5 alpha reductase and sebum production

[norwood4]

Hi, friends.
You know there´s been some contradictory results regarding the role of 5AR-1 in sebum production; you may remember that study showing no improvement in acne after taking a potent, specific 5AR-1 inhibitor, named MK386. But I´ve found another study regarding another such inhibitor, named butyl avocadate, with different results:



Pharmacological and Clinical Activities of 5-Alpha Avocuta : Application for the Management of Androgenic Disorders

Abstract number: 407

Piccardi1 N, Piccirilli1 A, Choulot1 JC, Chadoutaud2 B, Msika1 P

Androgen-dependent disorders, such as seborrhoea, acne and alopecia are among the most common diseases encountered by dermatologists in daily practice. These pathologies are in part related to an hyper-activity of 5-alpha reductase, the enzyme that metabolises testosterone into dihydrotestosterone (DHT) a major potent androgen in human skin. In this work, we have investigated the efficacy of a lipidic fatty ester: 5-alpha Avocuta (butyl avocadate). Butyl avocadate is obtained from refined avocado oil through a biotechnological process, and is purified by molecular distillation.

We have demonstrated using dermal fibroblasts in culture that 5-alphaAvocuta is a potent inhibitors of 5-alpha reductase type I activity (-49% for the smallest dose tested 0.01%).

A multi-centric clinical evaluation, under dermatologist control, was conducted on 27 volunteers. The purpose of this study was to test the efficiency of a shampoo (1% of 5-acute Aocuta) after 3 weeks of application (1 application/2 days). Analysis of sebum secretion (Sebufix® F16) by visual scoring and by image analysis (Skin Visiometer®, SV600, CK, Germany) demonstrate that this shampoo is able to significantly reduce sebaceous production. Clinical investigations by the dermatologist (analogic scale) show that the shampoo clearly improves greasy hair aspect, and is able to reduce itching and pruritus, as well as dandruffs. The auto-evaluation by the volunteers confirms these data. The efficiency of 5-alphaAvocuta, formulated at 2% in a skin care, has been also demonstrated in the management of the hyper-seborrhoea of the face. After 3 weeks (application twice a day), this specific formulation was able to reduce the sebum production (-30%) at the level of the face, to improve all the clinical parameters (-31% in average) and to reduce the number of open comedons. The volunteers have also approved the efficiency of the product (78% good opinion), and they have reported an improvement of their quality of life.

5-alpha Avocuta is a new and original inhibitor of 5-alpha-reductase type I activity with proven efficiency on human scalp and skin disorders related to hyper-seborrhoea. This natural active ingredient may open the way to the formulation of original and efficient products dedicated to the treatment of androgenic disorders.

2Clinical Research Consultant, France 1R&D Center, Laboratoires Expanscience, France.



Any thoughts on this...? Did you know about these compound?

 

[bcapop]

Good find! Here's a patent on it: http://www.freepatentsonline.com/20050244362.html. I wonder if normal avocado oil does this also.

 

[Armando Jose]

HI guys;

I am inclined to think that this product is similar to others FFA's in order to diminish sebum production. The patent provided by bcapop confirm my idea that they want to have a special product patented in the market.

Armando

 

[norwood4]

Hi, Armando! Nice to see that we both post internationally too! (both of us participate in a large spanish forum).

I´d like to add that the study regarding mk 386 (the 5AR-1 specific inhibitor) didn´t measure the production of sebum; it only showed no significant improvement in acne lessions. And now I´d like to present this study:



A correlation between the severity of acne and facial sebum secretion is generally accepted,[4-10] but previous studies have failed to consider topographical variations in facial sebum secretion. Facial areas can be categorized as T- and U-zones (high and low sebum secreting areas, respectively) on the basis of sebum secretion levels.[3,12] Moreover, the distribution patterns of acne lesions are heterogeneous on an individual basis. Some patients may have acne lesions in an oily area, whereas others may have lesions in a dry area, and even patients with dry facial skin present with severe acne. However, previous studies on the correlation between sebum secretion levels and the severity of acne have measured the amount of facial sebum only on the forehead, a representative oily area of the face. Thus the data collected cannot reflect local variations in sebum secretion and their effects on acne development. Another shortcoming of these earlier studies is that the methods used for acne severity evaluation were crude. In fact, no single acne grading system is generally accepted, and several systems are used on a preferential basis. A global three-grade acne classification system (i.e. mild, moderate and severe) has been used in previous studies,[6] as has the Leeds technique.[4] However, these assessment systems depend wholly on a rater's impressions, and do little to circumvent issues of internal validity and reproducibility. The Leeds technique is limited by its complexity and because it can only be used on en face photographs, and thus it gives little weighting to lesions of the cheeks and chin. Acne lesion counting is another method used for acne severity evaluations, but it has high inter- and intrarater variability, and there is a risk of duplicate lesion counting.[11]

In this study, we measured sebum secretion at five locations on the face to consider regional variations in sebum secretion. In addition, our study incorporates an acne grading system which increases the evaluation accuracy. However, our study has its limitations. The Sebumeter® was used as a measuring tool, and its measurement area is limited to skin contacting the unit's cassette probe. However, the areas in which lesions were counted were larger than this sebum measuring area, and thus there is a possibility of a disparity between the lesion count area and the sebum measuring area.

The absence of correlation between sebum secretion and lesion counts in most facial regions suggests that secreted facial sebum cannot be the only factor inciting the development of acne lesions. Increased sebum secretion is a major component in the pathogenesis of acne, but increased sebum secretion simply increases the likelihood of developing acne lesions, and does not constitute a direct and unique cause of lesion development. For example, the scalp secretes high levels of sebum, but comedogenesis is rarely observed even in patients with severe acne.[13] The present study shows that noninflammatory comedones on the chin, and inflammatory and total lesions in the U-zone, were significantly associated with local sebum secretion. However, their correlation coefficients did not show strong associations, which implies that other factors play an important role in the development of acne in these regions. Increased sebum secretion with follicular obstruction in the same follicle could incite comedogenesis, but increased sebum secretion without follicular obstruction cannot create comedones. Thus, repeated facial washing to remove seborrhoea from the skin surface would not be expected to improve clinical acne. A recent study with orally administered type I 5?-reductase inhibitor, which suppresses facial sebum secretion, showed that the suppression of facial sebum production does not improve acne lesions.[14] This study supports our results.

One more point is worth considering. We performed this study in women, and sebum secretion patterns differ in men and women. Thus there may be a different association between sebum secretion and acne lesion development in men. A further study including males should therefore be performed.

In conclusion, increased facial sebum secretion in women with acne was not found to be the primary cause of acne lesion development, or even of the formation of noninflammatory comedones or inflammatory acne lesions. Rather it is just an epiphenomenon or an aggravating condition in patients with acne. A future study on local androgen receptor variations in follicle openings, which may lead to follicular obstruction, may clarify the association between variations in regional sebum section and acne development.





This may suggest that, while specific 5AR-1 inhibitors may not improve acne lessions, it doesn´t imply that they don´t reduce sebum production. That´s why mk 386 could still work for sebum suppresion, but this wasn´t tested in the experiment. A pity...

 

[Armando Jose]

Nice to meet you my friend.

Armando