DocGMarcovici

Hi All- A word of disclosure to begin this blog. I am directly affiliated with and compensated by HairGenesis®, a naturally derived product line focused on the treatment of pattern hair loss. Although its not my intention or desire to use this forum as a platform to pitch my spiel, I want to make it clear that what I do for a living these days, has a a lot to do with the HairGenesis® product line. That said, I believe my years of experience in this industry may provide value that transcends pointing candidates toward a treatment product, mine or anyone else's. Instead, I'd like to offer myself as a passingly experienced professional resource, able to pass along and discuss the latest advances in hair loss research as well as some of the underlying mechanisms which influence the disease process --- some of which that are only now coming to light. Some of you know a lot about the physiology of hair loss, and the treatment options available. Some, very little. I'm not an M.D. and I cannot and will not offer medical advice. But I will bet there are few out there, regardless of their credentials possessing the depth and breadth of knowledge I possess in this area. Because I've also spent more than ten years as a partner in a surgical hair restoration clinic I think I can offer a generally sensible opinion in and around that subject. Moreover, prior to my involvement in transplant surgery, leading to pure research today, I spent several years working in a center that dealt solely with non-surgical hair replacement systems. So I learned a bit about that side of the industry too. It might interest you to know that I entered this field with a genuinely personal agenda. When I was about 24 years old my previously thick and dense head of hair began to thin -- at an alarming rate (at least it was alarming to me). Because I was working as a professional model at the time the loss of my hair impacted my livelihood, not just my ego. Though more than half a lifetime ago, I still remember the sense of incredulity and anguish I felt at the dearth of good treatment options available in the mid 1980's. Pretty quickly I decided I could do more to help improve things working from the inside rather than lamenting from the outside. Twenty six years later, and though my contributions have been vanishingly modest at best, I'm still at it. This then is a bit about me. I will close where I began by promising to offer as unbiased an opinion as someone in my position can offer. Let's see if I can be helpful --- that's really my intention here. Geno Marcovici, Ph.D. Chief Scientific Officer HairGenesis®

As a fellow who's been around the block a time or two with surgical hair restoration drug trials, as well as someone with more than a passing familiarity in basic science research, there are several concerns that I have with the purported use of laser technology to stimulate hair growth. First, the underlying basis for mechanism of action for lasers as hair growth agonists appears neither well articulated nor well thought out. To begin with, there are good reasons that a cut heals faster than a burn. The type of cytokines and chemokines recruited in remodeling a burn injury (this is the way that most lasers work) do not lend themselves to accelerating wound healing. Second, there is no hair growth pathway that I can think of wherein a laser could exert a positive influence. Actually quite the opposite is true. Most burn wounds induce upregulation of inflammatory markers such as TNFa and NFkB. I could be mistaken, but it seems to me that trying to enhance wound healing by upregulating these markers (i.e. by introducing high energy/light/heat into a biologic system) is a little like trying to put out a fire by spraying gasoline. This is relevant inasmuch as recent data supports the notion that the dermal papilla is a repository for pluripotent stem cells which are key to skin homeostasis and wound remodeling. Furthermore, as other far more knowledgeable contributors to this post have already observed, the supporting clinical data for LLLT are less than robust. Lasers certainly have a place in medicine. However, I cannot see LLLT for hair growth as a particularly good use of the technology. Geno Marcovici, Ph.D.

I appreciate the feedback and I recognize that additional studies enrolling larger numbers of study subjects will be a useful goal. However I'm not sure of the basis under which JohnS arrives at his conclusion that the published study ".....falls way below the standards science has established for a true double blinded placebo controlled study." The fact is, modest though the number of study subjects was, the was indeed a true double-blind, placebo-controlled, randomized clinical trial. The purpose of the work was to establish a proof of principle --- which it did. Were this not up to the appropriate standards, the manuscript describing the data would never have not been accepted in the peer-reviewed medical literature. Modest though it was, I see the need to defend this study for a number of reasons. First and foremost, our research, including this published work, represents, by far, the most objective and critical analysis undertaken in examination of naturally-derived substances in their ability to ameliorate the clinical progression of pattern hair loss. Given the known negative side effects associated with current pharmacotherapy, I'd think that our efforts would be lauded, not vilified. No one, least of all us, is trying to say that we have run phase 1, 2, & 3 drug trials on HairGenesis?„?. We're merely reporting the fact that for the first time ever, a non-drug hair loss treatment has been subjected to reasonable objective review and passed muster. Is this really cause to slam us for our efforts? Perhaps the, essentially non-existent research efforts of our competitors warrant greater praise? Unlike so many others in the hair loss industry, we are investing a substantial share of our capital as well as our time and effort into validating our products. We're working to make better formulas to ease the mental anguish that comes with pattern hair loss. This is who we are. This is why we're here. So while I appreciate the need for critical review, I think maybe some of these folks are kicking the wrong dog. Please Mr. JohnS explain, what exactly am I failing to grasp? signed, Geno Marcovici, Ph.D.

Bill- I appreciate the opportunity to respond to the excellent questions you've raised. I'll do my best below. I will [bracket] my comments so as to ease differentiation from yours. You are asking questions that, to a substantive degree, require third-party citation. Accordingly, I will provide the Journal cite in the body of each response as appropriate. Upon your review, I look forward to your additional questions or comments. I'm going to need to use a lot of "three dollar words" in my response. If you have any questions about a word or a concept, let me know and I'll try to explain in plain English. Geno, Since you are here representing HairGenesis, and believe in its efficacy, I feel that a more detailed discussion would certainly benefit our members and guests. I admit that I am a skeptic of just about any hair loss product until I see the proof which includes clinical evidence and public third party before/after photos. [Fair enough.] My cynicism is a bi-product of the promotional propoganda of companies making too many promises without delivering. Marketing tactics (that I feel should be illegal) go far beyond the hair loss industry but is certainly prevalent here. [i agree. Please bear in mind that I also came from the perspective of a consumer searching for the most useful options to treat my own hair loss. In 1984 I was just a guy who hadn't given the subject much thought until I started losing my hair. I quickly became shocked and then dismayed by how few -- and how substandard the treatment options were.] So keeping an open mind but skeptical, here are some questions and comments for consideration. 1. You say that saw palmetto extract (serenoa repens) inhibits both type II and type I 5-alpha-reductase. Since type I 5-alpha-reductase enzymes are found mostly in the brain, what potential dangers are there from using saw palmetto extract long term? This question lingers for dutasteride, which also inhibits both types. [Actually, type 1 5AR localizes to many tissues other than CNS (i.e. brain), including liver, prostate &, importantly, squamous stratifying epithelia (e.g. skin/hair follicles). There are numerous published cites which articulate this fact, here are two. If you would like ten or fifteen more, please let me know and I'll provide them. Eur Urol. 2008 Feb;53(2):244-52. Epub 2007 Nov 5. Biochem Biophys Res Commun. 2008 Apr 18;368(4):858-64. Epub 2008 Feb 5 Your question re. dutasteride presupposes a conclusion that I cannot support; i.e. that dutasteride and saw palmetto operate through like mechanisms of action. To my knowledge, saw palmetto works in the steroid hormone pathway by modulating the pH level of the cellular membrane. This necessarily affects the intracellular milieu -- and specifically -- it disrupts the efficiency by which androgen receptor binds to its endogenous ligand for translocation to the cell nucleus. As you may be aware, to influence gene transcription of the relevant protein products in the hair follicle it is necessary for the androgen receptor ligand complex to move from the membrane to the nucleus. This process is thought to be interrupted by the mechanism I've just described. By way of contrast, dutasteride, finasteride and other anti-androgens operate by competitively blocking the conversion of T to DHT thus changing the homeostatic level of these steroid hormones. This is one reason why the potential for feminizing birth defects and other negative side effects exist via the use of these drugs. Importantly, this mode of action is distinct from that which governs the activity of saw palmetto. If I understand it correctly, second part of your question asks what the long-term risks are for saw palmetto. Historically, saw palmetto has been used as a tool in traditional medicine for many hundreds -- perhaps thousands -- of years. Saw palmetto has also been used to treat BPH in Europe for at least 50 years. In Europe, saw palmetto is treated more like a drug than a nutritional supplement. Accordingly, the substance has undergone a great deal of empirical scrutiny. It is noteworthy that in the context of BPH saw palmetto, ingested orally, has established a remarkable track record for safety. In our clinic, we began testing saw palmetto and other novel substances against pattern hair loss in 1994. Importantly, we only used substances and dose levels that we knew to be safe. From 1994 to 1998, using various test formulations, we ran a number of open label (patient knows what they are ingesting) trials. Since the patient population testing these formulas was also part of our larger surgical/research population, regular blood assays were performed. The patients were also monitored during scheduled clinical evaluation visits. It is useful to point out that during this period, our clinic was also functioning as an IRB monitored drug study site. So the facility itself was audited for good clinical practices on a frequent basis. The outcome of these studies showed safety and efficacy. This led to the design and implementation of a placebo-controlled study. Additionally, HairGenesis?„?, which contains high levels of saw palmetto, has been in widespread use for more than ten years. The product has likewise demonstrated an excellent safety track record.] 2. Your ingredients in the oral softgels are listed below from your website: A PROPRIETARY ORAL FORMULATION CONTAINING: Saw Palmetto Berry Extract, Capric acid, Caprylic acid, Caproic acid, Lauric Acid, Palmitic Acid, Oleic Acid, Beta-Sitosterol, Stigmasterol, Cycloartenol, Lupeol, Lupenone, 24-Methyl-Cycloartenol, Oligomeric Proantho-Cyanidin, Gamma Linolenic Acid, Gamma Linoleic Acid, Lecithin, Niacin, Macadamia Nut Oil, Borage Oil, Evening Primrose Oil, Epigallocatechin-3-Gallate, Genestein, Pygeum Africanum, Japanese Green Tea Extract, Biotin, Glycerin, Purified Water, Yellow Beeswax, Extra Virgin Olive Oil, Gelatin, Titanium Dioxide, FD&C Red #40, Yellow #6, Blue #1 I am pretty researched in saw palmetto however, what, if any other ingredient found in the softgel has been conjectured/proven to fight hair loss? What synergistic effect (if any) exists between saw palmetto and any of these other ingredients? Do you have any proof or documentation on this? [As we've learned through hard experience, our competitors are very good at "borrowing" our ideas and using the fruits of our hard work as their own. So we must be reasonably cautious in what we disclose. In plain English, there is a fine line between disclosing what we know about our product's composition and printing a roadmap for our competitors to follow. Let's start by taking a selection from our formulation composition and providing a third-party published cite demonstrating positive benefit in a relevant tissue model, in particular the inhibition of 5 alpha reductase. BETASITOSTEROL Betasitosterol, a glycoside of saw palmetto, showed up on our radar screen because of its ability to inhibit the activity of 5 alpha reductase mediated pathology in the hair follicle. However, as we've learned, beta sitosterol exerts pleiotropic affects that may enhance the utility of this interesting material. Proc West Pharmacol Soc. 2003;46:153-5. EPIGALLOCATECHIN-3-GALLATE EGCG is touted for its benefit as a cancer-preventative. The substance is also noteworthy for its role in modulating steroidogenesis, and in particularly, its activity in inhibiting 5 alpha reductase. Like certain other naturally-derived chemicals, EGCG will find use in many treatments for skin conditions and other pathologies. Biochem Pharmacol. 2002 Mar 15;63(6):1165-76 GENESTEIN Genestein also exhibits multi-faceted activity. It is being extensively studied for its utility in the context of neoplastic ablation. For our purposes, it has been observed that genestein is a non-competitive inhibitor of 5 alpha reductase. J Endocrinol. 1995 Nov;147(2):295-302.] 3. The ingredients in your topical solution are listed below from your website: PROPRIETARY TOPICAL FORMULATION CONTAINING: Isoproyl alcohol, Oleic Acid, LSESr 85/95% Liposterolic Content (Saw Palmetto Extract), Lauric Acid, Palmitic Acid, Beta-Sitosterol, Stigmasterol, Cycloartenol, Lupeol, Lupenone, 24-Methyl-Cycloartenol, Oligomeric Proantho-Cyanidin, Oleth-20, Evening Primrose Oil, Genestein, Pygeum Africana Extract, Japanese Green Tea Extract, GLA Borage Oil, Macadamia Nut Oil, Propylene Glycol, Nonoxynol 10, Polysorbate 80, Camellia Sinesis Extract, Biotin I was honestly surprised not to see ketoconazole or azelaic acid in the list. In my research, I have not found any studies supporting that saw palmetto used topically effectively inhibits DHT. What support, if any, exists tjat saw palmetto or any of these other ingredients can help prevent, slow down, or stop hair loss. What about reversing the miniaturization process? [Long ago, we considered and ruled out both ketoconazole and azelic acid for our formulations. As to the notion of using saw palmetto or other substances locally to treat hair loss, a paradigm for this approach exists in the treatment of other skin disease. Let me explain. Many people have had a skin rash and been given oral medication and topical creams with similar drugs in both compositions. The reason for this is that the skin is uniquely amenable to local and systemic therapy. When we recognize that hair follicles are merely skin appendages, the idea of using concomitant therapy makes even more sense.] 4. The claims on your website state that your shampoo and conditioner block DHT. Which ingredients when applied in the forum of shampoo and conditioner are proven and where can I find the evidence for this? What synergistic effect if any of the combination of ingredients have? Is there any public documentation on this? [Please see the descriptive response for genestein, EGCG & beta sitoserol above.] Now some comments... I'd suspect that if a product really works, especially in a day where information is widely available on the internet, especially public discussion forums, it surprises me that I have not read real HairGenesis patient success stories with compelling before/after photos on this forum in the past. [This is a valid observation. It is as unfortunate as it is true that "in this day and age" a great deal of money is required for publicity and marketing. We also could have put the bulk of our capital into marketing. And with the benefit of 20/20 hindsight, I think we would have done a better job in this regard. But instead, we put a great deal of money into research. And we put another big pot of money into business litigation. The result of this is that we have better supporting research, and arguably better formulations than our competition, but we've been limited in our ability to disseminate this fact because marketing costs are astronomical.] The photos on your website are extremely poor in quality, resolution, and in different lighting and angles. Educated members of this community expect good quality realistic photos and won't buy into marketing propaganda. I would expect more compelling photos including closeups of areas showing an increase in terminal hair count. [in a separate email I will send you high resolution photos. At some point in the not too distant future, we will be sponsoring a new clinical study within which more longitudinal patient photos will be gathered. I will also send you a selection of unsolicited customer comments describing their experience in using our product.] My advice to you is.... If your products work (apart from any additional treatment such as finasteride, minoxidil, etc.), let's see some real compelling high resolution photos instead of the blurry thumbnails that are hardly conclusive on your website. [Feel free to post what I send you along with your critical feedback] I hope you will stick around and indulge us and if you can provide the proof your product works, you may just make a believer out of me. [Time permitting, I will be happy to interact on your forum. As previously mentioned, we're in the midst of new research. Presuming the outcome is noteworthy, this work will hopefully be published in the literature. We will also have a press release which I will send to your attention. Thanks for giving me a chance to interact with you and others on this forum. I enjoy the challenge. kind regards, gm] Best wishes, Bill

To begin with, calling a person a thief and their product snake oil is probably not the best way to get them to help you. I also think it is salient to point out that there are tens of thousands of satisfied HairGenesis?„? customers, some of whom have been regularly using the product for more than ten years. Obviously, we can't make every single person happy and clearly in your case, we have fallen short of the mark. If you will try to work with me instead of attacking me, I will do my best to help you resolve your concerns. I would suggest that the best way to get this in motion is for you to provide us with some contact info. so that we can follow up. Once we hear from you I'll ask our customer care manager to contact you in order to see what we can do to help get the matter taken care of. I will also stay in the loop as appropriate. Please direct an email to hairgenesis@aol.com and we'll go from there. signed, Geno Marcovici, Ph.D.

Hi Bill- Thanks for the kind words. Thanks also for your comments on saw palmetto. Actually, I concur with much of what you say. Saw palmetto is an interesting substance, but it is not, in and of itself, "the" answer to pattern hair loss. However imperfect as a monotherapy, there is in our view, something useful to be learned from LSESr (the liposterolic extract of serenoa repens). To cite but one example, mechanistically, the sterolic fraction of saw palmetto (e.g. betasitosterol) seems to operate by modulating the target cell membrane rendering it a less efficient "door" whereby androgen receptor may translocate to the cell nucleus. This is in contradistinction to drugs like finasteride which actively block the conversion of T to DHT causing modification in the endogenous level of androgen steroid hormone (thus triggering the potential for negative side effect). This data point also helps explain the pharmacodynamic differences between botanical and drug drug (i.e. renal clearance). Also noteworthy are basic science experiments, for example the work conducted by DeLos et al. (J Steroid Biochem Mol Biol. 1995 Sep;54(5-6):273-9.) wherein the authors observed a manifold greater 5 alpha-reductase enzyme inhibition profile for LSESr than finasteride. Equally interesting, in my opinion, was the fact that LSESr targeted both isoforms where finasteride selectively targeted only type 2 5AR. For those who would scoff by noting that [type 2 5AR is the sole relevant isoform in AGA], I would caution that the jury is still out on that "fact". Although 5 alpha reductase occurs in two isoforms distinguished by their respective pH, there is mounting evidence that each may play a role in a number of steroid hormone mediated metabolic cascades --- including those pertaining to the skin and its ectodermal appendages --- e.g. the underlying structures which produce scalp hair. However, your primary point remains valid. LSESr is one tool against a complex trait disorder system (AGA) that cries out for want of a whole tool box. This is an important reason why the more recent versions of HairGenesis?„? have incorporated substances and not just LSESr. Our work continues. We're learning new things almost every day. You may rest assured that when the time is right, we will submit our new information in the form of scientifically objective data. kind regards, Geno M.

Hi Bill- Okay, you asked, so I'll go through some of the background on HairGenesis?„? that will hopefully provide useful context. I apologize because this is going to be a LONG response. But I think you'll find it informative. The fact is, the product was created in response to a need that I perceived in our surgical clinic population. As most of your forum members realize, transplanting donor hair into a recipient zone that is actively thinning can sometimes accelerate hair loss in the untransplanted tissue around the newly transplanted grafts. Alternatively, transplanting into a denuded frontal area will also leave the untransplanted hair behind it thinning. So you often wind up chasing a receding hair line. Another problem is donor supply. What happens if/when you run out of donor? Or, put another way, how should a person best use their donor hair to provide the greatest cosmetic benefit. All of these issues were top of mind for many years in our clinic and probably most other transplant clinics worldwide. Obviously, one possible solution is to use pharmacotherapy concomitant with transplant surgery. Good idea, but not without a downside. Because the drug-based treatment options also come with known side effects, --- some quite serious, many patients, then as now, were reluctant to incorporate them into a surgical treatment plan. Interestingly, in 1994 I attended a research lecture that happened to mention some of the herbal treatments being used in Europe for BPH. Specifically, saw palmetto was being used to treat BPH patients, with reasonable clinical outcomes, and an excellent safety track record. As you may know, BPH shares a striking degree of etiological similarity to AGA. This is when I had a "eureka" moment. The thing that was running around in my head was that biochemically speaking, nature is extremely conservative and frugal. So, metabolic pathways --- such as for example, steroid hormone-mediated pathways --- are repeated across different organ systems. By the same token, treatment agents that work well in one system may offer interesting therapeutic benefit in another. Long story short, we began by testing saw palmetto for hair loss in our clinic. It sometimes worked, but usually not very well. But it was a start. So we began looking at the constituent fatty acids and sterols that make up saw palmetto. This provided some useful clues that allowed us to refine the initial composition into a better formula. Then we started looking at different naturally-derived reagents to see if they might offer additive or synergistic benefit. However, in so doing we ran into another problem. The useful fatty acids and sterols (e.g. betasitosterol) derived from saw palmetto did not like to stay in solution very well with some of the other things we were testing. Also, the compositions tended to denature. There were pH issues and solubility problems galore. These were technical challenges that, by soliciting some very sharp collaborative assistance, we were eventually able to overcome. We kept working and ultimately got to a point that our clinic results were positive and reproducible. At this point we engaged a third-party clinical site to test the formula in an IRB monitored, placebo-controlled, randomized trial. For a small independent clinic like ours, this was an ambitious and expensive gamble but we were hopeful that the positive results we were seeing in our clinic would hold up. They did. Hoping that our fellow clinicians and scientists would find merit, we then submitted the work for publication in the peer-reviewed literature. Happily, the manuscript describing our pilot study was accepted for publication in the Journal of Alternative & Complimentary Medicine in 2002. Now here's the thing. I'm a pretty good scientist. But I'm a lousy businessman. Unfortunately, the business partners I became involved with turned out to have a different philosophy than I did. This meant that instead of working in the lab to make newer and better formulas, I spent the better part of eight years in business litigation. Another thing your readers should probably be made to understand. The fact is, there are very very few dedicated scientists working in this area of research. If you don't believe me, look at all the hair products offered for sale today. Now look at, or rather try to find, the hard science that supports them. An uncomfortable number of these products actually quotes my study in support of their products!!! There is an excellent Yiddish word for this. It's called chutzpah. For the hair loss affected public, this meant that nothing much new in the category has been brought to fruition for a number of years. Good news. This is all about to change. Now that I am past my litigation, my hands have been untied and I have been hard at work with some very gifted collaborators to take the non-drug hair loss treatment methodology forward in a substantive way. I can't say too much right now. But I will tell you that, hopefully before the year is out, we will issue a press release that will probably be of interest to the folks who frequent this website --- and other hair loss focused websites. More on this at the appropriate point in time. best wishes, Geno M.

If I may offer a suggestion; in order to determine the benefit a hair loss treatment is providing, it is a very good idea to take baseline (before) photos. Take regular monthly follow up photos from approximately the same angle and with the same lighting. Over a period of three to six months you will establish a reasonably objective set of data points that will help you determine the benefit the treatment is --- or is not providing. Geno Marcovici, Ph.D.

Dr. Robert Bernstein is a respected colleague and one of the finest hair restoration surgeons practicing anywhere. You might want to schedule a consultation with him. Another highly gifted surgeon is my former partner, Dr. Dan Didocha. Unfortunately, Dan does not work in NYC but practices in Michigan and elsewhere. For a third choice, you can count on consistently excellent results from the partnership of Dr. Martin Tessler, & Dr. Aronovitz, also in Michigan. If money is no object, you would do well to consult with a number of surgeons, and not just in one geographic area. Best of luck... Geno Marcovici, Ph.D. Chief Scientific Officer HairGenesis?„?

Sounds like you need help with a prognosis rather than a diagnosis. Since I spent the better part of ten years mapping out surgical hair restoration plans, I can probably offer a useful thought or two. If you like, send me your photos. I'll give you my honest opinion. Geno Marcovici, Ph.D. Chief Scientific Officer HairGenesis?„?

Greetings, since I am the guy who invented this product, I can probably answer questions. I am surprised to see anyone refer to the line as "junk" since HairGenesis?„? represents the sole example of a non-drug hair loss treatment that is supported with published peer-reviewed IRB-monitored placebo-controlled clinical data. In all events, I'm happy to address whatever questions you folks may have about our product line. kind regards, Geno Marcovici, Ph.D. Chief Scientific Officer HairGenesis?„?