Category Archives: Pseudocatalase

The Cure for Grey Hair

I originally published this important post on a cure for grey hair in January 2016. This is a second comprehensive update since that time. The post is now too lengthy and disjointed, but still worth a thorough read.

Update: June 22, 2022 — A new gene therapy treatment for a rare genetic disease (cystinosis) resulted in major hair darkening as a side effect. Four of the five patients have gotten significantly darker hair, and the fifth just started re-growing his hair post treatment. Of note, this gene therapy entails modifying blood cells, and only changes the DNA of a small fraction of the patient’s cells.

Update: June 2021 — A new experiment mapped human hair greying in relation to recent life stress events. I am very skeptical about stress causing premature hair greying in most people. I have devoted a whole section to this popular subject in the second half of this post.

Update: April 2021 — Harvard University scientists and a team from South Korea are developing a treatment for grey hair using pigment stem cells in hair follicles.

Grey Hair Reversal
50 percent of grey hair is re-pigmented after dupilumab treatment. Before and after at 16 weeks. Source: The Journal of Dermatology.

Update: September 2020 — Japanese scientists discovered an unexpected side-effect of dupilumab: reversal of hair graying. Dupilumab is a dual inhibitor of interleukin 4 and interleukin 13. It is used to treat allergic diseases such as eczema, asthma and nasal polyps.

Update: June 2020 — Chinese scientists found re-pigmentation of hair in a majority of Alzheimer disease patients after prolonged cholinesterase inhibitor therapy.

Hair Repigmentation
Hair repigmentation after Ustekinumab. Source: Ann Dermatol. 2021 Jun;33(3):300-301.

Update: June 2020 — South Korean researchers presented the first case of Ustekinumab-associated hair re-pigmentation. Ustekinumab is a monoclonal antibody medication that targets interleukin 12 and interleukin 23. It is used to treat Crohn’s disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis.

Update: January 2020Medication-Induced repigmentation of grey hair review.

“As evidenced by the many cases of gray hair repigmentation in the literature, the development of gray hair may not be an irreversible process. Gray hair is a natural course of aging; however, it may not be an inevitable or permanent process.”


Grey Hair Treatment

Over the past few years, I have collected quite a few interesting links related to a cure for grey hair. I kept delaying writing this post because a permanent reversal of grey hair is obviously far less important than a cure for hair loss. However, there are some interesting ideas in reversing graying hair that are also relevant to reversing hair loss. Both problems also seem to have some common pathways and genetics.

Moreover, whenever we get back a full head of hair, the vast majority of us will no doubt prefer that the new hair is pigmented. At that point, grey hair will be deemed to be a significant problem unless one prefers the salt and pepper distinguished look.

Finally, for younger people who are both balding and prematurely graying, it is a double whammy. Hair loss shampoos and anti-aging products such NAD and NMN supplements do not seem to impact hair color in most people. See the comments in this May 2022 video on NMN and reversing hair greying and skin aging.

Why Does Hair Turn Grey?

A person’s hair color is determined by his or her pigment producing stem cells known as melanocytes working in conjunction with his/her hair follicle stem cells. Hair color depends on the presence and ratios of two types of melanins: eumelanins (brown and black pigments); and pheomelanins (red and yellow pigments).

As people age, a natural buildup of hydrogen peroxide occurs in their hair follicles. This in turn causes oxidative stress, melanocyte destruction and subsequent graying. Side note: many women use hydrogen peroxide solutions to go blonde.

In 2009, a team of scientists from Germany and the UK figured out why this hydrogen peroxide buildup occurs in people as they age. They also found out why hydrogen peroxide is to blame for graying hair. Basically, in younger people an enzyme called catalase breaks down hydrogen peroxide into water and oxygen.

However, as people get older, they often have lower levels of this enzyme. They also have lower levels of other enzymes (MSR A and B) that repair hydrogen peroxide related damage to hair follicles. On Amazon, products containing catalase often have at least some favorable reviews regarding the hair darkening side effect.

The combination of high levels of hydrogen peroxide and low levels of MSR A and B disrupts the formation of tyrosinase. That enzyme is important to melanin production in hair follicles. Scientists think that something similar is at play in the skin condition called vitiligo. One interesting and unusual thing about white nonpigmented hair is that it is thicker and grows faster than pigmented dark hair.

Our bodies produce molecules called free radicals that often react adversely with other molecules. These free radicals can cause a lot of damage, but they are countered by beneficial antioxidants. However, it the balance between these two classes of molecules shifts towards free radicals, we get damaging oxidative stress.

Also make sure to listen to this interesting 2020 Podcast on reversing gray hair.

Anti–interleukin (IL)-17 Therapy Reverses Grey Hair

In May 2018, Italian scientists reported a complete reversal of grey hair in one 61-year old patient. He first started getting white hair around the age of 45. He was undergoing interleukin-17 therapy with secukinumab to treat scalp psoriasis. The below before and after photo after 6 months of treatment is truly astounding. The 10-month follow up showed maintenance of results.

Note that this patient also saw new hair growth. The conclusion of the scientists is especially motivating: “hair whitening and thinning caused by the aging process might be reversible”.

Grey Hair Reversal Anti–Interleukin-17.
Grey hair reversal after anti–Interleukin-17.

Minoxidil could Reverse Grey Hair

In 2017, Dr. Wilma Bergfeld told the New York Times that:

“In early testing of the anti-hair-loss drug minoxidil, she and other researchers noticed the drug sometimes also restored hair color, suggesting it was rejuvenating the melanocytes”.

In 2021, I asked Dr. Bergfeld if there was any further research on the above phenomenon. She responded that she is unaware of anything new.

It is surprising that this phenomenon is not discussed by many other physicians, since Minoxidil has been in use for decades. Make sure to read my post on how Minoxidil works to regrow hair for more on this important FDA approved hair loss drug.

Update: May 1, 2022 — Well known dermatologist Rodney Sinclair said the following in a Reddit AMA:

“I have seen hair darkening with minoxidil in my patients.”

Hair Repigmentation after Immunotherapy

Grey Hair Becomes Dark Again.
Grey hair cured and becomes dark again. Source: JAMA Dermatol.

In 2017, scientists were able to reverse grey hair in 13 of 14 patients using a new immunotherapy based cancer treatment.

The treatment entailed anti–programmed cell death 1 (anti–PD-1) and anti–programmed cell death ligand 1 (anti–PD-L1 ).

Hair Repigmentation
Hair repigmentation after cancer treatment.

The before and after pictures of two of the patients are extraordinary. I have included both in this section.

In recent years, research has found a connection between immune system involvement in both hair loss and hair premature greying of the hair.

Stem Cell Factor Protein, Krox20 and Hair Color

In 2017, scientists at UT Southwestern Center in the US led my Dr. Lu Le found that a protein called stem cell factor (SCF) was essential for hair pigmentation. Full study here. They found that the mice without SCF in Krox20 lineage cells developed grey hair early in life.

Is PC-KUS (a modified pseudocatalase) a False Flag?

In 2013, the same Germany and UK based team that was discussed earlier in this post came out with a potential way to reverse grey hair. According to the article:

The researchers found that this massive build up of hydrogen peroxide can be reversed with a UVB-activated compound called PC-KUS, a modified pseudocatalase. The research team developed this new proprietary treatment.

PC-KUS was also supposed to cure vitiligo. However, according to the UK’s NHS, the research and subsequent publicity on PC-KUS curing grey hair was a bit of a sham.

I am not sure if this avenue of work is definitely over, and perhaps these same scientists will surprise us and come out with better news in the future.

L’Oréal: A Pill to Prevent Grey Hair Forever

During the past decade, France’s cosmetics behemoth L’Oréal has led global research in the private sector when it comes to a search for a cure for grey hair. The company’s head of the “Hair Biology Group”, Mr. Bruno Bernard, is a co-inventor of a topical product to protect and/or regenerate the melanocytes of hair follicles. The patent for this product was filed in 2009.

Moreover, In 2011, L’Oreal announced that it was developing a pill that would prevent grey hair forever — as long as you continued to take the pill once a day permanently! The medicine contains an undisclosed fruit extract that mimics the chemical tyrosinase-related protein (TRP-2), an enzyme that protects pigment production.

Unfortunately, this pill will not cause existing grey hairs to darken, but instead, just prevent new grey hairs from forming. The pill was supposed to become available in 2015, but now we are now well past that year.

Dr. Mayumi Ito, Wnt Signaling and Hair Pigmentation

Dr. Mayumi Ito is a renowned Japanese hair loss research scientist who got her Ph.D from Nagoya University in 2003. She now does research and teaching at New York University. She has co-authored numerous papers on the impact of Wnt signaling on hair follicle growth and regeneration. On this blog you can find many posts that discuss this important subject matter.

In 2011, Dr. Ito found that Wnt signaling also explains hair losing its pigmentation. Her team even restored hair color in mice in 2011 via manipulating the Wnt pathway. It remains to be seen when they will experiment in humans (via stem cell injection or gene therapy) and see a successful reversal of grey hair.

Update: Also in April 2016, scientists (led by Dr. Ito) at NYU Langone Medical Center in New York found the molecular pathways responsible for creating the color of skin and hair. They found that a signaling pathway known as Edn/EdnrB interacts with other pathways (in particular, the Wnt signaling pathway). This in turn causes the proliferation of melanocyte stem cells (McSCs) that are involved in the earliest stages of skin and hair pigmentation. This suggests that targeting Edn/EdnrB signaling in McSCs can be a therapeutic approach to promote hair pigmentation retention.

Is Dr. Cotsarelis also Working on Hair Pigmentation?

Interestingly, in December 2011, the renowned Dr. George Cotsarelis and Dr. Mayumi Ito co-filed for a patent titled: “Methods for generating new hair follicles, treating baldness, and hair removal.” This patent was approved in December 2015.

In the description to the patent, it ends with “The present invention also provides methods for hair removal and inducing hair pigmentation.” Incredible. A three-in-one solution (hair regrowth, body hair removal, and grey hair reversal). If only Dr. Cotsarelis’ predictions and optimism would be realized faster than he thinks or claims.

Can Finasteride Make Grey Hair Darker?

Over the years, I have read quite a few testimonials on hair loss forums where Finasteride users have claimed that their hair darkened while on Finasteride (which reduces DHT levels). The majority of these patients had very limited quantities of grey hair to begin with, so it was hard for me to tell from their before and after photos (when available) if this phenomenon was true or not. Also see my post on natural DHT blockers.

However, in 2014, forum member “bverotti” who is a hair transplant clinic representative in Belgium posted a stunning now deleted before and after image of one of the clinic’s patients on Finasteride. While it shows blonde hair turning brown, I think of that as the same as grey hair turning brown or black. Also, see this hair darkening on finasteride post on Reddit.

I think that DHT, besides making many people go bald, also makes some of them go grey much sooner. I do not know if this has ever been shown to be true in any kind of study, and I could be wrong in my observation.

Using similar logic as in the above paragraph regarding Finasteride, I think that the much stronger Dutasteride can also reverse grey hair. Moreover, a few of the commentators in my post on Dutasteride Testimonials mention that the drug darkened their hair.

Could Platelet-Rich Plasma (PRP) Darken Hair?

I have covered PRP to treat hair loss many times on this blog. While the results are never guaranteed and PRP will not bring back hair in totally bald areas of the scalp, there are now numerous doctors who believe in the product. I am skeptical, but willing to listen to them.

More relevant to this blog post’s subject matter, in November 2015, Dr. Carlos Wesley started an interesting thread on the BTT forums with a photo showing PRP and ACell mesotherapy darkening some previously transparent scalp hair. This was very surprising to me. Moreover, he states that “An additional finding that has also been observed by other practices throughout the world is that PRP can help return some of the original hair color to follicles.” It seems like PRP could be stimulating melanocytes in hair follicles.

Update: A number of other doctors have confirmed this phenomenon of PRP darkening hair color in rare instances.

Grey Hair Reversal PRP

Stem Cell Transplants to Cure Grey Hair

I have discussed Dr. Takashi Tsuji on this blog numerous times in the past. Several of his old videos have shown black pigmented hair growing on a mouse after stem cell transplantation. Moreover, this article on his work has the following sentence in it: “He combined a number of stem cells to adjust the density and color of the hair, raising the possibility of a cure to graying strands.

Will Telomerase Activation Therapy Reverse Grey Hair?

There are a number of online testimonials regarding telomarase therapy via the ingestion of the TA-65 supplement reversing grey hair and/or growing new hair. There are also many opinions to the contrary. I cover all this and more in my post titled “TA-65. telomerase activation and hair regrowth“.

Cancer Treatments that lead to Hair Repigmentation

There have been various reports of people reversing their grey hair while being on drugs to treat cancer. For example:

Supplements and Vitamins

Natural treatments and remedies for hair loss can sometimes also benefit hair color and pigmentation modestly. However, popular vitamin supplements such as melatonin, B-12, biotin, iron, calcium, zinc, copper, manganese, vitamin D, cysteine and selenium will rarely change hair color significantly.

Fo-Ti Root

Several studies as sell as numerous online anecdotal success story reports suggest that Fo-Ti root can darken grey hair. Fo-Ti is also knows as Fallopia multiflora, He Shou Wu and Polygonum multiflorum. Dr. Jerry Cooley told me that some of his patients have  seen grey hair reduction when on a shake product containing Fo-Ti.

Make sure to read reviews and search for user experiences in relation to hair color changes before purchasing Fo-Ti root. Also of note, a new popular supplement pill product called Not Today Grey contains Fo-Ti Root as a key ingredient.

Warning: Please note that excessive consumption of Fo-Ti root can damage your liver. See details in the bottom part of this article.

Alpha-Ketoglutarate

Calcium Alpha-Ketoglutarate (Ca-AKG) is though to have anti-aging properties. At least in aged mice. Some reviewers of an AKG acid supplement on Amazon (scroll down) mention that their hair darkened while on the product. Dr. Arvind Poswal of India told me that his Ca-AKG product has darkened hair color in multiple people. Also note this study that found α-ketoglutarate (α-KG) stimulated quiescent (telogen) hair follicles to anagen phase hair growth.

Iodine

Some patients have iodine deficiency, often due to underactive thyroid gland or hormone disorders. Supplementing with iodine can darken grey hair or prevent further graying.

B Vitamins

Vitamin B12, Biotin and other B-complex supplements can help with your hair color in rare instances. However, make sure to get tested first to make sure that you are really deficient in B-12, folate or other B vitamins.

N-Acetyl Cysteine

N-Acetyl Cysteine (NAC) is sometimes touted on sites such as Reddit as benefitting hair color. Not much evidence on this, but its key benefit is proclaimed to come via an increase in glutathione levels.

Iron Deficiency

One of the most common reasons for premature hair loss is iron deficiency. This is especially true for pregnant women, vegans and people on extreme diets. In rare instances, a lack of iron can cause premature grey hair.

Mucuna Puriens

A 1989 report found that treating an 85-year old woman with Mucuna pruriens extract powder for her Parkinson’s disease resulted in drastic darkening of white hair.

Fluoxetine (SSRI)

Antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs) have been known to cause hair loss. However, in 2017, a report from Germany discussed how Fluoxetine promoted hair follicle pigmentation. However, the work was done in dissected sample hair from two females and not on actual scalps.

Grey Hair Cure Scams

While not as proliferate as in the hair loss cure industry, the grey hair reversal market is still full of scams. Moreover, while some products have been FDA approved and proven to reverse hair loss in numerous patients, nothing of that sort can be said for products that are touted to reverse grey hair to pigmented hair. Most of these products are natural supplements that will do nothing for your hair color.

In 2015, the US government went after various companies that were making fraudulent claims about their products being able to treat grey hair successfully. Prior to that, in 2013, a nutritional supplement company called “Rise-N-Shine” promised a pill that would permanent cure grey hair. Wonder if that pill ever came into stores, and if so, how many gullible people purchased it?

Proctor & Gamble’s ME+ Molecule Hair Dye

Until a cure for gray hair does come out, people will have to accept their graying locks, or continue to use hair dyes. In 2013, Proctor & Gamble came out with a supposed permanent hair dye based on a new proprietary ME+ molecule. The new molecule (chemical name 2-Methoxymethyl-p-Phenylenediamine) was apparently a result of 20 years of research.

Proctor & Gamble’s website also raved about ME+ in early 2014, but it does not seem like all this early optimism has led to any kind of new blockbuster permanent dye product.

Stress and Plucking will not Cause Grey Hair

Most of the articles I have read on this subject seem to indicate that for the vast majority of people, stress will not cause early premature graying of hair. Plucking hair will definitely not cause it to go grey. Both of these myths are old wives’ tales.

Some articles suggest that US presidents have grayed a lot while in office. However, in my opinion, these presidents’ parents were also usually fully grey haired in their old age. So it is not surprising to see more white hairs appearing on presidents’ heads when they are in office in their 50s and 60s. In all likelihood, it is grey hair genes rather than stress that causes middle-age greying.

Update: A new 2021 study found that grey hair could possibly be reversed by relaxation and taking vacations. Small sample size, limited results, and only in those below age 40.

A 2020 study found that hair turned grey and white more rapidly in mice when exposed to major stress. The effects were via the sympathetic nervous system (fight or flight response).

Grey Hair is not Always a Sign of Ageing

Since grey hair usually only affects people in their mid-30s and aftermath (and a full head of white hair is almost never seen in those below the age of 50), most people assume that it is a sign of ageing. However, this is not always the case. There is no shortage of celebrities on TV that have grayed at a very early age.

Perhaps the two most famous examples here in the US are Anderson Cooper and Jay Leno, who both look very young for their age in that video despite graying in their 20s. Cooper started to go grey at just 20 and Leno at 29 according to his statement in that video. Neither of them seem to have any health issues despite now having been grey for decades. If anything, both seem to be aging at slower pace then the average human.

Grey Hair in Men versus in Women

Grey hair is a far greater concern for women than for men. For the former, it represents a sign of aging and an almost certain end to careers in acting and modeling unless the hair is dyed all the time. For the latter, this is not true, and some men are even purposely buying grey hair dye in order to look like George Clooney. However, some famous men such as Mr. Giuliani prefer to darken their hair even in old age.

New Research

Update: In April 2020, a new synthetic melanin nanoparticle coating method was deemed as a safer, nontoxic and longer lasting way to dye hair.

Update: In March 2020, Eirion Therapeutics had its patent for a grey hair treatment published. It entails using plasminogen activator inhibitor 1 (pai-1) inhibitors to prevent hair graying. Eirion’s pre-clinical product candidates for hair loss and grey hair prevention are ET-02 and ET-03.

Update: In January 2020, scientists from the US and Brazil found that excess stress can turn pigmented hair white. Moreover, when cyclin-dependent kinase (CDK) protein was suppressed in mice, their fur did not change color.

Update: A September 2019 case report from India found premature hair graying reversal after the use of Melitane 5% lotion and oral hair supplements. Melitane ™ from Redenhair is a biomimetic peptide agonist of an important melanocyte-stimulating hormone.

Update: In May 2018, researchers from the NIH and the University of Alabama discovered a connection between hair color and immune system activity. Lead researcher Dr. Melissa Harris runs a lab that researches melanocyte stem cells.

Update: In August 2017, a study concluded that forced epilation in mice resulted in melanocyte cell and hair color regeneration. i.e., a potential grey hair cure in humans.

Update: In June 2017, a very unique experiment on one South Korean patient showed significant hair darkening. This success was achieved after treatment with a 1,927-nm fractionated Thulium laser and Polydeoxyribonucleotide injections.

Update: In April 2016, a Forbes magazine cover story on Samumed suggested that the company’s SM04554 hair regrowth product that targets the Wnt pathway could also cure grey hair.

Update: In March 2016, researchers in the UK discovered key genes for grey hair and more. The IRF4 gene’s presence seems to correlate with an earlier loss of hair color.