As early as 2006, researchers examined the association between atopy, markers of impaired folate (the natural form of vitamin B9) metabolism and dietary intake of B vitamins. Folate metabolism is closely linked to methylation, which has received increasing attention for its link to cardiovascular disease, neurodegenerative disorders, autism, chronic inflammation and other immune disorders, of which atopy is just one.
A Danish study of 1,671 patients aged 30 to 60 years and found that “impaired folate metabolism may be causally related to the development of atopy.” A subsequent 2009 study found that those with the lowest folate levels had a 31 percent higher risk of atopy (allergic symptoms) than people with the highest folate levels.
What is the relationship between a deficiency in B9 and atopy/allergy?
A 2013 study looked at the “vitamin-mediated regulation of intestinal immunity” and the “crosstalk between immunocompetent cells and endogenous (e.g., cytokines and chemokines) as well as exogenous factors (e.g., commensal bacteria and dietary materials).”
The study concluded that low levels of B9 “dramatically alter the immune response.” Vitamin B9 is crucial in the maintenance of regulatory T cells (formerly called suppressor T cells) and homeostasis in the intestine:
“Once naïve T cells differentiate into regulatory T (Treg) cells, they express folate receptor 4 (FR4), and require vitamin B9 for their survival. The absence of sufficient amounts of vitamin B9 induces the apoptosis of Treg cells, with decreased expression of Bcl-2 and subsequent increased intestinal inflammation.”
Natural Treg are characterized as expressing both the CD4 T cell co-receptor and CD25, which is a component of the IL-2 receptor. Treg are thus CD4+ CD25+.
While deficiency in folate itself (and other B vitamins) from the diet (found in leafy greens) clearly plays a role, research has explored the MTHFR (C677T) gene variation as an important contributing factor in atopy.
MTHFR C677T is a gene that codes for the enzyme methylene-tetrahydrofolate reductase involved in many important methylation reactions including the metabolism of folate. A mutation in this gene has been implicated in folate deficiency and thus also in immune dysregulation and atopy.