Update #5 – Having Legal Problems While Trying To Get Help – August 1st, 2013

The month of July was very productive for me because I managed to get into a groove in terms of being very consistent in the amount of research, and writing for this website. This website is getting more and more influential each month I think as the ways at which it can reach people has increased.

Things that happened in July…

Big Thing #1

The month of July has also been very difficult in terms of Legal and Technical Issue for the website. The people who represent a certain company who sell a product which I personally stated is ineffective had written a Cease & Desist Letter which I call a DMCA to my hosting company to try to take down the post I had written about this product. I contacted my hosting company and they gave me bad legal advice on what to do and I followed through on their advice by issuing a counter-DMCA which turned out to be wrong since a person can not do counter-DMCAs due to a complaint on Trademarks, but only for Copyright. This website was threatened multiple times and was taken down for over a day before I had to negotiate the terms of my website with my hosting company to bring it back. The problem with the website is currently resolve.

The entire thing was a big wake up call on just what can happen when one becomes too big and starts to be a threat to other corporations in the same niche. I plan to make sure that this type of situation does not happen again by being more protective on the information on the website.

Big Thing #2

After exchanging emails with Tyler at a snails pace over the last 3 months on getting him to join the website, I managed to create a profile for him as one of the administrators of this website with the title of Editor. He has written two posts on what his progress has been and how his proposed Lateral Synovial Joint Loading has been going for other experimenters.

I was planning on actually doing another Podcast episode where we two get back together to talk about the research we have recently been up to. However, I am currently having technical difficulties over getting the Voice Recording Software for Skype to work. I don’t know what is wrong, but it just doesn’t seem to be able to turn on or record properly anymore. So this means that even though I want to, I can’t record any phone calls or do any interviews with people over Skype for the podcast currently.

Big Thing #3

I plan on shifting my focus away from the website temporarily for around 1-2 months as I divert all of my effort, time, and energy to working on another business project I have started. In addition, some personal issue with my family has come up and I need more time to resolve some issues while I travel outside the country (again).

There will be one last big post I will put up this month, which is “A Complete Guide To Limb Lengthening Surgery“ which will be the best, most informative guide I can currently create from reading multiple threads on the Make Me Taller boards. (I hope that people can comment on the post so that I can edit, add, and revise it to make it better and more informative for future readers. It will be put in as its own page/category on the website, under the Supplement Guide tab in the header).

After that, I am hoping that Tyler can take over the load in research and writing so that I can focus elsewhere. He is a great contribution to the website and to the cause and so far, his insight, feedback, and expertise has been very useful in helping me and other researchers see what is missing in our own understanding of what needs to work.

Epic Posts

This month lead to me really sitting down and studying on the research and really analyzing just what is causing the biggest amount of problems and where we are stuck. I managed to write a post that is almost 6,500 words to explain just why the research is so difficult entitled “Why Growing Taller With Closed Growth Plates Is So Difficult To Figure Out And Impossible To Almost All People“. 

The connection between pregnancy and unusual cases where women gain height is brought back with at least 4 new cases where women noticed that they were getting taller form being pregnant. I wrote about it in the post “Another Case Of Pregnancy Causing Woman To Grow Taller And Increase In Height“

It was found that there have been some new compounds which we discovered which has very osteogenic uses like pleiotrophin, as well as Vitamin K2 (menaquinone type 4) combined with Vitamin D3 which has resulted in some unique cases of adult height increase.

Changes In Height and Weight

So the obvious question is “Has my own height changed in the last month?” – It has been very hard to tell since my hair has been growing out like everyone else’s hair. With the way that my hair naturally falls, it sometimes looks like I might be 1-2 inches taller than I really am. I tried to measure every morning and night but the results have not been good. I did cut my hair very recently and looked at the mirror and seem to have stayed the same as before.

• Height when getting out of bed in the morning: 6′ 0″ (exactly or 1.828 meters tall)
• Height at night when going to bed:  a little less than 5′ 11.25″ (or around 1.81 meters tall) 

The 3 mm of increase from a few months ago is still noticeable and stayed around. I have a very accurate measurement tape.

So have I been doing to increase flexibility and height this month? 

I have been focusing on trying to do two exercises, 1) the supine flexion for stretching out the lower back and 2) doing aquatic vertical suspensions where I float on the surface of the water with weights hanging  out on my feet

I wrote about both of these techniques in the the following posts…

• Restore Spinal Disk Height And Increase Height Temporarily Through Land Based Supine Flexion
• Restore Spinal Disk Height Through Aquatic Vertical Suspension (Breakthrough!)

I have been trying to clamp on my knees doing LSJL for a few days but did not keep up the routine. I have been trying to test which location and at what angle of loading on the knees would be the most effective.

As for weight

My weight is another story, which has gotten better from last month. I changed my diet dramatically by reducing my rice/noodle/grain intake by half. Any time I go out to eat, I look for meat & vegetable intensive foods and eat only half of the grain. The protein-sugar theory seems to be true.

Changes in Exercises and Training

Starting Swimming

Recently I found out that my weight was around 97 kgs or 213 lbs and that meant that my weight did decrease from the 219 lb it was last month when I took the trip to Osaka. I was at the Olympic Pool at the Sports Complex in Gangnam, Seoul which was where the Olympics were held in 1988. Olympic sized pools are 50 meters long (164 feet) while most pool in the US, which uses american units, are 25 yards long (75 feet long). The pool at the Sports Complex is really great since the cost of one swim is only around 5000 korean won but the amount of time is very little, only 45-50 minutes before the lifeguard blow the whistle and kick everyone out. I usually only manage to get 15-16 laps in before it is over.

Getting back to Pushups & Situps

My goal to reach at the end of this year is to be able to do 100 pushups, and 200 situps consistently (everyday). So far, since the days are soooo HOT where I live, and the exercise equipment is outside in the sun, I have been very hesitant to get out in the sun, risk melanoma, just to get skinnier.

Using a Back Massager 

Some places do sell a hand held back massager (I got two , one for 30,000 korean won and other for 60,000 korean won) which really works well to release the tension in the back muscles. This allows for the intervertebral discs to rehydrate and increase in thickness. I currently have something known as the Swan Softouch Handheld Percussion Massager , which is very good for kneading muscles that are very tight or cramped. It worked miracles for my tight lower back muscles when I got it back in 2008 and it still does a reasonably good job in making the lower back decrease in tension, reducing the likelihood of injuries.

After we learned that the old somatomedin hypothesis (that IGF-1 was the mediator between the GH and growth plate chondrocytes) was not completely correct and needed to be altered to account for the ability of GH to affect the chondrocytes directly, as well as the fact that besides the liver, IGF-1 seems to be produced in all types of organs and tissue, I wanted to focus on just how exactly IGF-1 helps the GH in longitudinal growth. It was shown that for lab rats that were genetically manipulated to be IGF-1 null, it was shown that the number of chondrocytes in the resting zone and the proliferation rate of the chondrocytes did not change that much.

This study I found seems to suggest that IGF-1 augments the effects of GH by acting only on the chondrocytes that are differentiating into the hypertrophy stage.

Study #1: Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy – JIE WANG, JIAN ZHOU and CAROLYN A. BONDY

Abstract

Longitudinal bone growth, and hence stature, are functions of growth plate chondrocyte proliferation and hypertrophy. Insulin-like growth factor 1 (Igf1) is reputed to augment longitudinal bone growth by stimulating growth plate chondrocyte proliferation. In this study, however, we demonstrate that chondrocyte numbers and proliferation are normal in Igf1 null mice despite a 35% reduction in the rate of long bone growth. Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wild-type at all levels of the hypertrophic zone. The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth. The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3β (GSK3) is hypo-phosphorylated in Igf1 null chondrocytes. Glycogen levels were significantly decreased and ribosomal RNA levels were reduced by almost 75% in Igf1 null chondrocytes. These data suggest that Igf1 promotes longitudinal bone growth by ‘insulin-like’ anabolic actions which augment chondrocyte hypertrophy.

—Wang, J., Zhou, J., Bondy, C. A. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy.

Analysis

This study is one of the most interesting studies I have found in a long time. This study shows that when it comes to modulation of the growth plate chondrocytes, the IGF-1 has an affect mainly on the process of differentiating into the hypertrophy stage. The most interesting is that the number of chondrocytes and the rate of proliferation does not seem to change for lab rodents which were born with the IGF1 gene deactivated.

This means that the IGF-1 has effects only on hypertrophy.

The effects of the having a deficient IGF-1 gene are the following…

1. a 35% reduction in the rate of long bone growth
2. have lower levels and rates of collagen type X and alkaline phosphatase release by the hypertrophic chondrocytes
3. the hypertrophic chondrocytes are reduced in linear dimension by 30%
4. expression of GLUT4 is significantly decreased
5. GSK3 is hypo-phosphorylated
6. Glycogen levels were significantly decreased
7. ribosomal RNA levels were reduced by almost 75%

If we look at the last 4 of the effects, they are all related to insulin like effects on the tissues. IGF-1 is very similar to Insulin in structure and function. This shows that its function for the growth plates is also from insulin similar anabolic actions which combines with the GH to get chondrocyte hypertrophy.

We see that at least for lab rats that while the bone length is not completely stunted, there is still a very substantial reduction, by as much as 35%. This could potentially turn a guy from 6 feet to 5 feet tall. The releasing of the specific proteins that are indicators of hypertrophic chondrocytes do occur but dramatically decreased.

This study reveals that it might be possible to modulate the growth rate of children through IGF-1 increase, while making sure that it does not reach levels that are too high resulting in disruptions to other types of metabolisms.

This was a post that I found from a new blog I discovered which seems to write about the short stature condition known as Achondroplasia which is caused usually by a mutation on the FGFR3 gene. It seems that there is a company Biomarin, a pharmaceutical company working in therapies for rare and genetic conditions, which stated that they were coming out with a drug that can treat the mutation of the FGFR3 that has been responsible for Achondroplasia. It is supposed to be the first pharmacological therapy out there for Achondroplasia treatment.

The article is taken from the blog http://tratando-acondroplasia.blogspot.com/ entitled “CNP, the first potential pharmacological therapy for achondroplasia” (the blog is written in Portuguese so using the browser Chrome would be better to instantly translate what is on the pages into English)

Under great expectations, parents and relatives of children bearing the fibroblast growth factor receptor type 3 (FGFR3) mutation, the cause of achondroplasia, have been following the news about the development of the first real potential drug therapy to treat this condition. In the last quarter of 2010, Biomarin, a pharmaceutical company working in therapies for rare and genetic conditions, announced it was planning to start the clinical research with a compound called BMN-111. BMN-111 was described as a C-type Natriuretic Peptide (CNP) analogue. An analogue is a compound (or molecule) which has a very similar structure compared to the original one, normally keeping the same properties or with enhancements to a given characteristic of that compound.

During 2011, new updates have been released and, in the last International Congress of Human Genetics held in Montreal, a poster describing the results of the BMN-111 tests made in a mouse model of achondroplasia was presented, showing impressive results in terms of the ability of this molecule in restoring the bone growth of those animals: F. Lorget et al. BMN 111, a CNP analogue, promotes skeletal growth and rescues dwarfism in two transgenic mouse models of Fgfr3-related chondrodysplasia.

December 2011, Biomarin has released new information about the pre-clinical development of BMN-111, presenting results of tests made not only in mice but also in non-human primates, a requisition for any candidate drug to be accepted as an investigational new drug (IND) by regulatory bodies such as the Food and Drug Administration (FDA).

More recently, Biomarin has also announced that it was starting the first clinical trial, a Phase 1 study, to learn how the drug acts in the human body.

Ever since the a commenter who calls himself Raja has shown me the study of the link between FGFR3 and Achondroplasia and I realized that it might be one of the easier, most promising ways that real companies have been doing to try to help at least children increase in height, I realized that I should take a more serious look at what this researcher had to say. So I asked him/her about the research they have been doing. Here is our exchange of emails.

Me —> D Inventor

Your response to one of my posts have been very interesting. I plan to write a detailed post about the study and see where it will take the research.

——————-

Children: To the best of our knowledge there is currently only one company worldwide, that researches an innovative height increase therapy: ProChon Biotech (http://www.prochon.com), established in  Israel in 1997. ProChon is developing a monoclonal antibody for the treatment of achondroplasia. This antibody approach targets specifially the FGFR3-gene and hasn´t reached the stage of human clinical trials yet. If it is successful, it will only work for children with achondroplasia. – http://www.makemetaller.org/index.php/topic,578.0.html

——————-

D Inventor —> Me

I’ll give you a summary of what I’m working on.

Basically, our bodies are designed to only grow to a certain extent – this is really why our height is determined by our genes. Growing taller than our “predetermined” height is called skeletal overgrowth. When I started researching, I found an article on CNP in which scientists increased substantially the plasma concentration of CNP, which resulted in skeletal overgrowth of the mice models (1, 2). You can really just google this for more info, but I’ve provided the links at the end of this message. I read another article which found a family with genetic mutation that caused an overexpression of the NPPC gene, which controls the expression and production of CNP (3). Basically, everyone in this family was really tall.

Another interesting article was on FGFR3 knockout, which lead to skeletal overgrowth in mice models (4). CNP works as an antagonist to FGFR3, which is evident as CNP is able to rescue achondroplasia models with constitutive FGFR3 activation.

Here’s how CNP works (just some technical information, but this is important for when we get into the pharmaceuticals specifications):

– CNP activates its receptor GC-B, which releases cGKII (5)
– cGKII works by inhibiting the conversion of Ras into Raf (look up FGFR3 phosphorylation)
– This acts as a inhibitor to the activation of the MAPK cascade. This is important to endochondral ossification as it inhibits ERK1/2 phosphorylation.

Essentially, one way that CNP exerts its bone promoting effects is through the inhibition of ERK1/2 activation (one of two pathways that are activated with FGFR3). You can really just search up “ERK1/2 inhibition” on google and see that other scientists have achieved skeletal overgrowth in mice models in which they inhibited ERK1/2.

OKAY, enough with background info. If I’m rabbling, I apologize. It’s just that there really is a lot of information on this.

Back to FGFR3 – its inhibition leads to skeletal overgrowth and it WILL increase a person’s final height. Many people with mutations that diminish FGFR3 expression have really tall stature.

So, for us, people who want to be taller, the easiest way for us to get taller is to inhibit FGFR3. The article I posted on your website discusses how there was an increase in the height of the growth plate in a person whose growth plate was about to close (or was in fact closed). This is interesting because in the article, the individual’s growth plate was reduced to a growth scar. This usually happens when the growth plate is just about to close. However, if used in conjuction with LSLJ (if this method really does cause microfractures), then it MIGHT be effective for people with closed growth plates, since it MIGHT just help regrow growth “plates” on a micro scale, and could possibly lead to a few more inches.

So, back to FGFR3 inhibition. As far as I’ve researched, this seems to be an effective method for people with open growth plates. The problem with current FGFR3 tyrosine kinase inhibitors is the lack of specificity. But, I’ve found a novel drug which seems very specific to the FGFR family, called AZD 4547. So far, at least in vitro studies, it is by far the most selective that I’ve found, towards FGFR3. The benefit of chemical inhibitors is that they target everywhere in the body, so that growth is proportional.

While I can’t really advise anyone to take this compound, I’m trying to find a synthesis method for this compound.

If you need any more info, feel free to ask.

References:

1. Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice, Source: http://ajpendo.physiology.org/content/297/6/E1339.full.pdf

2. C-type natriuretic peptide and overgrowth. , Source: http://www.ncbi.nlm.nih.gov/pubmed/19293575

3. An Overgrowth Disorder Associated with Excessive Production of cGMP Due to a Gain-of-Function Mutation of the Natriuretic Peptide Receptor 2 Gene, Source: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042180

4. Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. , Source: http://www.ncbi.nlm.nih.gov/pubmed/8630492

*Just a note, while it says it causes deafness, this on a genetic knockout study. Deafness is caused by a developmental defect when the mice are embryos or just as they are growing. In humans (that are mature and fully developed), with inhibition of FGFR3, there should not be any problems with deafness (to the best of my knowledge).

5. Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. – Source: http://www.ncbi.nlm.nih.gov/pubmed/12193576

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My Response to D Inventor

Tyler noted the link between FGFR3 and CNP as well as the link between FGFR3 and ERK 1 & 2. I  have absolutely no research on ERK 1&2 and don’t even know what they are yet. I can not comment or make any good judgement on how ERK affects everything.

I’ve done the research on CNP before and the research was done by many other height increase researchers in the past from the GrowTallForum.com which is now closed. They tried to increase their height through finding compounds that could increase the level of CNP or Nitric Oxide in their systems. I found at least one patent by some Japanese guy who showed that increased CNP would help children who are suffering from idiopathic short stature.

It is very clear that there is a chance that increased CNP levels in the blood would negate the function of FGFR3 to a certain level in humans suffering from Achondroplasia. Refer to the post CNP, the first potential pharmacological therapy for achondroplasia. 

From that post, it states “Biomarin, a pharmaceutical company working in therapies for rare and genetic conditions, announced it was planning to start the clinical research with a compound called BMN-111. BMN-111 was described as a C-type Natriuretic Peptide (CNP) analogue.”

So from this article, it shows that there is still a lot of options and hope for kids who are still growing . CNP does not have to be the only option.

I read over the article you referenced quite extensively entitled “Cartilage Dysplasia and Tissue Mineralization in the Rat Following Administration of a FGF Receptor Tyrosine Kinase Inhibitor”

I wanted to first make the point that the study was done on lab rats, not humans. It might not even be able to be translated to humans. The reason for this is like I said before, mature rats still have growth plate cartilage.

In the paper, the mature mice were defined to be around 11 months old. I googled the term “at what age do rats stop growing”. The information is mixed but the general answer is that they usually stop growing around the 8-10 month range. Refer to RatForum.com. So technically the “mature” rats in the experiment should have stopped growing in bone length.

The paper does say that the cartilage in the mature rats did go through hyperplasia. However, the main point and problem I would bring up is that unlike humans, even mature and old rats (and possible mice) still have bands of cartilage in their limbs. The long bones of old rats are not completely bone, but have portions that are stil cartilage. Humans don’t have that physiology. Our limbs become all bone except at the ends.

Remember that most of the people who ever ask about how to grow taller already have their plates fused. They are already in a very difficult position when they start to ask for help and look for solutions.

What happens usually is that while a person is still young and have open plates, even if they are short they still rationalize in their mind and hope that they just haven’t gotten the chance to go through their growth spurts yet, even if they never will get one. Everyone hopes that they would be one of the lucky ones who gets to go through a 6-7 inch growth spurt and that would happen to them. For most people, that doesn’t happen. So they wait and don’t do much except wish and hope, and they run out of time when the cartilage is all gone. After they notice that they are still short even after puberty, then they start worrying since they never got the growth spurt that they ‘deserved’ or expected to get and start to search. It is already too late.

Me and the other researchers have found multiple ways for children with open growth plates get taller. That is easy. Finding a way for fused cartilage has been the problem, and will always be the problem. That is the real solution we want to find.

What we always focused on was a solution for people with bone maturity, because we all understand that ultimately, that is the real solution.

In a very recent article published on the website for the magazine Scientific American entitled “How to Regrow a Head – A single gene switch makes worms regenerate their whole bodies from their tails” it seems that scientists have figure out how to potentially increase the regenerative ability of animals by knocking out certain genes that have been regulating the Wnt and Beta-Catenin Pathway.

Now, we have researched and studied both the Wnt and the Beta-Catenin Pathway just to learn much more about molecular biology and biology. Post were written…

The Connection Between The Wnt Beta Catenin Signaling Pathway And Growth, Part I

There was also some research done on the PI3K and AKT pathway in the post “The PI3K, AKT And mTOR Signaling Pathway”

The facts are that for most people who have ever taken a molecular biology class, or done some graduate level work on studying cells, they would be quite familiar with the Wnt-Beta-Catenin pathway and the PI3K-Akt pathway. These pathways are some of the most well known and extensively studies extracellular signaling pathways in cells.

For the article itself, I would guess that the news is not a big shocker for anyone who has been studying the Wnt- Beta-Catenin pathways for a while, but for people who are not in the field, it might seem crazy and be new information. From the article, here is a recap of what these genes and signaling pathways do…

…Wnt genes, which code for a series of enzymes that relay information from outside the cell to the nucleus, eventually producing proteins called β-catenins, which regulate gene expression…

Genes create a type of protein known as enzymes which help chemical reactions and biological process occur in cells. For the Wnt genes, they create a type of enzyme that will going to affect how signals and kinases that come to the surface of the cell from the outside wil do to the stuff inside the outer membrance. The end result is another type of protein known as Beta-Catenin, which regulates what types of genes are expressed.

In the experiments the researchers wanted to find out if a lack of Wnt gene expression was responsible for the poorer regenerative abilities in particular worm species. What they found was that “… in wounds that did regrow heads, genes coding for a series of enzymes involved in the Wnt pathway had their expression turned up”

Now, the gene that causes the regenerative properties seem to be modulate/controlled by other types of proteins. If these other proteins are themselves inhibited, then the regenerative ability of the animal beng studied should increase. “…both teams found that by suppressing a gene that regulated Wnt function in their flatworms, they could get chunks of the normally non-regenerative tissue to grow fully functional heads”

There was actually three studies, three experiments, three groups of researchers, and three papers submitted to whatever prestigious journal is in the field of their expertise. The 3rd team located in Japan, noted that they found out that another signaling pathway, the extracellular signal-related kinase (ERK) pathway also had a function in regenerative abilities. 

One of the scientists “Umesono suggests that the effects of ERK proteins and Wnt proteins counteract each other. If the Wnt pathway dominates then it signals tail growth, but if ERK suppresses its influence then heads can form”

I have also done some research on the ERK pathway in the post “The Mitogen-Activated Protein Kinase, MAPK And Extracellular-Signal-Regulated Kinases, ERK pathway”

These proteins created just make sure certain genes are either turned on or off, and the rate at which expression does (or does not occur).

Implications For Body Part Regeneration

Since the Wnt, Beta-Catenin, and ERK pathway is already understood quite well, it would not be too hard to try to knockout the genes that controls the expression of the pathway, and create people with altered genomes which allow them to heal body wounds much faster and more efficiently than the regular human.

Implication For Height Increase

If we can get our own bodies to develop regenerative abilities through genetic engineering, it would be very easy to increase our height. All that is needed to be done to get a new layer of growth plate cartilage is to make a distraction in the bone, and the wound would start to form blastema which can then be controlled using differentiation modulators into the cartilage that is needed.