Ketoconazole shampoos have become an increasingly popular way to treat hair loss.
This in-depth guide will take a close look at ketoconazole: its uses, how it works, and the relevant research studies.
What Is Ketoconazole?
An antifungal drug used primarily in the treatment of fungal infections, ketoconazole was discovered in 1976 by Janssen Pharmaceutica in Belgium.
There are a few brand names under which it is sold, such as Extina, Xolegel, and Ketoderm. However, the most popular brand name is Nizoral. This is one of the most common anti-dandruff medications on the market today.
This article will look primarily at the shampoo version, but ketoconazole is available in many forms. These include gel, foam, cream, and even oral tablets.
How It Works
The main mechanism by which ketoconazole operates is through its killing of fungi and yeasts. The drug stops the production of an organic molecule commonly found in fungus and yeast – ergosterol – and this interferes with the cell membrane of both organisms.
With the cell membranes compromised, the organisms are no longer able to reproduce.
Ketoconazole is what you call a “broad spectrum” drug. This means it is effective against many species of micro-organisms. These include not only the fungus responsible for most cases of dandruff (discussed below) but many other, often more severe, fungal infections of the scalp.
Ketoconazole can also be taken to trust candidiasis (thrush).
Is Ketoconazole a Hair Loss Treatment?
It is important to stress at the outset that ketoconazole is sold as an over-the-counter medicated shampoo for the treatment of dandruff and certain fungal infections. Depending on its form (topical or oral) ketoconazole can be used to treat fungal infections in most parts of the body.
Male pattern hair loss is not a fungal condition. So neither the manufacturer markets Nizoral shampoo as a treatment for pattern hair loss nor has the FDA approved it for this indication.
Having said that, in recent years ketoconazole shampoos have gained somewhat of a following among certain segments of the hair loss community. Supporters of ketoconazole often reference a handful of research studies conducted some years ago. The authors of those studies looked at ketoconazole shampoos outside of their intended use, and in particular as a treatment against male pattern baldness.
Ketoconazole, Dandruff, and Seborrheic Dermatitis
Dandruff is the number one scalp condition affecting millions of people worldwide each year.
This condition – characterized by itching and large, white flakes – is more than just a case of dry scalp.
All healthy people lose skin cells on their scalp and the rest of their body all the time, but these are normally not visible. In dandruff, this changes.
The white, ugly, crusty flakes seen in dandruff are actually a cluster of dead skin cells that for one reason or another retained a high degree of cohesion and detached as one piece from the scalp.
This is a condition believed to have many causes, including airborne chemicals and even stress. But in most cases, the chief culprit is a fungus by the name of Malassezia. This is a family of fungi normally found in the scalp of healthy people. But in dandruff, Malassezia multiplies out of control, and it basically takes over the scalp.
The exact mechanism by which Malassezia causes dandruff is not clear. Be that as it may, the evidence implicating Malassezia in the pathogenesis of dandruff is strong. For example, a 2014 study found Malassezzia to be present in the scalp of 84% of a sample of dandruff patients. This was in contrast to healthy people, where Malassezia was only found in 30%.
Whatever the mechanism is, the fact is that getting rid of Malassezia often helps get rid of the symptoms of dandruff. Ketoconazole is very good at doing this.
With a powerful anti-fungal like ketoconazole, the yeast is no longer able to reproduce or survive. This leads to less scaling, and reduction of the other bothersome symptoms, like itching and redness.
A related condition to dandruff is seborrheic dermatitis (SD).
Like dandruff, SD is characterized by inflammation, itching, scaling, redness, flaking (yellowish or white), and overproduction of grease. Unlike dandruff, it can also occur in areas outside the scalp. These include the ears, eyelids, neck, upper back, chest, and armpits.
While there is no exact cause pinpointed, it is believed that SD is dependent on a number of factors. These include age, gender, and immune system health. And, as with dandruff, Malassezia is also thought to play a role.
Unsurprisingly, given what has been discussed so far, SD often responds very well to treatment with ketoconazole. When the SD affects the scalp the shampoo version can be used, but for SD of the face or other areas of the body, the cream is applied.
What about Ketoconazole and Hair Loss?
As mentioned above, ketoconazole is not licensed or sold as an anti-hair loss drug, but some balding men do use it for this purpose.
A 2005 Japanese study was one of the first to directly study ketoconazole’s role in hair growth. This was performed on mice, and the results were quite promising.
A similar study was performed in 2014 – again on mice – but this time it compared ketoconazole to minoxidil and minoxidil with tretinoin (an acne treatment).
The mice were first split into four groups (of five mice), and their dorsal hairs were shaved. A stain was then applied so researchers could better track the growth of new, non-dyed hairs.
The groups were split as follows:
Group I was the control, and it received 1 mL of 95% ethanol once daily for 6 days/week for 3 weeks.
Group II received Ketoconazole solution 2%, 0.1 mL once daily for 3 weeks.
Group III received Minoxidil solution 5%, 0.1 mL once daily for 3 weeks.
Group IV received equal amounts of Minoxidil solution 5% + Tretinoin 0.1%, 0.1 mL once daily for 3 weeks.
As results were compared after three weeks, it was obvious that ketoconazole, minoxidil, and minoxidil with tretinoin were all superior to the placebo group. This was shown when comparing both the number of hair follicles, as well as the mean diameter of hair follicles.
Of course, these results were also visually significant, as shown by the side-by-side comparison image below.
On the left is the control group, showing insignificant growth (as noted by the presence of dye). On the right is the ketoconazole treatment group, showing significant growth in just three weeks’ time.
As noted by the researchers, the positive effects of ketoconazole likely “stem from its antiandrogenic properties.”
When it comes to battling male pattern baldness (or androgenetic alopecia – AGA) one of the best ways to do so is to target and remove DHT from the scalp. DHT (dihydrotestosterone) is one of the four androgens, or male hormones. It is also the primary molecule implicated in male pattern baldness.
This is because those with AGA are sensitive to DHT, and this can cause irritation and miniaturization of the hair follicle. As the follicle miniaturizes, the hair growth cycle slows and, eventually, ceases completely.
Medications like finasteride work by block DHT all over the body, but blocking DHT in the scalp also works, probably just as well.
It turns out ketoconazole may also play a role in inhibiting the synthesis of DHT when applied directly on the scalp. Studies with prostate cancer patients have also confirmed the potent antiandrogenic properties of ketoconazole. These studies find that when taken orally, ketoconazole brings about a significant reduction of testosterone levels.
One of the first studies on the topic was published more than 20 years ago.
The study recruited 39 men with androgenetic alopecia, or which 27 used Nizoral shampoo for a 21-month period. The other 12 men used regular unmedicated shampoo.
At the end of 21 months, the men in the Nizoral group showed improvements in the proportion of anagen hairs (i.e. hairs in the growth phase of their cycle) as well as in the average diameter of their hair shaft.
This combination of more growing hairs that were also thicker led to fuller hair after 6 months of the treatment. The gains continued until they stabilized after 15 months. The men who were using the unmedicated shampoo, on the other hand, continued on the slow but steady decline that is typical of AGA.
The results of this first study spurred the researchers to conduct a second study (both of these studies were reported in the same paper).
In this second study, two groups of men were studied. There were four men in each group. One group used Nizoral shampoo, and the other group applied daily topical minoxidil (while also using regular, unmedicated shampoo).
After six months, both groups of men showed an increase in hair density which was 18% in the ketoconazole group and 11% in the minoxidil group. The median hair shaft diameter in both groups increased by 7%.
The authors concluded that ketoconazole shampoo results in an unequivocal increase in hair density, size, and proportion of anagen hairs.
There have been more recent studies on the topic, including those performed in 2002, 2006, and 2011.
While each of these studies did see hair growth in most of its subjects, there were some limitations. These include sample size and consistency of use among test subjects.
How to Use Ketoconazole Most Effectively
If you decide to add ketoconazole to your hair loss treatment plan, there are a number of other methods that you can use alongside it. These methods are natural, and they can further promote hair growth.
As the enzyme necessary to convert testosterone to DHT, the inhibition of 5-alpha-reductase (5AR) can go a long way in preventing male-pattern hair loss.
This can be done in two ways: through topical application of proven 5-alpha-reductase inhibitors, or through oral ingestion of similarly inhibiting substances.
As 5AR converts testosterone to DHT, inhibition of this enzyme can prevent male-pattern hair loss. For example, you can easily add reishi mushroom and green tea to your daily diet, or you can create a shampoo or hair growth serum that contains saw palmetto.
Costs and Availability
While tablets and creams are the typical prescription method, there are a few over-the-counter formulas available for purchase. These consist of shampoos (both 1% and 2%), as well as ointments.
As a popular over-the-counter fungal treatment, there are a number of brands to choose from. The most common brand is Nizoral, and an 8-oz bottle can typically be purchased for around $15.
While this may seem a bit pricey, the product is only used a few times per week at the beginning of treatment. This means that the product will last a reasonable length of time.
Ketoconazole Side Effects
As with any medication, ketoconazole has a few possible side effects that may interfere with its continued use or make continuation altogether impossible.
In 2013 the FDA issued a warning and limited the usage of ketoconazole tablets. The FDA warned of potentially fatal liver problems and serious adrenal gland problems. The agency also warned of potentially very serious drug interactions.
The label of the drug was changed, and the FDA recommended the drug no longer be a first-line treatment for fungal infections. As mentioned, these warnings apply to the oral version of the drug, not the shampoo.
What about the shampoo version – what are the most common side effects?
According to the Mayo Clinic, the most common of these are itching, stinging, burning, or irritation. On rare occasions, the shampoo may cause hair loss.
In the event side effects occur, they may subside as your body adjusts to the medication. If you find these side effects are too strong and cause distress, discontinue treatment and consult with your doctor.
As with any medicated product, it is a good idea to consult with your physician prior to usage anyway. This is especially true if you are currently on any prescription medications, or if you have any chronic health conditions.
How to Add Ketoconazole to Your Hair Care Routine
As a readily available shampoo, ketoconazole products can be easily added to your regular hair care routine.
As a medicated product, it is recommended that you follow a consistent regimen for six to eight weeks. This means using the shampoo every two to four days for the mentioned length of time, and then using it periodically ( one to two times per month) for continued benefits.
How to Use Ketoconazole Shampoo
If you decide to use ketoconazole, you will want to ensure you are using it most effectively. Here is a closer look at the instructions:
- Wet the area of the scalp affected by hair loss.
- Apply the ketoconazole shampoo directly to the area affected by hair loss, and a large radius around it.
- Massage the shampoo into the affected area for one minute, allowing it to fully lather.
- Let sit for 5 minutes.
- Rinse with lukewarm/cool water.
Practically, it will be much easier if you start your shower by applying the ketoconazole. You can then wash the rest of your body while you let the ketoconazole act on your hair.
While ketoconazole shampoo can be applied to the entire scalp, you want to ensure you pay particular attention to the area of hair loss. This means focusing the majority of your massaging efforts there, and using a circular motion while doing so.
By allowing it to sit, you also ensure the ingredients penetrate the scalp and hair follicles.
But you may be wondering:
“Why must I rinse with lukewarm/cool water?”
The fact is, hot water causes damage to the scalp and hair follicles. It leads to dryness, inflammation, and irritation and it should be avoided whenever possible.
By rinsing your scalp with lukewarm/cool water, you prevent any irritation from occurring.
Cold water rinses have other benefits, too! Namely, increased circulation which is great for oxygen/nutrient delivery and waste removal.
There is no doubt that ketoconazole can help significantly in the treatment of SD and dandruff. The jury is still out on its hair-growth properties, though there is some compelling evidence in this regard.
This does not mean, however, that it is the best option available to you.
Remember that dandruff and hair loss are conditions best resolved internally. Such methods will lead to longer-term results, and will also have a number of other positive health effects. Such a task is not always easily undertaken, but the results can be worth it in the long run.