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Nizoral Shampoo Review - Does it Help Hair Loss

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Nizoral shampoo is commonly used to treat dandruff and other skin infections. However, recently, there are evidences from various studies indicating that Nizoral shampoo can actually stop hair loss and even promote hair regrowth. This article examines some of those studies and discusses the active ingredient in Nizoral shampoo, how it works and how it performs compared to the popular hair loss products.

What is Nizoral?

Nizoral is the topical 2% ketoconazole liquid preparation manufactured by Janssen Pharmaceutical.

This shampoo product has a red-orange color and it suspends the active ingredient in a mixture of these inactive ingredients: coconut fatty acid diethanolamide, disodium monolauryl ether sulfosuccinate, F.D.&C. Red No. 40, hydrochloric acid, imidurea, laurdimonium hydrolyzed animal collagen, macrogol 120 methyl glucose dioleate, perfume bouquet, sodium chloride, sodium hydroxide, sodium lauryl ether sulfate, and purified water.

Nizoral has a broad-spectrum antifungal action and it is most commonly used to treat skin infections such as tinea versicolor, dandruff, and seborrheic dermatitis.

Regarding tinea versicolor, Nizoral is active against the fungus, Pityrosporum orbiculare also known as Malassezia furfur. In the treatment of dandruff and seborrheic dermatitis, Nizoral targets a related fungus known as Pityrosporum ovale.

Generally, the active ingredient of Nizoral, ketoconazole, acts by disrupting the cell membranes of fungi. More specifically, it blocks the production of ergosterol which is required by these microbes to make cell membranes.

Even though Nizoral has been in use for some many years, and given that it is effective against a lot list of fungi, microbial resistance to ketoconazole (its active ingredient) remains uncommon.

Once applied to the skin surface, very little of Nizoral is absorbed through the skin. Therefore, the risk of systemic toxicity is very low. In addition, Nizoral does not become toxic or trigger allergic reactions on the skin on exposure to sunlight. This means that the topical agent can be safely applied during the day.

However, mild skin irritations following the application Nizoral have been reported. These skin reactions can be caused by ketoconazole or one of the inactive ingredients of the shampoo.

Furthermore, Nizoral may also cause chemical irritation when it comes in contact with mucosal surfaces such as the membranes of the eyes.

Other reported adverse reactions to Nizoral shampoo include rash, itching, contact dermatitis, dry skin and burning sensations. On the hair, Nizoral may cause hair loss, hair discoloration, abnormal hair texture, dry hair, oily hair and the uncurling of waxed hair.

Depending on the severity of these adverse reactions, the user may have to discontinue Nizoral.

Adverse skin reactions and generalized hypersensitivity reactions involving shortness of breath and facial swelling caused by Nizoral should be considered medical emergencies and treated as such.

Safety studies on Nizoral are inconclusive or lacking. Therefore, pregnant women should only use the shampoo when the benefits outweigh the risks. Even then, the available studies show that ketoconazole does not reach the plasma even with chronic shampooing.

To use Nizoral Shampoo, dampen the affected area and the surrounding skin before applying the liquid. Lather the shampoo on the skin and leave it on for 5 minutes before washing it off.

What is Ketoconazole?

Ketoconazole is a synthetic drug known for its broad antifungal properties.

It was discovered in 1976 and marketed as a drug in 1981. Ketoconazole is the second oral antifungal drug released (the first one is griseofulvin).  

This antifungal drug is commonly used to treat skin infections caused by fungi and it is the drug of choice in people with weakened immune systems such as cancer patients on chemotherapy and AIDS patients.

Ketoconazole is available in oral dosage forms like tablets as well as in topical preparations such as creams but most commonly as shampoos.

By its fat-soluble nature, ketoconazole can be easily absorbed into fatty tissues where it can accumulate. While this is an advantage for the topical actions of the drug especially on the skin, this property is also responsible for the toxicity of ketoconazole.

When taken orally, the absorption of ketoconazole requires high acidity levels in the gut. Therefore, drugs like antacids that reduce stomach acidity will reduce the absorption of ketoconazole.

Ketoconazole is a member of the azole antifungal agents. It specifically inhibits the enzyme, 14-alpha-demethylase, a cytochrome P450 enzyme that fungi use to synthesize ergosterol from lanosterol through a string of intermediates.

By preventing fungi from making ergosterol, ketoconazole deprives them of a stable membrane to wrap up their cellular structures. This immediately leads to the death of these microbes.

The topical fungi infections for which ketoconazole is most commonly prescribed include ringworm, thrush, athlete’s foot, jock itch, candidiasis, tinea versicolor, and eumycetoma.

Ketoconazole is also commonly used to treat dandruff. There are different topical formulations of ketoconazole but the shampoo is the most popular.

Besides fungal infections, ketoconazole is also used to treat other medical conditions because of some of its desirable side effects. For example, one of the side effects of ketoconazole is the suppression of testosterone. This side effect is the reason doctors prescribe ketoconazole for treating hair loss and prostate cancer.

Another side effect of ketoconazole is its suppression of glucocorticoid production. This side effect is exploited in the treatment of Cushing’s syndrome.

Studies on Ketoconazole Shampoo and Hair Loss

Of Mice and Men

To investigate the possible benefits of 2% ketoconazole shampoo on hair growth in mouse models, a group of Japanese researchers applied ketoconazole or placebo on the dorsal skin of 7 week-old genetically modified (C3H/HeN) mice after shaving off the hair.

The 2% ketoconazole and placebo solutions were applied once daily for three weeks.

The results of this study were published in The Journal of Dermatology in 2005. These results showed that 2% ketoconazole clearly stimulated hair regrowth.

The researchers repeated this experiment and achieved the same results. They concluded that 2% ketoconazole shampoo was effective in treating male pattern hair loss accompanied by seborrheic dermatitis.

The Anti-inflammatory Effect of Ketoconazole

A 1998 study published in the Swiss journal, Dermatology, by a group of Belgian researchers compared the efficacies of 2% ketoconazole shampoo and an unmedicated placebo shampoo mixed with or without 2% minoxidil.

The results showed that both 2% ketoconazole and 2% minoxidil were effective for stimulating hair growth. These topical agents increased hair density as well as the size and population of hair follicles during the anagen phase of the hair growth cycle.

The researchers believed that ketoconazole was able to increase hair growth because of

  • its broad antifungal activities against the microbes colonizing the scalp flora; and
  • its anti-inflammatory properties

Both of these effects are believed to be linked. For example, the chief scalp fungi that were killed off by ketoconazole in this study belong to the Malassezia species.

These fungi can cause local inflammation on the skin. Therefore, by killing them off, ketoconazole provides two ways to prevent the inflammation of the hair follicles.

The Comparative Studies

In a 2002 study published in The Journal of Dermatology, researchers compared the efficacies of different combinations of drugs used in the treatment of androgenetic alopecia.

This open, randomized clinical trial recruited 100 male patients suffering from this form of hair loss. They were divided into 4 groups corresponding to the drug(s) given to them.

  • Group I – 1 mg per day of oral finasteride (30 patients)
  • Group II – 1 mg/day oral finasteride + 2% topical minoxidil solution (36 patients)
  • Group III – 2% topical minoxidil solution (24 patients)
  • Group IV – 1 mg/day oral finasteride + 2% ketoconazole shampoo

The patients were placed on the drug combinations throughout the one-year duration of the study.

The results of this study showed all 4 groups of patients experienced significant hair growth. However, the best results were observed in patients in Group II followed by Group IV, I and III.

This study showed that ketoconazole shampoo ranks high amongst the drug used for treating androgenetic alopecia. Even though this is not its primary indication, it outperforms minoxidil solution and has an effectiveness comparable to finasteride.

This is all the more remarkable given that ketoconazole shampoo is a lot more affordable than minoxidil and finasteride.

The superiority of the combination of finasteride and ketoconazole was further confirmed by a 2004 study published in the journal, Medical Hypotheses. In this study, the researchers demonstrated that ketoconazole amplifies the inhibition of DHT (dihydrotestosterone, an androgen produced from testosterone) that is begun by finasteride.

Therefore, the combination of oral finasteride and topical ketoconazole is the most effective way to treat androgenetic alopecia.

A 2002 study published in the International Journal of Cosmetic Science compared ketoconazole with a different set of drugs.

In this study, 1% solutions of ketoconazole, piroctone olamine, and zinc pyrithione were the anti-dandruff shampoos randomly allocated to 150 men suffering from androgenetic alopecia accompanied with dandruff.

These topical solutions were administered 2 – 3 times per week for 6 months.

The researchers measured hair density at the crowns, the hair shaft diameter, the percentage of hair in the anagen phase, and the rate at which sebum is being secreted.

The results of the study showed that all 3 shampoos got rid of itching and dandruff quickly. In addition, while the 1% solutions were not strong enough to increase hair density, they did reduce hair shedding (ketoconazole > piroctone olamine > zinc pyrithione).

In addition, ketoconazole and piroctone olamine shampoos increased the thickness of hair shafts while reducing the rate at which sebum is pushed to the surface of the scalp.

This study further proves that ketoconazole even at 1% concentration can provide some benefits for people experiencing hair loss. At this concentration, ketoconazole can stop further hair loss while marshaling some of the factors that can promote the growth of new hair.

How Nizoral Stops Hair Loss and Promotes Hair Regrowth

Anti-inflammatory and Sebum Reduction

These two mechanisms have been mentioned above. The 2% solution of ketoconazole found in Nizoral has been proven to reduce local inflammation on the scalp.

This inflammation is mostly caused by colonizing fungi and the immune response to the damage done to hair follicles by androgens such as DHT as well as these causative fungi.

Ketoconazole has a direct anti-inflammatory property that can help stop these inflammatory reactions. Such inflammations will definitely reduce the output of the hair follicle cells and, therefore, disrupt the hair growth cycle.

In addition, ketoconazole can also indirectly reduce scalp inflammation by its anti-fungal actions.

By ridding the scalp of the fungi that trigger inflammatory responses, the active ingredient of Nizoral addresses scalp inflammation by two mechanisms.

Besides its anti-inflammatory properties, ketoconazole can also reduce sebum production in the scalp.

By turning down the secretion of sebum from the sebaceous glands attached to the hair follicles, ketoconazole prevents the skin pores of the scalp from clogging up. It frees the path of hair follicles and provides the right environment for new hair growth.

As An Antiandrogen

Although a side effect, the antiandrogen property of ketoconazole is chiefly responsible for the effectiveness of Nizoral shampoo in the treatment of hair loss.

Androgenetic alopecia is the most common form of hair loss. It involves the conversion of testosterone to DHT in hair follicles. The accumulation of DHT in the hair follicles soon leads to the rapid decline in the rate of hair growth.

There are 2 mechanisms by which ketoconazole acts as an anti-androgen.

The more important mechanism is blockage of androgen hormone syntheses in the adrenal gland and testicles. This is commonly achieved with a high dose of oral ketoconazole.

Since Nizoral is a topical solution of ketoconazole and the active ingredient is poorly absorbed through the skin, this mechanism contributes very little to the effectiveness of the shampoo in hair loss treatment.

However, the oral route and androgen suppression at the testicles are responsible for the use of ketoconazole in the treatment of prostate cancer.

The second mechanism is the inhibition of androgen receptors. Ketoconazole is an antagonist at these receptors. This means that it blocks androgens such as testosterone and DHT from binding to these sites.

When these androgens are blocked from these receptors, they cannot harm hair follicles.

This is a secondary mechanism for the effectiveness of oral ketoconazole pills. Even at high doses, oral ketoconazole cannot effectively block androgen receptors. However, topical ketoconazole serves as an antiandrogen chiefly by this mechanism.

The ketoconazole permeating the scalp from Nizoral shampoo can block the androgen receptors found in hair follicle cells. Therefore, Nizoral can provide a local but potent antiandrogen effect on the scalp.

By blocking DHT from binding to these receptors, Nizoral stops hair loss and allows the hair follicles to recover enough to resume the production of new hair.





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