Fertig RM1, et al Microneedling for the Treatment of Hair Loss? J Eur Acad Dermatol Venereol. 2017 Dec 1. doi: 10.1111/jdv.14722.
Abstract: Microneedling is a minimally invasive dermatological procedure in which fine needles are rolled over the skin to puncture the stratum corneum. This therapy is used to induce collagen formation, neovascularization, and growth factor production of treated areas. It has been used in a wide range of dermatologic conditions, including androgenetic alopecia and alopecia areata, among others. While there are a limited number of studies examining this therapy in the use of hair loss, microneedling has been successfully paired with other hair growth promoting therapies, such as minoxidil, platelet rich plasma, and topical steroids, and shown to stimulate hair follicle growth. It is thought that microneedling facilitates penetration of such first line medications and this is one mechanism by which it promotes hair growth. To date, the area most studied and with the most success has been microneedling treatment of androgenetic alopecia. While the current evidence does not allow one to conclude superiority of microneedling over existing standard therapies for hair loss, microneedling shows some promise in improving hair growth, especially in combination with existing techniques. This review summarizes the current literature regarding microneedling in the treatment of alopecia and calls for further studies to refine a standard treatment protocol.
Dr Proctor sez "PRP (Platelet Rich Plasma) helps regrow hair loss in rats"
Orliac S, et al, Efficacy of subcutaneous injection of platelet-rich plasma (PRP) in alopecia: A clinical and histological pilot study on a rat model with a six-month long-term follow-up experience. J Cosmet Dermatol. 2017 Nov 11. doi: 10.1111/jocd.12425.
PURPOSE: To assess the potential of platelet-rich plasma (PRP) subcutaneous injection of to treat hair loss and to evaluate local toxicity.
MATERIALS-METHODS: Twelve Hairless rats were used. At D0, we performed systematic clinical examination and divided the rat back into four quadrants (Q). We initiated subcutaneous injection using either PRP in PRPQ+, platelet-poor plasma (PPP) in PPPQ+, physiological serum (PS) in PSQ+, or no treatment (Q4). At D7, D14, D21, and D28 but also second month (M2), M3, M4, M5, rats had exactly the same injection procedure. Follow-up with PRP efficacy and toxicity at D28 and M6 using clinical and histological evaluation was performed.
RESULTS: Hair density was significantly improved at D28 and at M6 for PRPQ+ vs PSQ+, PPPQ+. Significant histological improvement was observed between D28 and M6, for PRPQ+ vs PPPQ+ and PSQ+ for vessels, collagen, and epithelium with no local toxicity.
CONCLUSION: Our study suggests that subcutaneous PRP injections using controlled concentration of platelets and leukocytes improve hair growth.
Another new minoxidil formulation
Gupta AK, Foley KA., 5% Minoxidil: treatment for female pattern hair loss. Skin Therapy Lett. 2014;19(6):5-7.
Abstract: Minoxidil is a US FDA-approved medication for hair loss in men and women. While 5% minoxidil foam has been approved for men since 2006, Health Canada and the FDA only approved 5% minoxidil foam for female pattern hair loss (FPHL) in 2014. Recent clinical trials showed the effectiveness of once daily 5% minoxidil foam for treatment of female pattern hair loss, where a significant change from baseline in the target area hair count was observed compared to placebo. Similar changes in hair count for 5% foam and twice daily 2% minoxidil solution established noninferiority of the 5% foam formulation in hairloss treatment. Five percent minoxidil foam is an option for women with pattern balding and will soon be available in Canada.
A new formulation of minoxidil
Lee HJ1, et al, Preparation and in vivo evaluation of lecithin-based microparticles for topical delivery of minoxidil. Arch Pharm Res. 2017 Aug 2. doi: 10.1007/s12272-017-0934-x
Abstract: Minoxidil is widely used for treatment of male pattern hair loss. Commercial products containing minoxidil are usually in solution form. Repeated applications of minoxidil solution can lead to adverse effects such as skin irritation and horniness. The aims of this study were to prepare lecithin-based microparticle in minoxidil solution for enhancement of minoxidil topical delivery and skin protection and evaluate the ability of lecithin on in vitro delivery, in vivo hair growth, and skin trouble improvement compared to commercial minoxidil solution. In in vitro skin permeation study, minoxidil solution containing lecithin microparticle showed higher skin penetration rate and higher retention of drug inside the skin compared to minoxidil solution without lecithin. After topical application of minoxidil solutions with or without lecithin to C57BL/6 mice, minoxidil 5% solution containing lecithin microparticle showed hair re-growth as efficient as commercial product of minoxidil 5% solution. It also significantly improved skin troubles while commercial product presented horny substance and crust formation. Therefore, the lecithin-based microparticle in minoxidil 5% solution has good ability to promote hair growth without adverse effects.
Adil A1, Godwin M2.The effectiveness of treatments for androgenetic alopecia: A systematic review and meta-analysis. J Am Acad Dermatol. 2017 Apr 7. pii: S0190-9622(17)30306-7. doi: 10.1016/j.jaad.2017.02.054.
Abstract: Androgenetic alopecia, or male pattern hair loss, is a hair loss disorder mediated by dihydrotestosterone, the potent form of testosterone. Currently, minoxidil and finasteride are Food and Drug Administration (FDA)-approved, and HairMax LaserComb, which is FDA-cleared, are the only treatments recognized by the FDA as treatments of androgenetic alopecia.
This systematic review and meta-analysis assesses the efficacy of nonsurgical treatments of androgenetic alopecia in comparison to placebo for improving hair density, thickness, growth (defined by an increased anagen:telogen ratio), or subjective global assessments done by patients and investigators.
A systematic review of randomized controlled trials was conducted. PubMed, Embase, and Cochrane were searched up to December 2016, with no lower limit on the year. We included only randomized controlled trials of good or fair quality based on the US Preventive Services Task Force quality assessment process.
A meta-analysis was conducted separately for 5 groups of studies that tested the following hair loss treatments: low-level laser light therapy in men, 5% minoxidil in men, 2% minoxidil in men, 1 mg finasteride in men, and 2% minoxidil in women. All treatments were superior to placebo in the 5 meta-analyses
CONCLUSIONS: This meta-analysis strongly suggests that minoxidil, finasteride, and low-level laser light therapy are effective for promoting hair growth in men with androgenetic alopecia and that minoxidil is effective in women with androgenetic alopecia.
Another paper on possible sexual dysfunction with Finasteride (Propecia).
"Persistent Sexual Side Effects of Finasteride (Propecia) for Male Pattern Hair Loss," Irwig, Michael S. et al. The Journal of Sexual Medicine , Volume 8 , Issue 6 , 1747 - 1753
ABSTRACT: Finasteride has been associated with reversible adverse sexual side effects in multiple randomized, controlled trials for the treatment of male pattern hair loss (MPHL). The Medicines and Healthcare Products Regulatory Agency of the United Kingdom and the Swedish Medical Products Agency have both updated their patient information leaflets to note that “persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use.”
Aim: We sought to characterize the types and duration of persistent sexual side effects in otherwise healthy men who took finasteride for MPHL (Male Pattern Hair Loss).
Methods: We conducted standardized interviews with 71 otherwise healthy men aged 21–46 years who reported the new onset of sexual side effects associated with the temporal use of finasteride, in which the symptoms persisted for at least 3 months despite the discontinuation of finasteride.
Main Outcome Measures: The types and duration of sexual dysfunction and the changes in perceived sexual frequency and sexual dysfunction score between pre- and post-finasteride use.
Results: Subjects reported new-onset persistent sexual dysfunction associated with the use of finasteride: 94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale. The mean duration of finasteride use was 28 months and the mean duration of persistent sexual side effects was 40 months from the time of finasteride cessation to the interview date. Study limitations include a post hoc approach, selection bias, recall bias for before finasteride data, and no serum hormone levels.
Conclusion: Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride.
Slightly-edited for Blog use
Dr P notes-- more on ATK-activation and hair regrowth.
Effect of sinapic acid on hair regrowth in human hair follicle dermal papilla cells via Akt activation. Woo H1, et al.Arch Dermatol Res. 2017 Mar 20. doi: 10.1007/s00403-017-1732-5
Hair loss also or alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair regrowth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.
Dr Proctor sez: Intersting paper on using low-level red light to treat hair loss.
Friedman S, Schnoor P.,Novel Approach to Treating Androgenetic Alopecia in Females With Photobiomodulation (Low-Level Laser Therapy). Dermatol Surg. 2017 Mar 21. doi: 10.1097/DSS.0000000000001114.
BACKGROUND: Photobiomodulation, also referred to as low-level laser therapy (LLLT),is used for the promotion of hair regrowth.
To better clarify the effects on the human hair follicle and surrounding tissue structures of laser light at 650 nm. ow-level laser treatment of the scalp every other day for 17 weeks is a safe and effective treatment for androgenetic alopecia in healthy females with Ludwig-Savin Baldness Scale I-2 to II-2 baldness patterns. Subjects receiving LLLT at 650 nm achieved an increase in hair counts compared with sham-treated control patients in this multicenter randomized controlled trial.
Thus, low-level laser therapy may play a potentially significant role in health care providers' armamentarium for androgenic alopecia or male pattern hairloss.. (edited for blog use)
Arif T1, et al, Dutasteride in androgenetic alopecia: An update. Curr Clin Pharmacol. 2017 Mar 10. doi: 10.2174/1574884712666170310111125.
BACKGROUND:Androgenetic alopecia is a common condition characterized by thinning of scalp hair. Conversion of testosterone to dihydrotestosterone, a more potent androgen, by the enzyme 5-a-reductase is responsible for underlying pathogenesis. Dutasteride, a synthetic 4-azasteroid, is a selective and competitive inhibitor of both type-1 and type-2 isoenzymes of 5-alpha-reductase. Finasteride and minoxidil are the only approved drugs for androgenetic alopecia. Dutasteride has been demonstrated to be effective in several randomized, double-blind, placebo controlled trials in androgenetic alopecia. In this review, after the pharmacology of dutasteride, the authors have discussed the status of dutasteride in androgenetic alopecia and has compared its efficacy with that of finasteride.
OBJECTIVE:This article aims to review the current status of dutasteride in androgenetic alopecia. The structure, mechanism of action, pharmacokinetic and side effects are discussed along with its comparission with finasteride in androgenetic alopecia.
One of our agents, Tempol, inhibits JAK-STAT signaling. This may account for at least some of its effectiveness in hair loss treatment.
McCormick J1, et al, "Free radical scavenging inhibits STAT phosphorylation following in vivo ischemia/reperfusion injury.", FASEB J. 2006 Oct;20(12):2115-7.
The signal transducer and activator of transcription (STAT family are latent transcription factors involved in a variety of signal transduction pathways, including cell death cascades. STAT1 has been shown to have a crucial role in regulating cardiac cell apoptosis in the myocardium exposed to ischemia/reperfusion (I/R) injury. The free radical scavenger, tempol, is known to have cardioprotective properties, although little is known about the molecular mechanism(s) by which it acts. In the present study, we assessed the levels of phosphorylated STAT1 and STAT3 and examined whether tempol was able to affect STAT activation after in vivo cardiac I/R injury. We observed a reperfusion time-dependent increase in the tyrosine phosphorylation of STAT1 and STAT3 at residues 701 and 705, respectively. Here we show for the first time that tempol dramatically reduced STAT1 and 3 phosphorylation. The reduction in STAT1 and 3 phosphorylation was accompanied by a concomitant decrease in cellular malondialdehyde (MDA) levels. To verify the role of STAT1 in modulating the cardioprotective effect of tempol, rats were injected with the STAT1 activator, IFN-gamma, and tempol during I/R injury. We found that the presence of IFN-gamma abrogated the protective effects of tempol, suggesting that the protective effects of tempol may partly operate by decreasing the phosphorylation of STAT1. This study demonstrates that careful dissection of the molecular mechanisms that underpin I/R injury may reveal cardioprotective targets for future therapy.
Harel, S. et al, "Pharmacologic inhibition of JAK-STAT signaling promotes hair growth." Sci Adv. 2015 Oct 23;1(9):e1500973. doi: 10.1126/sciadv.1500973
Abstract: Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells.
Dr Proctor sez-- Papers on on PRP (Platelet-Rich Plasma) Treatment of Hair loss.
By Moustafa A. et al, "Platelets Rich Plasma Versus Minoxidil 5% in Treatment of Alopecia Areata: A Trichoscopic Evaluation", October 28, 2016
Abstract: Alopecia areata is a common cause of nonscarring alopecia that occurs in a patchy, confluent, or diffuse pattern. Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases. Topical minoxidil solution 5% and platelet rich plasma are important modalities used in treatment of alopecia areata. We aimed to evaluate the efficacy of PRP versus topical minoxidil 5% in the treatment of AA by clinical evaluation and trichoscopic examination. Ninety patients were allocated into three groups; the first was treated with topical minoxidil 5% solution, the second with platelets rich plasma injections, and the third with placebo. Diagnosis and follow up were done by serial digital camera photography of lesions and dermoscopic scan before and every 1 month after treatment for 3 months. Patients treated with minoxidil 5% and platelets rich plasma both have significant hair growth than placebo. Patients treated with platelets rich plasma had an earlier response in the form of hair regrowth, reduction in short vellus hair and dystrophic hair unlike patients treated with minoxidil and control In conclusion, platelets rich plasma is more effective in the treatment of alopecia areata than topical minoxidil 5% as evaluated by clinical and trichoscopic examination.
Gupta AK, Carviel J., A Mechanistic Model of Platelet-Rich Plasma Treatment for Androgenetic Alopecia.Dermatol Surg. 2016 Sep 14.
BACKGROUND: Platelet-rich plasma (PRP) therapy is a novel procedure used to treat androgenetic alopecia (AGA).
OBJECTIVE: Propose a mechanism of action of PRP therapy for AGA.
METHODS AND MATERIALS: A thorough literature search including PRP research for AGA therapy as well as PRP research in other areas of medicine was conducted.
RESULTS: A mechanistic model for the action of PRP on the hair follicle was created.
CONCLUSION: Platelet-rich plasma therapy stimulates hair growth through the promotion of vascularization and angiogenesis, as well as encourages hair follicles to enter and extend the duration of the anagen phase of the growth cycle. The process is accomplished through growth factor-mediated increased activation of wingless (Wnt)/β-catenin, extracellular signaling regulated kinase (ERK), and protein kinase B (Akt) signaling pathways, which leads to the necessary cellular proliferation and differentiation.
Tempol and JAK kinases
Recently, medical researchers discovered that JAK kinase inhibitors such as Ruxolitinib and Tofacitinib are hair growth stimulators. As this paper shows, Tempol likewise modulates the action of JAK kinases. Tempol is in all our products and is a much safer agent.
Banday AA1, Lokhandwala MF. Oxidative stress causes renal angiotensin II type 1 receptor upregulation, Na+/H+ exchanger 3 overstimulation, and hypertension. Hypertension. 2011 Mar;57(3):452-9. doi: 10.1161/HYPERTENSIONAHA.110.162339. Epub 2011 Jan 31.
Abstract Oxidative stress modulates angiotensin (Ang) II type 1 receptor (AT(1)R) expression and function. Ang II activates renal Na(+)/H(+) exchanger 3 (NHE3) to increase sodium reabsorption, but the mechanisms are still elusive. In addition, the upregulation of AT(1)R during oxidative stress could promote sodium retention and lead to an increase in blood pressure. Herein, we investigated the mechanism of Ang II-mediated, AT(1)R-dependent renal NHE3 regulation and effect of oxidative stress on AT(1)R signaling and development of hypertension. Male Sprague-Dawley rats received tap water (control) or 30 mmol/L of l-buthionine-sulfoximine, an oxidant, with and without 1 mmol/L of Tempol, an antioxidant, for 3 weeks. l-Buthionine-sulfoximine-treated rats exhibited oxidative stress and high blood pressure. Incubation of renal proximal tubules with Ang II caused significantly higher NHE3 activation in l-buthionine-sulfoximine-treated rats compared with control. The activation of NHE3 was sensitive to AT(1)R blocker and inhibitors of phospholipase C, tyrosine kinase, janus kinase 2 (Jak2), Ca(2+)-dependent calmodulin (CaM), and Ca(2+) chelator. Also, incubation of proximal tubules with Ang II caused Jak2-dependent CaM phosphorylation, which led to Jak2-CaM complex formation and increased Jak2-CaM interaction with NHE3. The activation of these signaling molecules was exaggerated in l-buthionine-sulfoximine-treated rats, whereas Tempol normalized the AT(1)R signaling. In conclusion, Ang II activates renal proximal tubular NHE3 through novel pathways that involve phospholipase C and an increase in intracellular Ca(2+), Jak2, and CaM. In addition, oxidative stress exaggerates Ang II signaling, which leads to overstimulation of renal NHE3 and contributes to an increase in blood pressure.
DR P sez: Note how TEMPOL, used in our hair loss treatment formulation, "restored hair cycle"
Liu N, et al, Chronic Restraint Stress Inhibits Hair Growth via Substance P Mediated by Reactive Oxygen Species in Mice. PLoS One. 2013 Apr 26;8(4):e61574. doi: 10.1371/journal.pone.0061574. Print 2013.
BACKGROUNDS: Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown.
OBJECTIVES: The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle.
METHODS AND RESULTS:Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation.CONCLUSIONS: Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.
G. Douauda, et al, Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment, PNAS, vol. 110 no. 23, 9523–9528
Abstract: Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer's disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.
Catalase and graying hairWe are getting questions about recent media reports of the use of catalase and pseudocatalase to prevent hair from greying. Briefly: Hydrogen peroxide produced in metabolism prevents the production of the pigment melanin and make hair turn grey. Agents such as catalase itself or with catalase-like activity (pseudocatalase) such as PC-KUS destroy hydrogen peroxide and thus prevent hair from turning gray.
This is not exactly new information. Dr Proctor is a world-recognized expert on melanin pigment and on catalase. In fact, Dr Proctor published papers on the experimental use of catalase as medical treatment nearly three decades ago and is a pioneer in this field. Similarly, part of our experimental apparatus in melanin research is in the Smithsonian Institution's American Museum of History collection of pioneering items in semiconductor science. See: Organic Semiconductors.
Thus, we have long added agents which block the inhibitory action of hydrogen peroxide and other "active oxygen species" on hair pigmentation and hair graying. This includes "pseudocatalases". And yes, our agents do inhibit graying of hair. However, if gray hair and not hair loss is your only consideration, arguably, the best thing is just to dye it.
Shah AA, Sinha AA., Oxidative stress and autoimmune skin disease. Eur J Dermatol. 2013 Feb 1;23(1):5-13. doi: 10.1684/ejd.2012.1884. antioxidants play the important role in our body of neutralizing free radicals and peroxides that are formed during normal physiologic events. While these reactive oxygen species are necessary for numerous biological processes, when created in excess they can have deleterious effects. The skin as an organ is constantly under attack by reactive oxygen species from both endogenous and exogenous sources. The pathophysiology of many autoimmune diseases is unknown and recently oxidative stress has come to light as a possible triggering mechanism. Recent investigations attempting to link autoimmune skin diseases and oxidative stress have had varying degrees of success. In this article, we review the current literature regarding antioxidants in hair loss due to alopecia areata, pemphigus vulgaris and other blistering diseases, vitiligo, and psoriasis, and suggest possible future studies and treatment options.
KEYWORDS: alopecia areata, antioxidant, autoimmune, free radicals, catalase, psudocatalase,oxidative stress, pemphigus vulgaris, reactive oxygen species, organic semiconductors, vitiligo,gray, grey, graying, PC-KUS
Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. Methods: Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D(2) levels were determined for each participant. Results: Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D(2) levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. Conclusion: Low serum ferritin and vitamin D(2) are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease.
Dr Proctor comments on the following paper: We hold the primary patents for TEMPOL and use it in our hair loss treatment formulations. As the abstract below reports, part of its efficacy may be that it prevents pathological increases in the numbers of androgen receptors and thus makes antiandrogens work longer and better. We long-ago discovered that TEMPOL works in hair loss treatment. Preventing tissue reflex hyperandrogenicity is an unexpected bonus that may partially explian why TEMPOL seems to work so well as part of combination treatment:
Thomas R, Sharifi N., SOD mimetics: a novel class of androgen receptor inhibitors that suppresses castration-resistant growth of prostate cancer, Mol Cancer Ther. 2012 Jan;11(1):87-97. Epub 2011 Dec 15
Abstract: Advanced prostate cancer is the second leading cause of cancer-related deaths among American men. The androgen receptor (AR) is vital for prostate cancer progression, even in the face of castrate levels of serum testosterone following androgen ablation therapy, a mainstay therapy for advanced prostate cancer. Downregulation of superoxide dismutase 2 (SOD2), a major intracellular antioxidant enzyme, occurs progressively during prostate cancer progression to advanced states and is known to promote AR activity in prostate cancer. Therefore, this study investigated the effects of SOD mimetics on AR expression and function in AR-dependent LNCaP, CWR22Rv1, and LAPC-4AD prostate cancer cells. Treatment with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a SOD mimetic, not only lowered cellular superoxide levels but also concomitantly attenuated AR transcriptional activity and AR target gene expression in a dose- and time-dependent manner, in the presence and absence of dihydrotestosterone, the major endogenous AR agonist. Inhibition of AR by Tempol was mediated, in large part, by its ability to decrease AR protein via increased degradation, in the absence of any inhibitory effects on other nuclear receptors. Inhibitory effects of Tempol on AR were also reproducible with other SOD mimetics, MnTBAP and MnTMPyP. Importantly, effects of Tempol on AR function were accompanied by significant in vitro and in vivo reduction in castration-resistant prostate cancer (CRPC) survival and growth. Collectively, this study has shown for the first time that SOD mimetics, by virtue of their ability to suppress AR function, may be beneficial in treating the currently incurable CRPC, in which SOD2 expression is highly suppressed.