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By Jasmine Laws
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Researchers from National Taiwan University have developed a serum that caused hair regrowth in mice in just 20 days, raising questions about what the finding means for the treatment of human baldness.
"Though we did not test these fatty acids in human skin directly in clinical trials, our results suggest these fatty acids might also work in human to stimulate our hair follicle stem cells to promote hair growth," Dr. Sung-Jan (Jerry) Lin, one of the authors of the study and a professor in the department of Biomedical Engineering and department of Dermatology at the National Taiwan University, told Newsweek.
Why It Matters
Male baldness is common in the United States, with 42.68 percent of men bald, according to the World Population Review, making it the nation with the fourth-highest percentage of bald men after Spain, Italy and France.
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Baldness can be caused by many factors, including genetics, aging, certain medical conditions, diet, and stress.
There are a number of treatments already available for baldness, such as topical treatments, prescription medications, and transplants, but the study offers deeper insight into the processes that can rejuvenate hair growth.
What To Know
The researchers published their study on October 22 in journals such as ScienceDirect and Cell Metabolism, which found that skin injury or irritation may kickstart a process in the body that regenerates hair growth.
Skin irritation caused by sodium lauryl sulfate, commonly found in shampoo, was found to induce a "skin inflammatory response," Lin said. That inflammation "involved not only the superficial skin but also extended to the underlying fat tissues," he added.
After a skin injury, the researchers found that macrophages, a type of white blood cell, infiltrate dermal adipose tissue, a tissue found in the layers of the skin.
There, these cells promote the release of free fatty acids, which play crucial roles in metabolism, from adipocytes (fat cells) through a process called SAA3-dependent lipolysis. This, in turn, was found by the researchers to promote hair regrowth.
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"Therefore, the inflammatory process induced by skin injury is not all bad. It also promotes regeneration," Lin said, adding that he believed "this is an evolutionally conserved protective mechanism in mammals because we can see it in both human and other animals like mice."
In simple terms, the study highlights how skin irritation and inflammation caused by chemical compounds or wounds "triggers a resting hair follicle to go into a growth phase," Dr. George Cotsarelis, professor and chair of the Department of Dermatology at the University of Pennsylvania, told Newsweek.
This process "is likely related to some immune type signaling that gets triggered with trauma," Dr. Luis Garza, a professor of Dermatology at Johns Hopkins University, told Newsweek.
This connection has been known for many decades, Cotsarelis noted, but said the study "provides new details of how irritation and injury of fat cells triggers inflammation and stimulation of hair growth in mice."
Cotsarelis also said he was not certain this finding could have any implications for the treatment of human baldness. He said the study was "highly unlikely to have relevance to human hair growth," because in a mouse, "all the hair follicles are in a resting stage, so shaving the hair then triggering growth looks dramatic because the hair regrows where you applied the irritant."
In humans, though, more than 90 percent of scalp hair follicles are "in a growing phase, so the stimulation of resting hair follicles is not going to have a dramatic effect," he said.
That said, in male and female pattern baldness, there is an increase in resting hair follicles (to around 15 to 20 percent versus less than 10 percent normally), so "causing irritation will push these into a growing phase, and if you look 3 to 4 months later, you’ll see some new hair growth," Cotsarelis said.
Minoxidil, a topical treatment applied directly to the scalp to stimulate hair growth, is an effective form of treatment for baldness that is already available, and it works by keeping the hairs "in a growing phase," Cotsarelis said.
When applying the principles of these findings to potential human use, there may also be concern about whether inducing skin irritation in humans raises new issues.
"Skin irritation could have unintended consequences such as decreasing the efficacy of our normal barrier. This is important for example to keep out allergens," Garza said.
However, Li said that "we can induce hair regeneration by topical application of monounsaturated fatty acids, bypassing the need of injuring skin."
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What People Are Saying
Dr. Luis Garza, a professor of Dermatology at Johns Hopkins University, told Newsweek: "The authors cleverly show that they can use monounsaturated [fatty acids] instead of irritation, though the effect might not be as pronounced. So there is a possibility this could be a therapy. But there will be many barriers, such as identifying the best delivery mechanism to get this into the skin. Human skin is thicker and more challenging for drug penetration than mice. The biggest challenge for the authors to commercialize this into a product, however, is to solve whether this actually treats the disease-specific molecular features of common alopecias like male or female pattern alopecia. This might be a general mechanism that might help hair grow, but not solve the particular problem in alopecias."
Mayumi Ito Suzuki, a professor of dermatology and cell biology at NYU Langone, told Newsweek: "Skin irritation broadly affects other cell types beyond adipocytes and hair follicle stem cells. Long-term effects on other cell types, including fibroblasts, and on innervations and vascularization would need to be considered before considering inducing skin irritation for human applications."
She added, "It is exciting; they have revealed the cascade of events to demonstrate a new role of macrophage-adipocyte communications for inflammation-induced hair growth in mice. The authors have not tested whether this mechanism is active in human skin in vivo. This study shows that fatty acids may promote hair follicle stem cell activation in the context of injury-driven hair follicle growth.
"However, another study suggests that fatty acids can also damage hair follicle stem cells during fasting. Understanding the careful examination of a complete picture of how fatty acid works in the distinct physiological context of mice, and then human skin, would be necessary before applying it to humans."
What Happens Next
As the researchers have only conducted this research in animal-based trials, there is still a significant amount of investigation to be done in order to understand whether the effect will be translatable in humans, and if this could have implications on baldness treatments.
"These monounsaturated fatty acids are all natural fatty acids present in our body and therefore relatively safe," Li said. "In the next stage, we need to find out the effective dosing, such as the concentration and formulation of the fatty acids and the frequency of use, that can stimulate human hair growth before we can use them for the management of hair loss."
Read Newsweek's full interview with Dr. Sung-Jan (Jerry) Lin, one of the authors of the study:
Q1: Can you explain in simple terms how skin irritation can promote hair growth?
"We found that skin irritation with sodium lauryl sulfate induced a skin inflammatory response, named irritant contact dermatitis. Irritant contact dermatitis is one of the most common skin diseases characterized [by] redness, skin swelling and itching. We found that the inflammation involved not only the superficial skin but also extended to the underlying fat tissues, where adipocytes quickly released their stored lipids as fatty acids into the skin through a process called 'lipolysis.' These released fatty acids were absorbed by the adjacent hair follicle stem cells and used by them as fuels to power their activation. These supercharged hair follicle stem cells quickly awakened from a resting state and started to work, regenerating new hair fibers. Therefore, the inflammatory process induced by skin injury is not all bad. It also promotes regeneration.
"We speculate that this is an evolutionally conserved protective mechanism in mammals because we can see it in both human and other animals like mice. Beside human, the skin of most mammals is covered by a dense hair coat (human lost the dense body hair coat during evolution). In most mammalian animals, the dense hair coat is the first line of protective barrier while the skin serves as the second protective barrier. When the second protective barrier, the skin, is irritated or damaged, it is a warning to the animal that the first protective hair coat is lost or damaged and the animal needs to regenerate new hair to restore the protective hair coat."
Q2: Are there any implications of inducing skin irritation in this way? Could this increase sensitivity of the skin over time?
"Conventionally, fat inflammation, or called panniculitis clinically, is considered as a diseased condition. Chronic panniculitis often leads to tissue fibrosis or systemic inflammation. For example, obesity induces chronic fat inflammation, which subsequently leads to systemic inflammation and perturbs the normal systemic metabolism. There are also skin diseases, such [as] autoimmune diseases like lupus erythematosus or malignant lymphoma, that are featured as chronic panniculitis clinically. Our study is the first to show that that transient fat inflammation in response to tissue injury is beneficial for tissue regeneration in that they can power the adjacent tissue stem cells through the release of stored fat. We think this tissue regeneration principle may also operate in other adipose tissue-enriched organs to enhance tissue regeneration after tissue damage.
"We also found that only specific natural fatty acids, including such as oleic acids (C18:1) and palmitoleic acids (C16:1), released from the fat can charge hair follicle stem cells. These fatty acids belong to a category of fatty acids named 'monounsaturated fatty acids.' These fatty acids can efficiently be used by hair follicle stem cells as fuels to produce energy through a process called 'fatty acid oxidation.' They are not only enriched in our fat cells but also in plant oils, such as olive oil, soybean oils, etc. On the contrary, saturated fatty acids, such as stearic acid (C18:0), released from fat cells, are not effective in charging hair follicle stem cells.
"It has been shown that these fatty acids can effectively penetrate into skin. When we tested them in mouse skin, we found that application with natural monounsaturated fatty acids, including such as oleic acids (C18:1) and palmitoleic acids (C16:1), only can also induce hair regrowth. Therefore, we can induce hair regeneration by topical application of monounsaturated fatty acids, bypassing the need of injuring skin."
Q3: Do you think this serum will soon be able to be used in people? Why/why not? What are the next stages?
"In our study, we tested the fatty acids in human hair follicle cells in test tubes. We found a positive result similar to that from mouse hair follicle cells: monounsaturated fatty acids, including such as oleic acids (C18:1) and palmitoleic acids (C16:1), are capable of promoting the growth of human hair follicle cells. Though we did not test these fatty acids in human skin directly in clinical trials, our results suggest these fatty acids might also work in humans to stimulate our hair follicle stem cells to promote hair growth.
"These monounsaturated fatty acids are all natural fatty acids present in our body and therefore relatively safe. In the next stage, we need to find out the effective dosing, such as the concentration and formulation of the fatty acids and the frequency of use, that can stimulate human hair growth before we can use them for the management of hair loss."
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