Sterol intermediates of cholesterol biosynthesis inhibit hair growth and trigger an innate immune response in cicatricial alopecia.

PLoS One. 2012;7(6):e38449. Epub 2012 Jun 7.
Sterol intermediates of cholesterol biosynthesis inhibit hair growth and trigger an innate immune response in cicatricial alopecia
Panicker SP, Ganguly T, Consolo M, Price V, Mirmirani P, Honda K, Karnik P.

Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, United States of America.

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders.

Amazing find, CS. Thanks for this. I wonder if any type of cholesterol metabolism interference could be implicated in hair loss and more general MPB. Could any type of oxidative process that adversely effected cholesterol potentially create these molecules like these intermediates that might incite an immune reaction? This would really emphasize the importance of eating not only healthy fats but also antioxidants like EC and Vit E. Perhaps it isn't this specific process, but could a similar process be involved in androgenetic alopecia? It would give a lot more weight to what I now believe to be a hyper-immune state in the hair follicle.

For me at least, this is one of the most important studies I've ever seen.

anthonyspencer54 - I agree this is an important finding. One factor in particular that negatively affects cholesterol synthesis is a presence of mercury.

Specifically the mercury that leaks from mercury amalgams. Cholesterol values can be ultra low in some with mercury fillings. In other cases, quite high. When the offending amalgams are properly removed using safety procedures (mask and rubber dam, etc.) and with proper detox following, those values can normalize.

This would lend credence to why chelation helped me out tremendously and why it appears all the supplements work much better now.