Biochemistry of male pattern baldness

Last updated Jan 10, 2023

Disclaimer: I am not a doctor and nothing I write constitutes medical advice. This article is for informational purposes only, might contain inaccuracies, and should not be used as a substitute for professional medical advice. Read the full disclaimer here: Medical disclaimer

I wrote an intro article on my substack. Read that first. I’m going to organize this page later, but for now, bullet points:

• Is hair loss pathological or adaptive?
  • Heat theory ( Larson et al. )
    • Sweating is more effective on bare skin; that’s why humans don’t have fur
    • The skin of the scalp is highly vascular, and shedding hair may be an adaptation that assists heat regulation
    • Heat is known to cause mast cell degranulation in a disorder known as heat urticaria
    • (my own speculation) Shower water is nearly hot enough (~105F) to trigger some known heat receptors (TRPVs)
• Could shampoo or conditioner cause hair loss?
  • Hard to say. It’s completely possible that there’s some common chemical that causes a subclinical allergic response (-> mast cell degranulation -> PGD2 exocytosis) with repeated exposure.
• Fish oil contains omega-3 fatty acids (specifically eicosapentaenoic acid (EPA) & docosahexaenoic acid (DHA)) that inhibit PGD2 formation in human mast cells in vitro ( Obata et al. ).
  • Two possible reasons
    • Dietary EPA is known to modify the phospholipid membrane fatty acid composition ( Lee et al. ). When EPA is used as a substrate for COX-2 instead of arachidonic acid, the resulting compounds (isoprostanes) may not target the same receptors as the prostaglandins.
    • EPA/DHA may inhibit COX-2 through some other mechanism
  • A study reports that a supplement containing omega-3, omega-6 acids & antioxidants improved hair growth ( Le Floch et al )
• Calcitriol (vitamin D) inhibits expression of COX-2 in mice ( Wang et al. ). This may not be relevant, because the mice were given much, much more vitamin D than one would get from a supplement.
• Tocotrienols (a form of vitamin E) significantly improves hair growth ( Beoy et al. ). Possibly due to antioxidant effects, but the precise mechanism is unclear.
  • Looks like tocotrienols and tocopherols are PPAR ligands, which explains their effect.
• COX-2 is upregulated by a variety of inflammatory stimuli (LPS, TNF-alpha…). Could something somewhere else in the body be involved? (needs more investigation)