Retinoic acid (vitamin A) found to cause inflammation in certain individuals

Over the years, several of my celiac and non-celiac gluten sensitive patients have reported a dry "gritty" feeling in their eyes--often along with difficulties to focus vision and mind, reddish fingertips, and other signs of active inflammation.

On further inquiry into food changes prior to these signs and symptoms, my patients invariably cite larger than usual intake of foods high in vitamin A. Among the foods named most frequently are beef or chicken liver, carrots, sweet potatoes, pumpkin, winter squash, cantaloupe, dandelion, kale, spinach, collard greens, and a few other foods.

It appears that the presence of certain HLA-DQ2/DQ8 gene alleles leaves the immune system open to an assault of retinoic acid. In an odd twist, nature reverses the important anti-inflammatory and growth factor related role of vitamin A: its metabolite retinoic acid partners with interleukin-15 (IL-15) to produce inflammation in some HLA-DQ2/DQ8 gene carriers.

This inflammatory action particularly appears to affect non-celiac and celiac gluten sensitive individuals as well as some individuals with related autoimmune disorders. Several research papers recently have addressed retinoic acid (a Vitamin A metabolite) causing inflammation in individuals of a certain genetic background.

The following abstract is well worth sharing

Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens: Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.[1]

So much for our parents who told us to eat our carrots for better vision!

At this point, there is no clear measure or suggestion to eliminate or reduce vitamin A in certain non-celiac and/or celiac gluten-sensitive individuals. It may, however, make a valid point for genetic HLA typing to rule in or out a possible pro-inflammatory reaction of retinoic acid in conjunction with the immune cell component IL-15.

Furthermore, since vitamin A toxicity has been widely documented in the general population and in prenatal birth defects (read the recently published GMI article Why Is Birth Defect-Linked Vitamin A Used In Prenatals?) for the non-celiac and celiac gluten sensitive patient a cautious approach even to food-derived vitamin A / retinoic acid may be well advised

References

[1] https://www.ncbi.nlm.nih.gov/pubmed/21307853 Nature. 2011 Mar 10;471(7337):220-4. Epub 2011 Feb 9.