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Polyacrylamide and Alginate Hydrogel Used As Scaffold Is Alternative To Autologous Chondrocyte Implantation

This study I found suggest that instead of the traditional approach in tissue engineering where the scaffold where the stem cells or growth factor is placed is made of not very strong or elastic in terms of material and machanical properties, it might be possible to add a scaffold made out of polyacrylamide and a type of alginate hydrogel which has much better mechanical and material properties.

Update – Link seems to NOT work: New hydrogel may help cartilage regeneration research

Link #2 – New ‘hydrogel’ shows promise for cartilage repair in proof-of-concept trial

This link is nothing new to me but shows that in terms of the development of certain types of biomedical research into actual application, it has taken a long time. For the last decade or so scientists and researchers around the world have been using a stem cell w/ scaffold combination to regrow bones and cartilage. Only now has this news been reported, and from John’s Hopkins University. Like the article states, many defects seen in the articular cartilage in humans have been traditionally fixed using the microfracture surgery, where a small drill is done at the defect area. The marrow inside pours out, forming a layer of fibrocartilage which is just not as good as the hyaline cartilage that was there before. This scaffold idea which is supposed to be a ‘breakthrough” is really not. It might be that researchers at JHU have been trying out thousands of scaffold composition or formulation combinations before they finally found a good enough hydrogel/scaffold/alginate combination for stem cells to really grow. The combination of the idea of stem cell in scaffold along with microfracture surgery is not a big leap in understanding or application. I say that it was bound to happen eventually. The main thing I guess that is important is in showing that if you use the scaffold and microfracture in combination, it is much better than just going with the microfracture sugery route along.

The results are…

After six months, the researchers found that hydrogel recipients had new cartilage filling 86 per cent of their defects, on average, compared with just 64 per cent for patients with microfracture alone.

In addition, patients who received the hydrogel implant reported a greater improvement in their levels of knee pain.

Study #1 – Highly stretchable and tough hydrogels

Summary – Hydrogels has been used in many types of applications but they are not very good due to having certain types of mechanical properties. They are not very elastic and break after they are stretched even slightly. Compared to other materials like cartilage and rubber, the hydrogel does not have a very high fracture energy, making them much more brittle. At the current moment, multiple researchers are looking for ways to make a type of hydrogel that is much stronger and more elastic. There are already some synthetically made hydrogels that have a fracture energy of 100–1,000 J m^(-2) which is up to 2 magnitudes greater than average. 

However, for this study, the researchers show that they have developed a new type of hydrogel that is much more elastic and have much higher fracture energy and stretchability. They report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked network

These new synthetic hydrogels can stretch up to 20 X their length, have fracture energy around 9000 J/m^2 and be composed of 90% water.

They state that the gels’ toughness to the synergy of two mechanisms:

  1. crack bridging by the network of covalent crosslinks – Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading.
  2. hysteresis by unzipping the network of ionic crosslinks – The unzipped ionic crosslinks cause internal damage, which heals by re-zipping.

Implications For Height Increase Application

I personally think that the best and most likely alternative to the limb lengthening surgery is doing a type of synthetic tissue implant into the bone of a person. If we can create a strong enough type of growth plate in a scaffold formation, then it would definitely be a real alternative. This requires the understanding of stem cell mechanisms and tissue engineering practices. From tissue engineering practice, the use of scaffolds is very big. The use of hydrogels as scaffolds is very common, if not universal. I have been trying to figure out what types of hydrogels would be best to be used in combination with formed cartilage-bone tissue that is growing volumetrically.

As I stated in one of the most important posts on the website, we have been able to create growing cartilage tissue aka functional growth plates however I had stated that I worried that even if we implanted the cartilage into the body, they would not be able to withstand the loading by an adult human. This is why I felt that maybe we need to find a good enough transport system aka scaffold we can put not just stem cells in, but also expanding cartilage tissue. If the hydrogel scaffold is strong enough, the synthetic growth plate with strong & elastic scaffold combination being implanted would probably work, at least with multiple testing done.

From the study “Elastic, Superporous Hydrogel Hybrids of Polyacrylamide and Sodium Alginate“…

These hydrogels are distinguished from other porous hydrogels in terms of their pore sizes and the methods used to generate the pores. If any portion of a superporous hydrogel is exposed to water or aqueous fluids, fluid is immediately absorbed through the open channels to fill the whole space. This capillary-driven absorption mechanism helps dried superporous hydrogels to swell very quickly into a very large size.

These products are very resilient and resistant to compression and elongation. In their water-swollen state, elastic superporous hydrogels can be repeatedly stretched to almost twice their original length without breaking. These novel products may find applications in the development of drug and protein delivery systems, fast-dissolving tablets, occlusion devices for aneurysm treatment, scaffolding, cell culture, tissue engineering, water-absorbent pads, hygiene products (baby diapers, feminine pads) and many others.

It might be possible that we might use the Superporous hydrogels (SPHs) since they are made from hydrophilic polymers with so many pores and they also have the interesting property that the hydrogels EXPAND when they absorb water. It could be that the properties of Superporous hydrogels will be very good with the synthetic growth plate cartilage implanted since both will be expanding.

Mesenchymal Stem Cells Injected Into The Intervertebral Discs Does Increase Height and Restore Lost Height From Aging

This is sort of old news in terms of how advanced our research have become. Me and the other height increase researchers have known for quite some time that many types of growth factors will lead to height increase from the height lost from just the normal agin process. The most obvious one is the BMP-7 (aka OP-1) which was shown to increased the intervertebral disk height in White New Zealand Rabbits in.

It seems that a few other source around the internet have also picked on the idea and wanted to report that apparently from just a simple needle injection of the mesenchymal stem cells into an aging adult’s intervertebral disk, their lost height can be restored.

The article below was taken from a website called Healio Orthopedics Today

New research underscores potential for stem cell use in disc regeneration

Culture conditions affect the ability of mesenchymal stem cells to differentiate into intervertebral disc cells.

  • Orthopaedics Today Europe [Archives], Issue 5

VANCOUVER, Canada — Techniques that may employ mesenchymal stem cells to regenerate cells of degenerated human intervertebral discs showed that microenvironment plays an important role in cell proliferation, as does the cells’ ability to produce extracellular matrix.

Results of three laboratory studies and one using a rabbit model that investigated these areas were presented here during the International Society for the Study of the Lumbar Spine 30th Annual Meeting.

The concept of rescuing degenerative discs by injecting them with cultured mesenchymal stem cells (MSC) is not new, but more information is needed about the best MSC sources, culture conditions that support cell differentiation, and techniques that yield the greatest number of cells.

Me: I think we have reached the same agreement with the orthopedic surgeons. We can get height back from cultured MSCs however at this point, we just don’t know which mixture of growth factors and which source of MSCs would be the best and allow for the highest level of cell proliferation.

Also stated are these facts…

“Mesenchymal stem cells have the potential as an ultimate alternative in cell transplantation therapy for degenerative disc disease,”

“…found that within the disc environment, transplanted MSCs differentiated into disc-like cells, survived and proliferated, preserving disc structure”

“Disc height 26 weeks after degeneration was 90 ±8% in the transplanted group compared to 67 ±8% in controls…”

“MSC transplantation restored synthesis of a proteoglycan-rich matrix.”

“Our study has implicated the potential of MSCs to differentiate into intervertebral disc cells, which provides new information in MSC research”

Interpretation Of The Facts

The idea of doing transplants of cells as a type of therapy to treat degenerative dics disease is extremely possible and viable. The cells that are transplanted do differentiate into disk like cells, don’t die out, and do multiply thus maintaining the extracellular matrix environment of the annulus fibrosus and nucleus pulposus that they were injected into. This shows that the cells that are basically foreign objects seem to go along with how their environment is like and does not try to disrupt the collagenous and cartilagenous tissue content. The two groups in the experiment showed that compared to the controlled group, the rabbits that did get the injection got a significant amount of disk height back. The MSCs restored the synthesis of the matrix which has a lot of proteoglycan.

Furthermore, another group of researchers from John’s Hopkins University School of Medicine, the department of orthopaedic surgery at Thomas Jefferson University in Philadelphia, and the Injury, Repair and Rehabilitation Research Group at the University of Manchester, England states about their research…

“…investigated whether bone marrow-derived MSCs could stimulate the anulus fibrosus (AF) and nucleus pulposus (NP) cells they might eventually interact with during clinical application…”

“…Human NP and AF cells isolated from adult degenerative discs cultured in a commercially available MSC medium yielded higher glycosaminoglycan (GAG) content, which increased over time, compared to controls of NP and AF cells…”

“Co-cultured disc cells and MSC could aggregate and produce an extracellular matrix, and there is upregulation of the GAG content between the cells…”

“…degenerative disc cells may be stimulated in vivo by implantation of autologous MSCs to restore some of the disc properties…”

“given the proper microconditions, MSCs can express a phenotype like that of NP cells”

“Hypoxic conditions in combination with the alginate culture and the growth factor that we chose, which was TGF-ß, were really optimal for achieving an NP-like phenotype…MSCs cultured in alginate and pellet culture had the most chondrogenic characteristics, forming an extracellular matrix similar to that seen in vivo”

“…MSCs grown in monolayer in basic media transfected with SOX-9 differentiated and expressed type II collagen, aggrecan and SOX-9, but not type I collagen…”

“…Differentiation improved and there was high-level matrix production using TGF-ß1 in combination with SOX-9,…”

What we are seeing is just how powerful and potentially good the MSCs can be towards height increase at least for the torso region. The autologous implantations of MSCS can stimulate increased glycoaminoglycan content. They can also turn into the nucleus pulposus phenotype with the right environment. This can be achieved using a hypoxic induced environment with the growth factor TGF-Beta. The results is the formation of extracellular matrix that is similar to the annulus fibrosis and nucleus pulposus. The other idea is to put the SOX-9 gene in a vector to alter the MSCs to differentiate and produce the right type of compounds that would form the matrix. The type of compounds the MSCs would make are the Collagen Type II, Aggrecan, and possibly Hyaluronic Acid like glycoaminoglycans that we have seen in the matrix of ordinary hyaline cartilages.

What Happened To The Old Grow Tall Forum

This is what I have managed to piece together from reading over the comments made by people like Nidzo and TheOtherAdam from the other forums that are still around.

Ever since the internet came to being, there have been forums, message boards, Yahoo! Groups, and pockets around the internet which all had some core idea that the online community was formed around. There were message boards for bodybuilding, health, vegans, sexuality, relationships, etc. For the subject of height increase, it was no exception.

Many websites and forums on height increase have come and gone. The internet technically was started in the early 90s, and back then most people didn’t even know what it was. There was Compuserve, America Online, and Altavista, Ask Jeeves, and things were skyrocketing where Venture Capitalists saw so much potential. This was before the Dot Com bust.

If I was to guess at what was the first website ever created for the purpose of selling something that promised people that it could make them taller, it would have been the website www.growtaller.com whose owner named Ken Kalsi based in Blaine, WA copyrighted the website back in 1999. The domain name was perfect, and when the Google Engine was first started, it’s algorithm was not that intelligent yet. This website would have gotten a lot of visitors, and the guy might have sold some E-Products since they were so new and unique back then. However it looks like the website is inactive now, and the person has moved on past selling E-Products on the internet to make a living for themselves.

I look at something known as the Network 54 which has a very old message board, the Impartial Height Increase Message Board and see that it was started (on page 94 currently) in January 15, 2002. That was almost 13 and a half years ago! The main admin of that board, Joey is still around giving the occasional message to any old members who stop in to drop a few lines to see if there are any updates.

From 1999 to 2013, there have been at least a hundred websites that have been created with the website creator trying to get the highest ranking for the key words “grow taller” and “height increase”. Many people have come up and none of them have really succeeded in achieving the holy grail of height increase.

This includes Sky who created the EasyHeight.com and LimbCenter.org websites and tried to talk about microfractures and how to possibly tensile load the bones to stretch them out. After 6-8 years of effort, he would give up without growing any height, and moved on with his life becoming the pharmacist he said he was and make 6 figures a year.

When I use the WayBack Machine to see the beginnings of what was once the largest forum or discussion board on the internet for people who were interested in growing taller, I am amazed that something like that could last that long. It was started in 2007 and the website was taken down in what I think was the beginning of the 2012 year. 5 years and thousands of members all talking about one idea, trying to find a solution to this problem that has plagued the human species since time began.

So what happened?

The person that the remaining members who are still around blame goes by the name Halcyon who was also called Nico, who closed the forum and supposedly took another member’s formulation for height increase, Alkoclar’s Trial #2, and never talked with anyone else again. This is told by someone named Alpha or Alphagenetik

The other influential person was someone named XCrunner, who was followed by PhenolHCL. There seems to be some notes from this guy someone in the very beginning gave me. I wrote a post about all the information entitled “From GrowTallForum.com, Xcrunner211 Notes On Height Increase For Teenage Males With Open Plates, Warning NSFW

There was supposed to be someone named Bubabooey (sp?) who was the person who actually created the original M.E.N.S. Routine.

Apparently another member named Fusion started another grow taller forum called HeightCatalyst.com, which I would write a quick post about. However I have checked that website and nothing is being shown.

These days the member of the old Grow Tall Forum have moved to different forums and become scattered out. The forums that are visited now are…

  1. Grow Tall Forum 2.0 – http://grow-tall-forum.proboards.com/index.cgi
  2. GTF Beta Version – http://growtallerforumbeta.freeforums.net/
  3. Grow Taller Forum – http://www.growtallerforum.com/
  4. Grow Tall Info – http://growtallinfo.com/forum/
  5. Grow Tall Forum Chat – http://growtallforum.chatango.com/

I thought about creating another forum for the members and I did buy the domain name NaturalHeightGrowthForum.com and started to set it up but decided not to go through with the plan because of the amount of drama that had happened in the previous one. If the forum associated with this website did eventually become very large, would I have the time and energy to shoulder this much drama and try to satisfy the demands of thousands of people who will constantly be harassing me to do something for them? I see that many of the forum members still are giving messages to this Alkoclar guy hoping to get a message from him to explain where he is in his formulations. Really?

The truth is that it took at least 4 years for the old Grow Tall Forum to get the type of traction that it had to develop into the large community that it did. By that time, it had become the #1 place for people to gather and talk about their hopes, struggles, and frustrations to become taller. It was shut down rather abruptly, and it seemed that around the end, people had stopped really being helpful, spam was really spreading, and people were sort of leaving and becoming very negative and cynical over this thing.

It is a shame that the place was shut down just as my website was starting because it would have been a nice resource to reference and use. I have been finding that many of my discoveries were already done and found by older members on that forum so it feels like I am often reinventing the wheel. However, I accept that this work has

Many people like Nicki would come and ask me what had happened to the old Grow Tall Forum website even when Natural Height Growth was just 2 weeks old, and I had no answer for her. Other people have come out and asked that I find Hakker/Thomas and get him to talk about what happened, and his side of the story. Some also ask that I be a magician and retrieve information from certain now dead threads and posts. How am I supposed to do that? I did get him on the phone for the 5th Podcast Episode but his lips were shut about the more personal stuff.

So what should the reader take away from all this?

There is no such thing as a free lunch. This thing is going to be damn hard and 99.99% of the time, most people will fail to ever see any height increase. There is a VERY HIGH chance that I will fail in finding anything that will work in the way that most people hope for. There is a very good reason why almost all physicians and surgeons, who are 100X smarter and better educated than most of us think that growing taller is impossible to achieve, especially after we finished our natural growth progress.

If one thinks that they can just be a lurker on those forums and one day by a miracle find the name of the exact compound/chemical/supplement/pill that would solve their height increase desires, then they are probably delusional. Don’t wait for Alkoclar because he will never come back.

I wrote about this fantasy in the beginning in the post “There Is NO Magic Bullet

You can not wait and expect that other people will do all the work, all the research, and think that you can get the rewards and fruit of their labor without giving something of insane value back in return. Join in and help me and the others in doing the research. We need to have hard science to back up what we are doing. That is what I think will be the only way for us to find something real.

Review Of HeightFX From The Old Height Effects Website

Height FX PillsI have been recently looking more towards the old Grow Tall Forum website for clues on what types of research and methods height increase seekers before me were up to. One website or company which were claiming that they had a working product was called Height FX which had the website HeightEffects.com. I typed in the url but nothing showed up. A look through the forums back in 2008-2009 shows that this website was definitely something that was talked about. From checking the WayBack Machine it seems that the website was around from 2008 to 2011. The board members seemed to show some serious interest in it and whoever was the person doing the scientific research on trying to figure out a proposed method was doing real research.  

It seems that through using the WayBack Machine and clicking on a save copy of the website from back in Feb of 2011 I managed to get a copy of the pills/product that was being sold on the website. I managed to do a clipping of the website and pasted the pics below.

Height Effects

Height Effects 2


I looked for a copy of the ingredients and science section of this product and did find an old copy of the information on the page. There seems to be nothing on the Research page but when I clicked on the “view the science behind this” link I am taken to a section is quite scientifically intensive.

I took the liberty to copy and paste all of the information from the old website to this post which is below….
Note: My review of the website and the science of this proposed pill is at the very bottom of this post, which you will have to scroll all the way down to read. This proposed height increase idea is quite advanced.

 

 


HeightFX Biotechnology

Introduction to the HeightFX Technology

The HeightFX longitudinal growth complex is unlike any other height growth product ever developed. Based upon real science to provide real results, HeightFX incorporates some of the most cutting edge science available today. The HeightFX formulation can be broken down into 4 major components detailed below. Each component shown below includes decades of clinical research conducted by a wide variety of institutions from around the world in support of the technologies used. Many of the components used in HeightFX mimic the very same mechanisms used in clinical hormonal treatments for short stature by the medical community. .These mechanisms represent the leading and most effective treatments for short stature currently available.

Proprietary Extraction Techniques

Not all plant extracts are created equal. Many plants contain dozens, if not hundreds, of naturally occuring active compounds called phytonutrients. The extraction technique used determines what fraction of these phytonutrients is captured in the finished extract, and it is these phytonutrients that elicit the potent effects behind HeightFX. We at the Herbal Height company, alongside our manufacturing partners, are continuously developing and refining our own proprietary extraction techniques to capture the optimal phytonutrient fractions of the plants used in the HeightFX formulation. The plant extracts used in HeightFX contain highly specialized, custom tailored, phytonutrient compositions not found replicated in other extracts of the same plants. It is these fine details that define the effects of HeightFX, and set it apart from other extracts currently available on the market today.

Anti-Fusion Inhibiting Complex

One of the primary mechanisms behind the revolutionary HeightFX formulation is its ability to suppress estrogen production within the body by inhibiting activity of the P450 cytochrome families aromatase enzyme in a reversible manner. The aromatase enzyme is responsible for converting a portion of testosterone into estrogen within the male body. This same mechanism has had a major impact in shaping the clinical therapies used in the new millenium for treatment of short stature. Ample clinical studies conducted in recent years, as well as novel cases of aromatase enzyme gene mutation in certain individuals, have shown that the suppression of estrogen in the male body by use of aromatase enzyme inhibitors delays growth plate fusion, thereby extending the length of time the patient can continue to grow taller and significantly increasing their final adult height [1, 2, 3, 4, 5, 6], an outcome in direct defiance of their genetics. Recorded medical cases [7, 8], as well as clinical studies, have shown that estrogen is the major mediator of epiphyseal growth plate fusion, likely through agonist activity at the estrogen receptor alpha [9, 10, 11]

The HeightFX longitudinal growth complex utilizes dual inhibitors [12, 13, 14] of the aromatase enzyme to accomplish significant suppression of endogenous estrogens thereby extending the period of time that the users epiphyseal growth plates can continue to develop new skeletal tissue . However, unlike clinically used aromatase inhibitors (AI) such as the triazole family of reversible inhibitors; Letrozole and Anastrozole, the primary AI used in HeightFX, a proprietary extract of grape seeds, has been shown not only to inhibit existing aromatase enzymes, but also to suppress the expression of the aromatase enzyme gene [5]. Suppression of aromatase enzyme gene expression can result in an overall decrease in the amount of newly forming aromatase enzymes, thereby furthering the effectiveness over time of HeightFX’s anti-fusion inhibiting complex.

HeightFX’s anti-fusion inhibiting complex leads to a delay in growth plate fusion thereby allowing the user to continue to grow taller for a longer period of time than they otherwise could naturally.

Androgen Optimizing Complex

Considered to be the most potent class of clinical hormonal therapy utilized for the acceleration of height growth in growing adolescents, androgen therapy is a cornerstone of the HeightFX longitudinal growth complex. The most well known androgen is the male sex hormone Testosterone. Other androgens used in the clinical treatment of short stature include the synthetic anabolic androgenic steroids Oxandrolone and Fluoxymesterone. The administration of androgens, wether naturally occuring or synthetic, leads to a significant acceleration in the rate of longitudinal height growth with minimal side effects, are well tolerated in the majority of patients, and result in the most significant increases in height growth of any treatments used clinically [15, 16, 17, 18, 19, 20, 21, 22]

HeightFX elicits functional androgenic effects by increasing androgen receptor agonist activity in the epiphyseal growth plates. The first major androgenic mechanism utilized involves the use of sex hormone binding globulin inhibitors to prevent its binding to its receptors and circulating androgens [23, 24, 25, 26]. Sex hormone binding globulin (SHBG) is a glycoprotein found in both sexes that binds with androgens and estrogens circulating through the blood stream and deactivates them. A portion of the testosterone and other androgens in circulation are bound to SHBG and therefore inhibited from eliciting an androgenic effect on tissue [27, 28]. Certain phytonutrients utilized in HeightFX function by binding to existing SHBG and rendering it incapable of deactivating endogenous androgens. The result is an increase in the serum blood levels of active-unbound androgenic hormones able to promote longitudinal growth.

Another major mechanism by which the phytonutrients utilized in HeightFX increase androgen receptor binding activity is by directly increasing production of androgenic hormones, primarily testosterone and its 5-alpha-reductase catalyzed derivative dihydrotestosterone. One way in which HeightFX accomplishes this is by increasing steroidogenesis, the production of testosterone, within the leydig cells of the testicles [29, 30, 31, 32, 33, 34, 35]. The aromatase inhibitors used in the HeightFX formulation also work to increase testosterone levels through endocrine feedback mechanisms and by preventing a portion of produced testosterone from being aromatised into estrogen. Additionally, HeightFX employs the novel phytonutrient Icariin which elicits a testosterone-mimetic effect by directly binding to androgen receptors thereby functioning as a selective androgen receptor modulator (SARM) [36]

The androgen optimizing complex utilized in HeightFX leads to a significant acceleration in the rate of longitudinal height growth.

Somatotropic Signaling Complex

Human Growth Hormone (HGH) and Insulin-like Growth Factor-one (IGF-1) have long been used alone or in combination with androgens clinically to treat growth disorders such as short stature by accelerating longitudinal growth velocity [37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51]. Growth hormone and IGF-1 elicit the majority of their height growth promoting benefits through the modulation of chondrocyte activity, cartilage cells, within epiphyseal growth plate tissue [52, 53, 54, 55, 56, 57, 58]. Additionally, studies suggest that HGH and IGF-1 have direct effects on osteoblasts and osteoclasts and therefore play a major role in not just the growth of growth plate cartilage, but also the ossification of that cartilage to bone as well as the remodeling of existing skeletal structures [59, 60, 61]

HeightFX has a vast spectrum of somatotropic effects within the growth plate, effects that promote a far broader array of synergistic benefits than that experienced from increasing HGH and IGF-1 levels alone. The cornerstone of HeightFX’s somatotropic signaling complex is its direct effects regulating the release of HGH and IGF-1 through a cutting edge complex of secretagogues and sensitizing agents. HeightFX’s androgen optimizing effects are able to blunt the negative feedback mechanisms controlling the pulsatile release of growth hormone [62], thereby allowing greater release of growth hormone from the pituitary gland in response to HGH secretagogues utilized in the HeightFX formulation. Research studies also show that androgens increase IGF-1 receptor abundance and gene expression in skeletal chondrocyte tissue [63, 64], an effect that allows a stronger IGF-1 growth response to occur. Further evidence suggests that increased androgen activity, such as that promoted by HeightFX, modulates HGH and IGF-1 release responsiveness at different points in the somatotropic endocrine cascade [65, 66, 67, 68, 69]

The primary mechanism making up the somatotropic signaling complex utilized in HeightFX involves the combination of an acetylcholinesterase inhibitor [70, 71, 72] alongside a potent growth hormone secretagogue [73, 74, 75, 76, 77, 78, 79, 80]. Inhibition of acetylcholinesterase potentiates growth hormone release response to the primary secretagogue used in HeightFX [81], a result of increased acetylcholine levels resulting in the inhibition of somatostatin [82, 83, 84, 85, 86, 87]. Furthermore, the inhibition of somatostatin also prolongs the duration of growth hormone secretion pulses [88]

The end result of HeightFX’s somatotropic signaling complex is a rapid acceleration in the rate of chondrogenesis by stimulating increased chondrocyte proliferation and hypertrophy.

Intracrine Augmenting Complex

The intracrine systems of the epiphyseal growth plates are extremely complex systems of autocrine origin hormones, cytokines, growth factors, binding proteins, morphogens, and other highly specialized cellular signaling ligands, many of which are specific to skeletal tissue only. The majority of HeightFX’s growth promoting effects focus on accelerating chondrogenesis, the creation of new cartilage within the epiphyseal growth plate. One major element of HeightFX’s intracrine augmenting complex however, focuses on enhancing osteogenesis, the calcification of newly formed growth plate cartilage into bone tissue. Osteogenesis is the result of osteoblast cell activity depositing calcium into the cartilage matrix formed by chondrocytes, and the HeightFX formula aims to accelerate osteogenesis in harmony with chondrogenesis.

HeightFX promotes increased osteogenesis by stimulating the differentiation and proliferation of osteoblasts via the increased production and mRNA synthesis of bone morphogenetic protein-2 levels (BMP-2) in osteoblasts, as well as by increasing osteoblast alkaline phosphatase (ALP) activity [89, 90, 91]. HeightFX can also accelerate the proliferation and ALP excretion capabilities of bone marrow stromal cells (BMSCs), resulting in greatly improved osteogenesis activity of BMSCs [92].

The overall result of the intracrine augmenting complex used in HeightFX is a significant increase in osteoblast activity leading to an acceleration in the formation of new skeletal tissue via endochondral ossification.

Biotechnology Summary

HeightFX accomplishes its incredible height growth promoting effects through mechanisms that mimic those employed in the most effective and widely used clinical therapies for short stature. It is through this wide spectrum of synergistic pharmacologic effects that makes HeightFX unlike anyother height growth product to ever exist on the market. The inhibition of the aromatase enzyme and its gene expression allows a dramatic prolonging of the longitudinal growth phase in growing adolescents, while the increased androgenic, somatotropic, and intracrine effects simultaneously accelerate the rate of longitudinal skeletal growth to supraphysiological levels otherwise unachievable. This unique complex of growth promoting mechanisms makes HeightFX the first and only product ever made available to the height growth community that uses real science supported by real research to promote real height growth. You no longer have to accept the height your genetics have dictated for you, biotechnologies as effective if not more effective than those used in clinical treatments are now available at your fingertips thanks to the HeightFX longitudinal growth complex brought to you by the Herbal Height company.

The Future of HeightFX

The Herbal Height company will continue to develop, refine, and improve the HeightFX longitudinal growth complex for years to come. Not only do we have many plans for future generations of the HeightFX formula, some of which are currently in development stages, but we are also developing additional products and informational resources to be used in conjunction with the HeightFX longitudinal growth complex, or on their own.

Clinical Study References

[1] Zhou P, Shah B, Prasad K, David R. (2005) Letrozole significantly improves growth potential in a pubertal boy with growth hormone deficiency.

[2] Hero M, Norjavaara E, Dunkel L. (2005) Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial.

[3] Wickman S, Sipilä I, Ankarberg-Lindgren C, Norjavaara E, Dunkel L. (2001) A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled trial.

[4] Faglia G, Arosio M, Porretti S. (2000) Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up?

[5] Dunkel L, Wickman S. (2003) Novel treatment of short stature with aromatase inhibitors.

[6] Mauras N, Gonzalez de Pijem L, Hsiang HY, Desrosiers P, Rapaport R, Schwartz ID, Klein KO, Singh RJ, Miyamoto A, Bishop K. (2008) Anastrozole Increases Predicted Adult Height of Short Adolescent Males Treated with Growth Hormone: A Randomized, Placebo-Controlled, Multicenter Trial for One to Three Years.

[7] Eric P. Smith, Jeff Boyd, Graeme R. Frank, Hiroyuki Takahashi, Robert M. Cohen, Bonny Specker, Timothy C. Williams, Dennis B. Lubahn, and Kenneth S. Korach. (1994) Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man

[8] MacGillivray MH, Morishima A, Conte F, Grumbach M, Smith EP. (1998) Pediatric endocrinology update: an overview. The essential roles of estrogens in pubertal growth, epiphyseal fusion and bone turnover: lessons from mutations in the genes for aromatase and the estrogen receptor.

[9] Weise M, De-Levi S, Barnes KM, Gafni RI, Abad V, Baron J. (2001) Effects of estrogen on growth plate senescence and epiphyseal fusion.

[10] Juul A. (2001) The effects of oestrogens on linear bone growth.

[11] Nilsson O, Falk J, Ritzen EM, Baron J, Savendahl L. (2003) Raloxifene acts as an estrogen agonist on the rabbit growth plate

[12] Elizabeth T. Eng, JingJing Ye, Dudley Williams, Sheryl Phung, Roger E. Moore, Mary K. Young, Ugis Gruntmanis, Glenn Braunstein, Shiuan Chen. (2003) Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds.

[13] Kijima I, Phung S, Hur G, Kwok SL, Chen S. (2006) Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression.

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A Personal Assessment of the Science

It is quite clear that the website, which is only 5 pages big from what I can tell is quite accurate on many of the big points. The main ways that these groups of people/researchers are trying to help kids who are still growing is to promote 4 process that are all controlling somatic growth, which they have called

  1. Anti-Fusion Complex
  2. Androgen Optimizing
  3. Somatotropic Signaling
  4. Intracrine Augmenting

Aftre spending a good 30 minutes reading over the notes, I am going to write a very simple summary of what each process is supposed to do.

For the anti-fusion complex, it seems that there is a part of this pill formulation that inhibits the formation and function of estrogens to delay the closure of the plates. The exact inhibition is on something known as the P450 cytochrome family of aromatase enzyme. The exact compound that is supposed to do the inhibiting is “a proprietary extract of grape seeds” which is said to also be able “to suppress the expression of the aromatase enzyme gene”.

For the androgen optimizing, here is another part that causes more testosterone to go through the body as well as increase the amount of testosterone receptors and testosterone receptor sensitivity. There is many studies that support the theory that man who have more testosterone going through their body are on average slightly taller and bigger than males with less testosterone going through their body. Some synthetic anabolic androgenic steroids like Oxandrolone and Fluoxymesterone have been used multiple times to increase longitudinal growth. The phytonutrient Icariin is used and there is another part of the formulation that is supposed to inhibit globulin.

For the somatotropic signaling, supposedly the formula has another part (a combination) that can cause more IGF-1 and GH to go through the system and make them more effective, without the usual negative feedback loop which would limit the rate of the amount of GH that can be release by the pituitary. This is done from a combination of an acetylcholinesterase inhibitor with growth hormone secretagogues in the pill. It turns out that if you increase the level of acetylcholine in the brain, the level of somatostatin is decreased. By removing the negative feedback loop, the GH secretagogues would be more effective on the pituitary since the somatostatin was inhibited.

For the intracrine augmenting, the idea is that bone deposition below the growth plate will be increased through increasing osteoblast formation and increased alkaline phosphatase. Apparently there is some element in this pill that can cause the mRNA of BMP-2 to be increased.

Overall Assessment

The science is right, and the information is better presented and written than anything that I can do at this time. Whoever wrote the page has a better grasp on how to make children with open growth plates grow then probably even me or Tyler, however the same problem occurs again. This formulation has a good chance on working on children if it does have the many compounds that it claims it does.

Tyler wrote a post reviewing this website entitled Height FX Review from back in April of 2010.

It seems that in the post, he notes that the website is quite impressive in the depth of their knowledge on the subject. The thing Tyler wanted back then was that this company who is selling a product should go through with a clinical trial to make sure that any results that they did see was not due only to the placebo effect.

However the critical part is from HeightQuest.com which found the list of ingredients inside, which are…

  • L-Dopa
  • Grape Seed Extract
  • Urtica Dioica Extract
  • Huperzia Serrata Extract
  • Cordyceps Sinesis Extract
  • Eurycoma Longifolia Extract
  • Epimedium Brevicornum Extract

It is a little hard for me to believe that this 7 group of extracts would be able to do 4 process, increase osteogenic deposition in the growth plate, slow down growth plate senescence through inhibition of aromatization, increase the level and sensitivity to testosterone in the body, and get more GH released by the pituitary gland.

I really hope that this 7 ingredients are not the only ingredients because the people stated that there was supposed to be Icaritin in the formulation but I don’t see it.

Tyler stated that this guy or group has definitely done their research and that at least for the their claim that “high levels of testosterone inhibit negative feedback of growth hormone” they are right. So for the androgen optimizing, the increase of male androgen/testosterone is correct.

Tyler stated that while the science on why this would work is well explained, the company who is selling the pill should bring their pill to do clinical trials to prove that it can really do what it claims. The idea is again is the question “How can we be sure that if we do see increased height growth after taking this pill of multiple extracts formulated together, that increase is the result of the pill and not just due to natural height increase?

Tyler asked for at least one clinical study where there will be a control group and an experimental group, a double blind study, where one group takes a sugar pill and the other group takes the actual pill, and see how the growth rates look between the two group after a certain amount of time. He even states that for this situation, we might not even need a placebo, just a control group where people don’t take anything. However there might be some reason to think that maybe the belief from taking a pill that one might increase their growth rate might actually cause a slight increase in growth rate.

Overall, if the clinical study does go through, the difference in the increased height  (growth rate) between the two group must be large enough to say that this formulation of 7 extracts have any function at all. I don’t know much about the other extracts except that for at least the grape fruit extract, it might have some antiviral, antibacterial properties which means that it mean less oxidative stress on the body meaning senescence is slowed down, allowing for the growth plates to last just slightly longer.

The company has just one sentence written which said that might be a very small possibility this formulation might work for people with closed plates, and that they are looking into it. The main claim is that this formulation would work on children with open plates. So at least this website is not making any insane claims that it would work on people with fused plates.

However the fact that the website was taken down and no pill/product is sold anymore makes me and other height increase seekers wonder just whether it was real or not. The fact that the website looked just like any other Internet Marketing Scam for Height Increase selling a useless grow taller pill makes everyone including me and other serious researchers uneasy with great doubt.

A List Of Natural Aromatase Inhibitors

This link I found seems to validate some ideas previous height increase researchers had about possible supplements that can be orally taken to lead to increased growth.

The website or source I found this list from is Healing Pastures back in 2009. The entire list and details is taken from that website posting. However I would like to give an analysis of the list at the end of this post to see whether we can find any useful information that can help us in our own research.


Quercetin – Cabbage, kale, brussel sprouts, onions and garlic, citrus fruits, apples, parsley, tea, and red wine are the primary dietary sources of quercetin. Olives and olive oil, grapes, black currants, cranberries, dark cherries, and dark berries such as blueberries, blackberries, bilberries, lingonberries and red raspberries are also high in flavonoids, including quercetin. Quercetin seems to work better when used in conjunction with bromelain, a digestive enzyme found in pineapples.

Chrysin 
– This is a flavonoid from the passion flower plant, bee propolis, bee pollen and raw honey. Chrysin has poor bioavailability so it is normally taken as a supplement along with piperine (from black pepper) which greatly enhances its bioavailability.

Naringenin  – This is found in all citrus fruits, like orange, tangerine, lemon and lime. Avoid obtaining it from grapefruit or grapefruit juice, which has an inhibitory effect on the human cytochrome P450 isofrom, another enzyme in the same complex as the aromatase enzyme. This enzyme is involved in breaking down and metabolizing sex hormones and preventing their excess accumulation in the body, so inhibiting it will allow estrogen levels to rise.

Apigenin
– Dietary sources include celery, parsley, artichokes, basil, chamomile, thyme, peppermint, gingo biloba, and other herbs like horsetail herb, lemon balm herb, perilla herb, vervain herb, and yarrow. The highest concentrations of apigenin seem to be in chamomile and thyme.

Genistein  – This is an isoflavone found in herbs like red clover (the herb of Hippocrates), parsley, sage, green vegetables, fruits and particularly pulses and legumes like chick peas and beans, and soy. Soy and soy foods contain high amounts of plant estrogens or phytoestrogens. These estrogens are very weak and have almost no harmful effects. They compete with the estrogen receptor sites in the body, and prohibit the more potent and harmful estrogen. Phytoestrogens are only 1/500th as potent as estradiol, the most dangerous form of estrogen. The body senses the estrogen level to be high and stimulates the P450 system in the liver to metabolize the estrogen. This helps keep estrogen levels where they should be. There is some controversy about whether soy is protective against breast cancer or promotes it. Much depends on variables like genes. Asians have a long history of soy consumption and their bodies process it far more efficiently than Westerners.

Diadzein – Another isoflavone found in soy products. Genistein accounts for approximately 50% of total soy isoflavones, whereas daidzein accounts for about 40%.

Oleuropein 
– Oleuropein gives olive oil its distinctive flavor, It is found in abundance in the leaves of the olive tree.

Resveratrol  – Good sources are the skin and seeds of red grapes, grape seed extract, and black and red berries. Muscadine grapes, often used to make red wine, have the highest content. Although supplements of resveratrol are popular and widely available, getting resveratrol from red wine allows you to get the entire grape polyphenol group of nutrients, a group that has been shown to work much better synergistically. Breast tumor growth and metastasis to bone and liver have been shown to be better inhibited by the complete grape polyphenol complex.

Linoleic Acid  – An essential fatty acid from the Omega-6 family, linoleic acid can be found in common mushrooms like button mushrooms, shitake, portabello and crimin, as well as vegetables, fruits, nuts, grains and seeds. Good sources are oils made from safflower, sunflower, corn, soya, evening primrose, pumpkin, olives and wheat germ. In a study conducted by Dr. Shiuan Chen of the Beckman Research Institute of the City of Hope in Duarte, California, it was found that in laboratory and animal experiments, mushroom extracts reduced the proliferation of breast cancer cells. This study also surmised that it is the linoleic acid that may be responsible for the anti-cancer effects.

Interestingly, the study also found that white button mushrooms suppressed production of the enzyme 5-alpha reductase. This enzyme plays a big role in development of prostate cancer.

Progesterone  – A popular source is wild yam extract cream for topical application, such as Neways’ “Endau” progesterone cream. A study (Formby and Wiley, Journal Nat. Cancer Inst. June 7997) shows that natural progesterone actually inhibits growth and induces cell death in breast cancer cells by affecting p53 and Bcl-2 gene expression.

This followed work by Chang, Lee et al (Fertility and Sterility vol 63 7995) that showed that whilst oestradiol (the most potent oestrogen hormone) increases the number of cycling epitbelial cells, natural progesterone actually decreases them. The study further states that natural progesterone secretion suppresses oestradiol receptors in both the endometrium and breast tissue, and has an anti-oestrogen effect (just as, for example, the latest aromatase inhibitors aim to do), but that very high concentrations of synthetic progestins can stimulate human breast cancer cells.

Zinc – The best sources are wheat germ, oysters and liver, Less zinc-rich sources include meat, sesame, sunflower and pumpkin seeds, nuts like pecans and brazils, spinach, mushrooms etc.

Those searching for an aromatase-inhibiting diet may wish to take a closer look at the Mediterranean diet, Fresh fruits, vegetables, olive oil and red wine are components of this diet, the one diet that has consistently correlated with lower death rates from all causes. Flavonoids from each of these foods inhibit aromatase activity to reduce incidence of breast cancer.

A final thought: the aromatase enzyme resides in fat cells. It is no surprise that being overweight and obese is linked with breast and other hormone-sensitive cancers. Fewer fat cells in the body means that less unbalanced estrogen is produced. High levels of insulin, a big factor in weight gain and fat mass accumulation, promote production of the aromatase enzyme. Avoiding processed foods and foods with chemicals helps keep insulin levels under control, in turn resulting in lower levels of aromatase and as a consequence, lower levels of unbalanced estrogen in the body

Analysis

This list is interesting because of the first two types of compounds listed, Quercetin and Chrysin. At one point in the research, I had listed both of these compounds as possible things a person can ingest to grow taller in the Supplements Section of the website. I even at one point said that Quercetin might help people with closed plates grow taller.

Two posts were written about the height increase potential of the two compounds…

  1. Can Quercetin Really Help People Grow Taller And Increase Their Height After Reaching Adulthood?
  2. Increase Height And Grow Taller Using Chrysin

After doing more research, I had to state that it seems that I was previously wrong about the efficacy of these compounds. The whole idea with chrysin was that it was an aromatase inhibitor. With Quercetin, I forgot why it was a viable idea.

Two of the compounds were isoflavones which can be found in soy products. The section that I will talk about is on the phytoestrogens, which is something which I have been looking into recently…

“Phytoestrogens are only 1/500th as potent as estradiol, the most dangerous form of estrogen. The body senses the estrogen level to be high and stimulates the P450 system in the liver to metabolize the estrogen. This helps keep estrogen levels where they should be.”

There is enough evidence that estradiol is harmful towards growth in the literature but this section seems to imply that phytoestrogens may be actually good for growth, since they prevent the much stronger estrogens from binding to estrogen receptors. There is even ways for the human body to regulate estrogen levels using the liver to metabolize estrogen.

The last compound which is something which I am remotely curious about is the compound progesterone. I wrote about the connection between progesterone and growth in the old post “Analysis On The Possible Cause For Height Increase During Pregnancy”

The Link Between Childhood Obesity And Early Puberty Resulting In Stunted Growth

I was doing research for adipose derived stem cells when I read something from the Wikipedia article on Adipose Tissue which made me see that there might indeed be a connection between the issue of childhood obesity, an earlier onset of puberty, and possible effects of stunted growth leading to shorter final height.

It seems that adipose tissue, which is what our fat is greatest peripheral source of aromatase in both males and females.

Since we know that having a lot of aromatase means more conversion into estrogen, it would means that there are going to be higher levels of estrogen, which is something which we have always said for the developing child with open growth plates is a bad thing.

I remember reading years ago about the fact that “fatter” than average children would start puberty earlier in age than children who are not as overweight. The journalist who wrote the article would talk about how the over excess of food and eating behavior caused an increase in the amount fo hormones going through the body.

This idea seems to have some validation when we realize that adipose tissue is supposed to be the biggest source of aromatase in the bodies of females and males.

Aromatase would convert any type of hormones that can be converted into estrogen or estrogen like compounds which would cause the initial spark in physical development starting puberty. As we know from our research, an earlier onset of puberty usually means an earliest onset of complete endochondral ossification closure. It doesn’t always have to mean that earlier puberty means earlier growth plate closure, but there is a positive correlation.

This would then imply then that people who have more adipose tissue probably have a higher level of aromatase in their blood stream than a person of similar age with different tissue composition.

We know that females are supposed to have higher fat composition levels than males on average. This is supposed to be because the female reproductive organs and hormones require more fat than the male reproductive organs and hormones. If the fat percentage in the female body falls below a certain amount, their fertility rate would actually drop. This is often seen when female bodybuilders start to take supplements to make their body fat percentage to drop. They develop masculine and male physiques and traits, increased muscularity, muscle leanness, etc. In addition, their fertility also sees strange changes.

It could be that from the higher body percentage fat in females, that is one of the main reasons why they go through puberty as a an earlier age than men. This also leads to females being on average shorter than men.

So the correlation goes…

Overweight child or Obese Child —> Increased levels of fat to overall body composition —> The fat is composed of adipose tissue —> The adipose tissue is the main peripheral source of aromatase —> The increased aromatase causes more estrogen to be made from aromatization —-> The extra estrogen causes puberty to start earlier —> There is less years for natural growth —-> Earlier onset of bone maturity leading to a shorter final adult height

The correlation may be weak, but I would guess that the correlation is still positive.

From another source, the USMLE Forum, a post did ask about which places aromatase seem to come from, besides just the adipose tissue. 

Other locations where the aromatase seems to originate are….

  1. Granulosa Cell –
  2. Sertoli Cells –
  3. Leydig Cell – 

For the sertoli cell someone writes…

“…aromatase is present in sertoli cells ….here it converts testosterone to estradiol…one third of estradiol in men comes through this, remainder comes by aromatase in adipose tissue..
leydig cells make testosterone that is made from cholesterol. this testosterone is secreted and taken up by sertoli cells.”

For the leydig cell something states…

“…i just wanted to say that leydig cells are also capable of producing aromatase in klienfelters synd….but goljan book says hyperplasia of leydig cells and incresed aromatase there caused by increased FSH….so increase conversion of testosterone to estrogen…reason for increased estrogen in kleinfelters”

The discussion seems to reach a really interesting ending by the post by someone named JonBC

“Testicular production of estrogen is poorly understood. The Sertoli cells manufacture estrogens during fetal and neonatal life. However, beginning at puberty and continuing through adulthood the site of estrogen synthesis shifts to the Leydig cell. The Leydig cells express high mRNA and protein levels of the CYP19 (aromatase) enzyme. The mechanisms regulating the site of estrogen synthesis, and the shift of estrogen production between Sertoli and Leydig cells, are completely unknown.”

Analysis:

This may be a good breakthrough for the research because this is the first place where I finally realize that apparently the location of where estrogen is produced actually changes from when the human is in develop in the uterus and when the person is going through the stages of puberty.

This might explain why estrogen levels cause the onset of puberty. Let’s look at what the person says…

  • Sertoli Cells – manufacture estrogen during fetal and neonatal life.
  • Leydig Cell – site of estrogen synthesis during puberty and throughout adulthood.

It seems that the leydig cells express high mRNA and protein levels of the aromatase enzyme, which goes by the name CYP19.

So for the height increase seeker, does that mean that the spark in every person’s development, which causes them to go from Sertoli Cell to Leydig Cell production of estrogen is what causes this entire thing???

The person does state that the mechanism of how estrogen production is shifted from Sertoli Cell to Leydig Cell is not known at this time. This may be the very key that we should be looking for. This may be the key to everything. If we can somehow break the process of the shift, by preventing the Leydig Cells from ever given the chance to produce estrogens, since they are the cells that really have the high mRNA and protein production of the aromatase, then maybe we can completely hold off puberty until we want to.

This would be the one step in the entire growth process where we can manipulate and modulate slightly to control our growth rate and how long we would wish to grow. Remember, if we can control at which age we wish to start puberty, we can control the amount of time we have left to grow, which means that we can continue to grow as much as we want, at least theoretically.