Rosemary oil, is being sold on Amazon.com for hair loss. Hair loss is a normal part of the cell cycle. The amount of hair on a person’s head depends on the time spent in each cycle.
Open and inactive ion channels, a tricky concept
We are going to be discussing the ZCaV1.2 and TRPV Ca2+ channels. A Ca2+ channel lets Ca2+ from outside the cell were the concentration is high to the inside where the concentration is low. Once inside the cell Ca2+binds to signalling molecules that direct the cell’s response to the outside world.
What terpenes are in rosemary essential oil? Is there any reason to think these terpenes might impact hair loss and/or growth? Valtcho Zheljazkov of Oregon State University at Pendleton USA and coauthors from Dalhousie University in NS Canada and the Bulgarian Agricultural University published a nice study on the role of steam distillation times on the terpene profile of rosemary essential oil. The rosemary seeds came from Bulgaria. The plants were cultivated in the southern US state of Mississippi.  As exciting as this international effort is, w consumers have to wonder about product variability.
What is in rosemary oil?
The authors were trying to establish the optimal times for steam distillation to obtain the desired terpene products.  This peer reviewed publication is open to the general public. The reader is invited to it it for themselves for greater details.
Several dozen terpenes were detected in steam distilled rosemary essential oil.  If we assume a distillation time of 160 minutes the rank yield is as follows, followed by potential receptors:
The role call of primary terpenes in rosemary essential oil 
- α- and β-pinene… GABAA receptor is a chloride channel. The α- isoform of pinene is more abundant than the β- isoform. Many studies have been conducted with a racemic mixture of the two.  For now GABAA will receive the brief comment that a rodent study induced psychological stress via chronic restraint to test the hypothesis that this would slow hair growth. GABAA receptor inhibitors ginkgolide and picotoxin alleviated this inhibition of cell cycle enzymes and hair growth. 
- eucalyptol TRPM8 L-type VGCC VGCC is an acronym for voltage gated Ca2+ channel. CaV1.2 is one member of this family. The connection of the voltage gated calcium channel CaV1.2 is via the rare mutation in this channel that causes Timothy Syndrome which is manifested by a minor symptom of baldness at birth.  Bulge stem cells have been found to express CaV1.2  In contrast, treatment with L-type channel blockers that induce channel inactivation cause an early entry into anagen and can reverse the TS phenotype. In additional experiments, Cav1.2 was found to regulate the production of the bulge-derived BMP inhibitor follistatin-like1 (Fstl1), which binds to bone morphogenic protein 4 BMP-4 and TGF-β1 and acts to inhibit stem cell quiescence.  The authors concluded that Cav1.2 provides a calcium-independent signal in hair follicle stem cells that inhibits quiescence and promotes tissue regeneration. Because the closed and open channel states demonstrated similar phenotypes in delaying anagen the authors hypothesized that the inactivated state of the channel by blockers would stimulate anagen, which turned out to be the case. 
- camphor TRPV3 see the next section
- camphene PPAR-γ ,,,according to Wikipedia authors PPARγ is a transcription factor that binds various lipid small molecules that mediate the transcription of genes involved with fat accumulation. PARγ promotes the differentiation of sebocytes in hair follicles.  A mouse was generated that expressed PARγ in the womb but ceased to express this transcription factor post natal.  PpargΔ/Δ mice had no sebaceous glands. Morphogenesis and marker protein expression was delayed in postnatal hair follicles in these knockout mice, Adult PpargΔ/Δ mice developed scarring alopecia and severe perifollicular inflammation.  Lipodystrophy was associated with the onset of hair follicle dysfunction.  PARγ may stimulate Bulge stem cells and sebocytes. The bottom line seems to be that the hair follicle needs its own source of energy. Unlike glycolysis of glucose, the mitochondria are absolutely required for converting fatty acids to ATP. This is where CopperOne niacin might come in. Copper is a cofactor in mitochondrial cytochrome C oxidase. Niacin is a vasodilator that, theoretically, increases blood circulation to the growing hair follicle.
- myrcene TRPV1 increases opening
- linalool Voltage gated calcium channel VGCC, have been discussed. A second target is PPARα. PPARα agonist clofibrate has been shown to lead to cessation of hair follicle growth at 1 μM. Low clofibrate, 10 nM, enhanced survival of human hair follicles in culture.  PPARα activation tends to favor fatty acid catabolism towards the production of ATP. Collectively these data suggest that rosemary essential oil contains the terpenes to promote hair follicle fat accumulation as well as tapping in to those fat reserves if the relative amount of linalool is low. What is the point of saving money in the “fat bank” if we don’t sometimes tap into it when we want to grow something new like a hair shaft?
This family of Ca2+ channels is discussed in greater detail on the Trp page of this site. The perplexing thing about these channels that they have an auto shut off mechanisms. See the turning TRPV1 off post.
Brief aside, other essential oil terpenes that gate TRPV3
These channels were expressed in HEK293 cells, a common system for studying ion channels. Thymol and carvacrol are not considered main constituents of rosemary essential oil but could be terpenes to think about. The vexing thing about the TRPV family of channels is turning them on “too much” results in them being turned off.  This is the perplexing difference between being off and inactivated. “Off” can be turned “on” while “inactivated” cannot.
TRPV1 and hair growth inhibition 
TRPV1 is a cation, mostly Ca2+, channel that is opened by capsaicin, the noxious compound in chili peppers. Eniko˝ Bodo and coauthors gave a brilliant introduction to this multifunctional ion channel that responds not only to capsaicin but also heat, acid, and lipid peroxidation products.  This group studied the affect of capsaicin on growth of cultured human hair follicles. Figure 1 they compared the amount of transcripts for the TRPV1 in cultured cell lines CHO and C6 transfected with the gene for TRPV1, non transfected controls (NTC) and the human hair follicles. cDNA refers the messenger RNA converted to DNA for PCR quantitation.
One interesting thing to note is that human hair follicles express TRPV1 in amounts similar to that of cultured cells genetically “engineered” to express large amounts of this channel.The * in figure 2 are differences that are significant at p<0.05, or in other words, differences we are 95% confident are not due to random variations. I-RTX is an inhibitor of TRPV1. It reverses the inhibition of capsaicin on elongation. 
Figures 3 and 5 explored altered states of human hair follicles cultured with 10 µM capsaicin for 5 days (Fig 3) or only 2 days, Fig 5. Ki-67 is a marker for cell proliferation whereas TUNEL is a measure of DNA fragmentation that is part of apoptosis, programmed cell death. TGFβ2 is an established mediator of apoptosis, programed cell death, and catagen. In other figures not shown in this post, the authors proved that use of capsaicin was increasing intracellular calcium in cells expressing TRVP1 as well as inhibiting proliferation. 
Some colleagues at CopperOne are convinced that cuprous nicotinic acid reverses hair turning white. Note that melanin synthesis requires a copper cofactor. See Copper and Gray hair.
Table 1 paints a general picture of inflammation and cell death. Interestingly, the production of structural hair proteins is relatively unaffected. Annexin-V corroborates the TUNEL assay suggesting that capsaicin promotes apoptosis.
TRPV3 and hair growth inhibition 
A similar Turkish study examined the role of TRPV3 channels in the outer root sheath keratinocytes of human hair follicles in culture.
TRPV3 mRNA expression was assessed by quantitative real-time PCR in human anagen and catagen HFs, outer root sheath ORS keratinocytes (ORSK), dermal papilla DP fibroblasts (DPF), and dermal fibroblasts (HDF). Data are expressed as mean±SEM of three independent determinations performed in triplicate.
The Turkish study added some twists. They used the synthetic Trpv3 agonist 2-aminoethoxydiphenyl borate (2-APB) as well as the essential oil component eugenol. This is not to be confused with eucalyptol in rosemary oil. 
These authors also spent a fair amount of effort proving that TRPV3 functions as a Ca2+ channel, figure 3 not shown in this post. In panels 4b and 4c presented experiments in which that the TRPV1-6 inhibitor Ruthenium Red was used. Adding this inhibitor had the same effect as low Ca2+ in terms of reversing the 2-APB and eugenol decrease in proliferation and mitochondrial membrane potential, presented in 4a.
The authors addressed the issue that TRPV1 may also be in the primary cultured keratinocytes. They addressed this issue by using interfering RNA that prevents TRPV3 transcripts from being translated into protein. As a control it is typical to add a scrambled sequence. In theory, the scrambled sequence should behave just like no RNA addition at all, which was shown in supplemental data.
Rosemary oil clinical trial 
Rosmarinus officinalis L essential oil was compared with the gold standard of androgenetic alopecia (AGA): 2% minoxidil which is a valsodilator. The authors claimed rosemary essential oil elicits “enhancement micro capillary perfusion” in the abstract of this study. For 6 months 50 AGA patients each received these treatments for hair loss. After baseline assessment patients were evaluated at 3 and 6 months. Neither treatment produced a change in mean hair count by 3 months though significant increases in hair count were seen by 6 months compared to previous time points. (P > .05). No significant difference was found between the study groups regarding hair count either at month 3 or month 6 (> .05). Both treatments caused scalp itching at the 3- and 6-month time points compared to the baseline (p < .05). Scalp itching was more frequent in the minoxidil group than rosemary oil at both assessed endpoints (P < .05).
More on TRPV3 modulation 
These authors idscuss Ca2+CaM (calmodulin) being responsible for turning off TRPV3 , like TRPV1, ATP also entered the discussion of turning TRPV3 off. It is no wonder that rosemary oil took 6 months to have an effect. 
Feature image disclosure 
The review article for which the featured image (with modifications) was derived was about frontal fibrosing alopecia (FFA).  There are many forms of hair loss. Wikipedia authors cite two treatments for Pattern hair loss: vaso dilator minoxidil and finasteride, a 5α-reductase inhibitor. 5α-redluctase takes testosterone to dihydro testosterone leaving the hair follicles to fade away. The summary cartoon of Maio and coauthors 2022  provided and excellent starting point for this post to explore where terpenes in rosemary oil might it into the big picture.
Why copper and niacin might help
Let’s go back to the blood flow and minoxidil. There are more natural ways to achieve this end. Niacin is one as explained by Oxford BioLabs. eHealthme discusses caution of ultra high therapeutic doses of oral niacin for cholesterol issues in females over 60 years old. Perhaps topical niacin is better. The beauty site Byrdie offers tips on using topical niacin as well as links to hair care products that contain niacin. What about copper? In all of this discussion about copper we have forgotten that growing hair is an energy intensive business.
- Cytochrome C oxidase is a copper cofactor enzyme required for ATP production in the mitochondria.
- Lysyl oxidase is a copper cofactor enzyme that cross links collagen fibers for optimal strength.
- Tyrosinase is a copper cofactor enyzme required for melanin production. Think colored hair instead of white hair.
- Menke’s Disease, a genetic disease that causes copper deficiency results in hair that is kinky. brittle and white. https://en.wikipedia.org/wiki/Menkes_disease
A so-called copper peptide is marketed for hair loss. Rosemary essential oil might be an attractive compound to combine with copper and niacin. While the terpenes in rosemary oil may increase blood flow, as assumed by the authors of the clinical trial  , these same terpenes do much more. Many laboratories that service the cannabis industry will profile the terpene content of essential oils. Some of these terpenes might increase the delivery of copper and/or niacin to hair follicles.
- Zheljazkov VD, Astatkie T, Zhalnov I, Georgieva TD. Method for attaining rosemary essential oil with differential composition from dried or fresh material. J Oleo Sci. 2015;64(5):485-96. free article
- Salehi B, Upadhyay S, Erdogan Orhan I, Kumar Jugran A, L D Jayaweera S, A Dias D, Sharopov F, Taheri Y, Martins N, Baghalpour N, Cho WC, Sharifi-Rad J. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules. 2019 Nov 14;9(11):738. PMC free article
- Wang X, Su Y, Cai Z, Xu Y, Wu X, Al Rudaisat M, Hua C, Chen S, Lai L, Cheng H, Song Y, Zhou Q. γ-Aminobutyric acid promotes the inhibition of hair growth induced by chronic restraint stress. Life Sci. 2023 Mar 15;317:121439. PubMed
- Yucel G, Altindag B, Gomez-Ospina N, Rana A, Panagiotakos G, Lara MF, Dolmetsch R, Oro AE. State-dependent signaling by Cav1.2 regulates hair follicle stem cell function. Genes Dev. 2013 Jun 1;27(11):1217-22. PMC free article
- Sardella C, Winkler C, Quignodon L, Hardman JA, Toffoli B, Giordano Attianese GMP, Hundt JE, Michalik L, Vinson CR, Paus R, Desvergne B, Gilardi F. Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion. J Invest Dermatol. 2018 Mar;138(3):500-510. PMC free article
- Billoni N, Buan B, Gautier B, Collin C, Gaillard O, Mahé YF, Bernard BA. Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPAR alpha involvement in hair growth. Acta Derm Venereol. 2000 Sep-Oct;80(5):329-34. free article
- Vogt-Eisele A. K., Weber K., Sherkheli M. A., Vielhaber G., Panten J., Gisselmann G., Hatt H. (2007) Monoterpenoid agonists of TRPV3. Br. J. Pharmacol. 151, 530–540 [PMC free article]
- Bodó E, Bíró T, Telek A, Czifra G, Griger Z, Tóth BI, Mescalchin A, Ito T, Bettermann A, Kovács L, Paus R. A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Am J Pathol. 2005 Apr;166(4):985-98. PMC free article
- Borbíró I, Lisztes E, Tóth BI, Czifra G, Oláh A, Szöllosi AG, Szentandrássy N, Nánási PP, Péter Z, Paus R, Kovács L, Bíró T. Activation of transient receptor potential vanilloid-3 inhibits human hair growth. J Invest Dermatol. 2011 Aug;131(8):1605-14. PMC free article
- Panahi Y, Taghizadeh M, Marzony ET, Sahebkar A. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial. Skinmed. 2015 Jan-Feb;13(1):15-21. PMID: 25842469. PubMed
- Wang G, Wang K. The Ca2+-Permeable Cation Transient Receptor Potential TRPV3 Channel: An Emerging Pivotal Target for Itch and Skin Diseases. Mol Pharmacol. 2017 Sep;92(3):193-200. PMC free article
- Miao YJ, Jing J, Du XF, Mao MQ, Yang XS, Lv ZF. Frontal fibrosing alopecia: A review of disease pathogenesis. Front Med (Lausanne). 2022 Jul 25;9:911944. PMC free article