6 replies to this topic

[gymrat7676]

http://cat.inist.fr/?aModele=afficheN&cpsidt=18993051

[someday]

I found this interesting. I thought it may be one of those lab-locked studies that never amounted to anything. So I googled "triethyl citrate and ethyl linoleate " and the only commercial venture I could find that was pushing this combo was skinmed uk - with this product-line called "aknicare". I was tempted to actually buy the spot-treatment stuff (not cheap) but decided to hold off til I did some more research.

Did anyone ever actually try this?

[someday]

Found this insightful rebuttal of the above study in the British Journal of Dermatology.

http://www3.intersci...88273/HTMLSTART

Linoleic and linolenic acids and acne vulgaris
A.C. Logan
Integrative Care Centre of Toronto, 3600 Ellesmere Road, Unit 4, Toronto, ON, M1C 4Y8, Canada
E-mail: aclnd@cfs-fm.org

Conflicts of interest: none declared.

Copyright 2007 The Authors Journal Compilation 2007 British Association of Dermatologists
KEYWORDS
acne • inflammation • leukotriene B4 • linoleic acid • linolenic acid • prostaglandin E2
ABSTRACT


No Abstract

--------------------------------------------------------------------------------

DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2133.2007.08317.x About DOI


Article Text
Sir, I read with great interest the recent article by Charakida et al.1 This group reported that a commercially available lotion containing triethyl citrate and ethyl linoleate was of therapeutic value in acne vulgaris. The authors claim that an increase in topical linoleic acid serves to inhibit 5α-reductase; however, the reference (a letter to the editor) used to justify this activity2 incorrectly identified linoleic acid as a potent 5α-reductase inhibitor. Actually, the research in question showed that linoleic acid has only weak 5α-reductase inhibition, even at high concentrations.3 Rather, it is γ-linolenic acid that has been shown to be a potent 5α-reductase inhibitor.3,4 As for linoleic acid, it has recently been shown to work synergistically with testosterone in elevating the synthesis of 5α-dihydrotestosterone and sebaceous lipids.5

Charakida et al. also make note of the potential anti-inflammatory effects of linoleic acid in acne. This may be overstated, particularly as it is well known that linoleic acid has the potential to promote inflammation via its positive influence on prostaglandin E2 (PGE2) and leukotriene B4 (LTB4).6 Recently, investigators reported that inhibition of LTB4 reduces sebum production and improves inflammatory acne, and experimental studies indicate that combined blocking of both PGE2 and LTB4 may enhance the therapeutic value.7,8 As research shows that the sebocytes have all the enzymatic machinery necessary for the manufacture of PGE2 and LTB4 from their precursors (linoleic acid and arachidonic acid),7 the low levels of linoleic acid in skin lipids of patients with acne may be a result of increased turnover to support the production of these inflammatory chemicals. It is also noteworthy that γ-linolenic acid (oral and topical) has anti-inflammatory properties as it diminishes PGE2 and LTB4 production,9 making it a potentially more attractive therapeutic option for acne.

Charakida et al. used a preparation with an undisclosed concentration of triethyl citrate, a chemical not found in the placebo vehicle. As topical preparations of glycolic, lactic and/or citric acids have the potential to induce noticeable short- and long-term changes to the skin appearance,10 it is entirely possible that users of the commercially blended ethyl linoleate/triethyl citrate were more likely to be aware that they were indeed in the 'active' group. There is no discussion of exit data concerning patient awareness of which group they were in, active or placebo. Finally, the authors claim that the lotion efficacy was based on the synergistic action of the ethyl linoleate and triethyl citrate, yet without isolated investigation of both of these agents there is no way to determine if the effect of this combination is greater than the sum of its parts.



References


1 Charakida A, Charakida M, Chu AC. Double-blind, randomized, placebo-controlled study of a lotion containing triethyl citrate and ethyl linoleate in the treatment of acne vulgaris. Br J Dermatol 2007; 157:569–74. Links
2 Namazi MR. Further insight into the pathomechanism of acne by considering the 5-alpha-reductase inhibitory effect of linoleic acid. Int J Dermatol 2004; 43:701. Links
3 Liang T, Liao S. Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids. Biochem J 1992; 285:557–62. Links
4 Liang T, Liao S. Growth suppression of hamster flank organs by topical application of gamma-linolenic and other fatty acid inhibitors of 5alpha-reductase. J Invest Dermatol 1997; 109:152–7. Links
5 Makrantonaki E, Zouboulis CC. Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes. Br J Dermatol 2007; 156:428–32. Links
6 Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006; 60:502–7. Links
7 Alestas T, Ganceviciene R, Fimmel S et al. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med 2006; 84:75–87. Links
8 Zhang Q, Seltmann H, Zouboulis CC et al. Involvement of PPARgamma in oxidative stress-mediated prostaglandin E(2) production in SZ95 human sebaceous gland cells. J Invest Dermatol 2006; 126:42–8. Links
9 Kapoor R, Huang YS. Gamma linolenic acid: an anti-inflammatory omega-6 fatty acid. Curr Pharm Biotechnol 2006; 7:531–4. Links
10 Yamamoto Y, Uede K, Yonei N et al. Effects of alpha-hydroxy acids on the human skin of Japanese subjects: the rationale for chemical peeling. J Dermatol 2006; 33:16–22. Links

Note "y-linolenic" or Gamma -Linolenic acid is GLA - widely available in supplement form eg Borage Oil /Evening Primrose oil.

[bryan]

Found this insightful rebuttal of the above study in the British Journal of Dermatology.

Article Text
Sir, I read with great interest the recent article by Charakida et al.1 This group reported that a commercially available lotion containing triethyl citrate and ethyl linoleate was of therapeutic value in acne vulgaris. The authors claim that an increase in topical linoleic acid serves to inhibit 5α-reductase; however, the reference (a letter to the editor) used to justify this activity2 incorrectly identified linoleic acid as a potent 5α-reductase inhibitor. Actually, the research in question showed that linoleic acid has only weak 5α-reductase inhibition, even at high concentrations.3 Rather, it is γ-linolenic acid that has been shown to be a potent 5α-reductase inhibitor.3,4 As for linoleic acid, it has recently been shown to work synergistically with testosterone in elevating the synthesis of 5α-dihydrotestosterone and sebaceous lipids.5

2 Namazi MR. Further insight into the pathomechanism of acne by considering the 5-alpha-reductase inhibitory effect of linoleic acid. Int J Dermatol 2004; 43:701. Links
3 Liang T, Liao S. Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids. Biochem J 1992; 285:557–62. Links
4 Liang T, Liao S. Growth suppression of hamster flank organs by topical application of gamma-linolenic and other fatty acid inhibitors of 5alpha-reductase. J Invest Dermatol 1997; 109:152–7. Links
5 Makrantonaki E, Zouboulis CC. Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes. Br J Dermatol 2007; 156:428–32.

I'm going to have to rebut the rebuttal!

Anybody who has actually read the referenced studies (3) and (4) above know that linoleic acid IS a pretty good 5a-reductase inhibitor, even though it's not as potent as γ-linolenic acid. In my opinion, it overstates the case to call it a "weak" inhibitor.

.

[bryan]

Note "y-linolenic" or Gamma -Linolenic acid is GLA - widely available in supplement form eg Borage Oil /Evening Primrose oil.

GLA from natural oils like borage or evening primrose won't have any effect at inhibiting 5a-reductase, although those oils _may_ have an anti-inflammatory effect if given in large oral doses. Not sure if they would be anti-inflammatory if applied topically, but I'm somewhat doubtful of that.

.

[temp123]

All I know is that ibuprofen is a massive inhibitor of prostaglandins, and the total ibuprofen dose needed to do that topically is tiny.

[Reti]

Thank you for these additional comments. Very helpful.

Edited by Reti, 18 April 2011 - 07:01 PM.