Almost 99% of the messages we get to the email are just not helpful at all and people asking us to post the PDF for the Grow Taller 4 Idiots E-Book, which we can’t do anymore. Sometimes a reader of the website does provide some interesting new information for us to read, and reconsider. This series of emails were given to us by a reader, who goes by the first name Jacob. We read the series of emails, looked at the links, and wanted first to post them down, before we wrote another post giving our analysis and thoughts on what they said, since the entire series of messages is quite long.

May 25th

Hi, Tyler

On making your next post on your website, I suggest a possible further research on this topic.

Do you remember Guy name of Alkoclar and XCrunner mentioning about Methyl Protodioscin?

Well I thought it’s lab made but apparently it’s also extracted from either Tribulus Terristris or Dioscorea Nipponica Makino.

In many of Methyl Protodioscin compound that is sold especially on Alibaba, most of them happen to be extract of Dioscorea Nipponica. Few of them were also extract of Tribulus Terristris. Chemical compound of Methyl Protodioscin nonetheless happen to be C52H86O22. I’m not too keen on chemistry and I had several theories behind this which was shut down by several people.

There are lab made compound of Methyl Protodioscin that is produced in America (several labs I checked) but unfortunately they are only sold to doctors and researchers with chemical lab company ties. Ordinary people may not be able to obtain them or the price is too high for few mg even for sample purpose.

The link below is worth checking out because it says that Dioscorea Nipponica (from ethyl acetate extract method) INHIBITS Pi3K pathway

But we need stimulation of Pi3K (along with CNP expression and IGF-1 and HGH) for bone growth to occur and many of these pathways are dependent on each other.

http://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=759832

On May 27th

Found something on Methyl Protodioscin (DNA methylation wasn’t mentioned and am still going to research on this as I go along)

But it says something about osteoclast

From the pdf (attached) … quote below

…… methyl protodioscin， a major constituent ， possessed the strong inhibitory activity both on the formation of osteoclast・and the bone resorption ，…..

On May 27th 

as far as osteoclast is concerned, (if I”m not mistaken), osteoclast eat away the osteoblast and osteblast proliferation is needed for growth (one of many factors) and this methyl protodioscin (particularly) from Dioscorea Spongiosa has shown to inhibit osteoclast behavior and promote osteoblast behavior.

On June 18th

Suggestive idea:

I was thinking… Since Methyl Protodioscin is hard to obtain and they only get released to doctors and laboratory and even if we did obtain them, they are expensive like usually hundred of bucks for few 20 mg or so but we need A lot of them to promote DNA methylation, I have alternate idea which might be cheaper.

Since Methyl Protodioscin is claimed to have the Methylated Protodioscin and the Methylated part just gives off the CH3 to the nearby group, couldn’t we substitute it with SAM-e + regular protodioscin and consume it together?

That way the methyl group from SAM-e gets detached and possibly gets re-attached to protodioscin becoming “Methyl Protodioscin”.

There was a rather famous article that Forbes wrote two months ago talking about the multi-billion dollar company Samumed, started by 6 guys who all originally came from Turkey. The main guy they were talking about is Osman Kibar, who is a billionaire himself as well as a extremely proficient poker player. This guy has a rather extensive history. He went to school at Pamona College, than Caltech, and finally got his Ph. D. at UCSD, which I had the pleasure of dropping by just a few days ago. The article says that he started the company Genoptix while still in Graduate School, which Novartis eventually bought from his for around $400 Million. Not bad at all. Later on, a chance meeting with a old college buddy from school at the airport who worked at Greywolf Capital allowed Kibar to get about $3.5 Mil in funding. That led to Wintherix, which eventually became Samumed.

Apparently Samumed as calculated by the analysts at Forbes is apparently the most valuable biotechnology startup in the world already just based on hype and excitement. Will this be similar to Soon-Shiong’s Nantkwest, who is also started by a rather flamboyant billionaire who is looking to actually solve incredibly difficult biomedical related world problems? On the first glance, the similarities are there.

Without any approved drugs yet, it has already been valued at $6 Billion. Let’s keep in mind that the science and the mechanics on how the treatments work is not that secretive in some black box, unlike Theranos, which only recently was shown to have lied and falsified their claims. As for Elizabeth Holmes, her new net worth of $0 dollars reveals that one must be very cautious when it comes to venturing into the field of biotechnology entrepreneurship. I have personally worked at 2 startup companies who were trying to find treatments for HIV and Cancer (Prostate) and eventually both of those startups went down, due to the inability of the companies to show that their drugs efficacy. We have already talked extensively on the Wnt Pathway before on this website, but it might be worth it to go over the details at a later time. This pathway is one of the 3 main pathways which we have talked about before, which basically is the flow of proteins interacting with each other between the nucleus of a cell and the surface membrane of the cell. There is the canonical pathway, and the non-canonical pathways, as well as the integrated pathways, which as the name sounds, combines certain parts of of the canonical and the non-canonical. (What does the term “canon” mean? That is just another word for original, or general)

So far, the article in Forbes reveals that the R&D people at the company are currently working on 3 main types of biomedical applications.

1. Baldness Treatment – SM04554
2. Arthritis Treatment – SM04690
3. Wrinkle Removal – Not stated in article

The treatment that has the biggest influence would definitely be the SM04690. In the article, it is said that over 27 million Americans suffer from arthritis and every year a supposed 700,000 people get replacements for their knees and another 300,000 get hip replacements.

In terms of the science, after the treatment of the SM04690, when the patients had their knees X-rayed it was found that the space between the femur and the tibia had increased, suggesting that the articular cartilage between the two bones might have regrown back.

This type of news be might not seem that important for us, since I have already written probably 20 articles before showing that thousands of researchers around the world are already working on getting the hyaline cartilage to regenerate to solve the problem of arthritis and osteoarthritis. It isn’t a bold claim to say that the entire goal of all of the Orthopedic Research being done in around the world is all for the goal of cartilage tissue regeneration.

Bone tissue regeneration and growth has already been successful multiple times over.

Here is the excerpt from the article which I have cut and copied below. This shows just how big the solution can be, just for solving the arthritis problem, which is so much easier.

What we are talking about here may sound like a lot of extreme claims but it is honestly not that far away from possibility.

The investor Finian Tan, is basically making this insane claim. If you can create just 1 millimeter of cartilage from a small, quick injection of whatever is the treatment (in Samumed’s case, it is their special formulation) you can create a company that is even bigger than Apple.

The last I checked, on June 16th, 2016, the value of Apple market cap is at $534 Billion. That is insane.

Just think about this for a minute. If you can create just 1 millimeter of cartilage from a simple injection, you will create a company that is worth more than half a trillion dollars. 

Let’s remember something else here. We are not asking the Ph.Ds to create new growth plates here or reopen the growth plates. We are asking the scientists to regenerate the layer of hyaline cartilage that is on the ends of the femur and/or the tibia. That is it.

Yes, we realize that is still hard due to the intrinsic nature of cartilage, which don’t have any vascularization due to the SOX9 gene being expressed, which is actually a good thing. No vascularization means the necessary cells that are usually transported to a wound area for accumulation and wound closure quickly does not get to the wound area.

This arthritis problem is much, MUCH, MUCH easier to solve and figure out than the neo-epiphyseal problem, which is 100X harder, if not impossible, at least in our lifetime.

Here is the last toe/finger clamping progress post.  Essentially, I’m using finger and toe clamping as a proof of concept with LSJL without being limited by force.  I’m still doing LSJL on ankles, knees, wrist, and elbows but also on these smaller joints as well.  Last time someone mentioned hiking as increasing shoe size by two.  Pregnancy also tends to increase shoe size and that could be linked to hydrostatic pressure so that’s why I’m attempting toe clamping.

Here’s the before pic.  It’s not optimal but it’s something.  I’ve been hand clamping my right toe at least 5 minutes a day.  I took this picture on May 14th.  So now it’s been about a month.

I realized that keeping my heel on the floor would make things more level but if I get more significant results I can always go back to the first image.  The right toe looks bigger in the after picture but it also looks bigger than the left in the before picture too.  I’ll have to keep clamping and see if there are further developments.  One thing to note is that shoes feel tighter around my right foot so that’s a positive indication.  Hopefully I’ll keep clamping and will eventually outgrow a shoe.

Here’s the finger clamping progress:

Yeah I know it’s slanted but so was the eariler thumb pic shown in the link above.  It used to be that the left thumb was longer than the right but now they appear more equal in length.  Not much right now but enough for me to try to clamp harder to try to squeeze out more results.

The most promising clamping.  I could always get an xray to validate but with all the other stuff I’m clamping I haven’t been clamping as intently as I could be.

So basically I don’t have enough yet but I have enough indications that I’m starting to get some results so I should try clamping harder/more intently until I have something more concrete.

For fingers I always have the hand xrays I got before so I can get new x-rays and compare.  For toes I don’t have x-rays however if I no longer fit into the same shoe that’s a strong result.

This study is focused mainly on bone formation but it looks at MSCs in general and stimulating stem cells would be an important step in growing taller.

Dynamic Fluid Flow Mechanical Stimulation Modulates Bone Marrow Mesenchymal Stem Cells.

“Osteoblasts are derived from mesenchymal stem cells (MSCs){Also chondrocytes are derived from MSCs}, which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation (DHS), we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension (HLS). To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point: age-matched control, HLS, and HLS+DHS. DHS was delivered to the right mid-tibiae with a daily “10 min on-5 min off-10 min on” loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. the mechanism of MSC induction in response to mechanical loading [is time sensitive], and for the optimal design of osteoporosis treatments. ”

Whether MSCs are driven towards osteo or chondrogenesis could be related to the microenvironment.  So how strong the existing bone is could be a key as to whether the MSCs are driven torwards chondro or osteogenesis.

“DHS was delivered through a custom-made inflatable cuff placed around the right hind limb above the tibia.{so maybe occlusion bands could help?} An oscillatory actuator-driven syringe, a force-controlled syringe and a pressure sensor, were connected to the stimulation cuff. The actuator-driven syringe was controlled by a programmable 100 MHz waveform/signal generator. The hydraulic pressure was monitored by the pressure sensor throughout the entire treatment. With a stimulation frequency of 2 Hz, the pressure stimulation magnitudes were 30 mmHg static pressure + 30 mmHg (peak-to-peak) dynamic pressure. Daily stimulation of the “10 min on-5 min off-10 min on” loading regime was applied to each stimulated animal, while under anesthesia (isoflurane inhalation), for five days/week.”<-This is less than 0.01MPa well below the 0.1 to 10MPa to induce chondrogenesis.

Hydraulic Stimulation increased the number of bone marrow by 50%.

Dynamic fluid flow induced mechanobiological modulation of in situ osteocyte calcium oscillations.

“Distribution of intramedullary pressure (ImP) induced bone fluid flow has been suggested to influence the magnitude of mechanotransductory signals within bone. As osteocytes have been suggested as major mechanosensors in bone network, it is still unclear how osteocytes embedded within a mineralized bone matrix respond to the external mechanical stimuli derived from direct coupling of dynamic fluid flow stimulation (DFFS). While in vitro osteocytes show unique Ca(2+) oscillations to fluid shear, the objective of this study was to use a confocal imaging technique to visualize and quantify Ca(2+) responses in osteocytes in situ under DFFS into the marrow cavity of an intact ex vivo mouse femur. This study provided significant technical development for evaluating mechanotransduction mechanism in bone cell response by separation of mechanical strain and fluid flow factors using ImP stimulation, giving the ability for true real-time imaging and monitoring of bone cell activities during the stimulation. Loading frequency dependent Ca(2+) oscillations in osteocytes indicated the optimized loading at 10Hz, where such induced response was significantly diminished via blockage of the Wnt/β-catenin signaling pathway. The results provided a pilot finding of the potential crosstalk or interaction between Wnt/β-catenin signaling and Ca(2+) influx signaling of in situ osteocytes in response to mechanical signals. Findings from the present study make a valuable tool to investigate how in situ osteocytes respond and transduce mechanical signals, e.g. DFFS, as a central mechanosensor.”<-Our main concern isn’t Ca2+ oscillations as those are not likely to induce chondrogenesis directly although it’s still possible that it may have an impact or that Ca2+ could be complementary.

“Changes in the pressure or velocity of bone fluid flow (BFF) act as a communication medium that connects external loading signals and internal cellular activities in bone, which ultimately regulate the bone remodeling process”<-can we manipulate this loading signals and cellular activities in such a way that we grow taller?

“DHS[Dynamic Hydraulic Stimulation] generated local ImP that acted independently from simultaneous bone strain.”

Here’s a diagram of how Calcium signaling may alter a cell.  So Ca2+ is anabolic but it doesn’t really seem to have a direct impact on what lineage a cell traverses(osteo- versus chondro-).

Interrelation between external oscillatory muscle coupling amplitude and in vivo intramedullary pressure related bone adaptation.

“Interstitial bone fluid flow (IBFF) is suggested as a communication medium that bridges external physical signals and internal cellular activities in the bone, which thus regulates bone remodeling. Intramedullary pressure (ImP) is one main regulatory factor of IBFF and bone adaptation related mechanotransduction. Our group has recently observed that dynamic hydraulic stimulation (DHS), as an external oscillatory muscle coupling, was able to induce local ImP with minimal bone strain as well as to mitigate disuse bone loss. The current study aimed to evaluate the dose dependent relationship between DHS’s amplitude, i.e., 15 and 30mmHg, and in vivo ImP induction, as well as this correlation on bone’s phenotypic change. Simultaneous measurements of ImP and DHS cuff pressures were obtained from rats under DHS with various magnitudes and a constant frequency of 2Hz. ImP inductions and cuff pressures upon DHS loading showed a positively proportional response over the amplitude sweep. The relationship between ImP and DHS cuff pressure was evaluated and shown to be proportional, in which ImP was raised with increases of DHS cuff pressure amplitudes. A 4-week in vivo experiment using a rat hindlimb suspension model demonstrated that the mitigation effect of DHS on disuse trabecular bone was highly dose dependent and related to DHS’s amplitude, where a higher ImP led to a higher bone volume. This study suggested that sufficient physiological DHS is needed to generate ImP. Oscillatory DHS, potentially induces local fluid flow, has shown dose dependence in attenuation of disuse osteopenia. ”

“Direct ImP measurements in rats under DHS over a frequency spectrum indicated that its optimal loading at 2Hz can generate maximum ImP of 14.48±3.10mmHg. On the other hand, dynamic components with large loading amplitudes typically result in pronounced osteogenic responses”

“a micro-cardiovascular pressure transducer was carefully inserted into the tibial marrow cavity through a 1mm drilled hole, and was then tightly sealed within the drilled hole”

” the observed ImP inductions were found to be positively proportional to DHS cuff pressure, namely, which indicates promising potential of DHS loading dose dependency on ImP related bone adaptation.”

“DHS loading at 2Hz between 28.41±10.50 mmHg and 33.75±10.69 mmHg cuff pressures can induce significant ImP increases. Coincided with these observations, our 4-week in vivo study showed that DHS loading at 2Hz with 15 mmHg and 30 mmHg dynamic pressure was able to mitigate disuse trabecular bone loss in a rat functional disuse model.”

“At baseline, normal heart beats generated approximately 1mmHg tibial ImP within the marrow cavity.”

Dynamic hydraulic fluid stimulation regulated intramedullary pressure.

“Physical signals within the bone, i.e. generated from mechanical loading, have the potential to initiate skeletal adaptation. Strong evidence has pointed to bone fluid flow (BFF) as a media between an external load and the bone cells, in which altered velocity and pressure can ultimately initiate the mechanotransduction and the remodeling process within the bone. Load-induced BFF can be altered by factors such as intramedullary pressure (ImP) and/or bone matrix strain, mediating bone adaptation. Previous studies have shown that BFF induced by ImP alone, with minimum bone strain, can initiate bone remodeling. However, identifying induced ImP dynamics and bone strain factor in vivo using a non-invasive method still remains challenging. To apply ImP as a means for alteration of BFF, it was hypothesized that non-invasive dynamic hydraulic stimulation (DHS) can induce local ImP with minimal bone strain to potentially elicit osteogenic adaptive responses via bone-muscle coupling. The goal of this study was to evaluate the immediate effects on local and distant ImP and strain in response to a range of loading frequencies using DHS. Simultaneous femoral and tibial ImP and bone strain values were measured in three 15-month-old female Sprague Dawley rats during DHS loading on the tibia with frequencies of 1Hz to 10Hz. DHS showed noticeable effects on ImP induction in the stimulated tibia in a nonlinear fashion in response to DHS over the range of loading frequencies, where they peaked at 2Hz. DHS at various loading frequencies generated minimal bone strain in the tibiae. Maximal bone strain measured at all loading frequencies was less than 8με. No detectable induction of ImP or bone strain was observed in the femur. This study suggested that oscillatory DHS may regulate the local fluid dynamics with minimal mechanical strain in the bone, which serves critically in bone adaptation. These results clearly implied DHS’s potential as an effective, non-invasive intervention for osteopenia and osteoporosis treatments.”

” bone fluid flow (BFF) with altered velocity or pressure acts as a communication media between an external load and the bone cells, which then regulate bone remodeling. In converse, discontinuous BFF can initiate bone turnover and result in osteopenia”<-Initiating bone turnover could be a good thing if bone structure inhibits anabolism so lowering the frequency may be key.

“DHS was achieved through a costume-made inflatable cuff placed around the right tibia”

” the inflation and deflation of the cuff was driven by a syringe pump with the loading magnitudes and frequencies delivered by a programmable waveform/signal generator”

” 1mmHg tibial ImP and 5mmHg femoral ImP were generated by normal heart beat within the marrow cavities.”

” muscle contraction compresses the blood vessels in muscle, which generates an arteriovenous pressure gradient that further increases the hydraulic pressure in skeletal nutrient vessels and amplifies the capillary filtration in bone”

” using oscillatory muscle stimulation (MS), in which oscillatory MS induced maximal ImP at 20Hz. Oscillatory MS was achieved via two disposable needle-sized electrodes inserted into the quadriceps of the stimulated rats. The electrodes were then connected to the waveform generator with 2V supplies to induce muscle contraction”

“Due to the different physical orientations of how oscillatory MS and DHS contact the loaded tissue, as well as the different material densities and viscosities within hard and soft tissues, maximal DHS-induced ImP may result at relatively lower frequency compared to MS.  Direct hydraulic coupling may influence bone adaptation in a more physiological frequency range, where normal heart rate is 360 times per minute.”

“Changes of MSC number in response to DHS bias their differentiation towards osteoblastogenesis, leading to bone formation even under disuse conditions”

“increased bone fluid pressure and bone fluid flow regulation are strongly correlated, our current results of DHS-driven ImP induction suggest a possible mechanism that the induced ImP may subsequently enhance bone fluid flow.”