Drinking Milk Does Make People Grow Taller

pouring milk in a glass isolated against white background

p

Something I read recently made me think back to this old adage that drinking milk will somehow make a kid grow taller.

In the early days of the website, I had talked about and argued over the implied correlation between dairy consumption and perceived greater adult stature. There was never any real conclusive proof in the first post, and over time, after a few more posts, I started to switch my opinion that drinking milk could possibly increase one’s height, and increase the rate of height increase.

One particular life incident that will forever be in my memory makes me think back to this idea. I once met two extremely tall german girls, both around 6′ 2″, buying 2 gallons of milk each and telling me that they drink milk similar to how they drink water. Of course, just how much significance should one put into 1 very odd, outlier experience?

Here is a theory I propose which probably will not be possible to be validated without some serious effort by medical professionals, over a long period time that is not reasonable to most researchers.

Drinking Bovine/Cow derived milk does make people grow taller, but it is not in the way that people would hope.

Theory:

  1. If you started to take up the practice of drinking milk, even at the age of 10, when one is still growing, there would NOT be any noticeable increase in one’s adult height.
  2. However, if you can develop that milk drinking habit, and you also get your children, AND your grandchildren to drink milk from a very early age, basically the moment they are being weaned off drinking their mother’s breast milk, then your grandchildren will be taller from it.

I call it the grandchildren milk height theory, which I will shorten to GMHT.

Now, a lot of my time these days are focused on thinking at a subconscious level about orthopedics and orthopedic research, specifically because I have decided to dedicate my life towards this endeavor. I have personally read over a thousand studies, and there are a lot of ideas that run in the back of my mind. 90% of those ideas that I have while I am driving, showering, working out, etc. I write down but never decide to write up about, because they are either too scientific and have no actionable steps that the average reader can do.

Something that I recently really got into is the idea of using probiotics, or changing one’s gut biome/intestinal bacteria culture or composition. There was this stunning study that was done in fecal transplantation where you take a female who has been predisposed towards being overweight her entire life, and can’t seem to lose weight no matter what she did. She undergoes a fecal transplantation using the fecal matter from a woman who has been thin her entire life, who is predisposed towards thinness. The result is that the previous state of being always overweight is completely gone, and replaced by a women who basically seemed to have changed her genetic makeup. This study that I learned is absolutely stunning to me.

There is now even clinical studies being done to test this idea (Fecal Microbiota Transplant for Obesity and Metabolism) as well as proposed pills sold that is basically “poop”. In 10 years, it is possible that real doctors are going to be suggesting to their patients that they should swallow poop pills to help them loss weight. The most crazy thing about this is that I have read articles by people who have said that if you can created some pill that can help people loss weight and keep the weight off, you would become a billionaire. So it is kind of interesting to think about this idea – “Can a person become a billionaire by selling pills whose active ingredient is human feces?”

The famous podcaster Joe Rogan is famous for saying that he imagines the human species as just a very complex type of bacteria super-organism (Joe Rogan’s Theory on Life and People). In the medical lecture where I learned about fecal transplantation, the professor said that if we didn’t have any type of way to control, direct, and organize the bacteria in our body, we would pop like a balloon or shrivel up like beef jerky in minutes. In our stomach alone, there is supposed to be around 100 trillion microorganisms

This idea that we can change something that would seem to most people so intrinsic, brings back the idea of Lamarckian Evolution, which Darwin’s camp disproved more than a century ago. Before there was Darwin’s theory of evolution, there was Larmarck’s Theory of Evolution, which I have mentioned before multiple times on the site. What I am proposing is epigenetics, which most people who study/do research/work in the biological and medical sciences don’t believe in. Epigenetics and the field is indeed very controversial, and many studies that have been done to see if it is real has not stood up to the scrutiny of medical research professionals.

Based on darwin’s theory on how evolution really works, this theory I propose right now is basically wrong since the mechanism which I propose goes against how darwin explained why there is such diversity in the species in the world. Let’s make that clear.

Whereas Lemarck says that the features of our bodies change to “adapt”  to the the interaction of our bodies with the external world, which get passed onto our children, Darwin says that the changes that we find is due to random variations at birth. The net result of what we see, in terms of variation is from the variations that are not as successful not reproducing as much and dying off. Darwin is right on this point. This idea that we can do something to our bodies and/or genes, and have that change get passed onto our children is extremely unlikely. However, this theory does need to be proposed, since it is a Theory of Leap Of Faith. Its exact mechanism and steps are not completely logical, but there is just not enough data on to completely disprove this idea, since it is in “gray areas”. It just might work.

The Steps in the Mechanics of GMHT.

  1. Your start first with the first generation, where the still growing adolescent is given a lot of milk for consumption. – The result is no noticeable increase in height, if we compared their final height to say an identical twin which will be used as the control.
  2. This causes their gut biome to change – At this point, I can not tell the reader how the composition and culture of the bacteria in their stomachs will change. Just that the type, composition of bacteria in their intestinal tract will be altered.
  3. When the adult female becomes pregnant, they should immediate start to take calcium, vitamin d3, iron, and magnesium supplements, because those specific minerals are the exact ones that the developing fetus is going to be absorbing from their mother’s bodies. This is not just to ensure that the baby born will already be big, but also to prevent any possibility of hip fractures that can develop from the calcium deficiency causing pregnancy-induced osteoporosis.
  4. When the first generation has their kids, they immediately get their children, the 2nd generation to start having cow milk into their system immediately after they are weaned off their mother’s milk, which they should continue to consume until their are 2 years old (mother’s milk here, not the cow milk). This will have some dramatic effects on the ability of the develop infant’s body in being able to direct the calcium in their bodies towards the ossification centers in their bone. We are specifically talking about Calcium and VItamin D3 here. The gut biome changes again.
  5. When the 2nd generation have their children, they will repeat the steps done by the 1st generation towards the 3rd generation. The result is that the 3rd generation will grow into adult heights which will be noticeable taller than if they were not consuming the milk.

If we were to be completely analytical about this, we can even skip the 1st step. That first step might not be needed, but to explain the basic idea. This is indeed Lemarckian and Epigenetics, but the entire premise behind the website and this crazy endeavor of trying to manipulate one’s almost pre-destined height which is 80% controlled by one’s genetics, we have to use crazy, basically unvalidated ideas which most real scientists say is false.

What I am saying is that we can systematically change a person or a group of people’s heights by changing their gut biome with at least a 3 generation effort with increased dairy consumption to get the high level of Vitamin D3 needed so that when the children are still very young as infants, their immune system has already become altered. The extra Vitamin D3 will help be more effective in directing the calcium in their infant and adolescent bodies to go towards the bones.

It might be surprising but most American adult males are deficient in Vitamin D3 and most females are deficient in Iron and Magnesium.

The physiological changes that can happen are the following….

  1. Where once the grandparents (1st gen) were lactose intolerant, the grandchildren (3rd gen) or great-grandchildren (4th gen) are no longer. This is from a systematic almost forced changing of the gut biome to handle it when can be altered when the 4th generation was just an infant.
  2. Where once the 1st gen might have had celiac disease and have gluten sensitivity, the 4th generation don’t have it, and most medical professionals with their current testing devices will say that to the 4th generation that they don’t have a genetic predisposition towards gluten sensitivity, even thought their great-grandparents all had it. Same thing for other intestinal system chronic issues, like Crone’s Disease.

This obviously doesn’t sound as scientifically cool as say using the recently discovered CRISPR-Cas9 gene editing tool to create babies will superior height and intelligence, but in my eyes right now, it does sound viable. Like I said, it will take at least 3 generations to notice any effect.

I think back to the insane level of height increase that happened in the Netherlands over the last 100 years and imagine something similar. People are reminded that during Vincent Van Gogh’s era, the average Dutch adult male was quite short, and among the shortest in all of Europe. In 100 years, that stereotype of the Dutch has completely changed. Some people say that the incredible height of the Dutch was always there, just suppressed due to decades of malnutrition and bad childcare. That would suggest that the Dutch, and possibly all Northern Europeans, specifically the Scandanavians, are genetically somehow supposed to be a taller ethnic group than other ethnic groups in the world. Based on just data collection and looking at the tabulated anthropometric data over the last 50 years one can say that.

However, let’s remind the readers that there was a stunning article that the World Health Organization (WHO) published that I found two years ago which showed that when average out, it says that nearly all human tribes seemed to all have the exact same growth potential. That is saying that the stereotypically image of the short vietnamese male of the modern ega may be gone, when the adult males catch up in height in Vietnamese in 100 years to the “tall” dutch” that we find today. It was revealed that the Dutch society adult male did hit a plateau on their average height as early as even 2010, when census data was collected.

Summarizing It All

    • I propose GMHT, which says that drinking cow milk will make people taller, but it takes at least 3 generations of it to work.
    • You have to get the milk consumption to happen early, right after the baby stops drinking their mother’s milk.
    • The goal is to  change the gut biome of the person while they are still an infant, with a malleable immune system that can be altered.
    • This idea should work to cure lactose intolerance, which has been linked to the “short asian” idea since most east asian ethnic groups have a high occurrence of lactose allergy.
    • The milk has Vitamin D3 in it, which is critical in endochondral ossification development.
    • Vitamin D3 will help guide the calcium to the growth plates when the kid is still growing, making the interstitial growth of the long bones to become optimized.
    • Adult men have a Vitamin D3 deficiency
    • Adult females often have a Iron and Magnesium deficiency.
    • When the adult female becomes pregnant, she should immediately start to take calcium, vitamin d3, iron, and magnesium supplements.
    • Don’t supplement the just born baby with any supplements. The mother’s natural breast milk is enough to give the baby the right combination of hormones, vitamins, etc to ensure that the baby will have the most “fit” immune system. Nature had 5 billion years to perfect this natural process so let nature do its magic for the time when the mother is breastfeeding. Sometimes we have to take a step back.
    • Only when the stage of complete and only breastmilk consumption is over should the now infant be given supplements.
    • Add vitamin D3, calcium, Iron, and Magnesium powder in with the milk being consumed, so that the growing baby/infant reaches the full height and growth potential.
    • The full height and growth potential has been claimed by the WHO to be the same for most ethnic tribes in the world, not counting certain tribes that are pygmy due to environmental factors like Island Dwarfism.
    • This means that the male teenagers from stereotypically short ethnic groups may end up being just as tall as the dutch male teenager in a century or so, if they supplemented their next 3 generation of children and pregnant mother with milk and vitamins, at exactly the right stages.

(Note: This time I did NOT use any Amazon Affiliate links here. Too tired to do that.)

Updated Information About XCrunner and Alkoclar’s Claims On Methyl Protodioscin

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

This is contrary to XCrunner who said that Methyl Protodioscin creates DNA methylation and I have yet to find any article that supports this claim. Not doubting him but this is worth looking at because it seems contrary to his claim. You might want to put this in your next website because it’s worth checking out.

Also I found a Chinese herb named Si Wu Tang (on the other hand) that seems to proliferate Pi3K pathway.

http://www.ncbi.nlm.nih.gov/pubmed/24156308 – “Si-Wu-tang extract stimulates bone formation through PI3K/Akt/NF-κB signaling pathways in osteoblasts”

I also found another Chinese herb named Roots of Asparagus Cochinchinensis

which claims to have some Methyl Protodioscin in them but that root doesn’t belong to either Tribulus or Dioscorea family.

Interesting.

http://www.ncbi.nlm.nih.gov/pubmed/26379748 – “Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production

Cheers, Regards,

On May 27th

Yeah I will continue on from my previous email. Below is email conversation I had with ‘O’ (XCrunner)

https://snag.gy/D0bwRF.jpg

XCrunner

He mentions bmp7, osteogenic protein and gdf5 in addition to methyl protodioscin and dimethyl icaritin and also mentions that his latest client from Czech Republic (35 year old woman grew 2 inches in three weeks from 5’8″ to 5’10”.So from my thinking on this, it seems like methyl protodioscin and dimethyl icaritin isn’t enough; it seems like there needs to be more and from what I seen here, bmp7 and gdf5 is like protein in DNA (I could be wrong) and you can’t really get this from supplements. These “protein” seems like something you have to get from certain bio-chemical lab and have these inserted or injected into the bone or body.I’m also in a learning phase and this height increase topic has been an obsession with me. I could go on research like this on my own and not realize time flies by. Unfortunately we are all in a theory based learning and none of the users online (from my assumption) seem like they applied this because perhaps maybe most weren’t serious, they were skeptical, didn’t have enough money, not possible or all of the above.If I knew I was going to do this seriously, I should have majored in Bio Chemistry instead. All in all, take my posts with grain of salt. Some of what I said could be right or wrong.But I think as far as Dimethyl icaritin is concerned, it’s probably pure icariin (Horny Goat weed) that Xcrunner might have want us to obtain.

I try to order these compounds from alibaba (since it was impossible for me to obtain any of this in the United States because they don’t release these to ordinary people)… my attempt in trying to get these product from China (most of the sources in alibaba comes from China) has been futile from miscommunication from sellers not understanding what I specifically wanted to being inconsistent with their price and general bad feeling about ordering from overseas from possible customs objection in the states. Possible scam scheme is also probable and not to mention, the Chinese don’t have good reputation with quality products and I might not be able to know if what they sent me is real or not and also unfortunately I would not have any chemical source for me to send my product to for testing in case if it’s real or not.

On doc file of compiled XCrunner’s note, they are out there online and I even found one from your naturalheightgrowth website.

he mentions..

Methylprotodioscin, Icariin and Glycine Propionyl L-Carnitine.

About 500mg 2x a day, once in the morning and once later in the day (3-6pm)

This will re-open the growth plates + IGF-1 boost from the Glycine Propionyl L-Carnitine.

I will be combining the MENS routine with this as it will re-open the growth plates.

You can lift weights and fap.
Avoid junk food and don’t cycle these supplements.

——————–

Xcrunner never mentioned Glycine Propionyl L-Carnitine so I don’t know where this popped up. Perhaps he has more list of ingredients that he is not telling us. Either way, he contributed a lot regardless… but I’m just trying to verify whether what he said was true and I’m willing to put myself as a guinea pig …. reading is good but applying and attempting discovery is better.

Interestingly, when I typed in “Methyl Protodioscin height” in google (already pre-shown as google search word), one of the link I found was this…

http://shetoldme.com/Science/Growing-Tall-with-Protodioscin

On that website, the Methyl protodioscin they recommend seems to come from Tribulus Terrestris (Not Dioscorea Nipponica).

Another interesting link from the same source

http://shetoldme.com/Health/Guanyl-Cyclases-role-in-height-increase

I took some notes as I went on and read from variety of sources online and other scientific source. I also took notes from your website as well and try to tie all this as one puzzle piece like you said.

(+) CNP, (+) cGMP, and (+) Nitric Oxide, (-) PDE5, (-) Myostatin   so plus is “increase” and minus is “decrease”

increase CNP, cGMP, Nitric Oxide level in addition to inhibiting PDE5, Myostatin. I get were Icariin comes from since it seems to inhibit PDE5 and inhibit Myostatin,

Also there are many product that claims to have Icariin but when I read this,…. (some products have icariins with the “s” at the end. This link says to get icariin (60%) as best source. I thought they were biased since they might want to raise the sales but what they say makes sense

https://www.icariinhealth.com/blogs/frequently-asked-questions/8829065-do-we-sell-horny-goat-weed-containing-more-than-60-icariin-such-as-98-icariin

https://www.icariinhealth.com/pages/horny-goat-weed-icariin

Worth reading.

On Methyl Protodioscin…

The word Methyl threw me off at first so I had to research on this. XCrunner mentioned that Methyl Protodioscin increases DNA methylation. If we can use SAM-e supplements (that does the same by increasing Methyl Protodioscin), couldn’t we substitute that and just use SAM-e plus Icariin?

Chinese yam also has Methyl Protodioscin and if you can extract this using alcohol or Propylene Glycol then it might be possible to obtain Methyl Protodioscin without relying on chemist (although safer route seems to say that it is better relying on chemist) … I think ordinary people can extract roots too.

Introducing Methyl group CH3 by substituting CH3 and take out one of Hydrogen atoms…     Protodioscin is (C51H84O22)

Chuan Shan Long (Dioscorea Nipponica) has Methyl Protodioscin … If we can somehow shred this into a powder, soak it in boiling water and boil it off with alcohol. The US customs is pretty anal about what you can import from foreign countries and many natural products from China are banned from entering the America because many Asian plants are invasive (cause environmental harm) and are not FDA approved.

Recent find. (I emailed Alkoclar but he replies with short answer and it doesn’t seem like he is interested in giving out samples anymore..

http://grow-tall-forum.proboards.com/thread/14/research

username by the name of theotheradam put interesting post

#1 Raise FGF2 
Astragalus Membracaneus 

#2 Inhibit FGF3/RasingCNP

as far as I know Astragalus Membracaneus is in IGH-1 (pill that sells with Ghenerate) along with IGF-1 spray. 

Astragalus Membracaneus also sells by powder. 

I have A LOT to write on these topics… and I didn’t mean to bombard you with all this and more links to read. This should ALL tie together.

Like I said, this is my obsession and I could go on and on and research into this ALL day ALL night.

If you are interested, I like to talk to you more. You can add me on gmail and we can chat and talk more about this. Sorry about my writing style, it seems confusing with scattered notes style but I think you can pick up what I’m trying to say here.

On May 27th

Kaneka from network54 forum 177048 (Joey’s forum) and also mentioned by Easyheight

http://web.archive.org/web/20071212053553/http://www.easyheight.com/alfalfa.htm

32 year old man growing from 5’10 to 6’0″. I also hear few stories about people growing after their plates were “closed” so In some ways when XCrunner has told me that growth plate never closes but remain inactive.

Modified fast and junk food makes people obese, we have steroids that make people’s muscles HUGE… and there should be steroidal altered chemical compound from some plant extract that can make people grow taller past the puberty age.

You also mentioned Alfalfa, http://www.naturalheightgrowth.com/2012/09/09/increase-height-and-grow-taller-using-alfalfa/

I think the key ingredient is Isoflavones. Found this… interesting http://growingright.blogspot.com/2013/06/alfalfa-to-grow-taller.html

http://growingright.blogspot.com/2014/01/5-reasons-to-use-alfalfa-to-grow-taller.html

So the key here is to obtain Heirloom or Perennial Alfalfa

The Alfalfa that Kaneka megadosed is from company Holland and Barrett

I remember I megadosed Alfalfa same way and all I got was bloated gas and massive diarrhea but maybe my body wasn’t ready at that time. This was long time ago in 2005 or 2006 or so if I recall.
I also remember trying out Tim’s Adultheightincrease Super Monster homeopathic drops possibly in 2010… didn’t work for me…

On May 27th

My theory on http://www.naturalheightgrowth.com/2014/03/19/lsjl-work-wrong-big-breakthrough/

why gr0wthnut grew 1.5 inches at age 27 but Nixa Zizu didn’t was because (possibly supporting XCrunner’s theory), Nixa Zizu lifted weights… Even though Nixa said he try to avoid leg (deadlift and squat workout) and only did Bench press… still … Both of them did the LSJL very similarly BUT

gr0wthnut only did high stairs machine cardio at the gym (not sure if he lifted weights) but perhaps that might have something to do with it…

Xcrunner on his post said to avoid working out, lifting heavy weights and only masturbate twice a week for that negative feedback loop.

the HGH released all went to recover his muscles instead of going directly to his bones from doing LSJL.

so my assumption, they are all Dependent on each other… HGH, IGF-1, Pi3K pathway, Osteoblast formation, Chondrycyte induction, DNA methylation… all need to work WITH each other.

By the way, earlier I made a typo… Sam-e increases DNA methylation (Not Sam-e increases Methyl Protodioscin) … . still I need to find how and why Methyl Protodioscin and what that has to do with DNA methylation. My purpose was to replace and substitute Methyl Protodioscin if I can’t find it or extract it and use Sam-e instead.

Think link (Indian height increase website — they look like they sell things…) . It looks like Indian height increase website.

http://mediplex.in/ht/growing_tall_mechanisms.htm

Their explanation on height increase supports Xcrunner’s. Their last sentence quote below…

So you see growing taller isn’t about growth plate fusion, it’s about cells. Controlling the differentiation of those cells and increasing the proliferation of those cells. Don’t let growth plate fusion fuse your mind to the possibilities.

I’m 5’8″ and half (174 cm evening height on good days) … on “bad” days with too much movement (it’s 173.5 cm or even 173 cm). My morning height is usually 176 cm or 177 cm… Big height fluctuation.

My goal is 183 cm (6’0″) if more better. My age is 28.

On May 27th

Compiled note I made month ago (Compiled Notes Here)

Most of it you already know and you are more knowledgeable than I am in this regards but it’s also worth knowing from other’s opinion. If this all ties in together and we somehow find a method to grow taller, this demand (will be limitless)

(source includes naturalheightgrowth and youtube video notes)

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.

I couldn’t find any more than this and if this is true, then perhaps it is a step towards right direction.
On May 29th

From “Medicinal Plants in Australia Volume 4: An Antipodean Apothecary” – By Cheryll Williams

My (Jacob’s) thoughts: I put in red box and also on screenshot. This has been done on animals and detailed that methyl protodioscin stimulates osteoblast proliferation on animals. If it can be done on animals, it would probably make sense that it can work on humans as well. 
Similarly, icariin also seem to simtulate osteoblast proliferation 
quote from link … (shown below)
Osteoporosis – “…Animal studies indicate that Icariin also stimulates osteoblast activity in bone tissue, leading to the development and marketing of medicinal products based on Epimedium extracts for treatment of osteoporosis.
MethylProtodioscin_Osteoblasts

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”.

The Hyaline Cartilage Regeneration Solution Creates A Company Worth More Than Apple

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.

Samumed InvestorsWhat 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.

Finger/Toe Clamping Update

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.

toe before

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.

June foot comparison

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:

thumb compare

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.

finger compare

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.

 

Study that shows that Fluid flow stimulation like induced by LSJL stimulates MSCs

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

“Osteoblasts are derived from mesenchymal stem cells (MSCs){Also chondrocytes}, 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. This study indicates that 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. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, 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. 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”

“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-).

fluid flow stimuli

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 (R(2)=0.98). 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. This also suggests that 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.”

 

Quantifying bone adaptations then and now: Breakthrough from 1920 study

Is some of the recent scientific advancements hiding key features that may give the secrets to growth?  Compare this recent study to a 1920s study that provides an insight about adult longitudinal bone growth related to bone softening.

Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility.

In vivo micro-computed tomography (µCT) scanning of small rodents is a powerful method for longitudinal monitoring of bone adaptation{May be helpful to measure LSJL?}. However, the life-time bone growth in small rodents makes it a challenge to quantify local bone adaptation. Therefore, the aim of this study was to develop a protocol, which can take into account large bone growth, to quantify local bone adaptations over space and time. The entire right tibiae of eight 14-week-old C57BL/6J female mice were consecutively scanned four times in an in vivo µCT scanner using a nominal isotropic image voxel size of 10.4µm. The repeated scan image datasets were aligned to the corresponding baseline (first) scan image dataset using rigid registration. 80% of tibia length (starting from the endpoint of the proximal growth plate) was selected as the volume of interest and partitioned into 40 regions along the tibial long axis (10 divisions) and in the cross-section (4 sectors). The bone mineral content (BMC) was used to quantify bone adaptation and was calculated in each region. All local BMCs have precision errors (PE%CV) of less than 3.5% (24 out of 40 regions have PE%CV of less than 2%), least significant changes (LSCs) of less than 3.8%, and 38 out of 40 regions have intraclass correlation coefficients (ICCs) of over 0.8. The proposed protocol allows to quantify local bone adaptations over an entire tibia in longitudinal studies, with a high reproducibility, an essential requirement to reduce the number of animals to achieve the necessary statistical power. ”

“in rodents like mouse, bone growth spans across the animal׳s life time”

Here’s a 1926 study regarding the regeneration of bone:

THE REGENERATION OF BONE

An early theory of the bone: “the “juice” of bone is released by a fracture,
fills the gap between the ends and there solidifies.”

“The excision of a necrotic bone (the modern sequestrectomy) was more than once reported with complete reconstitution of the affected bone.”

“bone regeneration depends upon the periosteum.  the thickening of this membrane and its later consolidation into bone in experimental fractures and drill holes.”

The four main elements of adult bone: bone cells; periosteal cells; endosteal cells; calcified matrix.

The marrow cavity of a bone(that which contains the juice) is broken up by the trabeculae of spongy bone.

“the bony shell or cortex, we find a definite architecture. On the inner and outer
surfaces, the matrix appears in layers lying parallel to the surface. Further
in, these layers lose the parallel arrangement and are there grouped in a series
of concentric circles. In the center of each of these circles is an opening,
the haversian canal, containing a blood vessel and lined with a membrane.
Throughout the substance of the matrix between these canals and in the
parallel layers are numerous smaller openings, the lacunae, in which lie the
bone cells.”

“Enveloping the outer aspect of the bone is the periosteum, a membrane consisting
of several layers of cells resembling connective tissue cells, with an enlongated nucleus and abundant fibrillar intercellular substance.”

“solid bone will not grow in length from within by expansion. The calcified matrix cannot
expand. Whatever growth takes place must take place by accretion.”

“Completely calcified bone will not grow interstitially but soft bone will grow interstitially. The experiment just described, if done on a young bone not yet hard, will result in separation of the nails. This is an observation which has a curious reference to adult pathology. Bones in certain pathologic states that render them soft, will occasionally increase in length long after the epiphyseal cartilages are united. This growth is undoubtedly a genuine interstitial addition of new bone, a true expansion of the matrix
exactly comparable to such growth in young bones. The commonest conditions
in which this phenomenon is encountered are osteomyelitis, Paget’s distlase
of bone (osteitis deformans) and Recklinghausen’s disease (neurofibromatosis).
all of which result in a certain degree of decalcification, that is a softening of the bone”

“bones assume a shape adapted to the function they are to perform.”

“Suppose a small drill passed through the cortex of a bone into the marrow cavity. The first effect, of course, is hemorrhage. On withdrawing the drill, the defect fills with blood. Within a few hours this clot begins to be replaced by a plug of fibrin containing polymorphonuclear
leucocytes. Fibrin is the culture medium, so to speak, of young tissue. Then appears a proliferation of the periosteal and endosteal cells, the production of periosteal and endosteal fibroblasts which differ from connective tissue fibroblasts only in their inherent capability of producing bone. These proliferating cells heap up at the edges of the defect, producing a macroscopic thickening of the periosteum and endosteum, and then grow down and up respectivcly into the fibrin that fills the defect, until it is completely replaced. The
periosteal and endosteal reaction extends on the surfaces of the bone over a considerable distance from the point of injury.”

“Before the process of fibrosis is complete, ossification begins at the points where the periosteal and endosteal proliferation began, namely over the surfaces of the bone at the edges of the defect.”

“when a foreign body is brought into contact with bone, one must anticipate that the regenerative processes will be diminished and retarded and that actual bone destruction may occur.”

A discussion attached to the end of the paper suggests that periosteums function merely is a membrane that constrains the bone and that it’s the fluid within the bone that results in bone regeneration.  The periosteum also serves as a mechanism of communication with other tissues.  The commenter stated that the periosteum only appears after the bone has taken place.

Here’s the bone histology for Paget’s disease:

paget's disease bone histology

Here’s Paget’s disease in an x-ray of the spine:
pagets disease spine

Here’s someone with paget’s disease in the arm:
pagets disease arm

Paget’s disease can make bones longer but not in a real symmetrical way so it’s not really appealing.

Paget’s disease is a disease where bone undergoes break down and rebuilding much faster than normal(so basically faster bone remodeling cycle) and this results in weaker bones as bone does not have time to develop strength.  If there was a way that Paget’s disease was found to increase height we could mimic the effects somewhat by increasing the amount of bone remodeling that occurs.

Osteomylitis seems caused by infection which would be hard to manage.

Neurofibromatosis can cause overgrowth of specific extremeties related to NF1 and NF2 mutations.