The following study on Low-Level Laser Therapy was originally published by Lasers Surg Med. in February 2014. It has been edited for the Laser Cap Me (LaserCap.Me) website. This was done in order to shorten and condense the material. All rights retained by Lasers Surg Med.
Abstract
Objective
Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia affects 50% of males over the age of 40. Additionally, it affects 75% of females over 65. According to trials, two hair restoration drugs can treat pattern baldness. Minoxidil and finasteride can treat hair loss. However, a hair transplant is another treatment alternative. This review surveys the evidence for low-level laser therapy (LLLT) as a treatment for hair loss. Additionally, it discusses possible mechanisms of action.
Methods and Materials
Researchers used PubMed and Google Scholar to carry out using keyword searches. Searches included the words alopecia, hair loss, LLLT, and photobiomodulation.
Results
Studies have shown that LLLT stimulated hair growth in mice subjected to chemotherapy-induced alopecia. It also researched alopecia areata. Controlled clinical trials demonstrated that LLLT stimulated hair growth in both men and women. The main mechanism may be the stimulation of epidermal stem cells in the hair follicle bulge. This includes shifting of the follicles into the anagen phase.
Conclusion
In conclusion, Low-Level Laser Therapy for hair growth appears to be both safe and effective. However, the optimum wavelength, coherence, and dosimetric parameters remain to be determined.
Introduction
It has long been known that red or near-infrared laser light promotes tissue repair and regeneration. Additionally, low-level laser therapy (LLLT) stimulates cellular activity. After the discovery of lasers, there has been tremendous interest in using these devices to treat various medical conditions. The most commonly used devices have wavelengths in the range 500–1,100 nm. In other words, the so-called optical window of tissue.
Low-Level Laser Therapy has shown beneficial effects for a variety of medical conditions. These include wound healing, nerve regeneration, and joint pain relief. Home-use LLLT devices that emit low-power red light have been developed for hair growth. In this review, we focus on the use of Low-Level Laser Therapy as a potential treatment for several types of hair loss.
Hair and Types of Hair Loss
Hair is one of the fastest-growing tissues of the human body. The follicles undergo repetitive regenerative cycles. Each of these cycles consists of three stages: anagen (rapid growth, active stage), catagen (apoptosis-driven regression, physiological involution stage), and telogen (resting stage). The outer root sheet contains stem cells. They’re located just below the sebaceous gland. This coincides with the point of anchorage of the arrector pili muscle.
During the telogen to anagen transition, there is a tightly controlled activation of bulge stem cells. Within the same period, secondary hair germ cells give rise to TA progeny cells. Throughout the entire anagen phase, there is a robust proliferation of the TA cells. Consequently, proliferating trichocytes terminally differentiate to form the bulk of the hair filament. This is the final product of the hair cycle.
Androgenic Alopecia
Androgenetic alopecia is the most common form of hair loss in men. In fact, it affects almost 50% of the male population. AGA refers to hair loss in individuals caused by androgens including testosterone and DHT. Then, testosterone is converted to DHT. This is its more active form. There are two types of 5-α reductase. Type 1 is found in keratinocytes, fibroblasts, sweat glands, and sebocytes, while Type 2 is found in skin and the inner root sheath of hair follicles.
DHT binds the nuclear androgen receptor which regulates gene expression. Disruption of epithelial progenitor cell activation and TA cell proliferation form the essential pathophysiological component of this condition. In turn, this leads to continuous miniaturization of sensitive terminal hair follicles and conversion to vellus hair follicles. Some of the proposed genes responsible for hair growth are desmoglein, activin, and EGF. Others include fibroblast growth factor (FGF), lymphoid-enhancer factor-1 (LEF-1), and sonic hedgehog.
The most common methods to treat AGA are minoxidil, finasteride, and hair transplantation. Unfortunately, current therapies are not efficacious for all patients. Medical therapies require indefinite use and are limited by patient adherence. Hair transplants are limited by cost, each patient’s supply of donor hair. Additionally, you may experience scarring in donor sites. As such, Low-Level Laser Therapy has emerged as a new therapeutic approach to treat AGA.
Other Forms of Hair Loss
There are several other forms of hair loss such as alopecia areata (AA), telogen effluvium (TE), and chemotherapy-induced alopecia. AA is an autoimmune inflammatory condition, which presents with non-scarring alopecia. There are severe variants of AA. These include alopecia totalis, a total loss of scalp hair, and alopecia universalis, total loss of scalp and body hair. The most common treatment modality is intralesional corticosteroid injections. However, other treatments include topical and systemic corticosteroids, minoxidil, anthralin, contact sensitizers, psoralen plus ultraviolet A, cyclosporine, tacrolimus, and biologics such as alefacept, efalizumab, etanercept, infliximab, and adalimumab. TE is abnormal hair cycling causing excessive loss of telogen hair.
Common causes include acute severe illness, surgery, iron-deficient anemia, thyroid disease, malnutrition, chronic illness, and medications such as oral contraceptives, lithium, and cimetidine. Chemotherapy works by destroying rapidly dividing cancer cells. However, other rapidly dividing cells of the body such as hair follicles are also destroyed. This unwanted effect leads to chemotherapy-induced alopecia.
Low-Level Laser Therapy for Prevention and Reversal of Hair Loss
In the late 1960s, Endre Mester, a Hungarian physician, began a series of experiments on the potential of lasers by using a low-power ruby laser on mice. Mice were shaved as a part of the experimental protocol. To Mester’s surprise, the laser did not cause cancer but instead improved hair growth around the shaved region on the animal’s back. This was the first demonstration of “photobiostimulation” with Low-Level Laser Therapy, and it opened a new path in the field of medicine.
Recently, attention has been drawn towards an uncommon but striking adverse effect of lasers being used for hair removal. In some cases, an increase in hair density, color, coarseness, or a combination of these occurs at or around sites treated for hair removal. The name given for this phenomenon is “Paradoxical Hypertrichosis” and the incidence varies from 0.6% to 10%. A group of researchers also observed the transformation of small vellus hairs into larger terminal hairs upon low fluence diode laser treatment and named this phenomenon “terminalization” of vellus hair follicles.
Until today, different mechanisms have been proposed to explain paradoxical hypertrichosis. In one study, this was attributed to the presence of polycystic ovarian syndrome. Those women were undergoing IPL laser treatment for facial hirsutism. Another group of researchers suggested that this heat may be sufficient to induce follicular stem cell proliferation and differentiation by increasing the level of heat shock proteins. These play a role in the regulation of cell growth and differentiation. Sub-therapeutic injury caused by the laser could also result in the release of certain factors which could potentially induce follicular angiogenesis and affect cell cycling.
Low-Level Laser Therapy for Hair Regrowth, Proposed Mechanisms
As previously mentioned, Low-Level Laser Therapy was approved by the FDA as a safe treatment for male and female pattern hair loss. Laser phototherapy stimulates anagen re-entry in telogen hair follicles. Additionally, it may prolong the duration of the anagen phase. Finally, it increases rates of proliferation in active anagen hair follicles and prevents premature catagen development.
The exact mechanism of action of LLLT in hair growth is not known. However, several mechanisms have been proposed. Evidence suggests that LLLT acts on the mitochondria and may alter cell metabolism through photodissociation of inhibitory nitric oxide (NO) from cytochrome c oxidase causing increased ATP production, modulation of reactive oxygen species, and induction of transcription factors such as nuclear factor kappa B, and hypoxia-inducible factor-1.
These transcription factors in return cause protein synthesis. Consequently, this triggers further effects such as increased cell proliferation and migration. Additionally, alteration in the levels of cytokines, growth factors, inflammatory mediators, and increased tissue oxygenation may occur. Moreover, NO is known to be a potent vasodilator via its effect on cyclic guanine monophosphate production. Finally, LLLT may cause photodissociation.
LLLT Vs. Minoxidil
Some authors have drawn comparisons between the mechanism of action of Low-Level Laser Therapy and the mechanism of minoxidil. It is known that minoxidil contains an important cellular signaling molecule involved in many physiological and pathological processes. It is also a vasodilator. Furthermore, minoxidil is an ATP-sensitive channel opener. In turn, it causes hyperpolarization of cell membranes.
Given what is known about minoxidil, a mechanistic overlap can be identified. Depending on the treatment parameters, LLLT modulates 5-α reductase expression. In other words, it converts testosterone into DHT. Additionally, it alters vascular endothelial growth factor gene expression as well as matrix metalloproteinase. These have significant roles in follicle growth. In turn, the group reported stimulation of hair growth on human dermal papillae cells.
Notably, similar changes have also been reported with topical minoxidil use. Furthermore, Low-Level Laser Therapy has been demonstrated to modulate inflammatory processes and immunological responses. Additionally, a study conducted supported this assumption. Considering that inflammatory infiltrates are highly disruptive to hair follicle biology, the modulatory effects of LLLT on inflammation might have a significant role in the treatment of AA.
Low-Level Laser Therapy for Hair Regrowth in Animals
Wikramanayake et al. demonstrated the hair growth effects of Low-Level Laser Therapy to part the hairs. They improve the delivery of laser light to the scalp. At the end of the treatment, hair regrowth was observed in all the laser-treated mice. However, no difference was observed in the sham-treated group. An increased number of anagen hair follicles was observed in laser-treated mice. However, sham-treated mice demonstrated telogen follicles with absent hair shafts.
Shukla et al. investigated the effect of helium-neon laser on the hair follicle growth cycle of testosterone-treated and un-treated mice. Testosterone treatment led to the inhibition of hair growth which was characterized by a significant increase in catagen follicles. Consequently, results showed that exposure of testosterone-treated mice led to a significant increase in the number of hair follicles in the anagen phase when compared to the other groups.
However, the treated group showed a significant decrease in the number of anagen hair and an increase in telogen hair follicles. This is consistent with the biphasic effect of LLLT wherein low irradiation doses may cause biostimulation and high irradiation doses may cause inhibition. Cells growing at a slower rate or under stress conditions respond better to the stimulatory effects of LLLT.
Other Notable Observations in Low-Level Laser Therapy
Some of the anagen follicles appeared from deeper layers of the skin. Additionally, they possessed a different orientation which both represents the late anagen stage in the hair cycle that in turn suggests that laser irradiation prolongs the anagen phase. Furthermore, in testosterone-treated and irradiated skin, hair follicles originated from the middle of the dermis. These follicles represent the early anagen phase. In other words, the majority of catagen and telogen follicles re-enter into the anagen phase as a result of LLL irradiation.
The incidence of alopecia related to cancer treatments such as chemotherapy is close to 65% and it has severe negative psychological effects. Low-Level Laser Therapy may promote hair regrowth for chemotherapy-induced alopecia. In a rat model, each rat received different regimens of chemotherapy. Additionally, they received LLLT devices. Hair regrowth occurred 5 days earlier in all laser-treated rats when compared to control and sham-treated rats. Histology results demonstrated large anagen hair bulbs penetrating deeper into the subcutaneous adipose tissue in LLLT-treated skin. Furthermore, it did not compromise the efficacy of chemotherapy by causing localized protection of the cancer cells.
Low-Level Laser Therapy for Hair Growth in Clinical Trials
15 patients were studied using a PPLL-emitting instrument. The device produced a high output of infrared radiation. This was capable of penetrating into deep subcutaneous tissue. Every two weeks, the scalp was irradiated for 3-minute intervals and continued until hair regrowth was observed in at least 50% of the affected area.
As a result of this study, 47% of the patients’ hair growth occurred 1.6 months earlier in irradiated areas than in non-irradiated areas. However, 1 year after irradiation, all the lesions disappeared. Irradiated and non-irradiated lesions were the same in hair density, length, and diameter of hair shafts. In conclusion, this suggests that Low-Level Laser Therapy only accelerates the process of hair regrowth in AA patients. However, the method for assessment of hair regrowth, density, and thickness was not clearly stated. In other words, this proved to be one of the main limitations of this study. In the end, 83% of the patients reported satisfaction with the treatment.
Testing of Low-Level Laser Therapy
Satino et al. tested the efficacy of Low-Level Laser Therapy on hair growth and tensile strength on 28 male and 7 female patients. Each patient received an LLLT device to use at home for 6 months for 5–10 minutes every other day. In terms of hair tensile strength, the results revealed greater improvement in the vertex area for males and temporal areas for females. However, both sexes benefited in all areas significantly.
In terms of hair count, both sexes and all areas had substantial improvement (for temporal area: 55% in women, 74% in men, in vertex area: 65% in women, 120% in men) with vertex area in males having the best outcome. Patients used the device three times per week for 15 minutes for a total of 26 weeks. Reports showed a significantly greater increase in hair density compared to subjects in the sham device group. The study demonstrated multiple benefits. These included significant improvements in overall hair regrowth, a slowing of hair loss, thicker feeling hair, better scalp health, and hair shine.
A Double-Blind Study
Recently, a double-blind randomized trial reported a 35% increase in hair growth among male patients. Findings from a different study were in accordance with these results. Low-Level Laser Therapy increased hair count and shaft diameter. However, blinded global images did not support these observations.
Safety and Possible Side Effects
LLLT has demonstrated a remarkably low incidence of adverse effects. In the specific area of LLLT, the only adverse reports in humans were the temporary onset of TE. This developed in the first 1–2 months after commencing treatment. However, it disappeared on continued application. Some other possible considerations are the presence of dysplastic or malignant lesions on the scalp. Proliferative effects of LLLT stimulated growth.
Conclusion
LLLT has demonstrated promise in conditions from wound healing, stroke recovery, pain relief, and more. Animal and human data have slowly accumulated supporting LLLT for hair growth (Table 1). LLLT appears to improve a variety of non-scarring alopecias—AGA, AA, and chemotherapy-induced alopecia. Also, LLLT used after hair transplant surgery can aid in hair regrowth as well. In doing so, patients may facilitate the healing process. Finally, use may enhance the viability and earlier growth of the grafts.
While mechanisms are still emerging, Low-Level Laser Therapy may increase anagen hairs and may reduce inflammation in AA. However, more studies are needed to optimize treatment parameters and determine long-term efficacy. Most studies investigating the effects of LLLT on hair growth have used wavelengths that range from 635 to 650 nm. Moreover, no study has compared the effect of near-infrared wavelengths which have deeper penetrating capacities to red light. Also, light sources and delivery methods must be studied.
Footnotes
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Michael R. Hamblin is on the scientific advisory board and holds stock in Transdermal Cap Inc. He has been on the scientific advisory board and has received sponsored research funding from Lexington Int. He has been an expert witness for Advanced Hair Studio Australia. Other authors reported no conflict of interest.
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