Is gluten making you overstimulated?

There has been a lot of controversy lately over gluten sensitivity, but the existence of celiac disease is something no one can argue against. Celiac disease affects 1 in 141 individuals in the United States and can cause intestinal damage.

Figure 1. Healthy villi (left) are destroyed in celiac disease (right). Image from http://celiacdisease.about.com/od/celiacdiseaseglossary/g/Villi.htm

Celiac disease is an immune reaction to gluten, a molecule that can be found in wheat, barley, and rye. The immune system produces antibodies against gliadin (a gluten protein) and transglutaminase, an enzyme that modifies gluten. These antibodies increase the immune response leading to increased pro-inflammatory markers. These inflammatory markers increase inflammation both locally and systemically and lead to the destruction of the villi and microvilli in the small intestines. The villi and microvilli are responsible for the absorption of nutrients. Without the villi and microvilli, the body may not absorb enough nutrients for optimal health leading to weight loss, diarrhea, or decreased growth (in children).

Figure 2. Glutamate is converted into GABA by glutamate decarboxylase, which can be blocked by gliadin antibodies.

In addition to the issues caused by insufficient nutrition, celiac disease can directly affect neurotransmitter levels that can contribute to symptoms . Gliadin antibodies block the enzyme glutamate decarboxylase. This enzyme is responsible for converting glutamate into GABA. If the glutamate decarboxylase is not functioning, glutamate will not be broken down. The result is an increase in glutamate levels and a decrease in GABA levels.

Glutamate is considered the most excitatory neurotransmitter. It is important for learning and memory. High levels are associated with urges, cravings, and intestinal complaints. They can interfere with focus and concentration and sleep. High levels can also be excitotoxic and cause damage to cells. GABA is the primary inhibitory neurotransmitter and is needed to feel calm and relaxed. Low levels of GABA are correlated with anxiousness and sleep difficulties.

If your patient has celiac disease, you may want to check the neurotransmitter levels to see if an imbalance in glutamate or GABA is present.

References:

http://www.mayoclinic.org/diseases-conditions/celiac-disease/basics/definition/con-20030410

Cryan, J.F., et al. (2005). Don’t worry ‘B’ happy!: a role for GABAb receptors in anxiety and depression. TRENDS in Pharmacological Sciences, 26(1): 36-43.

Dong, E., et al. (2012). Effects of microinjections of Group II metabotropic glutamate agents into the amygdala on sleep. Brain Res, 1452: 85-95.

Hadjivassi, R., et al. (2004). Gluten sensitivity: from gut to brain. Trends in Immunology, 11: 578-82.

Nikolaus, S., et al. (2010). Cortical gaba, striatal dopamine and midbrain serotonin as the key players in compulsive and anxiety disorders-results from in vivo imaging studies. Reviews in the neurosciences, 21(2): 119-39.