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Original Contributions
A pilot study evaluating the efficacy of topically applied niacin
derivatives for treatment of female pattern alopecia
Zoe Diana Draelos,1 Elaine L. Jacobson,2,3 Hyuntae Kim,2 Moonsun Kim2 & Myron K Jacobson2,3
1Department of Dermatology, Wake Forest University School of Medicine, NC
2Department of Pharmacology and Toxicology, University of Arizona, AZ
3Arizona Cancer Center, University of Arizona, AZ
Background Female pattern alopecia is a common dermatologic condition that manifestsafter puberty. The only approved drug treatment for this condition is 2% minoxidil fortopical application.
Aims This pilot study examined the effect of topical application of two niacin derivatives,octyl nicotinate and tetradecyl nicotinate, on hair fullness in female alopecia.
Patients/methods Sixty female subjects with Ludwig types I–III female pattern hair losswere evaluated in a double-blinded, placebo-controlled (40 active, 20 placebo) designusing standardized 35-mm photographic analyses for assessment of efficacy after6 months of application.
Results The niacin derivatives demonstrated a statistically significant increase in hairfullness (P = 0.04 compared to the placebo).
Conclusion Whereas evaluation of hair growth in women is challenging, this 6-monthpilot study demonstrated statistically significant increase in hair fullness on blinded 35-mmphotographic analysis. Long-term topical application of nicotinic acid derivatives offerspromise for providing benefit in female alopecia and warrants further study.
Keywords: female pattern alopecia, niacin, niacin derivatives, topical delivery this hair loss pattern, which seem to be hormonally Introduction
mediated. A good indicator of female pattern hair loss is a Female pattern hair loss (alopecia) affects approximately widening part line or a thinning ponytail. Typically, daily 20 million women. The condition appears to be familial; hair loss counts do not exceed 100–125 hairs; however, however, the exact inheritance pattern is unknown.
hair follicles that enter the telogen phase do not reenter Hair loss begins at puberty and progresses throughout the anagen growth phase, resulting in a slow net loss of life. Early detection of the condition is difficult, which is active follicles. The treatment options for this condition unfortunate, as early diagnosis and treatment are are limited and include hair transplants, hormonal important in achieving optimal therapy. Hair thinning supplementation, and minoxidil, a drug that affects in women usually spares the anterior hairline with a calcium homeostasis.1 Topical 2% minoxidil, available generalized decrease in hair count noted over the entire over the counter, is the only approved drug therapy for top of the scalp. However, there are many variations of Limited treatment options available for female alopecia has led to the search for other agents that can providebenefit for this condition. A potential candidate for hair Correspondence: Zoe Diana Draelos, MD, 2444 North Main Street, High Point, North Carolina, 27262, E-mail: [email protected] growth promotion is niacin (nicotinic acid), in which studieshave identified several possible mechanisms of benefit.
Accepted for publication August 4, 2005 2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 258– 261
Topical niacin derivatives and female pattern alopecia • Z D Draelos et al.
The major bioactive form of niacin, nicotinamide adenine At baseline, subjects were dispensed a 1-month supply dinucleotide (NAD), plays a central role in cellular energy of assigned study product. The first dose was applied by metabolism and, as a rapidly proliferating tissue, the hair a study nurse at the research center. Subjects were follicle has a high energy requirement.2 NAD is also the instructed to apply once daily at night six metered drops substrate for enzymes involved in the maintenance of to the scalp in the following manner: one drop each to the genomic integrity3 and calcium homeostasis.4 Additionally, right anterior scalp, left anterior scalp, right middle top of skin has been shown to contain niacin receptors that the head, left middle top of the head, right posterior scalp, stimulate leptin release,5 and downstream regulators in and left posterior scalp. If the hair was washed, the study the leptin pathway are involved in skin homeostasis6 and medication was applied following hair washing. All hair follicle cycling.7 Whereas either niacin or its other subjects were supplied with shampoo (Pantene formula vitamin form, niacinamide, has the potential to be for damaged hair, Procter & Gamble, Cincinnati, OH).
converted to NAD, the nicotinic acid receptor responds The frequency of hair washing was self-selected. Subjects were asked to maintain the entry style, color, and curl of Although niacin has the potential to provide benefit to skin and scalp, delivery of niacin per se is not feasible in Subjects returned at monthly intervals for evaluation appreciable amounts as it causes intense vasodilation at of increased hair fullness, scalp irritation, or other the site of application and its physical properties do not adverse events and product dispensing. They were asked allow it to achieve a prolonged residence time in the skin.
to shampoo the morning of study visit and to avoid apply- This has led to the development of myristyl nicotinate, a ing styling products. Subjects were also asked to assess niacin derivative that effects delivery to skin cells without the appearance of their hair. Standardized photography vasodilation and creates a residence time, allowing was used for the assessment of hair fullness, as increases conversion to NAD9 and stimulation of the nicotinic in hair fullness over the 6-month study period are nor- acid receptor in skin cells.8 Myristyl nicotinate has been mally not detectable by either the investigator or the shown to promote epidermal differentiation, leading to a subjects. At baseline, month 3, and month 6, Polaroid strong enhancement of skin barrier integrity.10 A second images were captured of the scalp vertex, with the hair niacin derivative, octyl nicotinate, stimulates blood flow combed away from the vertex like the spokes of the wheel, with the expected result of enhanced nutrient delivery to and the central partline, with the hair combed smoothly the scalp and increased removal rate for metabolic end to both sides of the head. These images were taken products. Thus, the potential of myristyl nicotinate and in duplicate with one set provided to the subjects for octyl nicotinate to provide benefit to the hair follicle by personal comparison, and the second set remained at multiple mechanisms combined with the well-established the study center. Standardized 35-mm photography safety profile of niacin provided the rationale to clinically was conducted at baseline, 2, 4, and 6 months as follows: assess these niacin derivatives in improving hair full- vertex view with hair combed away from the crown, ness in women with Ludwig types I–III female pattern superior view with hair parted in midline, frontal view with headband to reveal the anterior hairline. Theimages were taken with the subject’s head in a three-point mount specially designed for hair loss photography Materials and methods
(Canfield Scientific). Evaluation was completed on the Sixty female subjects, ages 20–80, who completed an 6-month photographs as this represents a minimal informed consent procedure with Ludwig types I–III time to detect changes in hair fullness.
female pattern hair loss11 were enrolled in a 6-monthpilot study using a double-blinded, placebo-controlled Results and discussion
design. Subjects were assigned randomly to the placebo(20, vehicle only) or active groups (40, vehicle con- Of the total subjects enrolled in the study, 32 of 40 active taining 0.5% octyl nicotinate, and 5.0% myristyl and 12 of 20 placebo subjects completed the study.
nicotinate). Dispensed products were packaged in A relatively high withdrawal rate is typical for hair identical containers. Trisiloxane and dimethicone were fullness/growth studies, but it is interesting to note that major components of the formulation. Because the actives proportionally twice as many subjects in the placebo are vitamin-derived substances, both the placebo and the group compared to the active group withdrew in this active preparations studied are classified as cosmetics study. Overall tolerability of the topical formulations was under the current Food and Drug Administration very good. There were no serious adverse events reported, and the mild adverse events included 9 reports of scalp 2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 258– 261
Topical niacin derivatives and female pattern alopecia • Z D Draelos et al.
Table 1 Evaluation of nicotinic acid derivatives on female pattern
rated on a scale of −1 for decreased hair fullness, 0 for no change, or +1 for increased hair fullness. These data are summarized in Table 1. The data comparing the placebo and active groups demonstrate an increased benefit for the active group with a P value of 0.04 as analyzed by the one-tailed Mann–Whitney test for nonparametric data.
The placebo effect observed in this study is not uncommon for hair fullness studies. An example of the effect of nicotinic acid derivatives on thinning hair as documented *Number of subjects enrolled in study.
by 35-mm photography at baseline and 6 months of †Number of subjects who completed the study.
‡Active compared to placebo for one-tailed Mann–Whitney test.
To our knowledge, this study represents the first §Active contained 0.5% octyl nicotinate and 5.0% tetradecyl attempt to evaluate the effects of niacin derivatives in women with Ludwig stages I–III female pattern hair loss.
Female hair fullness studies are difficult to conduct stinging, 2 of scalp burning, 12 of scalp itching, 4 because maintaining a constant hair appearance is chal- reporting scalp redness, and 7 reports of eye irritation.
lenging and judgements of improved growth are difficult These events occurred in both placebo and active groups, based on hair length. Furthermore, it is not feasible to use indicating that the volatile vehicle and not the active was many standardized male hair loss assessment techniques in female subjects such as shaving a 1–2-cm area of the The study yielded investigator, subject, and photo- scalp and utilizing macrophotography at monthly inter- graphic assessments. Polaroid photos and subject vals to obtain hair counts because it is very difficult to assessments revealed a positive trend, but did not reach recruit female subjects willing to allow this assessment.
significance at a P value of 0.05, which was not unex- For this reason, this study used standardized photography pected for a 6-month study. The key assessment was to assess improvements in hair fullness.
based on the standardized 35-mm photographs that were Although this study indicates that use of niacin deriv- evaluated by a blinded investigator for assessment of atives offers promise for providing benefit to individuals improvement in hair fullness. Each set of images was with female pattern alopecia, several questions were not Figure 1 An example of the effect of nicotinic acid derivatives on thinning hair as documented by 35-mm photography at baseline and
6 months of application.
2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 258– 261
Topical niacin derivatives and female pattern alopecia • Z D Draelos et al.
answered by the present study. It was not possible to during solar radiation. J Photochem Photobiol B 2001; 63:
determine in this study whether the increased hair fullness was the result of increasing the density of active 3 Jacobson MK, Jacobson EL. Discovering new ADP-ribose hair follicles or increasing the quality of the existing hair polymer cycles: protecting the genome and more. Trends
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shafts. Additionally, it was not possible to determine 4 Lee HC. Multiplicity of Ca2+ messengers and Ca2+ stores: a in this study whether the benefit was provided by octyl perspective from cyclic ADP-ribose and NAADP. Curr Mol nicotinate, myristyl nicotinate, or a combination of the two Med 2004; 4: 227–37.
niacin derivatives. An extended study will be needed to 5 Kim H, Jacobson MK, Kim M, Jacobson EL, Qasem J. A topical answer these questions. Because female pattern hair niacin prodrug enhances wound healing by stimulation of loss is a prevalent problem with few treatment options, leptin secretion. J Invest Dermatol 2002; 119: 347.
further research regarding benefit of niacin derivatives 6 Komuves LG, Hanley K, Man MQ, Elias PM, Williams ML, Feingold KR. Keratinocyte differentiation in hyperproliferative
epidermis: topical application of PPAR alpha activators
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Acknowledgements
7 Sano S, Itami S, Takeda K, et al. Keratinocyte-specific This research was supported in part by NIH grant ablation of Stat3 exhibits impaired skin remodeling, but R43CA90085 and a grant from Niadyne Inc. MKJ and does not affect skin morphogenesis. Embo J 1999; 18:
ELJ are principals in Niadyne Inc., whose sponsored research is managed in accordance with the University of 8 Tunaru S, Kero J, Schaub A, et al. PUMA-G and HM74 are Arizona conflict-of-interest policies. Dr Draelos owns no receptors for nicotinic acid and mediate its anti-lipolytic stock in Niadyne and has no other financial interest in effect. Nat Med 2003; 9: 352–5.
9 Jacobson MK, Tashtoush B, Coyle DL, et al. Elevation of skin cell NAD content by topical application of pro-nad References
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10 Jacobson EL, Kim H, Kim M, Wondrak GT, Jacobson MK. 1 Li M, Marubayashi A, Nakaya Y, Fukui K, Arase S. Developing topical prodrugs for skin cancer prevention. Minoxidil-induced hair growth is mediated by adenosine In: DS Alberts, LS Hess, eds. Fundamentals of Cancer in cultured dermal papilla cells: possible involvement of Prevention. Berlin, Heidelberg, New York: Springer; 2005: sulfonylurea receptor 2B as a target of minoxidil. J Invest Dermatol 2001; 117: 1594–600.
11 Ludwig E. Classification of the types of androgenetic 2 Jacobson EL, Giacomoni PU, Roberts MJ, Wondrak GT, alopecia (common baldness) occurring in the female sex. Jacobson MK. Optimizing the energy status of skin cells Br J Dermatol 1977; 97: 247–54.
2005 Blackwell Publishing • Journal of Cosmetic Dermatology, 4, 258– 261

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