Stress Does not Cause Permanent Hair Loss

In my opinion, excessive stress can almost never cause permanent hair loss in humans. At worse, it causes temporary telogen effluvium hair shedding.

Stress effects the hair growth cycle.
Stress pushes hair into a resting Telogen phase.

Chronic Stress and Hair Loss

On March 31, 2021, researchers from Harvard University released findings (in mice) that chronic stress causes permanent hair loss. These findings were published in numerous newspapers around the world. The lead researcher was the respected Dr. Ya-Chieh Hsu, and the paper was published in Nature on March 4, 2021.

It was titled: “Corticosterone inhibits Gas6 to govern hair follicle stem-cell quiescence.” Chronic stress seems to increase levels of the corticosterone stress hormone in mice. This in turn prolongs hair follicle stem cell (HFSC) quiescence, resulting in hair follicles remaining in an extended resting phase.

The scientists believe that restoring Gas6 gene expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Another summary from Harvard Stem Cell Institute (HSCI).

“Stress essentially just elevates this preexisting ‘adrenal gland–hair follicle axis,’ making it even more difficult for hair follicle stem cells to enter the growth phase to regenerate new hair follicles.” — Dr. Hsu.

Ronald Reagan Hair
Ronald Reagan never had any hair loss despite insane levels of stress. But he was not a mouse of course.

Since that day, readers have regularly posted or e-mailed me links to newly published versions of the story. This has annoyed me, since I do not believe these findings hold much merit in humans. However, to avoid further e-mails, I am now writing my counterarguments.

Besides the fact that the research was done in mice, there are some obvious issues that the researchers have surprisingly failed to address.

Mice are not Humans

  1. Why do young people almost never go bald? In my whole life, I have seen just a handful of people younger than 14 being bald. And all of them seemed to have the rare condition of alopecia areata (or alopecia totalis and alopecia universalis). A few dozen people around the world also go prematurely bald due to progeria (Hutchinson-Gilford). I am of course not counting the few pre-teens who shave their head as a fashion statement.
  2. Major baldness is rare even in those who are younger than 20 years in age. And also not too common in those who are below 25. It is surely not believable that young people do not suffer from major stressful events!? If anything, stress is perhaps worst in those who are in high school and college. Permanent hair loss is almost always caused by male hormones (hence the term androgenetic alopecia) and NOT stress. More specifically, male pattern hair loss is usually due to a person’s genetic sensitivity to the effects of dihydrotestosterone (DHT). The latter in turn is converted from testosterone via the 5-alpha-reductase enzyme. Make sure to read my post on destroying the androgen receptor.
  3. Why do “pure” Native Americans never go bald? Are the Harvard Researchers implying that Native Americans never have chronic stress? If not, they should have at least posted a caveat that certain groups are genetically protected from stress induced permanent hair loss.
  4. The findings do not address why women are less likely to have significant hair loss in comparison to men. Especially in their younger years. Most news sources seem to suggest than women in fact have more stress than men. So if anything, they should have higher rates of baldness than men.
  5. Why does stress not seem to impact body hair growth? Or even nail growth. Most men get an increasing amount of body hair as they get older. I have never heard someone say that they permanently lost their body hair after prolonged stress. Nails are made from keratin, just like scalp hair. Yet stress does not seem to cause nail stem cells to go into a permanent “resting phase”. Even people over the age of 100 have to keep cutting their fingernails and toenails unfortunately.
  6. Mahathir Mohamad Hair
    95-year old Mahathir Mohamad has not lost any hair even with a lifetime of stress.

    Why do many people who go through tremendous stress in their lives still never go bald? Among the most famous examples of this are: 93-year old now deceased ex-US president Ronald Reagan. And 95-year old still living ex-Malaysian prime minister Dr. Mahathir Mohamad. These two men went through numerous periods of chronic stress during their long lives.

Stress and Hair Greying

The funny thing is that the same Harvard researcher (Dr. Ya-Chieh Hsu) and her team published a paper in January 2020 titled: “How stress causes gray hair.” At the time, I also ignored the work due to skepticism. Especially in regards to how findings in mice do not necessarily translate to humans. I did not even expand much on the findings in my regularly updated grey hair cure post.

Some of the same arguments I made earlier apply to these conclusions. Why do you almost never see children with grey hair? Young people often suffer from chronic stress. Yet I would guess that less than one percent of those below age 15 have prematurely graying hair.

I do think that the chances of getting more rapid development of grey hair after prolonged stress is at least somewhat possible in many humans. However, I do not believe that stress can cause permanent hair loss in almost any humans.

Follicum Phase IIa Trial Results Disapppoint

Update: May 6, 2021

Disappointing Results from Follicum FOL-005 Phase 2 Trial

Follicum just released top-line results of their Phase IIa study of FOL-005 for the treatment of hair loss. The results are disappointing.

“In those treated with the highest dose of FOL-005 studied, hair growth increased by 6.6 hair/cm2, compared to 5.6 hair/cm2 in the placebo group.”

The difference between the treated group and the placebo group was not significant. While I never expecting this treatment to be anything much better than Minoxidil, I was still hopeful. Follicum has been extremely professional and fast in its trial progression and updates since I first started covering them in 2015.

In any case, it is also rare for a company in the hair loss world to give us disappointing news in an honest manner. A number of other hair loss companies in the past (and present?) tend to extend their importance beyond a decade. Then they ultimately fold or go out of business.

Update: October 9, 2020 — Follicum has completed its over 200 patient enrollment in its Phase IIa trials for FOL-005. Treatment will finish in all patients at the end of January 2021. Results are expected to be announced in Spring 2021. So far, no adverse effects and no patients have discontinued with their participation in the trials.

Follicum Trials to Restart

June 8, 2020

Follicum chief business office Mr. Gunnar Gårdemyr just sent an encouraging e-mail, part of which I am pasting below. Note that these Phase IIa trials entail topical application of FOL-005. In two prior trials, FOL-005 was administered via intradermal injections.

“Some good news. We will restart the clinical Phase IIa study with a cream-like formulation of FOL-005 this month, following a pause due to the Covid-19 pandemic. To increase the recruitment rate, we have contracted a third study centre. The study comprises approximately 200 male patients with hair loss who are treated daily for four months with the newly developed formulation of FOL-005 or placebo.

The study is being conducted at the Clinical Research Center for Hair and Skin Science (“CRC”) in Berlin; proDERM in Hamburg; and the new center, CentroDerm in Wuppertal. The patients themselves will apply a cream with three different strengths of FOL-005 or placebo in the scalp, once daily in the evening. The study is expected to be completed and the results communicated in spring 2021.”

Follicum FOL-005
Follicum.

February 1, 2020

I have written about Sweden-based Follicum and its FOL-005 hair growth product numerous times. Several days ago, Follicum’s CEO Jan Alenfall announced that German authorities have granted the company approval to commence Phase IIa clinical trials for FOL-005. The go-ahead was granted by the German Medicines Agency (BfArM) and the German Ethics Committee.

Also see this recent article titled: “The rise of therapeutic peptides: Follicum at the forefront.” Key quote:

“Peptide-based drug candidates are more likely to reach the market compared to small molecule drug candidates.”

Follicum Phase IIa Trials in Berlin and Hamburg

The trial will comprise about 200 patients who will be treated with topical FOL-005 or placebo daily for 4 months. Results will be released in the fourth quarter of 2020. The upcoming phase IIa study will investigate the safety, efficacy and response to a topical formulation of FOL-005. Note that in 2018, an injectable version of FOL-005 produced a good safety profile and hair growth results.

The press release states that patient recruitment will start soon. I contacted Follicum to see if any of this blog’s European readers would be able to volunteer as test candidates. However, the company’s chief business office Mr. Gunnar Gårdemyr replied in the negative. He said that all 200 test male patients for the trials have now been recruited and are from Germany.

The trials will be conducted at:

  1. Charité Clinical Research Center for Hair and Skin Science (“CRC”) in Berlin. A highly reputable institute that I have covered in the past on this blog.
  2. Hamburg-based proDERM, which just celebrated its 25-year anniversary. The have an interesting website section on hair care and hair removal.

About FOL-005

According to Follicum, FOL-005 is a proprietary peptide. Its development was based on research involving the human protein osteopontin. FOL-005 is a shorter sequence of osteopontin. The sequence has been slightly modified, but is still based on natural amino acids according to Follicum.