New Hair Growth Mechanism Identified for Tocotrienols

Research has conclusively shown β-Catenin as a genetic signal for hair follicle formation encoded by the CTNNB1 gene.

  Although several growth factors and pathways have been implicated in hair cycling process, Wnt/β-catenin signaling is most prominently featured in hair follicle regeneration. 

β-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription.

Prior research on Tocotrienols has demonstrated a hair growth effect in human subjects with Androgenetic Alopecia. It was speculated that the mechanism of action underlying these hair growth stimulation effects was due to anti-oxidant effects. This was well founded due to the observed anti-inflammation effects.

Follow up research was shown that Tocotrienols exert effects on the genetic signaling pathways associated with hair growth, which suggest hair growth effects well beyond any obtained via anti-oxidant effects.

Mol Ther. 2017 Nov 1; 25(11): 2502–2512.

Published online 2017 Jul 20. doi: 10.1016/j.ymthe.2017.07.010

Epidermal E-Cadherin Dependent β-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling


Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of β-catenin and its nuclear translocation. Nuclear β-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of β-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/β-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin.

In a review, published in 2020, entitled “ Targeting Wnt/-Catenin Pathway for Developing Therapies for Hair Loss,” several plant based compounds where identified that are currently in the industry development pipeline. These included; Tocotrienols, Caffeine, Polygonum Multiforum (Fo Ti), Ginkgo Biloba, Ginseng , and Silymarin. Among these Tocotrienols, and Ginseng have direct evidence of their hair growth effects with oral supplementation: 

Effects of tocotrienol supplementation on hair growth in human volunteersHair-Growth potential of ginseng and its major metabolites: A review on its molecular mechanism

Of the diverse intracellular signaling pathways implicated in hair biology, Wnt/β-catenin signaling plays a key role in stimulating hair follicle stem cells and hair regeneration, and has been identified as a mechanism in several of our long standing supplement recommendations for hair growth. As is usually the case, these specific recommendations have a significant cross over benefit for age reversal as well.