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The trimethylated amino acid l-carnitine plays a key role in the intramitochondrial transport of fatty acids for beta-oxidation and thus serves important functions in energy metabolism. Here, we have tested the hypothesis that l-carnitine, a frequently employed dietary supplement, may also stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix. Hair follicles (HFs) in the anagen VI stage of the hair cycle were cultured in the presence of 0.5-50 microm of l-carnitine-l-tartrate (CT) for 9 days. At day 9, HFs treated with 5 microm or 0.5 microm of CT showed a moderate, but significant stimulation of hair shaft elongation compared with vehicle-treated controls (P < 0.05). Also, CT prolonged the duration of anagen VI, down regulated apoptosis (as measured by TUNEL assay) and up regulated proliferation (as measured by Ki67 immunohistology) of hair matrix keratinocytes (P < 0.5). By immunohistology, intrafollicular immunoreactivity for TGFbeta2, a key catagen-promoting growth factor, in the dermal papilla and TGF-beta II receptor protein in the outer root sheath and dermal papilla was down regulated. As shown by caspase activity assay, caspase 3 and 7, which are known to initiate apoptosis, are down regulated at day 2 and day 4 after treatment of HFs with CT compared with vehicle-treated control indicating that CT has an immediate protective effect on HFs to undergo programmed cell death. Our findings suggest that l-carnitine stimulates human scalp hair growth by up regulation of proliferation and down regulation of apoptosis in follicular keratinocytes in vitro. They further encourage one to explore topical and nutraceutical administration of l-carnitine as a well-tolerated, relatively safe adjuvant treatment in the management of androgenetic alopecia and other forms of hair loss.

The functional role of VR1, which we and others have recently identified on several epithelial and mesenchymal human skin cell populations, was investigated in the human hair follicle (HF), as a prototypic epithelial–mesenchymal interaction system. VR1 immunoreactivity was confined to distinct epithelial compartments of HFs in anagen and catagen, while dermal papilla fibroblasts and HF melanocytes were VR1 negative. In organ culture, VR1 activation by capsaicin resulted in a dose-dependent and VR1-specific inhibition of hair shaft elongation, suppression of proliferation, promotion of apoptosis, and induction of catagen transformation, possibly due to upregulation of a potent hair growth inhibitor TGFβ2. Cultured outer root sheath (ORS), as well as HaCaT, keratinocytes also expressed functional VR1, whose stimulation inhibited proliferation, induced apoptosis, and elevated intracellular calcium concentration. Finally, VR1 stimulation of cultured ORS keratinocytes upregulated the expression of recognized endogenous hair growth inhibitors (IL-1β and TGFβ2) and downregulated the expression of stimulators (HGF, IGF-1, and SCF), while key differentiation markers (CK17, CK14, filaggrin, and involucrin) remained unaffected. In conclusion, VR1 is a significant novel player in human hair growth control underscoring that its physiological functions in human skin far extend beyond sensory neuron-coupled nociception.