Yokohama National University, Junji Fukuda, Tatsuto Kageyama, TrichoSeeds

Yokohama and Fukuda Hair Multiplication Trials in 2023

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I have covered hair regeneration research by Yokohama National University (Japan) based scientist Dr. Junji Fukuda a few times in the past. His team’s most important work relates to hair multiplication via the production of hair follicle germs.

However, Dr. Fukuda achieved global notoriety in 2018 due to the French Fries chemical related hair loss “cure”. In recent years, the Yokohama Team has published numerous papers. Moreover, they plan to begin hair multiplication trials in humans in 2023.

I first wrote this post in 2021, and post new updates on top. I attach a great deal of importance to Dr. Fukuda’s groundbreaking work. Make sure to also check the Fukuda Lab site for the latest news. They seem to publish a new hair related study almost every couple of months.

Update: July 5, 2024

Fukuda Method versus Tsuji Method

A unique and interesting new interview with Dr. Junji Fukuda (h/t “Theo”). He discusses in detail the difference between his team’s hair multiplication method versus Dr. Takashi Tsuji’s team’s approach. Dr. Fukuda’s work is being undertaken via a company called TrichoSeeds. Dr. Tsuji’s work is being undertaken via OrganTech.

Dr. Fukuda mentions how the pioneer of hair transplantation (he probably means Dr. Shoji Okuda) is Japanese and one of the pioneers of hair regenerative medicine (Dr. Tsuji) is also Japanese. Shiseido (Japan) could end up also being a pioneer in the hair loss world.

Key quote:

“Dr. Tsuji and his team first extracted hair follicles and increased the epithelial and mesenchymal cells. We did the same thing up to this point. After that, Professor Tsuji and his team created individual hair follicle primordia by massing each type of cell in a centrifuge and combining them under a microscope. We took the approach of mixing epithelial cells and mesenchymal cells extracted from hair follicles in a culture solution and culturing them together.”

He also mentions that when fibroblast growth factor 2 (FGF2) was added to the base medium of Fukuda culture, the efficiency of hair regeneration was significantly increased.

Finally, he mentions the potential cancer side effect that prevents his team from easily creating hair follicles from iPS cells. Japanese laws governing regenerative medicine would allow the use of iPS cells in regenerating vital organs, but not for regenerating hair.

April 12, 2023

Yokohama Researcher Junji Fukuda’s New Interview

A detailed new interview with Dr. Junji Fukuda (h/t “Ben”). Nothing in there about their human trial plans for 2023, but nevertheless very interesting.

They are pursuing three different mechanisms for hair regeneration:

  • Reactivating the hair follicle tissue that remains in the scalp via transplant special cells. These cells give instructions on reactivation of dormant hairs as well as increasing the thickness of existing hair. For this method, they are working together with Rohto Pharmaceutical. Note that he expects human clinical trials for this method to begin “within the next few years”.
  • Inject (transplant) cell tissue prepared in vitro into the scalp and induce new hair follicle tissue to grow. This is based on their successful 2018 results related to “hair follicle primordia” that I discussed in the earlier hair follicle germs link.
  • Create and transplant hair follicle tissue containing hair from cells through culture. Based on their 2022 work in relation to “hair follicle organoid”. I discussed this in this very post in the prior updates further below.

In is interesting how much the students are involved in this research. Dr. Fukuda even gives credit to the last method above to one his student’s discoveries. Something that almost never seems to happen in the western world. Even the new company Trichoseeds is part owned by his student lab researchers:

“I founded a venture company together with the students in my laboratory so that the technology could be used for the practical application of hair regenerative medicine. I started the project because I thought that students would be more motivated if they were doing research for social implementation, so they would be able to benefit from it as well.”

October 21, 2022

The un-finalized paper that I mentioned in my prior June update was just released today. Lots of media coverage.

In yet another breakthrough, the Yokahama University team led by Junji Fukuda and Tatsuto Kageyama have managed to grow mature mice hair follicles in cultures. Actual paper here and was published today. The news is already being covered widely in a number of publications, including US News and Yahoo.

According to Newscientist:

Mature hair follicles have been grown in a laboratory for the first time, in a move that could one day treat hair loss.

The hair follicles grew for up to one month, reaching 3 millimetres length. According to Dr. Fukuda, this is probably due to the fact that the mice hair cycle is about one month. Quote from the good doctor:

Our next step is to use cells from human origin, and apply for drug development and regenerative medicine.

Also note that the same team released a new paper on October 1 titled: “Impacts of manipulating cell sorting on in vitro hair follicle regeneration.”

June 25, 2022

The updates from Dr. Fukuda and his team at Yokohama National University (YNU) keep coming and I am excited. Thanks to “Ben” for the links to the two latest papers. Also make sure to see Dr. Fukuda’s patents page.

Bioprinting Hair Yokohama
Bioprinting of hair follicle germs for hair regenerative medicine. Source: Acta Biomaterialia. Fukuda et al.

Junji Fukuda and TrichoSeeds

  • On June 16, the Fukuda Lab published a new paper titled: “Bioprinting of hair follicle germs for hair regenerative medicine.” This study outlines an approach for the scalable and automated preparation of highly hair-inductive grafts using a bioprinter (image above). The study link also includes two interesting videos at the bottom.

However, perhaps of most interest to me, they declare in the paper that:

“Ayaka Nanmo, Tatsuto Kageyama and Junji Fukuda are co-founders of TrichoSeeds, a company that provides hair regeneration medicine.”

This confirms the original YNU announcement about TrichoSeeds from earlier this year that a number of readers discussed.

  • Also published in June 2022 (but not yet peer-reviewed), the Fukuda and Kageyama team authored a paper titled: “Reprogramming of three-dimensional microenvironments for in vitro hair follicle induction.”

While doing research for this update, I discovered the below new April 2022 video published by Yokohama National University in regards to Dr. Fukuda. This all looks to be the real deal….although I said the same in the past about the Dr. Tsuji/Riken team. Also see this earlier 2017 video presentation from Dr. Fukuda.

Update: April 15, 2022

Yokohama University and Dr. Junji Fukuda

I consider Dr. Fukuda and his team to be among the five most important players in the world that are working on a hair loss cure. Per last year’s news (see further below), the Yokohama team plans to start human clinical trials in 2023.

In this latest research, the team managed to make new hair that was at first only growing underneath the skin of mice to sprout through the skin. They did this via the use of guide-inserted hair microgels (HMGs). They conclude:

“This approach is a promising strategy to advance hair regenerative medicine.”

Yokohama (Fukuda) Hair Multiplication Process
Yokohama National University Hair Multiplication Process. Dr. Junji Fukuda and Dr. Tatsuto Kageyama.

Update: April 7, 2021

Interview with Dr. Tatsuto Kageyama

Yesterday, in our Discord chat, “DrPhil” posted a link to a new April interview with Dr. Tatsuto Kageyama of Yokohama National University. It is worth a full read.

After some quick research, I realized that Dr. Kageyama is a co-author in Dr. Fukuda’s important 2019 paper titled: “Preparation of hair beads and hair follicle germs for regenerative medicine.”

This latest interview with Dr. Kageyama is extremely insightful and encouraging.

Human Trials to Start in 2023

The most important news is that human trials will start in 2023. Moreover, the treatment will not be too costly, and it will be safe.

Some key quotes after translation:

“We started basic research using human cells in 2018, aiming to start clinical trials in 2023. And we are working hard together with the members of the laboratory so that we can deliver it to everyone as soon as possible.”

“We also believe that we will be able to resolve cost issues.”

Apparently, they are convinced that the cost of this treatment will be much lower in comparison to other regenerative medicine treatments. A nice change from Dr. Tsuji’s expensive hair loss cure.

The team’s mass culture technology does not necessitate expensive equipment. Moreover, the required amount of hair follicle primordia can be produced with a single culture container.

Hair Follicle Primordium Creation

The Yokohama National University team’s hair multiplication process involves creating hair follicle primordia. Epithelial cells and mesenchymal cells mix to form a tissue called “hair follicle primordium“. This is essentially the seed for hair growth.

The process this team uses entails:

  1. Extract a few healthy scalp hairs.
  2. Increase the “epithelial cells” and “mesenchymal cells” that exist in those follicles.
  3. Thereafter, cultivate a large amount of hair follicle primordia.
  4. Transplant these new cells to balding regions of the donor’s scalp to regenerate the hair.

It will be possible to produce thousands of hairs from several hairs. The whole process is considered to be safe due to the autologous nature of the treatment.

Japan and Regenerative Medicine

Best of all, in Japan, clinical trials in regenerative medicine are expected to move along faster than in the US or EU. The country has a rapidly aging society with low birth rates. Therefore, it is a world leader in anti-aging related research.

The important triumvirate of Riken (Tsuji), Shiseido, and Yokohama (Fukuda) are all based in Japan. I am very hopeful that at least one of these three will finally succeed in bringing a next generation hair loss treatment or cure to the market.

Nizoral Shampoo, Dandruff, Ketoconazole

Nizoral Anti-Dandruff Shampoo

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This article was originally written on January 26, 2019. Last Updated on June 22, 2024.

Nizoral A-D Shampoo for Dandruff Treatment
Nizoral Dandruff Shampoo with 1% Ketoconazole.

Nizoral (with ketoconazole 1%) is an extremely popular dermatologist recommended dandruff shampoo. It also has modest anti-androgenic and hair growth properties according to a number of studies.

As of June 2024, Nizoral has almost 94,000 reviews on Amazon, with an average rating of 4.6 out of 5 stars. It costs just $14.10 for the smaller 7 fl oz (200 ml) bottle. The larger 14 fl oz (400 ml) bottle is currently priced at $27.53 on Amazon. This is a very affordable price when compared to other bestselling dandruff shampoos.

Update: June 22, 2024 — The Washington Post has an article suggesting that over-the-counter and prescription antidandruff shampoos that contain ketoconazole may help fight hair loss.

There is some evidence that ketoconazole blocks the synthesis of dihydrotestosterone in the scalp and acts as an antagonist of the androgen receptor. See the list of supportive studies at the bottom of this post.

  • A November 2023 study from India discussed the successful development and testing of a novel anti-dandruff shampoo incorporated with ketoconazole-coated zinc oxide nanoparticles. The researchers wanted to improve on existing ketoconazole (KTZ) based shampoos with weak skin epidermis absorption and permeability. The prepared nanoparticles showed enhanced activity against Malassezia furfur compared to regular KTZ (1%).
  • A May 2022 study from Brazil found that ketoconazole shifts the scalp skin lipid profile, affects Malassezia lipid metabolism and favors biotin-producing bacteria. Biotin improves inflammatory conditions.

Nizoral Shampoo

Nizoral shampoo (1%) is one of the highest rated and reviewed anti-dandruff shampoos that you can buy without a prescription. I rank it as one of the 15 best hair loss shampoos in the world. You can buy it at most stores, including Walmart (5,000 reviews), Target (4,900 reviews), CVS (3,700 reviews) and Walgreens (3,700 reviews).

Nizoral A-D Anti-Dandruff Shampoo with ketoconazole 1%, is consistently rated as one of the best products to counter dandruff, scalp itching, flaking and fungus. We all shed millions of dead skin cells every single day. However, some people have excessive skin turnover on the scalp, leading to dandruff.

Nizoral Ketoconazole 2 Percent Shampoo
Nizoral Ketoconazole 2% shampoo for dandruff. Prescription only in the US, but available off-the-counter in Canada and the UK.

Nizoral (often misspelled as Nizarol) can improve psoriasis symptoms, scaly scalp skin, yeast infections and even foot fungus. Some reports suggest it can also benefit fungal acne, although facial usage is not recommended.

A small bottle of this highly rated antifungal anti-inflammatory product will last for many months. Note that Nizoral 2% shampoo comes in a red bottle and is a different product that requires a prescription in some countries.

Ketoconazole 2 Percent Shampoo
Ketoconazole 2 Percent Shampoo from Canada.

The Nizoral 1 percent shampoo is an over-the-counter product, while the medicated 2 percent shampoo requires a prescription in the US. In the UK and Canada, you can purchase the latter off-the-shelf at pharmacies and on Amazon UK. It had 28,600 reviews as of June 2024, with an average rating of 4.6 out of 5 stars. Note that they delineate their units as 20 mg/g, which is the same as 2%. The bottle contains only 60ml of liquid.

Also worth noting, Nizoral shampoo can help reduce hair loss to a moderate extent due to its anti-androgenic properties. See the studies listed at the end of this post that support this point. Other popular hair loss shampoos include Revivogen and Shiseido Adenovital (number 1 in Japan) and Folligen (number 1 in South Korea).

Ketoconazole 1%: The Active Ingredient

The list of ingredients in Nizoral can be found in the FDA label pdf. The key active ingredient is ketoconazole 1%. Ketoconazole (abbreviated KCZ or KTZ) also has some anti-androgenic properties.

To date, only two drugs with very different mechanisms of action have been approved by the US FDA to treat hair loss: Finasteride (Propecia) and Minoxidil (Rogaine).

Nizoral Shampoo Ingredients
Nizoral A-D shampoo ingredient list. Includes Ketoconazole 1% to fight dandruff.

However, Ketoconazole also has some hair growth benefits. It is an imidazole anti-fungal agent that counters dandruff and scalp inflammation.

Ketaconazole will never be officially approved to treat hair loss, because its manufacturer is unlikely to ever file for approval. With sales of Nizoral already going strong globally, it is probably not worth going through all the rigorous expensive clinical trials to get little added benefit.

Ketoconazole is a synthetic drug that is used to treat fungal infections. In particular, the drug flushes out Malassezia (formerly known as Pityrosporum) yeast fungus. Malassezia has been implicated in problems such as dandruff and seborrheic dermatitis. The latter leads to clogged hair follicles.

Other names for similar fungal infections and overgrowth of the scalp include Pityriasis Versicolor, Pityrosporum Ovale and Malassezia Furfur. Skin conditions such as tinea and ringworm may also benefit from this product.

Ketoconazole was originally available in tablet form, but has since also been developed into topical forms such as creams, lotions and shampoos. Note that oral ingestion of ketoconazole can lead to serious side effects such as liver damage in some patients. However, topical cream and ketoconazole shampoo usage have generally not been linked to such side effects.

My Nizoral Experiences for Scalp Itching

A large proportion of hair loss sufferers seem to also get itchy and dry scalp conditions, including dandruff and seborrheic dermatitis. I am one of those, although the severity and frequency of my symptoms is moderate and sometimes goes away for months.

Some years ago, I started using Nizoral 1% anti dandruff shampoo for my itchy inflamed scalp instead of other regular shampoos. I was absolutely amazed at its effectiveness in completely eliminating my scalp itching and dandruff for at least a day or two after each application. My hair looked better and healthier, and it seemed like my daily hair shedding rate also declined.

However, starting in December 2023, I started using the Head & Shoulders medicated shampoo. Nizoral was making my hair a bit too dry and lifeless.

Nizoral Conditioner

Nizoral now also sells a popular deep moisturizing hair conditioner product. It is supposed to counter the drying effects of Nizoral shampoo.

The conditioner is free of sulfates, parabens, artificial fragrances and dyes. Among the key ingredients in the conditioner (which contains seven moisturizers) include:

  • Shea Butter.
  • Jojoba Seed Oil.
  • Peppermint Oil.
  • Tea Tree Leaf Oil.

How often Should you use Nizoral Shampoo?

I would recommend using Nizoral shampoo no more than twice a week in order to prevent excessive skin dryness. You also do not want your scalp microflora and fungi to become immune to the effects of ketoconazole. Overuse will make your scalp skin excessively dry and make your hair brittle. I would recommending rotating between several different products among the best dandruff shampoos available.

When you do shampoo with Nizoral, make sure to keep it on your scalp for at least 3-4 minutes after lathering and before rinsing. Some people recommend rinsing hair in cold water rather than hot water in the shower. The former prevents excessive moisture loss and skin drying out.

Shortages

In 2012 or so, it seemed like US drug stores and pharmacies such as Walmart, Walgreens and CVS stopped carrying Nizoral shampoo, at least when it comes to the most popular blue bottle variety (see photo further below). I thought this was because of the warnings related to side effects from taking oral ketoconazole. I later found out that the problems with availability were due to the shampoo’s manufacturer having production issues at its main plants, rather than any issues related to side effects.

Luckily, I had sufficient supplies to last me for a while, since you only need a small amount of Nizoral shampoo to make a big difference. Most people do not need to use it more than twice a week. However, this shortage continued in 2013 and I then had to pay a significant premium to buy it from a seller on ebay. A lot of people took advantage of this situation by selling their surplus Nizoral stock online in 2012 and 2013. In 2014, Nizoral came back on the market and the shortages finally ended. No supply issues have occurred since that time.

Nizoral Side Effects

As long as you are not taking Nizoral (i.e., Ketoconazole) orally, side effects are usually limited and transient. The main side effects that can arise from using Nizoral shampoo include:

  • Itchy scalp.
  • Dry scalp skin.
  • An unnatural hair texture and feel.
  • Rashes, hives and other allergic reactions.
  • Red inflamed eyes in case the product accidentally gets in there.

Ketoconazole and Hair Loss Studies

You can find many studies that suggest Nizoral causes a reduction in hair loss and thinning. Ketoconazole has anti-androgenic properties that could slow the progression of androgenetic alopecia (aka male pattern baldness). Below are some such studies in order of oldest to most recent:

In June 2018, Germany’s Stada acquired Nizoral from Johnson & Johnson. For more recent information, see Nizoral’s official Instagram page.