examining the factors that influence the immune system, many environmental causes have been suggested over the past 20 years: diet, stress, sleep, and chemicals, to name a few. While these factors likely play a role, the majority of people still do not develop type 1 diabetes or other autoimmune conditions.

Upon further investigation, one dietary factor stood out: folic acid, which, the scientists have learned, is a powerful immune system modulator. When it enters cells as a synthetic vitamin, as in the case of flour supplementation, folic acid can slow down the metabolic machinery of the cells by 1,500 times relative to naturally occurring folate found in green vegetables or meat products. This can damage the immune machinery, according to the researchers.

“We believe that this metabolic factor may actually be causing a general weakening in people’s immune systems that, in a person that has a genetic susceptibility, may lead to the development of not only diabetes but other autoimmune conditions as well,” said Dr. Fraker.

Correcting Autoimmunity

What can people do if they have already eaten products enriched with folic acid?

“For correcting this condition, I don’t think there is a simple fix because of the fact that if it is related to folic acid and you’ve consumed this food, you may have already done the damage to the immune system. Viruses can be reactivated within your body and it’s very difficult to get those under control,” Dr. Fraker said.

The researchers are continuing their study of NK cells to learn more about the potential effect of folic acid on the cells’ function to develop strategies to combat it.

“The long-term goal is to find a way to correct these defects and reset the immune system, hopefully eliminating autoimmune responses in the process, as we work to develop a biological cure for type 1 diabetes,” said Dr. Fraker.

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Nicole Lesson

Lori Weintraub, APR

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