The Hair Follicle Growth Cycle
All living things go through various stages or cycles of life. While the details differ from one thing to the next, all cycles include some form of birth or creation, development or maturation, and ultimately, some sort of expiration or death. Your hair is no different. Hair loss, hair restoration, and re-growth are all impacted by the hair follicle growth cycle, so let's take a closer look at that cycle to help better understand why you lose hair, and why hair restoration products, like Avacor's FDA-approved Physician's Formulation®, really do work.
The hair follicle growth cycle is broken up into three phases:
- The Anagen phase is the hair growth phase
- The Catagen phase is a transitional phase
- The Telogen phase is the resting phase.
The Anagen phase lasts anywhere from two to six years. This is the stage when hair follicles produce and grow individual hairs. Hairs grow about six inches a year on average, meaning that a few months into this phase, you can have hair that is a few inches long. The Anagen phase is further broken up into six stages; basic information about each stage is below.
- Stage 1: Cell division begins; hair growth at the microscopic level
- Stage 2: Follicle grows downward, and surrounds cells, which continue to grow
- Stage 3: Hair begins to take shape and melanin production begins
- Stage 4: Cells begin pigmentation (hair color)
- Stage 5: Hair shaft begins to sprout
- Stage 6: Follicle is completely developed
Another interesting fact about the Anagen phase is that at any given time, about 85% of the active hair follicles on your head are in this phase. As people get older, the Anagen phase might become shorter, resulting in smaller, finer hair. This is why adults sometimes experience thinning hair, and eventually, baldness.
The Catagen phase lasts one to two weeks in most cases. During this phase, the follicle base and hair shaft continue to move upward, thought the follicle shrinks to about 16% of the normal size.
The Telogen phase lasts between one and two months. During this phase, the hair does not grow, but it remains attached to the follicle. It is sometimes referred to as the "resting phase" because the hair basically just rests, without growing or falling out (shedding). Roughly 10 to 15% of all hair is in the Telogen phase at any given time.
At the end of the Telogen phase, the follicle starts the cycle over again. The old hair from the previous cycle either falls out on its own, or is pushed out when the new hair begins to grow in the Anagen phase.
Each hair follicle is on its own unique schedule of this growth cycle. If they were all in sync, you would lose all your hair at the same time, and regrow it at the same time. Because of the varying schedules, your hair is constantly growing, shedding, and growing again, simultaneously.
When you begin treatment to regrow or rejuvenate hair growth using Avacor Physician's Formulation , it is important to be patient. Your hair will not grow back overnight. Avacor Physician's Formulation has been clinically proven to revitalize hair follicles in as little as two months. However, when hair follicles are revitalized, they must still go through the hair follicle growth cycle to begin growing new strands of hair. Specifically, once revitalization occurs, the follicles must go through at least a few months of the Anagen phase to generate new hair that is a few inches long.
Stay tuned for the next post, which will discuss shedding in more detail.
Minoxidil and Pregnancy: What You Should Know
We were recently asked a question about whether women who are experiencing hair loss can use minoxidil when they are pregnant or breast-feeding.
When it comes to medications and your child, don't take any chances. It is very important to check with your doctor before using any medications while pregnant or breast-feeding.
First, we should mention that the FDA has not approved minoxidil for any indications other than pattern hair loss. According to a regulatory compliance guidance document from the FDA,1 minoxidil should not be used for hair loss associated with child birth. (“Do not use if… hair loss is associated with childbirth.”)
Information from both the FDA and the National Institutes of Health recommend speaking with a doctor or health professional before using minoxidil if you are pregnant or breast-feeding.
The FDA guidance document mentioned above states: “if pregnant or breast-feeding, ask a health professional before use.” The NIH's MedlinePlus website2 provides a similar recommendation: “Before using minoxidil… tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using minoxidil, call your doctor.”
While we are not aware of any large, systematic studies of minoxidil use during pregnancy, a group of physicians from the Università di Firenze in Italy reported a case of a woman who used 2% topical minoxidil during her pregnancy and whose fetus developed abnormally.3 While no causal effect was established, the authors conclude: “Further knowledge on minoxidil-induced fetal toxicity would be beneficial before allowing its use in pregnant women.”
Remember - if you are pregnant or breast-feeding, talk to your doctor before using any products that contain minoxidil. And please keep the questions coming!
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1. FDA Guidance: "Example Drug Facts Label for Minoxidil Topical Solution 2% for Men and Women". Link to FDA website
2. MedlinePlus drug information: Minoxidil Topical. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a689003.html
3. Smorlesi C, Caldarella A, Caramelli L, Di Lollo S, Moroni F. Topically applied minoxidil may cause fetal malformation: a case report. Birth Defects Res A Clin Mol Teratol. 2003 Dec;67(12):997-1001. Link to PubMed
The History of Hair Loss – Part 1: Hair Loss and Remedies Over Time
If you are experiencing premature hair loss, or thinning hair, you are not alone. In fact, premature hair loss has been an issue for people throughout history. Thousands of years ago, ancient Egyptians shaved their heads and wore wigs or elaborate head pieces to combat hair loss and display royalty and wealth. They also created a variety of potions, ointments, and other methods to treat hair loss. Some ointments included boiled porcupine hair or hippopotamus fat, according to the 1550 B.C. medical text, The Ebers Papyrus. Clearly, these options would not be FDA-approved today.
The Bible also mentions hair loss a few times. In 2 Kings 2:23-24, Elisha was mocked by a number of youths, shouting "bald head" and "baldy" at him as he walked into the town of Bethel. Angered and embarrassed, he cursed them and took his revenge by summoning two bears from the woods. It didn't cure his baldness, but it also didn't end well for the youths.
Julius Caesar wore the original Caesar hair style, but he was also bothered by his hair loss. According to Suetonius, Caesar combed his "scanty locks" forward to hide his thinning head of hair. Some also speculate that he wore the traditional laurel wreath to cover up his baldness. Oddly enough, the Latin word "caesaries" translates to "long/flowing/luxuriant hair."
In the Middle Ages, King Louis XIII of France began the big wig era by wearing a long, curly wig after losing his hair prematurely. This fashion trend spread throughout Europe and across the pond to the American colonies. Many European and American politicians and scholars—men and women alike—wore large wigs, not only to be fashionable, but to hide their thinning hair or bald heads. Even after the American and French Revolutions, when the big wig was seen as a symbol of the old regime, people wore white, powdered wigs.
Cowboys in 19th century America attempted to stop thinning hair with various snake oil products and messy grease rubbed into the scalp. Also, let's not forget the infamous cowboy hats, which offered protection from the sun, and conveniently hid bald heads underneath.
In the modern era, hair loss continues to be an issue. For some people, losing hair is an emotional and stressful time, while it is a health issue for others. Hair loss can lead to lower self-esteem, high anxiety, depression, and issues with sexual attractiveness and social acceptance. It can also trigger fears about getting older, and even dying. Avacor Physician's Formulation ® is an FDA-approved hair restoration and re-growth product that has been clinically proven to revitalize hair follicles in as little as two months. Thankfully, we live in a time when we do not need to rely on snake oils, obnoxiously large wigs, animal fats, or vicious bears.
Stay tuned for Part 2 of The History of Hair Loss, which will discuss the importance and symbolism of hair throughout history.
Thanks for being part of the Avacor community!
We really appreciate all the feedback we've been getting since we started the Avacor® Hair Regrowth Blog back in June of this year. We'd especially like to thank all of you, our readers, for trusting us as a source for reliable, scientifically-based information on hair loss and hair regrowth.
Many of you have either commented on a post or written to us directly. Some have simply said "keep up the good work," while others have approached us with detailed questions and concerns about their hair loss issues.
One reader (who hosts a medical show on satellite radio) tweeted that he was skeptical at first but "I read it and I was VERY impressed".
We've also received some good feedback from out in the blogosphere. A community reviewer from blogsearchengine.com said:
"If you need information on hair loss, one of the best places to look is The Avacor Hair Regrowth Blog. In this blog, you will get tons of info on the scientific reasons underlying hair loss and solutions to hair loss... If you really want to learn about the condition and how to treat it, then this blog ought to be part of your reading list!"
We would love to hear from you too! If there are any topics you would like us to cover in a future post, please feel free to drop us a line anytime and we'll try to address your suggestions with a post as soon as possible.
Thanks again for reading and being part of the Avacor® community!
The Future of Hair Regrowth: Part 4 – Stem Cells
Some of the most anxiously awaited treatments on the hair growth horizon are those that seek to harness the power of stem cells to regrow hair. This post will give you a brief introduction to stem cells and describe some of the research and development programs focused on developing treatments for hair loss.
Stem Cells 101
Each tissue and organ in the body is made up of cells with specialized structures and unique functions. These specialized cells are generated by a process called “differentiation”, in which immature, undifferentiated cells give rise to mature, differentiated cells that are equipped to carry out specific roles.
The most versatile type of stem cells, called embryonic stem cells (ESCs), arise in the earliest stages of development and give rise to every cell type in the body. The use of human ESCs has been a source of controversy because their isolation usually requires the destruction of an embryo.
Adult stem cells (ASCs), present in low numbers in the body throughout our lives, are capable of producing multiple cell types but are already committed to a particular developmental pathway. Examples of ASCs include hair follicle stem cells, which are responsible for the growth and maintenance of hair follicles, and hematopoietic stem cells, which give rise to the various red and white blood cells that carry oxygen throughout our bodies and protect us from infections.
Promising Research into Stem Cell-Based Treatments for Alopecia
Earlier this year, the research group of Dr. Roland Lauster at Berlin Technical University published an exciting report1 in the Journal of Biotechnology detailing a method that could lead to a stem cell-based treatment for hair loss.
Dr. Lauster's group isolated dermal papilla cells from human scalp hair follicles and cultured them using the same methods as have been used for culturing embryonic stem cells and mesenchymal stem cells. The cells first formed small clusters and approximately 13.5% of these “microfollicles” eventually began to grow hair-like fibers, as shown by light microscopy and electron microscopy in this figure from the paper.
The authors suggest that their “robust, reproducible method” is a “good jumping-off point for further work” on treating male pattern baldness or chemotherapy-induced alopecia. While the hairs produced in the study were similar to vellus (fine, peach fuzz) hairs, they suggest that “with further experimentation, it may be possible to cultivate hair of different thickness, color or texture.”
Eventually these microfollicles might be produced in large quantities from a patient's own cells and injected back into the scalp, where they could form new hair follicles and grow new hairs.
Histogen and Follica: Company Profiles
Two of the most notable commercial efforts in stem cell-directed therapies for alopecia are being spearheaded by the companies Histogen and Follica. Rather than implanting stem cells into the scalp to create new hair follicles, these companies are developing methods and formulations that would stimulate the development or activity of cells already present in the scalp.
Histogen, Inc.
Location: San Diego, CA
Background: Founded by Dr. Gail Naughton, former co-founder, President and Vice Chairman of the now liquidated human tissue engineering company Advanced Tissue Sciences, Inc.
(click here to listen to an interview with Dr. Naughton on TheBaldTruth.com)
Technology: Histogen's Hair Stimulating Complex (HSC) is a mixture of soluble protein factors such as Wnt7a, VEGF, KGF, and follistatin. These proteins are secreted by cells, called embryonic fibroblasts, which are grown in a controlled laboratory environment.
Development status: Histogen has completed a double-blind, placebo-controlled Phase 1/2 clinical trial of HSC to evaluate its safety and efficacy as an injectable for hair growth. According to the Histogen website, no adverse events were observed and HSC was found to increase hair count, hair thickness, and hair density at the 12 week endpoint with continued growth observed 12 months later.2 No Phase 3 details have been released yet.
Follica, Inc.
Location: Philadelphia, PA
Background: Founded around the pioneering research of Dr. George Cotsarelis, a professor at the University of Pennsylvania, who has been studying hair follicle stem cells for over 20 years and published an early pioneering article in the journal Cell in 1990.3
Technology: Cells in the scalp are coaxed into generating hair follicles by first wounding the target area and exposing the healing tissue to stem cell modulating factors such as Wnt pathway activators.4 The company is developing a device that would perform the wounding in a controlled fashion.
Development status: Follica's development program is still in its early stages. A recent article by Dr. Cotsarelis showed that stem cells are still present in normal numbers in the scalp of men affected by androgenic alopecia,5 suggesting that their focus may shift toward increasing the production of progenitor cells, the next cell type in the differentiation cascade. An article on Xconomy.com this year quoted the CEO as saying that clinical trials are underway outside of the U.S.
Conclusion
While stem cell therapies are exciting and may hold great potential for treating diseases and regrowing damaged tissues, they have proven difficult to commercialize: after 20 years, Geron, one of the leading developers of embryonic stem cell-based therapies for neurological diseases, has given up and shifted towards developing drugs for cancer.
Still, thousands of people who suffer from alopecia hope this promising field of research and development will eventually lead to a solution for hair loss.
Check back soon for the final installment of the Avacor® Hair Regrowth Blog’s series on The Future of Hair Regrowth to learn about some of the many novel, early-stage research programs that may lead to new treatments for hair loss in the future!
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1. Lindner G, Horland R, Wagner I, Ataç B, Lauster R. De novo formation and ultra-structural characterization of a fiber-producing human hair follicle equivalent in vitro. J Biotechnol. 2011 Mar 20;152(3):108-12. Link to PubMed
2. Histogen website. (accessed 11/16/2011) http://histogen.com/applications/hsc.htm.
3. Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990 Jun 29;61(7):1329-37. Link to PubMed
4. Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE, Cotsarelis G. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature. 2007 May 17;447(7142):316-20. Link to PubMed
5. Garza LA, Yang CC, Zhao T, Blatt HB, Lee M, He H, Stanton DC, Carrasco L, Spiegel JH, Tobias JW, Cotsarelis G. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. J Clin Invest. 2011 Feb 1;121(2):613-22. Link to PubMed
Micronutrients For Healthy Hair: Biotin and Vitamin B12
When people hear the word “nutrition,” they usually think about keeping their body healthy and staying in shape, but you may not realize that nutrition also affects your hair. Micronutrients like vitamins and minerals are especially important for keeping hair healthy.1
The micronutrients Biotin and Vitamin B12 are two of the most recent additions to our Avacor® All Natural Nutricap, a dietary supplement specially formulated to improve the health of your hair and scalp.*
In this post we have collected a few pieces of information about Biotin and Vitamin B12 that we thought were particularly relevant to healthy hair.
Biotin May Improve Hair Quality/Thickness
Biotin, also known as Vitamin H is a micronutrient that is known to be essential for maintaining healthy hair and skin.1 (According to some sources the H actually stands for "haar und haut", German for "hair and skin".)
Biotin is absorbed into the shafts of hair, where it “moderates the damage environmental or other factors may have caused, and increases the diameter of the hair shafts.” 2
“It is well documented that biotin deficiency in humans and animals causes pathological changes in the skin and its appendages such as desquamative dermatitis and alopecia,” 3 and in animal studies, a biotin-poor diet leads to dandruff-like skin irritation and causes hair loss.4
But biotin supplementation may also be beneficial for people who do not suffer from a known biotin deficiency:
“pharmacological doses of biotin have been shown to improve… the quality of nails and hair in humans in the absence of apparent biotin deficiency.” 3
Our All Natural Nutricap now contains 300 micrograms of Biotin to make sure you are getting enough of this important micronutrient.
Vitamin B12 for “Optimal Hair Growth Potential”
Vitamin B12, a water-soluble vitamin containing the element cobalt, is involved in cell metabolism and macromolecular synthesis in all cells throughout the body.
According to the scientific literature, “optimal hair growth potential” requires adequate levels of Vitamin B12 in the body.5 An article from WebMD quotes one doctor, a clinical professor of dermatology, as saying “it's not uncommon to find a B12 deficiency in women who come in seeking treatment for hair loss.”
Since Vitamin B12 is only found in certain foods, our All Natural Nutricap is now supplemented with 6 micrograms of Vitamin B12 to ensure that your body is equipped with the proper nutrition it needs to keep your hair healthy.*
Thanks for reading, we hope you've learned something new about hair and nutrition and that you enjoy the benefits of these improvements we've made to the Avacor® All Natural Nutricap!
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1. Daniells S, Hardy G. Hair loss in long-term or home parenteral nutrition: are micronutrient deficiencies to blame? Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):690-7. Link
2. Goldberg, M.E. Hair enrichment composition and method of use. US Patent No. 5,069,898. December 3, 1991. Link
3. Limat A, Suormala T, Hunziker T, Waelti ER, Braathen LR, Baumgartner R. Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin. Arch Dermatol Res. 1996;288(1):31-8. Link
4. Morganti, P. Medicinal formulation for promoting keratinogenesis and reducing seborrhea of the face and scalp. US Patent No. 4,863,950. September 5, 1989. Link
5. Rushton DH. Management of hair loss in women. Dermatol Clin. 1993 Jan;11(1):47-53. Link
*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.
Internet Hair Loss Forums: Great for Support but not Treatment Advice
Losing your hair is never easy. In addition to the obvious physical changes, premature hair loss can cause anxiety and fear about sexual attractiveness, social acceptance, and even mortality. Feelings of isolation and loneliness can make the process even more depressing.
(For a heart-felt article on this topic, read Spencer Kobren's "Depression and Hair Loss: You’re not Alone" on TheBaldTruth.com)
Finding other people with similar stories and sharing your experiences with each other can help with the psychological "trauma" that frequently accompanies hair loss. Internet forums are a great way to connect with people around the world with common interests and can serve as a sort of "virtual support network".
But when it comes to medical treatments for hair regrowth, be cautious about taking advice from other forum members. As you will see below, forums can sometimes contain treatment suggestions that may be ineffective or potentially harmful.
Hair Loss Forums
A recent book on online social support states that “[t]he electronic social network an online support group creates can potentially provide the benefits of social support traditionally conveyed face-to-face without conventional limitations of material resources, proximity, and temporality.”1
Two of the most popular internet forums for hair loss topics are the communities at TheBaldTruth.com and at HairLossTalk.com. These sites have forums areas for both men and women, but another popular site called Her Alopecia is specifically dedicated to women's hair loss discussions.
Internet forums can be great for support during difficult emotional times, but it is important to remember that other forum members may not know much more than you do and are not likely to be reliable sources for medical/scientific information on hair loss and hair regrowth.
Don't Try This at Home! (treatment advice from an internet forum)
We have seen countless posts that either get the science wrong or simply advocate dangerous, painful, and unproven treatments.
For example, one forum thread on Regrowth.com was dedicated to users discussing their attempts at an experimental approach to hair regrowth that they had adapted from early-stage research studies.
This approach involved wounding the scalp with sandpaper, needles, or organic acids and applying chemicals like cayenne pepper (in 90% alcohol) and lithium to the wounded areas in the hope of stimulating new hair growth.
“We're making it up as we go”
A new visitor to the site praised the other posters for having “more knowledge than any of the other forums” and asked for their recommendations on what chemical substances to incorporate in his wounding routine because he didn't “have the education to figure it out on [his] own.”
One of these 'knowledgeable' posters described his wounding regimen as "heavy sanding" and applying glycolic acid to the raw skin, leaving a "red mess of raw flesh" (although he didn't recommend other readers take their "wounding to that level"). In another post he admitted: “We're making it up as we go along armed with both scientific and anecdotal evidence. The quantities I use are measured in the most unscientific way possible as we don't really have any data on quantities.”
Another poster recommended applying cancer drugs to the scalp after wounding, which he suggested the forum members could purchase at a group rate from a cheap Chinese source he had found through an internet trading site. He also offered to "whip up" solutions of experimental drug combinations for the other forum members. Fortunately one poster drew the line at this point: “Personnaly I won't take anti cancer drugs just to regrow hair, it is far too dangerous...”
No proof that it even worked
As the thread developed, several posters asked for pictures of the results that some members claimed to be achieving. Here are some quotes from the discussion:
“anyone taking pictures?”
“Due to just having a cell phone camera, I'm not quite ready to take pictures yet”
“So how about some pics?”
“I don't own a digital camera but should the results (if any) warrant it, I shall obtain one and endeavour to post pics.”
“Looking forward to those pics.”
“For the pictures, I'll take them tomarrow because I have no working batteries”
“be sure to post the promised pics”
“When I'm comfortable taking a picture (when the skin heals better and hair grows out more) I definitely will.”
“I'm dying to see your results pictures. Day 26 and I have minimal growth and nothing cosmetically significant..”
“I've been so swamped with laser helmet requests lately[...] My regrowth seems to mostly be on the left side of my scalp, a few odd sprouts here and there. Perhaps I'll take some pics after my haircut this Saturday, haven't had a good cut in months!”
“I shaved the whole front of my scalp up about 2 inches just above my recession and sanded the entire area, been applying the same formula. So far I don't see a single new hair, this is pretty disappointing.”
In the end, no pictures were ever posted and there was no evidence that the painful and potentially dangerous treatments had any benefit for the self-proclaimed "guinea pigs".
Conclusions
Hair loss forums on the internet can provide a free and immediate social support network that can be helpful for meeting other people who are experiencing similar issues. This support can potentially help with some of the psychological issues that often accompany hair loss, such as anxiety and depression.
These forums also contain discussion threads about members' personal experiences with hair regrowth treatments. While most people mean well when they offer advice on the internet, they may not necessarily be qualified to give a professional opinion.
When it comes to scientific or medical issues, make sure to double check what you read on forums with a reputable source, preferably a physician or an expert in the field.
If you ever want to know more about something you've read online, feel free to contact us and we will be happy to answer your question or help you find an appropriate expert who can.
Thanks for reading this Avacor® Hair Regrowth Blog post and come back soon for more of the latest information on hair loss and hair regrowth!
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1. Bambina. A. (2007). Online Social Support: The Interplay of Social Networks and Computer-Mediated Communication. Youngstown, NY: Cambria. Link to GoogleBooks
The Future of Hair Regrowth: Part 3 – RNA Interference
Another possible strategy for combating androgenetic alopecia in the future could involve harnessing a molecular phenomenon known as RNA interference (RNAi) to block the expression of the genes that cause hair loss in the first place.
Molecular Biology 101: What is RNA?
Ribonucleic acid (RNA) is a biological polymer that is essential for all known forms of life. One type of RNA, known as messenger RNA (mRNA), carries genetic information derived from DNA (the master genetic "blueprint") out of the cell nucleus to the cytoplasm where it is translated into proteins (e.g., receptors or enzymes).
(For more details on RNA check out the entry on Wikipedia.)
The Science Behind RNAi
Years of research on gene expression in plants, worms, and eventually mammals, have led to the understanding that small fragments of nucleic acids like RNA can specifically block the production of any given protein in a cell.1
Small interfering RNAs (siRNAs) are short fragments of RNA, approximately 19-23 nucleotides in length, which recognize and bind to specific sequences in a target mRNA and recruit RNAi machinery (including an enzyme called "Dicer") that chop up the target mRNA. Once the mRNA is cleaved, it can no longer be translated into the corresponding protein it encodes. With the sequencing of the human genome completed, siRNA sequences can be designed to specifically target almost any gene.
RNAi technology could be utilized in the context of treating androgenetic alopecia to inhibit the production of proteins that are involved in hair loss or that slow the growth of hair.
Given the widely recognized role of dihydrotestosterone in hair follicle miniaturization and pattern hair loss, two particularly attractive targets for RNAi therapy are the androgen receptor (AR) and the 5-alpha reductase enzymes.
(For background information on DHT, AR, and 5-alpha reductases in hair loss, see our previous posts on anti-androgens here and here.)
This strategy is supported by several scientific papers, including one published in 2009 that focuses on blocking expression of AR:2
“Antiandrogen therapeutic oligonucleotides targeting the downregulation of the AR expression is advantageous because both will be possible to eliminate the only way for androgens to act and simultaneously this strategy allows the medication to be topically administrated. In fact, this could be very useful in a long-term treatment of, for instance, androgenetic alopecia...”
A Possible Manufacturer?
A company called Sirna Therapeutics described just such an approach in a patent application, published in 2005 as US 2005159376 A1. In the application, Sirna suggested using siRNA targeting either AR or 5-alpha reductase to treat alopecia:
“Specifically, the invention relates to small nucleic acid molecules [...] capable of mediating RNA interference (RNAi) against 5-alpha reductase and/or androgen receptor. Such small nucleic acid molecules are useful, for example, in providing compositions for treatment of traits, diseases and conditions that can respond to modulation of 5-alpha reductase and/or androgen receptor expression in a subject, such as alopecia, acne, polycystic ovary disease, prostitic hypertrophy, and prostate cancer.”
Since RNA does not cross the cell membrane or the skin barrier efficiently, one approach for delivering siRNA molecules is to encapsulate them in a sphere of "phospholipids" similar to those that make up the cell membrane. These spheres, known as liposomes, would cross through the skin and facilitate the entry of siRNA into the desired cells in the hair follicle.
“The siNA molecules of the invention are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells or tissues. The nucleic acid or nucleic acid complexes can be locally administered to relevant tissues ex vivo, or in vivo through direct dermal application, transdermal application, or injection, with or without their incorporation in biopolymers.”
Here is an example of how such a treatment might be delivered:
Not Quite There Yet
While the approach outlined above will theoretically be effective as a treatment for androgenetic alopecia, some details still need to be worked out. Delivery with simple liposomes works very well in cell culture models, but may not be as effective in the more complex environment of the skin. According to a review article published this year:
“More efficient drug delivery vehicles are therefore being sought. Among the newly emerging concepts, drug delivery systems based on nano- and microparticles, which efficiently penetrate via the follicular route, are highly promising approaches.”3
“Nevertheless, this is still a very incipient area that promises to bring new and highly targeted strategies for skin and hair diseases.”
As with all the other treatments described in this series of posts, any therapeutic strategy would need to be tested in clinical trials to make sure it is safe and effective before approval by the FDA.
Thanks again for joining us this week as we look into The Future of Hair Regrowth. Don't forget to come back soon for the next installment in the series, which will cover what may be the most promising area in hair growth research today: stem cells.
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1. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000 Mar 31;101(1):25-33. Link to PubMed
2. Dugour A, Hagelin K, Smus C, Balañá ME, Kerner N. Silencing the androgen receptor: new skills for antiandrogen oligonucleotide skin and hair therapy. J Dermatol Sci. 2009 May;54(2):123-5. Link to PubMed
3. Araújo R, Fernandes M, Cavaco-Paulo A, Gomes A. Biology of human hair: know your hair to control it. Adv Biochem Eng Biotechnol. 2011;125:121-43. Link to PubMed
High Dose Minoxidil Products – Lack of Evidence for Safety and Efficacy?
Several online distributors now offer products that contain minoxidil in higher doses than have been approved by the U.S. Food and Drug Administration (FDA) or that contain minoxidil in combination with additional active pharmaceutical ingredients.
Although the FDA has only approved minoxidil at concentrations of two percent (2%) or five percent (5%) for the treatment of hair loss, some products available over the internet contain minoxidil at concentrations as high as 15%. Many are formulated with additional ingredients such as azelaic acid, retinoic acid, caffeine, and even finasteride (the active ingredient in Propecia®), in combinations that have not been reviewed by the FDA.
The FDA evaluates two major concerns when considering new drug applications – safety and efficacy. Until these products are tested in clinical trials, there is no way to ensure that they are safe or to know whether high doses of minoxidil even provide any benefit over products that have been approved by the FDA.
Misleading Marketing?
Some consumers may find the marketing of these products to be misleading because of references to the FDA or to claims based on FDA-approved products containing 2% or 5% minoxidil.
The website for MinoxidilMax claims to offer “effective hair regrowth products... for male pattern baldness (alopecia androgenetica)” with “unmatched effectiveness.” Their products are manufactured “by an FDA registered cGMP compliant facility,” contain “the only effective ingredient approved by FDA in topical hair regrowth solution,” and have “the maximum strength of FDA approved hair growth stimulator (15% minoxidil).”
Consumers who read further on the company's website may be surprised to find that their products are not FDA-approved and that “the statement on this website has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease.”
Another manufacturer, Perfect Image Solutions, offers high dose minoxidil products “specifically formulated to treat conditions associated with male pattern baldness (Androgenetic Aloepicia).”
The FAQ section of the website relies on the long history of FDA-approved minoxidil products like Rogaine® to imply that high dose minoxidil products must also be safe:
“How do I know using a high concentration of minoxidil isn’t an overdose?
Minoxidil has been on the market for over 20 years with an extremely low incidence of side effects, especially from topical application.”
Although claiming that the products are “clinically proven to yield unparalleled results in the field of hair loss,” manufactured in an “FDA registered cGMP compliant facility,” and that all ingredients, “including Minoxidil must meet all FDA guidelines,” the website does not provide any evidence of clinical trials demonstrating the safety or efficacy of its products.
FDA Takes Action
Earlier this year, Regrowth LLC, a well known distributor of high dose "specialty" minoxidil formulations (formerly sold under the name Xandrox), released the following statement on its website:
“We're very sorry to inform you that Regrowth LLC has to suspend all operations at this time. In an ongoing audit, the U.S. FDA has deemed our medications to be 'unapproved illegal drugs'.”
Regrowth LLC had been selling minoxidil formulations containing 15% minoxidil (three times the FDA-approved dose contained in products such as Rogaine® and Avacor Physicians Formulation®).
On May 25, 2011, the FDA initiated a recall of 57,999 bottles of Regrowth LLC's products, stating that “[t]hese products are unapproved drugs and may present potential health hazards.”1 Based on this recall, it would not be surprising if the FDA takes action to stop other distributors of high dose minoxidil formulations/combinations from selling unapproved drugs in the future.
Conclusions
At the time of posting this article, we are unaware of any clinical trials proving that products containing higher concentrations of minoxidil than 5% are safe or more effective than FDA-approved products containing 5% minoxidil.
In January, Dr. Glenn Charles, a member of the International Alliance of Hair Restoration Surgeons, commented:
“I have not seen any studies comparing 5% Minoxidil with higher % Minoxidil concentrations. I would imagine that the incidence of side effects might be higher with greater % of Minoxidil. However, many of the reported side effects might actually be caused by the other ingredients in these hair loss products containing Minoxidil.”
If you are still interested in experimenting with formulations containing high dose minoxidil or combinations with other active ingredients, it may be a good idea to consult with a physician before you begin using any such products.
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1. Enforcement Report for May 25, 2011: RECALLS AND FIELD CORRECTIONS: DRUGS - CLASS II. FDA.gov (accessed September 8, 2011).
http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm256794.htm
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