Caffeine counteracts stress-induced hair damage and promotes healthy hair growth

The aim of this study was to investigate how effectively caffeine can counteract stress-induced hair damage triggered by the corticotropin-releasing hormone (CRH) in hair follicles. The results show that caffeine can significantly reduce the negative stress reactions and hair growth inhibitions caused by CRH as a stress hormone. This is further evidence that caffeine promotes healthy hair growth and can even counteract stress-related hair loss.

Human hair reacts very sensitively to stress. It is believed that the progression of hereditary hair loss (androgenetic alopecia, AGA) is worsened by stress. One possible reason for this is the presence of an equivalent of the hypothalamic-pituitary-adrenal axis – or stress axis (HPA axis) – in the hair follicles of the scalp.

In this research, a response in this stress axis was generated in an ex vivo hair organ culture model (HOKM) by targeting the so-called corticotropin-releasing hormone (CRH) in human male hair follicles that had a predisposition to hereditary hair loss.

The positive influence of caffeine in this model system was demonstrated in previous work. Here, caffeine was shown to be an antagonist of the hair growth-inhibiting hormone testosterone. In the hair organ culture model (HOKM), it was now investigated whether caffeine can counteract CRH-mediated stress in hair follicles.

Hair follicles were taken by biopsy from the area affected by hereditary hair loss (vertex area) and cultured in the hair organ culture model with CRH (10^-7 M) with (0.001 %, 0.005 %) and without caffeine.

Compared to the control experiment, CRH in this model significantly increased the expression of certain markers such as TGF-β2, which initiates the catagen phase (p<0.001), CRH receptors 1/2 (p<0.01), ACTH (p<0.001), and melanocortin receptor-2 (MC-R2) (p<0.001), as well as other stress-associated parameters such as substance P and the p75 neurotrophin receptor. Conversely, CRH inhibited the proliferation of matrix keratinocytes and the expression of IGF-1, a marker promoting the anagen phase, and the pro-proliferative receptor for nerve growth factor (TrkA).

Caffeine significantly counteracted the described stress effects in this model. Additionally, for the first time, an increase in IP3-R through caffeine in human hair follicles was demonstrated. These ex vivo results in human androgenetic hair follicles provide initial evidence that the stress mediator CRH not only triggers a complex intrafollicular HPA response to stress but also a non-HPA-related stress response.

Furthermore, it was shown that these effects could be effectively counteracted by the addition of caffeine. Therefore, these data support the hypothesis that stress can impair the physiology of human hair and cause hair loss. This provides initial evidence that caffeine appears to be capable of counteracting stress-induced hair damage and preventing stress-induced hair loss.

This ex vivo study demonstrates the positive influence of caffeine on stress-related human hair loss in individuals predisposed to androgenetic alopecia.

The positive effect of caffeine on hair growth is known from previous ex vivo studies on male and female human hair follicles(1, 2) as well as in vivo(3-7). For the first time, the CRH induction on the HPA stress axis in male human hair follicles (HF) from biopsies of the balding vertex area of men with hereditary hair loss (androgenetic alopecia, AGA) could be demonstrated.

• ACTH: The adrenocorticotropic hormone, also known as adrenocorticotropin, is a hormone normally released by the pituitary gland that, among other things, controls the release of corticosteroids by the adrenal glands.
• The anagen phase is the growth phase of the hair.
• Androgenetic alopecia (Alopecia androgenetica, AGA) is a hereditary form of hair loss that can affect both men and women.
• Biopsy (Greek "life" and "to see") is a surgical procedure to remove and examine a small amount of tissue from a living organism.
• Caffeine is one of the world's most well-known stimulants, found, for example, in coffee.
• Corticotropin-releasing hormone (CRH) is a hormone produced in the hypothalamus (part of the brain). Its function is to stimulate the production of adrenocorticotropic hormones, which in turn regulate the production of glucocorticoids, mineralocorticoids, and sex hormones.
• Ex vivo (Latin for 'outside the living') refers to procedures or processes in which living biological material, especially cells, tissues, or organs, are removed from a living organism and typically cultured outside it for a limited time.
• Hair loss is a permanent loss of hair where the fallen hair does not grow back. Technical terms for unwanted hair loss are effluvium and alopecia for visible thinning with or without abnormally sparse scalp hair.
• A hair follicle (HF) is the structure that surrounds the human hair root.
• The hair organ culture model (HOCM) is a standardised in vitro model in which human single hair follicles, e.g. from scalp biopsies, are extracted and cultured in medium. Under standardised growth conditions, growth parameters such as hair shaft elongation, anagen/catagen stage, Ki-67 proliferation marker, stimulation of "insulin-like growth factor 1" (IGF1), and inhibition of the catagen inducer "transforming growth factor β2" (TGF-β2) are investigated.
• The hypothalamic-pituitary-adrenal axis or stress axis represents a complex sequence of direct influences and feedback loops between three hormone glands:
  • the hypothalamus,
  • the pituitary gland (a pea-shaped structure under the hypothalamus),
  • and the cortex of the adrenal glands (small, conical organs sitting on top of the kidneys).
  • The interactions between these organs form the HPA axis. It is a major part of the hormonal system that controls stress responses and regulates many processes in the body, including digestion, the immune system, mood and emotions, sexuality, energy storage and usage.
• Insulin-like growth factors (IGF) are polypeptides that show a high sequence homology to insulin and act as growth factors. They are produced in liver cells, but also in other foetal and adult tissues. They are part of a complex system that body cells use to communicate with their environment.
• In vitro (Latin 'in glass') refers to organic processes that take place outside a living organism, as opposed to those that occur within a living organism (in vivo). In science, in vitro refers to experiments conducted in a controlled artificial environment outside a living organism, such as in a test tube or petri dish.
• The catagen phase is the transition phase of hair from growing to falling out.
• The keratinocyte is the most common cell type found in the epidermis. This cell type produces keratin and differentiates during keratinisation as it moves from the lowest layer of the epidermis to the uppermost layers. The result is the corneocyte.
• Cultivation in the biological sense refers to the creation and maintenance of conditions that ensure the growth of certain organisms.
• The melanocortin receptor 2 (MC2R), also known as the ACTH receptor (ACTHR) or corticotropin receptor, is expressed in the adrenal cortex and mediates the effects of ACTH. It is a G-protein-coupled receptor from the melanocortin receptor family.
• The pan neurotrophin receptor (p75 NTR) induces cell death of foetal nerve cells – in adult cells also following injuries, hence it is a target in the treatment of neurodegenerative diseases.
• Substance P is a neuropeptide consisting of eleven amino acids. It belongs to the group of neurokinins and is produced by nerve cells as well as leukocytes. The letter P originally stood for 'powder', as the substance was available in powder form; today, the P is interpreted as 'pain'.
• Testosterone is a sex hormone (androgen) that occurs in both sexes but differs in concentration and mode of action between men and women. The hormone testosterone is an important factor in the development of hereditary hair loss. It is enzymatically converted to dihydrotestosterone (DHT). DHT can initiate cellular processes through binding to androgen receptors, which, due to a decrease in energy levels, result in a shortened hair growth phase and thus hair loss. Gradually, the hair follicles can be reduced and ultimately destroyed, leading to the formation of a bald spot.
• Transforming growth factor-beta 2 (TGF-β2) is a protein with important cellular functions and vital significance during embryonic development.
• Tropomyosin receptor kinase A (TrkA) is a protein encoded in humans by the NTRK1 gene.
• Vertex area: The crown region of the back of the head.