Shedding Some Light on Hair Loss

Human hair is evolutionary, intended to provide protection, regulate body temperature, and assist with evaporation of perspiration, but society’s obsession with hair has little, if anything, to do with these functions. Concern about hair—and its absence or presence—is almost universally about youth, aesthetics, and by extension feelings of emotional wellbeing. We see these concerns on a daily basis in a range of patients with androgenetic alopecia (AA) who present early enough to have a chance of slowing hair loss before it becomes a major issue, as well as others who ultimately regret not seeking help sooner. AA affects more than 80 million Americans, resulting in pattern hair loss in both men and women. Unlike telogen effluvium, where hair follicles go into a prolonged resting state that results in global shedding over time, AA in men and women is caused primarily by a genetic predisposition and androgens like 5α-dihydrotestosterone (DHT) in the skin. Conversion of testosterone to DHT in the scalp accelerates the rate at which hair follicle miniaturization takes place, so as new hair follicles are generated they are smaller than their predecessors, eventually leading to miniaturized follicles that do not support hair growth.¹

Industry has responded to consumer demand for hair growth assistance, and the marketplace became overcrowded with products supported by unsubstantiated claims, leading to an environment that promotes skepticism instead of evidence-based decision making. Persistence in clinical and bench research and ongoing patient demand paid off, however, resulting in a great deal of research and development success over the past 20 years. Inhibition of DHT production in the skin has been shown to be effective in treating receding hair lines and other forms of male pattern baldness with the FDA approved 5α-reductase inhibitor, finasteride (Propecia, Merck).²

Oral finasteride, topical minoxidil (Rogaine, Johnson & Johnson Consumer), and dietary supplements like Viviscal and Nutrafol have all shown statistically significant improvements in net hair counts per cm² in well controlled clinical studies, making these important non-surgical therapies to consider in any hair loss regimen.

While pharmaceuticals have made great strides in the hair re-growth specialty, for the purpose of this article we will focus on laser- and light-based technology for hair growth and the future of medical grade LED light in scalp regeneration. Given the myriad variables involved, such as the type of light, amount of energy, skin tone, hair density, and hormonal considerations, among other things, it’s important to acknowledge that this is not a comprehensive review. It is a glance at some salient studies and noteworthy findings that helped move these hair-centric light-based techniques forward, as well as my observations on those efforts.

We’ll start in the early days, when serendipitous research found that laser energy resulted in unintended hair growth in a tangential area (paradoxical hypertrichosis) and continue to today’s well-controlled, red light therapy clinical studies.

Let There Be Light

Hair growth in patients who have AA has been successfully achieved through a range of in-office energy-based devices including fractional lasers and at-home low-level laser therapy (LLLT) devices. In the last two years alone, the number of approved items on the FDA’s 510(k) premarket notification list classified as laser, comb, cap, or hair product intended for growth of scalp hair has nearly doubled to a total of 50.³

The term low-level laser therapy is often used interchangeably with low-level light therapy or photobiomodulation (PBM). The delivery of this non-thermal, low intensity light of specific wavelengths (10mW–500mW) triggers biochemical changes whereby photons of light are absorbed by cellular photoreceptors and result in downstream alterations to gene expression or cell signaling cascades.⁴ Distinct wavelengths of light have been known to have various biological effects on humans. For example, light administered either through low-powered lasers or some LEDs with a wavelength in the red to near-infrared region of the spectrum (660-905nm) has been proven in clinical trials to have a good effect on pain, inflammation, and tissue repair.

LLLT was accidentally discovered in the 1960s when Hungarian scientist Endre Mester, MD attempted to repeat an experiment performed by the American scientist Paul McGuff, who had cured malignant tumors in rats using a ruby laser.⁵ As it turned out, Mester’s laser was much less powerful than McGuff’s, and he observed for the first time that a low-level laser induced hair growth and improved wound healing. It has been proposed that LLLT on the scalp increases the number of hair follicles and hair tensile strength through improved microvascular circulation, reduced inflammation, and increased cell energy in the form of adenosine triphosphatase (ATP).⁶ It has been demonstrated that LLLT can stimulate anagen re-entry in telogen hair follicles, prolong the duration of the anagen phase, increase the rates of proliferation in active anagen hair follicles, and prevent premature catagen development.⁷ These effects may be induced via increased blood flow, cytokine and growth factor induction, and direct keratinocyte stem cell or dermal papilla cell stimulation.⁸

Red Light Clinically Proven to Grow Hair

LLLT devices originally contained laser diodes that emit red light (e.g., 655nm) and were deployed in dermatology practices in overhead panels, bonnets, and caps. In the late 1990s, LLLT made the leap to at-home use. The earliest at-home use LLLT hair growth device was cleared by the FDA in 2007 as a comb. Investigators in one study of the HairMax LaserComb (Lexington International), found that patients in the treatment group experienced a greater increase in mean terminal hair density compared with those exposed to a sham device group, and that the therapy was safe and resulted in no serious side effects.⁹ However, lack of uniform light delivery and user required adjustment of the treatment area both limited patient compliance.

The FDA has now cleared numerous light-based hair regrowth devices that have varying helmet shapes, number of lasers, technical features, price, and level of clinical evidence. LLLT devices have an excellent safety profile and mounting evidence supporting their efficacy, however long-term, high quality studies comparing these devices in diverse populations are lacking.¹⁰ Recently Gupta and co-authors published a review on all of the available non-surgical treatments for AA in an effort to identify the most effective treatments.¹¹ A meta-analysis of the available literature on the six most common non-surgical treatment options including dutasteride 0.5mg, finasteride 1mg, LLLT, minoxidil 2%, minoxidil 5%, and platelet-rich plasma (PRP). Seventy-eight studies met the inclusion criteria, and 22 studies had the data necessary for a network meta-analysis. Relative effects showed LLLT might be a superior treatment, however, the authors concluded that high-quality randomized controlled trials and/or head-to-head trials are required to support these findings and aid in the development of more standardized protocols, particularly for PRP. Regardless, this analysis may aid physicians in clinical decision-making and highlight the variety of non-surgical hair restoration options for patients.

Medical Grade LEDs

Despite other light sources being available during the first 40 years of PBM research, lasers remained by far the most commonly employed device. However, in recent years, some non-coherent light sources, such as LEDs, have gained traction. LED light sources, based on the phenomenon of electroluminescence from semiconductor materials, can deliver discrete bands of light, tunable across the entire visible light spectrum based on the underlying substrate. The slightly broader bands of LED light can affect cellular metabolism by achieving greater photoreceptor target engagement across the chromophore absorbance spectrum. Observed effects include increased ATP, upregulation of nitric oxide production, the induction of transcription factors, alteration of collagen synthesis, stimulation of angiogenesis, and increased blood flow. Advantages of LEDs include lesser perceived laser safety considerations, small light weight footprint leading to ease of at-home use, ability to irradiate a large area of tissue with minimal power, and much lower energy cost per milliwatt.¹²

In 2000, NASA published a study showing the positive results of LED technology when using red light therapy to treat chemotherapy induced ulcers. That pioneering work helped launch the commercial development and use of medical grade LEDs for light therapy today.

The physics of light are consistent across laser and LED sources, as in 1 milliwatt of power equals 1 milliwatt of power regardless of the source. However, the uniformity of light and depth of light penetration can be very different. In some cases, more laser sources are required to achieve close to adequate coverage and end up requiring larger batteries or sometimes even a direct cord to an electrical outlet due to their power needs. It was also inaccurately reported that lasers were the only light source powerful enough to penetrate deep into the skin, and this thinking has been shown to be outmoded and inaccurate.¹²

Not all LEDs are made equally and unlike low quality non-medical grade devices, high quality LEDs with useful lives up to 50,000 hours can deliver 125-degree viewing angles that allow for large overlapping cones of light and deep skin penetration. In fact, given the enhanced functionality of LEDs, some newer hair growth devices have begun putting in LEDs to enhance coverage and increase ease of use and claim to have better results than laser alone devices. The iGrow Hair Growth System (iGrow) contains 21 5mW lasers (655nm) and 30 LEDS (655nm), in a bicycle helmet-like configuration and iRestore Essential helmet (Freedom Laser Therapy) also contains a combination of 21 lasers (650nm) and 30 LEDs (650nm).

Ultimately, medical-grade LED technology may represent the most efficient use of energy and the quality of light delivered for broad-coverage applications. The small size of the energy source allows for the creation of flexible, lightweight, and comfortable at-home wearable devices.

Dual Wavelength LED Light Therapy

With regard to hair growth technologies, there remain many variables with respect to how to best penetrate light as a function of skin type, the proper irradiance levels for maximum hair growth, potential synergies gained with color mixing, and which wavelengths of light provide the best results in combination with other therapies. These challenges and identification of what are effective/optimal parameters regarding the delivery of light are now being overcome through adequate and well controlled clinical trials.

For instance, a particularly noteworthy self-administered, at-home light therapy apparatus is the recently FDA-cleared Revian Red (PhotonMD), the first all-LED, dual wavelength red light therapy device. The Revian Red System uses a novel color combination of dark orange (620nm) and red light (660nm) to stimulate more nitric oxide production in the scalp. This device also includes a validated, mobile app required for use that activates the cap once daily for 10 minutes, and records daily treatment compliance to help patients maximize hair growth results. Preliminary results from a prospective, randomized, controlled, double-blind, parallel study to evaluate the efficacy and safety of the Revian System in men and women with AA revealed that subjects who were treated with the Revian Red cap and were at least 80 percent compliant for the duration of the study had an average of 21 more hairs per cm² compared to those who used a placebo device, after 16 weeks; and subjects treated with placebo continued to lose hair over the duration of the study.¹³

Improvement in total hair counts and an excellent safety profile are encouraging for patients who have pattern hair loss, and the addition of a cloud-based technology platform to enhance communication and compliance with the treatment regimen is an exciting advancement for the dermatology specialty as a whole.

Shedding Light

Clinicians and patients are just beginning to understand that LLLT can help retain hair that would otherwise be lost as well as grow new hair. Our role as clinicians is to translate the clinical data available on the various hair growth devices and educate patients on the potential benefits of LLLT when used as part of a comprehensive treatment regimen. To date, there are no contraindications for use and no known drug interactions reported between LLLT and pharmaceutical agents like finasteride or minoxodil or nutraceuticals. Furthermore, the natural scalp healing benefits of light appear to be complementary to the growth factors induced through PRP injections, although further studies are warranted to elucidate the effects of red light therapy in combination with autologous procedures. Future clinical studies will also shed more light on optimal treatment regimens and combination therapies.

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2. Leyden J, Dunlap F, Miller B, et al (1999) Finasteride in the treatment of men with frontal male pattern hair loss. J Am Acad Dermatol 40(6 Pt 1):930–937

3. Fayne, et al. (2020). Laser and Light-Based Therapies in the Treatment of Hair Loss. 10.1007/978-3-030-21555-2_5.

4. Hamblin MR. Photobiomodulation or low-level laser therapy. J Biophotonics. 2016;9(11–12): 1122–4.

5. McGuff PE, Deterling RA Jr, Gottlieb LS. Tumoricidal effect of laser energy on experimental and human malignant tumors. N Engl J Med. 1965;273(9):490–2.

6. Waiz M, Saleh AZ, Hayani R et al (2006) Use of the pulsed infrared diode laser (904 nm) in the treatment of alopecia areata. J Cosmet Laser Ther 8:27–30.

7. Wikramanayake TC, Rodriguez R, Choudhary S et al (2012) Effects of the Lexington LaserComb on hair regrowth in the C3H/HeJ mouse model of alopecia areata. Lasers Med Sci 27(2): 431–436.

8. Wikramanayake TC, Villasante AC, Mauro LM et al (2013) Low- level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA). Lasers Med Sci 28(3): 701–706. And Desai S, Mahmoud BH, Bhatia AC et al (2010) Paradoxical hypertrichosis after laser therapy: a review. Dermatol Surg 36: 291–298

9. Leavitt M, Charles G, Heyman E, Michaels D. Clin Drug Invest. 2009;29(5):283-292.

10. Erin M. Dodd, Margo A. Winter, Maria K. Hordinsky, Neil S. Sadick & Ronda S. Farah (2018) Photobiomodulation therapy for androgenetic alopecia: A clinician’s guide to home-use devices cleared by the Federal Drug Administration, Journal of Cosmetic and Laser Therapy, 20:3, 159-167.

11. Gupta 2018) Gupta, A. , Mays, R. , Dotzert, M. , Versteeg, S. , Shear, N. and Piguet, V. (2018), Efficacy of non‐surgical treatments for androgenetic alopecia: a systematic review and network meta‐analysis. J Eur Acad Dermatol Venereol, 32: 2112-2125.

12. Heiskanen V, Hamblin MR. Photobiomodulation: lasers vs. light emitting diodes? [published correction appears in Photochem Photobiol Sci. 2018 Oct 31;:]. Photochem Photobiol Sci. 2018;17(8):1003–1017.

13. PhotonMD data on file; ClinicalTrials.gov Identifier: NCT04019795.