Administration of capsaicin and isoflavone promotes hair growth by increasing insulin-like growth factor-I production in mice and in humans with alopecia.
OBJECTIVE
Insulin-like growth factor-I (IGF-I) plays an important role in hair growth. Capsaicin activates vanilloid receptor-1, thereby increasing the release of calcitonin gene-related peptide (CGRP) from sensory neurons, and CGRP has been shown to increase IGF-I production. We recently reported that isoflavone, a phytoestrogen, increases production of CGRP by increasing its transcription in sensory neurons. These observations raise the possibility that administration of capsaicin and isoflavone might promote hair growth by increasing IGF-I production. In the present study, we examined this possibility in mice and humans with alopecia.


METHODS
Dermal IGF-I levels, immunohistochemical expression of IGF-I in the skin and hair regrowth were examined after capsaicin and isoflavone administration to wild-type (WT) mice and CGRP-knockout mice. Plasma levels of IGF-I and promotion of hair growth were evaluated in 48 volunteers with alopecia after administration of capsaicin and isoflavone for 5 months.


RESULTS
Subcutaneous administration of capsaicin significantly increased dermal IGF-I levels at 30 min after administration in WT mice (p < 0.01), but not in CGRP-knockout mice. Dermal levels of IGF-I were significantly higher in WT mice administered capsaicin and isoflavone for 4 wks than in those administered capsaicin alone for 4 wks (p < 0.01) and in those administered neither of them (p < 0.01). Immunohistochemical expression of IGF-I at dermal papillae in hair follicles was increased in WT mice administered capsaicin and isoflavone and in those administered capsaicin alone at 4 wks. Hair regrowth was clearly more accelerated in WT mice administered capsaicin and isoflavone for 4 wks than in those administered capsaicin alone for 4 wks and in those administered neither of them. Plasma levels of IGF-I were significantly increased from baseline levels in 31 volunteers with alopecia at 5 months after oral administration of capsaicin (6 mg/day) and isoflavone (75 mg/day) (p < 0.01), while they were not increased in 17 volunteers with alopecia administered placebo. The number of volunteers with alopecia who showed promotion of hair growth at 5 months after administration was significantly higher among volunteers administered capsaicin and isoflavone (20/31: 64.5%) than among those administered placebo (2/17: 11.8%) (p < 0.01).


CONCLUSIONS
These observations strongly suggested that combined administration of capsaicin and isoflavone might increase IGF-I production in hair follicles in the skin, thereby promoting hair growth. Such effects of capsaicin and isoflavone might be mediated by sensory neuron activation in the skin.
Harada
Naoaki
N
Department of Translational Medical Science Research, Nagoya City University, Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Okajima
Kenji
K
Arai
Masatoku
M
Kurihara
Hiroki
H
Nakagata
Naomi
N
D000505:Alopecia / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency / Q000235:genetics; D002211:Capsaicin / Q000627:therapeutic use*; D006197:Hair / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007529:Isoflavones / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout
D007529:Isoflavones; D007334:Insulin-Like Growth Factor I; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin