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Azelaic Acid reduced sebum secretion: study


#1

Titre du document / Document title
Relationship between sebostatic activity, tolerability and efficacy of three topical drugs to treat mild to moderate acne
Auteur(s) / Author(s)
STINCO G. ; BRAGADIN G. ; TROTTER D. ; PILLON B. ; PATRONE P. ;
Résumé / Abstract
Background Acne is a multifactorial disorder in which the sebum plays an important pathogenetic role. Purpose of the study To evaluate the sebostatic effect of three anti-acneic ingredients (azelaic acid, adapalene and benzoyl peroxide) conveyed in cream and to determine whether there is a correlation with the therapeutic results. Materials and methods Sixty-five patients with mild or moderate acne localized on the face were divided into three therapy groups at random: 25 applied azelaic acid once a day, 20, benzoyl peroxide and 20, adapalene. All the patients were observed at the time of enrolling and a further four times at fortnightly intervals. At each visit the sebum casual level on the forehead, chin and one cheek was measured using a sebumeter. Furthermore, side-effects and clinical-therapeutic effectiveness were noted. Results Four patients did not complete the study. Azelaic acid showed an average reduction of 13.9% in sebum production on the forehead, 14.2% on the chin and 15.2% on the cheek. Benzoyl peroxide caused an increase of 10.5% in sebum production on the forehead, 10.3% on the chin and 25.4% on the cheek. Adapalene reduced sebaceous secretion by 0.2% on the forehead and 6.7% on the cheek whereas sebum production increased by 6.2% on the chin. All three drugs showed a clinical improvement in the acneic lesions with moderate adverse effects. Conclusion The three topical drugs bring about good therapeutic results with scarce side-effects that do not, however, seem to be correlated with the sebostatic activity.
Revue / Journal Title
JEADV. Journal of the European Academy of Dermatology and Venereology (JEADV, J. Eur. Acad. Dermatol. Venereol.) ISSN 0926-9959
Source / Source
2007, vol. 21, no3, pp. 320-325 [6 page(s) (article)]
Langue / Language
Anglais

Editeur / Publisher
Blackwell , Oxford, ROYAUME-UNI (1992) (Revue)

Mots-clés d’auteur / Author Keywords
acne ; adapalene ; azelaic acid ; benzoyl peroxide ; sebumeter ;
Localisation / Location
INIST-CNRS, Cote INIST : 27191, 35400014557962.0040

The percentages aren’t much, they are in the teens…but they are something. Perhaps it does have an effect on type ONE alpha five reductase anyway. This is what is so goddammed frustrating about looking into hairloss. Why doesn’t somebody do a six month topical test of azelaic acid on the head and see if its results are comprable to finasteride’s. Then we’d know. It would only take one man with baldness to do it. His increases in hair weights and photographic analysis would be enough to see if another larger study that was double-blind with placebo’s would be warranted. This could be done with other known “possible” anti-androgens like green tea extract, peppermint oil derivatives, cedarwood oil, licorice, clove, arnica, and rose fruit, and black tea extract. One cosmetics company could take ten men and find out once and for all----and put the pictures up. Instead we have to divine from meager information about sebum tests and tests in animals. Its so frustrating.


#2

Ive been thinking of concocting my own topical azeliac formula, sorta like the zix guy. However, chemistry isnt my strongest field of knowledge, ive been reading your posts and you seem very well versed, so i might as well ask you. For trans dermal purposes,can i use “ethyl rubbing alcohol 70%”, which my local pharmacy carries? Ethyl alcohol was suggested by the zix creator, i am wondering if what i saw at the pharmacy is the correct type of alcohol, I dont want to poison myself so any help would be appreciated.


#3

Apesmith:

Yes, “Ethyl” alcohol is what you need - Ethyl alcohol is also known as ethanol and grain alcohol, because it is distilled from corn and other grains. Although, 70% is not all that strong as it contains 30% water. Some people use Everclear which is pure ethyl alcohol. I don’t know if your local liquor store would carry it. You cannot drink “ethyl rubbing alcohol” only because they add minute quantities of poisons (denaturants) to make it undrinkable by law. You may often see “SD 40 Alcohol” on a product label. This stands for Specially Denatured, meaning that it has poisonous substances added to deter consumption.


#4

» Apesmith:
»
» Yes, “Ethyl” alcohol is what you need - Ethyl alcohol is also known as
» ethanol and grain alcohol, because it is distilled from corn and other
» grains. Although, 70% is not all that strong as it contains 30% water.
» Some people use Everclear which is pure ethyl alcohol. I don’t know if
» your local liquor store would carry it. You cannot drink “ethyl rubbing
» alcohol” only because they add minute quantities of poisons (denaturants)
» to make it undrinkable by law. You may often see “SD 40 Alcohol” on a
» product label. This stands for Specially Denatured, meaning that it has
» poisonous substances added to deter consumption.

First, JT is right about the alcohols. But second, if you want my opinion, a 15% reduction in sebum could be from just a blocking of type one alpha five reductase and not type two. Type two alpha five reductase doesnt effect sebum secretions at all as finasteride doesnt effect sebum. In other words, I have no idea whether azelaic acid effects the type of alpha five most associated with hairloss. Azelaic has other qualities that might make it somewhat useful in the baldness process…

If I were you, I’d empty about four capsules of green tea extract into a 2ml bottle of minoxidil If I were looking for an anti-androgen on the cheap in the now. Shake it up each time you use it.

Other things Im almost certain are anti-androgenic (but might not mix with alcohol) would be licorice, rose hips, peppermint, clove, cedarwood. Arnica is anti-androgenic but internally its poisionous----very much so. White curcumin is anti-androgenic also.


#5

As for azelaic acid, it is a VERY weak 5AR inhibitor, I believe. To me, it is a waste of time and money. Spironolactone would be a much better choice, IMO.


#6

And now for the NEGATIVE evidence on azelaic acid! :slight_smile: I came up with the following three studies from my Study Stack — there may be others, too, on its lack of effect on sebaceous glands, but I originally found these with just a quick search (the first two are in humans, the last one is in hamsters):

“Clinical and Laboratory Studies on Treatment with 20% Azelaic Acid Cream for Acne”, Cunliffe et al, Acta Derm Venereol (Stockh) 1989; Suppl 143: 31-34. “DISCUSSION […] No changes in sebum excretion rate were observed–hence azelaic acid does not modify sebaceous gland activity…”

“Effects of Azelaic Acid on Sebaceous Gland, Sebum Excretion Rate and Keratinization Pattern in Human Skin”, Mayer-Da-Silva et al, Acta Derm Venereol (Stockh) 1989; Suppl 143: 20-30. “Results of the Clinical Trial […] The size of the glands and the size and number of the gland lobules of each group in the population (normal, seborrheic and acne) were evaluated before and after treatment (AZA and vehicle). Skilled statistical evaluation of the specimens obtained before and after treatment revealed no differences between the AZA-treated side or the vehicle side of normal, seborrheic or acne skin…Our results show that AZA, when applied topically over a period of 3 months, does not induce alterations in the size of the sebaceous glands, leading us to suggest that AZA does not exert any direct influence on the functional activity of the sebaceous gland. Conclusion […] In contrast, no significant changes could be found after topical application of AZA with regard to the sebum excretion rate and the size of sebaceous glands.”

“Pharmacologic Investigation of Azelaic Acid”, Rach et al, J Invest Dermatol 1986; 86: 327. “The hamster ear lipogenesis model was used to evaluate the influence of azelaic acid on sebaceous gland activity. No effect on lipogenesis was observed following a treatment over a 4-month period with a 10% azelaic acid solution.”

.


#7

This would be from a Letter to the Editor from J.R. Marsden and Sam Shuster (Br J Dermatol 1983; 109: 723-724):

“…We have measured the effect on sebum excretion rate (SER) and acne lesion count of 20% azelaic acid cream applied twice daily to the forehead for 6 weeks. In nine patients (six male, three female, aged 17-32 years) mean SER was 1.8 ug/cm^2/min +/- 0.3 s.e.m. before treatment. After treatment there were small increases of SER in eight and a small decrease in one, so that mean SER was 2.0 ug/cm^2/min +/- 0.3 s.e.m. […] Interestingly, although seven out of nine patients said that the treated skin was ‘drier’, there was no change in skin appearance. With all previously studied sebostatic agents a therapeutically worthwhile decrease in SER would be easily detectable by the end of the 6-week treatment even with the small number of patients studied. Thus, unless azelaic acid has a unique cumulative action we conclude that it is unlikely to have a useful sebostatic effect.”

.


#8

Bryan,

First let me thank you for posting those studies…

It certainly appears (by 4 studies to 1) that Azelaic acid must not interdict 5Alpha Reductase type 1.

I must ask your opinon on this however…how in the world would one study note 15% or so reductions in sebum in human skin with even ONE study? The vehicle? Do you care to speculate?

I came across the study as a farce really. I noted Dr. Lee still sells the stuff and googled “azelaic acid and sebum” seeing if any study at all had been done in the past few years, and found the one I did and posted it.

You’ll note also…I didn’t tell anyone to go out and by AA as the percentages weren’t impressive enough to warrant that. Even if the test was “right”, we still dont know if it effected type 2 alpha five.

BTW--------------Im putting cedarwood oil (Scottish Alopecia Areata study) on by beard…will know if its an anti-androgen in a few months. I have a study from Johnson and Johnson that indicated that .6% cedarwood oil was the best sebum reducing agent that they tried.I’ll let everyone know if I see a reduction in beard hair. The reason Im excited to try Cedarwood oil is that the Scottish Study showed that it helped regrow head hair, so it cant be “bad” for head hair in anyway. Its the oldest baldness remedy that I know of as mummies have been found with cedarwood oil in their hair (Scottland peat bogs). Its the “first” essential oil in old hair growth remedies. We will see…thanks for posting the studies…


#9

» Bryan,
»
» First let me thank you for posting those studies…
»
» It certainly appears (by 4 studies to 1) that Azelaic acid must not
» interdict 5Alpha Reductase type 1.

Yep. The preponderance of the evidence seems pretty conclusive.

» I must ask your opinon on this however…how in the world
» would one study note 15% or so reductions in sebum in human skin with even
» ONE study? The vehicle? Do you care to speculate?

I really don’t know. BTW, this certainly isn’t the first time that we’ve seen studies with conflicting results. There have been other notable examples of that, like with the antiandrogen 11a-hydroxyprogesterone. There were some studies showing its effects at lowering sebum in humans, and then all of a sudden another one came out with hamsters showing NO effect at all on flank-organs. ZERO. ZIP. NADA.

» I came across the study as a farce really. I noted Dr. Lee still sells the
» stuff and googled “azelaic acid and sebum” seeing if any study at all had
» been done in the past few years, and found the one I did and posted it.

Don’t you think we need to forward all five of these studies to Dr. Lee for his careful perusal? :smiley:

» You’ll note also…I didn’t tell anyone to go out and by AA as
» the percentages weren’t impressive enough to warrant that. Even if the
» test was “right”, we still dont know if it effected type 2 alpha five.

Yep. It’s still just a really big question mark in my mind, and I find Dr. Lee’s own continued relentless and un-questioning dedication to such a highly dubious substance to be reprehensible. It may not be doing a DAMNED THING for all his patients using Xandrox, but he’s laughing all the way to the bank! :frowning:

» BTW--------------Im putting cedarwood oil (Scottish Alopecia
» Areata study) on by beard…will know if its an anti-androgen in a
» few months. I have a study from Johnson and Johnson that indicated that .6%
» cedarwood oil was the best sebum reducing agent that they
» tried.
I’ll let everyone know if I see a reduction in beard
» hair. The reason Im excited to try Cedarwood oil is that the Scottish
» Study showed that it helped regrow head hair, so it cant be “bad” for head
» hair in anyway. Its the oldest baldness remedy that I know of as mummies
» have been found with cedarwood oil in their hair (Scottland peat bogs).
» Its the “first” essential oil in old hair growth remedies. We will
» see…thanks for posting the studies…

Hmmm…but it was only for alopecia areata, right? Can you cite the study for me?

.


#10

Cedarwood oil at .6% was the most effective sebum-reducer they tested.
http://www.freepatentsonline.com/EP1172087.html

Quote:
The volunteer was requested to make a note of application of face wash and face cream daily on the given diary sheets. Sebumeter readings were taken 3 weeks and 6 weeks later.

Cedar wood and elubiol application led to a significantly greater fall in the sebum reading at 6 weeks as compared to 3 weeks. Treatment with Poplar bud, on the other hand showed no difference between 3rd and 6th week. A comparison between the treatments indicated that at 3 weeks the average percentage reduction in sebumeter readings on forehead and cheek was best with cedarwood (p <0.01 better than elubiol). The effect of poplar bud was comparable to elubiol.

At 6 weeks the effects of cedarwood were consistently maintained. The effect of elubiol improved, while poplar bud remained the least effective although this was not a consistent effect as seen by the wide variation in response. EXAMPLE 35

In this example the sebum control properties of moisturizing gels with plant extracts, cedarwood extract and hydrolysed soy protein, at a lower concentration of 0.5% is demonstrated.

This study was a double-blind, randomised, single centre study comparing 2 test gels (containing hydrolysed soy protein and cedarwood extract) with placebo Test products: Columns=2 ProductActive MTCedarwood extract - 0.5% DEHydrolysed soy protein - 0.5% BOPlacebo. 40 female volunteers aged between 13 to 19 years and having a sebumeter reading of 180 mu g/cm <2> took part in the study. These volunteers were instructed to avoid any other face cream, face wash or any other cosmetics during the 12 weeks of the study. During the first 2 weeks of the study, volunteers were instructed to use the face wash twice a day for washing their face. This period was considered as the conditioning period.

A baseline sebumeter reading was taken at the end of the conditioning period on 4 sites i.e. left forehead, left cheek, right forehead, and right cheek. Tubes containing the test products (which were coded and randomly allocated to each site) were dispensed to the volunteers. Each volunteer was given two test gels, one for left side of the face and the other for right side of the face. The choice of gel for the specific side of the face was made by random allocation. The volunteers were instructed to apply the test gels twice a day after washing the face with the given face wash for the next 12 weeks. Both volunteer and the study coordinator were not aware of the treatment dispensed ensuring the double blind nature of the study.

Adverse events were recorded. Results:

The two test products significantly reduced sebum readings as compared to the placebo.

The average % reduction for each of the three gels is tabulated below: Id=Table 1 (a) - Columns=5 Title: % Reduction (forehead) Head Col 1 AL=L: Treatment Head Col 2 to 5: Time (weeks) SubHead Col 1: SubHead Col 2: 3 SubHead Col 3: 6 SubHead Col 4: 9 SubHead Col 5: 12 HSP16.8441.0961.1463.41 Placebo14.123.4129.9739.62 Id=Table 1 (b) - Columns=5 Title: % Reduction (forehead) Head Col 1 AL=L: Treatment Head Col 2 to 5:

Time (weeks) SubHead Col 1: SubHead Col 2: 3 SubHead Col 3: 6 SubHead Col 4: 9 SubHead Col 5: 12 HSP19.1735.9448.7956.23 Placebo11.8923.1935.0946.02
Id=Table 2 (a) - Columns=5 Title: % Reduction (forehead) Head Col 1 AL=L: Treatment Head Col 2 to 5: Time (weeks) SubHead Col 1: SubHead Col 2: 3 SubHead Col 3: 6 SubHead Col 4: 9 SubHead Col 5: 12 HSP19.1735.9448.7956.23 Placebo11.8923.1935.0946.02 Id=Table 2(b) - Columns=5 Title: % Reduction (cheek) Head Col 1 AL=L: Treatment Head Col 2 to 5:

Time (weeks) SubHead Col 1: SubHead Col 2: 3 SubHead Col 3: 6 SubHead Col 4: 9 SubHead Col 5: 12 HSP20.2847.0558.6868.11 Placebo17.9132.5743.5151.81
Id=Table 3(a) - Columns=5 Title: % Reduction (Forehead+ cheek) Head Col 1 AL=L: Treatment Head Col 2 to 5: Time (weeks) SubHead Col 1: SubHead Col 2: 3 SubHead Col 3: 6 SubHead Col 4: 9 SubHead Col 5: 12 cw18.2140.7659.762.45 Placebo13.1224.9933.442.45 Id=Table 3(b) - Columns=5 Title: % Reduction (Forehead+ cheek) Head Col 1 AL=L: Treatment Head Col 2 to 5:

Time (weeks) SubHead Col 1: SubHead Col 2: 3 SubHead Col 3: 6. SubHead Col 4: 9 SubHead Col 5: 12 HSP19.741.2353.561.88 Placebo14.827.7339.1648.82
Id=Table 4.: Columns=6 Title: Reduction in sebum levels for the three gels at the end of 12 weeks. Head Col 1: Product Head Col 2: 0-3 Head Col 3: 3-6 Head Col 4: 6-9 Head Col 5: 9-12 Head Col 6: 0-12 CW0.041 * 0.006 * 0.004 * 0.0660.00 * HSP0.011 * 0.0012 * 0.0059 * 0.027 * 0.00 * Placebo0.060.120.230.180.00 * *P < 0.05 - Significant EMI31.1 EMI31.2 EMI32.1 EMI32.2 EMI33.1 EMI33.2 EMI34.1 Conclusions:

  1. The two extracts- cedarwood and poplar bud extract retained their activity at 0.5%. and effectively reduced the sebum levels. 2) The two extracts performed at parity at the end of the study period. 3) Though the placebo also appeared to lower the sebum level the activity was significantly lower than the test gels. EXAMPLE 36

In this example the lipase inhibition activity of cedarwood extract and hydrolysed soy protein is demonstrated. The test was carried out on female volunteers within the age group of 13-18 years having a sebumetre reading of 180 ug/cm2.

A lipase inhibition kit from Sigma was used for the study. This kit consists of a substrate, trezma buffer, and indicator. Standard lipase was procured separately.

The reaction mixtures and blanks were prepared as listed below: Columns=6 Head Col 1: Reaction mix. Head Col 2: Substrate Head Col 3: Buffer Head Col 4: Lipase Head Col 5: water Head Col 6: Extract (inhibitor) Test Std.10ml1ml1ml2.5ml- Test Mix. .10ml1ml1ml2ml0.5ml Blank10ml1ml-3.5ml-

The solutions were pippetted out into the test tubes as mentioned above. The tubes were shaken vigorously for around 5 secs. and were kept in a constant temperature bath at 37 DEG C for 3 hours. After the incubation period contents of the test tubes were poured into titration flasks and 3ml of ethanol was pipetted into each flask. Six drops of thymol phenophthalein indicator was added. In a burette 0.05 N NaOH solution was taken and used for titration. Each flask was titrated to a deep blue color which lasted for about 30secs. The blank and the test mixtures needed to show the same blue color. The final reading was noted and the initial reading subtracted from the final. This is the amount of NaOH required to neutralise the fatty acids liberated due to lipase activity.

The activity was calculated as follows: 0.05N NaOH used for test mix.- 0.05N NaOH used for blank = 0.05N NaOH required to neutralise fatty acids liberated. Lipase activity = Amount of 0.05N NaOH. Results: The burette reading for the test mixtures and the blank are tabulated below: Columns=3 Head Col 1: Test Mixture Head Col 2: Burette reading Head Col 3: Lipase Activity (Test mix- Blank) Lipase22- Lipase+CW15.212.4 Lipase+HSP16.213.4 Blank2.8-

Different concentrations of the inhibitor from 0.2-1.0% were used to determine the optimum concentration. The results of these are as given below: Columns=2 Title: Cedarwood Head Col 1: Concentration (%) Head Col 2: Lipase Activity 0.219.66 0.419.52 0.617.84 0.819.5 120.18 Standard Lipase20.3 Columns=2 Title: Hydrolysed soy protein Head Col 1: Concentration (%) Head Col 2: Lipase Activity 0.219.8 0.418.3 0.621.0 0.821.2 1.021.1 Standard Lipase22

Conclusion: The two extracts demonstrated lipase inhibition. The optimum concentrations were 0.4% for Hydrolysed Soy Protein and 0.6% for cedarwood respectively. EMI37.1 EMI37.2 EMI37.3 Conclusion

Bryan,

Johnson and Johnson Pacific PTY was the assignee of this study.


#11

The reason Im interested in that picture of regrowth with cedarwood, thyme, lavender, and rosemary is this…we can eliminate the possibliltiy that there is anything harmful for hair in cedarwood oil by that. If there was, that man assuredly would not have grown back all of that hair. I dont feel the same way about licorice or peppermint or clove or rose hips or arnica oil. They may reduce beard hair greatly, but they may be tough on hair period. Its unlikely that they are, but they might be. Cedarwood however, has been a substance that helped head hair regrow (44% positive responses in the Scottish study), and its the “first” essential oil for hair regrowth, its in all of the “old” remedies.

I cant find the article anywhere, but I’ll never forget reading about some 40 scottish mummies found in a peat bog years ago. The archaelogist noted that the men had “rock star” hair and all of them seemed to use cedarwood oil as a hair pomeade. The thing is, cedarwood oil would make a lousy hair pomeade, it would just make ones hair look greasy----kind of like reviogen does but a little more so.


#12

benji, do you know how much each oil they mixed together? and how they applied it i.e. only appllied at night, for all day etc? I’d like to give this a try!


#13

» benji, do you know how much each oil they mixed together? and how they
» applied it i.e. only appllied at night, for all day etc? I’d like to give
» this a try!

It was cedarwood, rosemary, lavender, and thyme with two different types of carrier oils. Some were given grapeseed oil and some were given olive oil. I dont know the “amounts” or drops that were put in the oils.

In my opinion, if they were found to be really useful, a company might have to use and emulsifier and a carrier. People aren’t crazy about that “oily” look if the oils are used alone.

I just want to see if cedarwood is very anti-androgenic. Im nosy…If it is, perhaps the contents of cedarwood can be examined to determine just which is the anti-androgen therein and cheaply manufactured. Who knows…


#14

» benji, do you know how much each oil they mixed together? and how they
» applied it i.e. only appllied at night, for all day etc? I’d like to give
» this a try!

So goata007, did you give it a shot in the end ?