RED CLOVER; A BALANCING HERBAL EXTRACT FOR THE SCALP

Red clover is a dark pink herbaceous flowering plant that contains coumestrol, a potent phytoestrogen and antioxidant.  Due its low molecular weight, coumestrol can pass through cell membranes and mimic the biological activities of estrogen whilst reducing the activity of reactive oxidative species.

Coumestrol has a similar binding affinity to that of estradiol to estrogen receptors, though the effect of coumestrol binding is lower than estradiol. As an anti-oxidising agent, coumestrol can reduce inflammation and encourage repair of the hair follicle niche.

RED CLOVER CONTAINS A WEAK ESTROGENIC COMPOUND

Estrogens are a category of steroid hormones responsible for the development and regulation of the female sex characteristics and reproductive health.  There are two major estrogens with estrogenic hormonal activity: Estradiol and estrone. Estradiol and estrone are the two estrogens that are involved in hair follicle cycling.

Estradiol is synthesised from testosterone and estrone is synthesised from androstenedione (a weak androgen) by the enzyme aromatase.  Estradiol and estrone increases vascularisation, collagen production and raises the activity of pigment cells within the hair follicle whilst suppressing hair follicle sebaceous gland activity.  This control of sebaceous gland activity regulates the sebum production where scalps are oily.

The molecular shape of coumestrol orients its functional oxygen and hydrogen group in the same position of the functional oxygen and hydrogen group as estradiol allowing for binding with estrogen receptors.  The binding of estrogen receptor α upregulates the expression of genes that code for insulin-like growth factor and epidermal growth factor, leading to a longer anagen (growth) phase in the hair cycle.

ESTROGENS MODULATE GROWTH FACTORS THAT CONTROL HAIR GROWTH

Hormonal alterations can affect hair growth because they can increase or decrease substances such as growth factors that influence hair follicle survival.  Growth factors directly control how long hair remains in anagen phase (growth phase) and when hair goes into telogen (resting phase) in preparation to be shed.

Induction of anagen phase is dependent on transforming growth factor beta and keratinocyte (keratin cell) growth factor (KGF) or fibroblast growth factor (FGF).  Maintenance of anagen phase is controlled by insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF).

Estrogens and estrogen receptors play an important role in the signalling pathways that regulate hair growth. The anagen-to-telogen-to-catagen transition involves crosstalk between keratinocyte growth factor and transforming growth factor-beta.  Functional crosstalk between estrogens and receptors regulate the action of growth factors that control the hair growth cycle.

Growth Factor Action Modulation
Insulin -like growth factor-1 (IGF-1) Stimulates hair growth Estrogen receptor crosstalk
Vascular endothelial growth factor (VEGF) Development of blood vessels that surround the hair follicle unit Estrogen increases production
Transforming growth factor beta (TGF-B) Stimulates resting and shedding phase of the hair cycle Estrogen receptor crosstalk
Keratinocyte growth factor (KGF) An important mediator of hair follicle growth and development Estrogen receptor crosstalk

WHAT ARE PHYTOESTROGENS?

Phytoestrogens are a general term for compounds of various structures, originating in plant sources and mimicking or modulating the action of estrogenic hormones.  The estrogenic potential of certain plants was first reported in the 1940s from an observation of sheep that suffered reproductive disorders because of a diet mostly based on clover.

Phytoestrogens in the body act like weak estrogens and when applied topically will not impact hormonal balance in the body.  Estrogens profoundly alter hair growth by binding to estrogen receptors in the hair follicle.  Besides altering estrogen dependant genes, estrogen modify hair follicle metabolism in the hair follicle and the sebaceous gland.

estrogen receptor

STUDIES SUPPORT THE USE OF PHYTOESTROGENS FOR ALOPECIA AREATA

In a study investigating the effects of phytoestrogens on hair growth it was found that hair regrowth in alopecia areata patients was greatly accelerated when phytoestrogens were administered in supplement form for 4 weeks. It was found that plasma levels of insulin-like growth factor were significantly increased from baseline. When compared to those given a placebo, the percentage of volunteers who showed hair regrowth was significantly higher, 64.5% experienced some level of hair regrowth within 5 months when compared to 11.8% given a placebo.

HOW DO PHYTOESTROGENS HELP HAIR GROW?

Two types of estrogen receptor are distinguishable in the human hair follicle.  Estrogen receptor α is involved in keeping the hair follicle in anagen (growth activation of the hair follicle), while estrogen receptor β is responsible for inducing telogen in preparation for the hair to be shed.  In humans estrogen receptor α is the predominant estrogen receptor in hair follicles.

Due to the mixed ability of coumestrol to interact with estrogen receptor α and estrogen receptor β, this compound can exert actions that increase hair follicle growth.  Human estrogen (17 β — estradiol) tends to interact with estrogen receptor β (the primary estrogen receptor in the hair follicle).

Phytoestrogens can act as an anti-estrogen by temporarily binding to estrogen receptor β, thus inhibiting the telogen inducing activity of human estrogen by blocking binding sites.  This means coumestrol can prevent activation of estrogen receptor β and reduce premature telogen and extend anagen phase.

Substrates binding to an estrogen receptor usually have a preferential affinity to one receptor type. In this regard, most phytoestrogens show a preference for estrogen receptor β, while coumestrol predominantly binds to estrogen receptor α.

THE FINAL WORD

Phytoestrogens are a powerful plant-derived agent that can support hair regrowth for men and women with alopecia.  Whilst research supports supplementation of phytoestrogens, topically applied phytoestrogens, such as coumestrol in red clover, may be preferable to prevent systemic changes of hormone concentration.