This follows on our previous post, where we take this beauty industry stalwart to task for promoting a product (Avon Anew Wrinkle Eraser Pro) that they claim increases activity of the PLOD2 gene, making it the first company in history (as far as we know) to not only admit, but to even widely publicize, that it uses ingredients that are well established in the medical literature to be associated with a clearly undesirable pathological skin condition -fibrosis. Many of you have been writing us and asking for an update. As of the date of this writing they (Avon) have chosen to ignore BFT (and our 40,000 readers per month). We know they are aware of our opinions, and presentation of the evidence, as that recent post has been read by quite a few people at Avon. Our friend Peter had indicated he would make sure insiders knew. I guess he was successful. Maybe they are still investigating, and that’s fine, we will offer them grace before we raise the alarm to defcon 5. But we hope we soon will get something more than a brush off (we already got that). We like Avon as a company, they are involved in many good works, especially women’s causes (e.g.advocacy to combat breast cancer). We understand they have been through some trying times, and have a new CEO. We know her to be an outstanding individual, both savvy and principled, an excellent leader, who probably has a lot on her plate right now. Shareholders have been fleeing, and the share price has suffered. But, we also think this kind of thing should be taken very seriously, and dealt with swiftly.
But first, some good news. A natural peptide has been isolated (not by Avon) which acts to oppose the effects of fibrosis. It lower levels of lysyl oxidase, the enzyme that causes abnormally stiff and unbreakable cross-links collagen. Lysyl oxidase, you may recall from our previous Avon post, is enzyme made by the PLOD2 gene, also known as the fibrosis gene. The abstract for this new study is appended to the end of this post.
This new anti-fibrosis peptide could be valuable because it provides a potential eraser for the fibrosis that can be caused by the Avon Anew wrinkle eraser. Of course, it would be a whole lot more desirable for Avon to commit to doing something to undo the damage before its done, for instance recalling the product until longer range studies can prove or disprove what the existing medical evidence base strongly argues — that their product would be fully expected to cause collagen cross linking of the type associated with fibrosis. And since Neostrata, who owns the patent on the PLOD2 inducer and gets royalties from Avon based on sales, has already presented histologic evidence that the early effects on human skin closely resemble what a pathologist looks for in early scleroderma (a disease that also causes fibrosis, by the same mechanism, involving the PLOD2 protein), some of that data probably already exists in their files. That data of course argues for fibrosis, not against. But we keep hoping they have some additional studies that would argue against that. We know just what those studies would be, and would be happy to review any exculpatory evidence they have. We continue to wait.
Readers in an older age category (along with me) may remember the way Johnson & Johnson handled the tainted Tylenol problem back in the 1980’s. Seven people in Chicago died as a result of Tylenol capsules laced with cyanide. J&J did a recall of Tylenol, costing them more than $100 million. J&J was exonerated of any wrongdoing (it was the work of a murderer; the case was never solved). J&J did the right thing. They were all over it from day one, and put people before profit. The media gave Johnson & Johnson many kudos for its handling of the crisis. For example, the The Washington Post said, “Johnson & Johnson has effectively demonstrated how a major business ought to handle a disaster.” For many years (until some more recent problems involving actual quality issues at J&J manufacturing plants, J&J enjoyed the highest “trust mark” of any company. I believe they recently fell from the top of the list.
Sherri McCoy, Avon’s new CEO, was a top executive at J&J before taking over the beauty empire’s helm. Now Ms. McCoy will know all about the Tylenol incident, even though it may have been before her time, because it is deeply woven into the J&J fabric, and is part of history, mentioned in many business school textbooks. It’s in the chapter on how to handle product-related controversies. Put customers first is a principle that is also at the core of the J&J credo, a statement of ethical business principles J&J takes very seriously.
I’m going to wager that when she took the job at Avon, Ms. McCoy was not aware of just how weird science the world of cosmetics can be. Maybe she still hasn’t grasped it. We would be happy to educate her. Even the curmudgeonly nerd/docs at BFT get surprised every day by the extent of the cancer and it’s clever ability to avoid detection (hype and hope are such close cousins).
At the end of the day, here is what we would like to see:
First, Avon needs to get in front of this. No more damage control mentality. Avon needs to be communicating to it’s critics, customers and shareholders on this matter.
Second, they need to investigate thoroughly, and either prove that there is not a problem with data they have not yet shared (i.e. solid medical evidence that there is a PLOD2 inducer that doesn’t cause fibrosis) or initiate an appropriate response (e.g. pull this product from the market until a full investigation can be completed). And, since Avon R&D doesn’t seem to know the difference between scleroderma (a disease entity) and fibrosis (one sign of that disease, not specific to that disease), Avon needs to hire some consultants or replacements. And if R&D is the one responsible for the cover up, their heads should certainly roll.
Next, they need to figure out how this kind of thing happened, so they can prevent it in the future. As regular readers know, we suspect this is just the tip of the iceberg (the inflammation-fibrosis connection). What happened to the medical scientists who used to watch the store at Neostrata? Did they not think there might be a problem when they saw the biopsies? Piled up pre-collagen and GAG’s is right out of the dermatopathology textbook. Where are the scientific quality controls? This product maybe should have been killed at the concept stage.
Finally, Avon needs to get on this bandwagon with BFT … first, do no harm (and second, call out anyone who doesn’t believe in the first principle). Avon prides itself in doing good things for women. As a beauty industry company, the very best thing they could do for the women they serve would be to work against abuses within their own industry, which harms women rather than helping them. Exploit may be too harsh a term, but if the pattern repeats over and over, then it becomes a fair descriptor. We would love to see Avon became an industry leader in reforming the very industry they help define.
In summary, do the J&J thing. Respond like you care. Adopt a credo that elevates real science to its appropriate status, deplores junk science, and puts the customer first.
Ms McCoy can establish early her own personal trust mark in the industry by shaking things up now. Impose a J&J style integrity to a company used to cutting corners out of expediency. Which is part of the reason she was chosen for the job in the first place.
Call us, we are always open to chat, on or off the record.
Now, for you deep science fans…. the eraser for the eraser:
A Peptide Derived from Endostatin Ameliorates Organ Fibrosis
Yamaguchi, Y, et. al. Sci Transl Med 30 May 2012
Fibroproliferative disorders such as idiopathic pulmonary fibrosis and systemic sclerosis have no effective therapies and result in significant morbidity and mortality due to progressive organ fibrosis. We examined the effect of peptides derived from endostatin on existing fibrosis and fibrosis triggered by two potent mediators, transforming growth factor–β (TGF-β) and bleomycin, in human and mouse tissues in vitro, ex vivo, and in vivo. We identified one peptide, E4, with potent antifibrotic activity. E4 prevented TGF-β–induced dermal fibrosis in vivo in a mouse model, ex vivo in human skin, and in bleomycin-induced dermal and pulmonary fibrosis in vivo, demonstrating that E4 exerts potent antifibrotic effects. In addition, E4 significantly reduced existing fibrosis in these preclinical models. E4 amelioration of fibrosis was accompanied by reduced cell apoptosis and lower levels of lysyl oxidase, an enzyme that cross-links collagen, and Egr-1 (early growth response gene–1), a transcription factor that mediates the effects of several fibrotic triggers. Our findings identify E4 as a peptide with potent antifibrotic activity and a possible therapeutic agent for organ fibrosis.
Why haven’t you taken his to the mainstream media? The authorities? This has all the markings of a major scandal. The general public should know.
Carla, we are patiently awaiting a response from Avon and/or NeoStrata. We assume they are looking into it, and want to do the right thing. If we don’t hear anything back in the next few days then we will presume they are thumbing their noses at BFT’s fact finding mission and will take what we now have and broadcast it.
Any news from Avon yet?
No, but they may have gotten distracted by the FDA warning letter which addresses the issue of claims that make them sound like drugs. The irony is that they are drugs in a very powerful sense, potentially causing (in the case of AF-33) fibrosis, a nasty side effect. But the FDA has no agenda to regulate that aspect, it seems. They would be happy if they just stop taking about it. We think there are some good people at Avon, and are trying to give them some grace, because they are under fire from many directions. But failing to respond is not an option, it would indicate a disregard for serious issues.
I just came across this post (and its predecessor) while trying to learn what in the heck A-F33 is. Has there been any more news on this story?
Also, I am wondering if there IS a safe duration of time for which to use this product? What would you suggest as a safer alternative? Are AHAs safe?
The news is this: Avon never responded. They continue to sell this stuff. Here is a seminal paper: Identification of PLOD2 as Telopeptide Lysyl Hydroxylase, an Important Enzyme in Fibrosis. They even submitted a patent on this stuff, never even mentioning the connection to fibrosis (a pathologic process). Here are a a few more scientific publications on PLOD2 and fibrosis.
1. Gene expression analysis of murine and human osteoarthritis synovium reveals elevation of transforming growth factor β-responsive genes in osteoarthritis-related fibrosis.
Remst DF, Blom AB, Vitters EL, Bank RA, van den Berg WB, Blaney Davidson EN, van der Kraan PM.
Arthritis Rheumatol. 2014 Mar;66(3):647-56.
2.TGF-ß induces Lysyl hydroxylase 2b in human synovial osteoarthritic fibroblasts through ALK5 signaling.
Remst DF, Blaney Davidson EN, Vitters EL, Bank RA, van den Berg WB, van der Kraan PM.
Cell Tissue Res. 2014 Jan;355(1):163-71.
3.Stimulation of fibrotic processes by the infrapatellar fat pad in cultured synoviocytes from patients with osteoarthritis: a possible role for prostaglandin f2α. Bastiaansen-Jenniskens YM, Wei W, Feijt C, Waarsing JH, Verhaar JA, Zuurmond AM, Hanemaaijer R, Stoop R, van Osch GJ.
Arthritis Rheum. 2013 Aug;65(8):2070-80.
4. Up-regulation of the lysyl hydroxylase 2 gene by acetaminophen and isoniazid is modulated by transcription factor c-Myb.
Kubota M, Shinoda A, Iguchi K, Takahashi Y, Usui S, Kiho T, Hirano K.
J Pharm Pharmacol. 2010 Apr;62(4):477-84.
5.Fox-2 protein regulates the alternative splicing of scleroderma-associated lysyl hydroxylase 2 messenger RNA.
Seth P, Yeowell HN.
Arthritis Rheum. 2010 Apr;62(4):1167-75.
6.Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells: Are mesenchymal stromal cells involved in scar formation? van den Bogaerdt AJ, van der Veen VC, van Zuijlen PP, Reijnen L, Verkerk M, Bank RA, Middelkoop E, Ulrich MM.
Wound Repair Regen. 2009 Jul-Aug;17(4):548-58.
7. TIA nuclear proteins regulate the alternate splicing of lysyl hydroxylase 2.
Yeowell HN, Walker LC, Mauger DM, Seth P, Garcia-Blanco MA.
J Invest Dermatol. 2009 Jun;129(6):1402-11.
8. Interleukin 4 and prolonged hypoxia induce a higher gene expression of lysyl hydroxylase 2 and an altered cross-link pattern: important pathogenetic steps in early and late stage of systemic scleroderma?
Brinckmann J, Kim S, Wu J, Reinhardt DP, Batmunkh C, Metzen E, Notbohm H, Bank RA, Krieg T, Hunzelmann N.
Matrix Biol. 2005 Oct;24(7):459-68.
9.Elevated formation of pyridinoline cross-links by profibrotic cytokines is associated with enhanced lysyl hydroxylase 2b levels.
van der Slot AJ, van Dura EA, de Wit EC, De Groot J, Huizinga TW, Bank RA, Zuurmond AM.
Biochim Biophys Acta. 2005 Jun 30;1741(1-2):95-102.
10.Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: implications for collagen cross-linking and treatment of fibrosis. Zuurmond AM, van der Slot-Verhoeven AJ, van Dura EA, De Groot J, Bank RA.
Matrix Biol. 2005 Jun;24(4):261-70.
11.Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon.
van der Slot AJ, Zuurmond AM, van den Bogaerdt AJ, Ulrich MM, Middelkoop E, Boers W, Karel Ronday H, DeGroot J, Huizinga TW, Bank RA.
Matrix Biol. 2004 Jul;23(4):251-7.