Mind Hack XII: The Power Of Galantamine To Increase Intelligence, Memory, And Just About Every Other Type Of Cognitive Ability

Me: I have recently found out from the website and publication Life-Enhancement about this really powerful supplement product called Galantamine and the articles and information about it is enormous. In my most recent post in Mind Hack XI I showed that IGF-2 dosage can increase memory ability but it seems that the pathway of IGF-2 is actually controlled by Galantamine. I had posted an article from the Nov. 2012 edition of LIfe-Enhancement. If you actually go through the entire LIfe-Enhancement website you will find that there are a lot of articles written about the power of Galantamine. 

Seriously, the entire Life-Enhancement website is FILLED with Galantamine articles and how it improves some form of mental/cognitive ability. From the research on the internet on the effectiveness and ability of galantine supplements, it seems that one of the effects of Galantamine is that gives you more vivid and even lucid dreams. It seems that quite a few studies have been tested on the ability of Galantamine to treat and reduce the effects of Alzheimer’s Disease.

Mind Hack XI: Improve Your Memory Using IGF-2 Injections And Galantamine

Me: I had stated before in a previous Mind Hack post that we can use creatine to improve intelligence by upwards of even 15 IQ points. Now from my research on IGF-2 I have found a few articles an studies down in 2011 that showed that mice which had IGF-2 injected into their hippocampus had increased levels of memory.

Further Analysis: It is really amazing since IGF-2 is one of the few molecules that can actually cross the blood brain barrier. It is suggested that a clinical way of getting humans to take it is through intra-nosal approach. To get the IGF-2 to actually work, it must “coincides with a stage in the learning process called “memory consolidation.” That’s a poorly understood transition period when a memory is still malleable but becoming more established and robust.” It is

From Live Science, Nature, ISSNAF, Science Illustrated, Science Mag, Life-Enhancement…

The article post below is from the LIfe-Enhancement link…

Better for your neurons in 3 ways …Galantamine protects, stimulates,and improves memory… through elevation of insulin-like growth factor 2 By Will Block

Intelligence is the wife, imagination is the mistress, memory is the servant.— Victor Hugo, Post-scriptum de ma vie (1901)

Insulin-like growth factor 2 (IGF2) significantly enhances memory retention and prevents forgetting. That’s what researchers reporting in Nature found last year.1IGF2 is known to be important in body growth and development, but its role in the adult brain has not been established. While highly expressed in the hippocampus, Alberini and colleagues (the authors of the Nature paper) showed that in this region IGF2 has a crucial role in memory consolidation and can make memories last longer.

Using what is known as inhibitory avoidance learning training—a hippocampus-depend­ent learning task that measures fear memory—the researchers placed rats in an environment where upon entering dark areas the rats received a shock to the feet. Their fear memory was enhanced as they learned to avoid the dark areas (into which they are naturally inclined to enter), and this in turn led to an increase in the hippocampal expression of IGF2.

The creation of this IGF2 requires the transcription factor CCAAT enhancer binding protein β,* which is also essential for memory consolidation. Furthermore, injections of recombinant IGF2 into the hippocampus, after either training or memory retrieval, significantly enhanced memory retention and prevented forgetting.

* CCAAT-enhancer-binding proteins are a family of transcription factors, composed of six members that promote the expression of certain genes through interaction with their promoter. Once bound to DNA, these transcription facts can recruit so-called co-activators that, in turn, can open up chromatin structure or recruit basal transcription factors. They are involved in different cellular responses, such as in the control of cellular proliferation, growth, and differentiation, metabolism, immunity, and memory enhancement.

The time factor for efficacy

To be effective, IGF2 needs to be administered within a sensitive period for memory consolidation. IGF2-dependent memory enhancement requires IGF2 receptors, new protein synthesis, the function of activity-regulated cytoskeletal-associated protein, andglycogen-synthase kinase 3 (GSK3). This is intriguing because GSK3 is a regulatory kinase that is implicated in a number of diseases, including type 2 diabetes, Alzheimer’s disease, inflammation, cancer, and bipolar disorder. In hippocampal slices, IGF2 promotes IGF2 receptor-dependent, persistent long-term potentiation after weak synaptic stimulation. Thus, IGF2 may represent a novel target for cognitive enhancement therapies.

Galantamine significantly increases IGF2

In a new study conducted in Japan, researchers examined the effects of acutegalantamine treatment on the mRNA levels of neurotrophic growth factors in the mouse hippocampus and prefrontal cortex.2

The systemic administration of galantamine at doses of 0.3–3 mg/kg (for 3/mg/kg, the human equivalent is 21 mg for a 187 lb person) caused a significant increase in IGF2 mRNA levels in the hippocampus, but not in the prefrontal cortex. The effect of galantamine was also observed at the protein level. IGF2 promotes cell growth, survival, migration, and differentiation and plays an important role in normal fetal development.

IGF2 significantly enhances memory retention and prevents forgetting.

IGF2 increases memory consolidation in rats

In the study cited above,1 it was shown that inhibitory avoidance learning led to an increase in hippocampal expression of IGF2, closely linking to memory consolidation in rats. The researchers showed that injection of recombinant IGF2 into the hippocampus after either training or memory retrieval enhanced memory retention and prevented forgetting. They also showed that IGF2 promoted IGF2 receptor-dependent persistent long-term potentiation after weak synaptic stimulation in the rat hippocampal slices.

Three-way neuronal help

Thus, IGF2 has been implicated in cognitive function associated with the hippocampus. In addition, another study recently demonstrated that IGF2 is an important regulator of adult hippocampal neurogenesis.3 As the authors of the Japanese galantamine/IGF2 study2 observed in a separate experiment, acute galantamine treatment (3 mg/kg) increased newly divided cell proliferation in the hippocampal dentate gyrus of mice 24 hours after the injection (unpublished).

IGF2 has a crucial role in memory consolidation and can make memories last longer.

When taken together, the present finding implies that galantamine: 1) protects neurons, 2) stimulates neurogenesis, and 3) improves cognitive dysfunction in Alzheimer’s disease via its action on IGF2 expression.

The researchers also observed that the higher dose of galantamine (3 mg/kg) caused a transient increase in fibroblast growth factor 2 (FGF2) mRNA level and a decrease inbrain-derived neurotrophic factor (BDNF) mRNA level in the hippocampus of mice. The exact reason for these effects is not known, but previous studies show that nicotine ornicotine acetylcholine receptor (nAChR) agonists increase the expression of FGF2 and decrease the expression of BDNF in the hippocampus.

What is suggested, however, is that the galantamine-induced changes in FGF2 and BDNF mRNA levels may be due to its action on nAChR, although galantamine even at low doses binds allosterically to nAChR and potentiates its function which is to make acetylcholine perform better.With regard to the effect of galantamine on BDNF levels, the Japanese researchers reported that galantamine increases phosphorylation of BDNF’s trkB receptor and transcription factor CREB† in the mouse hippocampus. Thus, it is thought unlikely that galantamine-induced reduction in the BDNF mRNA levels per se is involved in the facilitation of hippocampal neurotrophin signaling.

† CREB (cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes. cAMP (cyclic adenosine monophosphate) is a second messenger important in many biological processes.

Other signals that are not involved

Among the neurotrophic/growth factors examined in the study, galantamine did not affect NGF, VEGF, or IGF1 mRNA levels in the hippocampus and prefrontal cortex. Thus, these factors may not act as the downstream signals of galantamine in either brain region.

Galantamine 1) protects neurons, 2) stimulates neurogenesis, and 3) improves cognitive dysfunction in Alzheimer’s disease via its action on IGF2 expression.

Previous in vitro studies have shown that galantamine is an allosterically potentiating ligand of nAChR. In fact, the nAChR-modulating properties play a key role in the effects of galantamine, while muscarinic acetylcholine receptor (mAChR) activation contributes at least partly to the antipsychotic effect and improvement of cognitive dysfunction by galantamine in rodents.

Antagonists and agonists

The present study2 found that both a nonselective nAChR antagonist and a selective α7 nAChR antagonist block the galantamine-induced increase in hippocampal IGF2 mRNA levels. But, it is not blocked by a preferential M1 mAChR antagonist.

These findings suggest that α7 nAChR is involved in the increasing effect of galantamine on IGF2 expression.

Moreover, the injection of a selective α7 nAChR agonist, at doses of 0.3 and 1 mg/kg increased IGF2 mRNA levels in the hippocampus. These findings suggest that α7 nAChR is involved in the increasing effect of galantamine on IGF2 expression.

In contrast to galantamine, donepezil did not affect IGF2 mRNA levels in the hippocampus.

Getting the dose right

Concerning the effect of the selective α7 nAChR agonist, others have reported that its injection at doses of 1 mg/kg, but not 0.3 mg/kg, improved the performance of rats in the novel object recognition test and much higher doses (0.3 and 1 mg/kg, intravenously) reversed amphetamine-induced auditory gating deficits in rats. The apparent difference in the effect of this agonist at 0.3 mg/kg between the behavioral and biochemical studies may be due to the difference in pharmacokinetics of the drug between rats and mice. Rats have twice the surface area of mice, and this difference determines the right dose.

Donepezil, another inhibitor of acetylcholinesterase, fails

In another study,4 the effect of donepezil was also examined to study the role of galantamine as an allosterically potentiating ligand of nAChR. Donepezil, an inhibitor of acetylcholinesterase, increases extracellular levels of acetylcholine (ACh), which interacts with the α7 nAChR as well, but is not an allosterically potentiating ligand of nAChR.

Galantamine increases hippocampal IGF2 mRNA levels in a dose-dependent manner.

In contrast to galantamine, donepezil did not affect IGF2 mRNA levels in the hippocampus. This difference may be explained by the evidence that ACh has a lower affinity for the α7 nAChR compared to the α7 nAChR agonist references above, and that galantamine is an allosterically potentiating ligand of nAChR.

The present finding suggests that the effect of galantamine on hippocampal IGF2 levels may contribute to the mechanism for its neuroprotective and neurogenesis effects.

Recalling the music of memory

In conclusion, the Japanese researchers found that acute administration of galantamine increases hippocampal IGF2 mRNA levels in a dose-dependent manner. Their study suggests that the galantamine-induced increase in the hippocampal IGF2 mRNA and protein levels is mediated by the α7 nAChR. Recall that IGF2 has been implicated in cell growth and survival, and hippocampus-associated function. Consequently, the present finding suggests that the effect of galantamine on hippocampal IGF2 levels may contribute to the mechanism for its neuro­rotection or neurogenesis. This may be why people taking galantamine like they way that they feel, and that one musician who was forgetting certain music chords that he had known by heart for years, brought back those chords, instrumental to his music, with galantamine.

References

  1. Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, Blitzer RD, Alberini CM. A critical role for IGF-II in memory consolidation and enhancement. Nature 2011 Jan 27;469(7331):491-7.
  2. Kita Y, Ago Y, Takano E, Fukada A, Takuma K, Matsuda T. Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice. Psychopharmacology (Berl). 2012 Aug 30. [Epub ahead of print]
  3. Bracko O, Singer T, Aigner S, Knobloch M, Winner B, Ray J, Clemenson GD Jr, Suh H, Couillard-Despres S, Aigner L, Gage FH, Jessberger S. Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis. J Neurosci 2012 Mar 7;32(10):3376-87.
  4. Koda K, Ago Y, Kawasaki T, Hashimoto H, Baba A, Matsuda T. Galantamine and donepezil differently affect isolation rearing-induced deficits of prepulse inhibition in mice. Psychopharmacology (Berl) 2008;196:293–301.

Will Block is the publisher and editorial director of Life Enhancement magazine.

The interview below is taken from the ISSNAF link.

CRISTINA ALBERINI AWARDED THE DEAN’S AWARD FOR EXCELLENCE IN BASIC SCIENCE RESEARCH
May 2011 – Cristina Alberini, Professor in Neuroscience, Psychiatry and Structural and Chemical Biology at Mount Sinai School of Medicine in New York was awarded the Dean’s Award for Excellence in Basic Science Research. Earlier this year, the discovery of the IGF-II protein in the hippocampus earned her the cover on “Nature”. For Dr Alberini’s interviewCristina Alberini Awarded the Dean’s Award for Excellence in Basic Science Research

Cristina Alberini is a graduate in Biological Sciences at the University of Pavia and received her doctorate in Immunology at the University of Genoa. After holding positions at the Dana Farber Cancer Institute, Harvard Medical School in Boston, Columbia University in New York, the University of Brescia, and Brown University in Providence, Alberini has been Faculty at Mount Sinai School of Medicine  since 2001, where she currently is Professor in Neuroscience, Psychiatry and Structural and Chemical Biology. Among many other acknowledgments, Alberini received the Golgi prize in 2009. This year, she received a 300,000$ grant from the McKnight Endowment Fund for Neuroscience for a three year study on the Role of Astrocytes in Memory and Cognitive Disorders and the discovery of the IGF-II protein in the hippocampus earned her the cover on “Nature”.

Dr Alberini, what is the focus of your research?

I have now focused my interest on how the brain changes in response to external and internal stimuli.  In particular, I am intrigued by how memories are formed, stored and elaborated.  Memory is a fundamental biological function and a critical component of our identity. As such, it involves our brain, mind and psyche. I am interested in exploring the biological mechanisms underlying memory formation.  I am also interested in applying this knowledge to understand how memory becomes an integral part of pathologies such as addiction and trauma and how we can combat memory decay and memory loss.

 

Is IGF2 a growth promoting hormone during gestation? How did you realize that this hormone could be related with memory?

IGF2 is a growth factor that promotes growth during gestation; targeted deletion of IGF2 inhibits growth whereas over-expression of IGF2 promotes growth.

We have been studying the biological changes after learning and required for long-term memory formation in a brain region called the hippocampus. This region is important for the formation of long-term memory. We found that IGF2 levels are regulated by learning in the hippocampus. IGF-II is regulated as a target protein of a pathway that we know to be essential for memory formation. This pathway is the cAMP-response element binding protein – CCAAT enhancer binding protein (CREB-C/EBP), which are proteins that are necessary for the production of other new proteins, like IGF2.  Therefore, we identified a new function for IGF-II in the adult brain.
How did you inject IGF-II in the hippocampus? Are you going to try others methods in clinical tests?

We use a rat model in our lab. To deliver IGF2 into the hippocampus, we implant bilateral cannulae, which allow us to directly inject IGF2 acutely into a targeted brain region.

We are planning to try systemic injections as well as intra-nasal administrations of IGF2. As IGF-2 is one of the factors that readily cross the blood brain barrier, systemic (e.g.subcutaneous) administration of IGF2 would deliver IGF2 to the brain. Intranasal administration will also readily bypass the blood brain barrier, which is the structural barrier of that protects our brain from foreign substances in the blood.
Could you explain how memory consolidation works and how IGF-II is important to enhances memory?

Memory consolidation is the process through which newly learned information becomes long-term. If new  information we encounter is important it will become a long-term memory.  The new memory remains fragile and sensitive to disruption for some time, but over a day or two it becomes stronger and resilient to disruption. This process is the process of consolidation, that is the process that stabilizes a long-term memory. This process depends on the synthesis of new proteins. In our lab we are interested in identifying these newly synthesized proteins that are essential for long-term memory formation. We found IGF2 to be one of these newly synthesized proteins. First we found that the levels of IGF2 increase in the hippocampus after learning, and disrupting the new synthesis of IGF2 impairs the formation of long-term memory. Furthermore, we found that if we give IGF2 after learning, memory is significantly enhanced.  The enhancing effect is only seen if we administer IGF-II during the “active” period of memory: right after learning or after memory is retrieved. Retrieval (or recall) in fact reactivates the memory.  The active phase after memory retrieval is the reconsolidation phase, during which the memory is again labile for some time and restabilizes over time.
In your opinion, why IGF2 could represent a novel target for cognitive enhancement?

IGF2 is a physiological factor that’s produced is our body, so we don’t predict too serious problems with rejecting exogenously administered IGF2 or toxicity. However, careful studies need to be done to exclude that there are unwanted effects and to prove that the treatment is safe.  Since we found that even under an acute administration (single injection of IGF-2) after learning or memory retrieval, memory is robustly and persistently enhanced and forgetting prevented, it represents a simpler and easy to follow clinical regiment (it does not require multiple or chronic treatments) and would presumably also minimize side effects. Lastly, as I mentioned earlier, IGF2 readily crosses the blood brain barrier, so the route of administration won’t hinder its clinical applicability.

Increase Height And Grow Taller Through IGF-2 Localized Injections. (BREAKTHROUGH?)

Me: This is the first article I have posted that showed that using IGF-2 will also lead to longitudinal growth. The authors Zhang and Yokota are the same guys who have been doing the mice hind limb loading tests. This study showed that if you make a localized injection of IGF-2 in the distal epiphysis femur region you would get about an increase of 1.6-1.7% in length. The dosage of IGF-2 was 100 μg/kg/day for 5 consecutive days. Bone samples were taken after 14 days for analysis. The cause is the upregulated phosphorylation of an extracellular signal-regulated kinase in the treated femur.

Further Analysis: It is important to note that the purpose of the study was to see whether there was a way to correct for limb length discrepancies. Two things to note is the life expectancy and age at which mice will stop growing. Mice usually live 1-3 years, but the records have them at 5 years. Assume that mice live usually 2-3 years. The time they stop growing I’ve researched and the numbers seem to suggest that they can stop growing around 4-5 months or as early as 2-3 months. I would assume that the mice tested in the study at 8 weeks still had some growing to do. What is interesting is that the hormone was injected into the bone, specifically the epiphysis, but NOT the growth plate. I would guess that an IGF-2 Injection into the epiphysis while a patient goes through limb lengthening surgery will lead to a faster distraction rate. What I really wonder is whether the mice’s limb grew by themselves or was the lengthening a part of the greater speed of the growth plates which would still be there.

Overall the IGf-2 has been shown to be a really good supplement for muscle mass building, increased energy, and sexual enhancement and drive.

Places to get IGF-2: Bodybuilding.Com, MassNutrition.com, NutraPlanet.com, PredatorNutrition.com, StrongNutrition.com.  These places are only for the oral intake supplement variety of IGF-2 which would not work if you are already physically mature. The cost ranges from usually $40-$60 . However I don’t see any issues with grinding up the pill, mixing it with a saline compound and injecting it into the localized epiphysis area. I personally would try to get some mice from my local pet store, grow them to 1 years age, and repeat this experiment to see what would happen to their limbs with the IGF-2 injections. I know of many bodybuilders who inject themselves intravenously or Intramuscular with liquid IGF-2 and I would wonder where they got the liquid version. For our purposes we would have to get into the very bone to the center.

From PubMed study link HERE…

J Chin Med Assoc. 2012 Oct;75(10):494-500. doi: 10.1016/j.jcma.2012.07.009. Epub 2012 Sep 28.

Lengthening of mouse hind limbs with local administration of insulin-like growth factor 2.

Zhang P, Jiang C, Yokota H.

Source

Biomedical Engineering, Indiana University Purdue University, Indianapolis, Indiana, USA; School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA. Electronic address: pizhang@iupui.edu.

Abstract

BACKGROUND:

For devising potential clinical approaches for limb length discrepancies, we examined local administration of insulin-like growth factor 2 (IGF2).

METHODS:

C57/BL/6 mice (∼ 8 weeks old) were used in this study, and the mice were separated into two groups: an IGF2-treated group and a placebo group. In the IGF2-treated group, IGF2 was locally administered into the distal epiphysis of the left femur, and the right femur was used as a contralateral control. In the placebo group, saline was administered to the left femur as a vehicle control. The left and right tibiae, without any direct intervention, were employed as negative controls. The dosage of IGF2 was 100 μg/kg/day for 5 consecutive days, and bone samples were harvested on Day 14. Microcomputed tomography images did not show any anomaly at the IGF2 or saline injection sites.

RESULTS:

In comparison with the vehicle control as well as the contralateral control, the results revealed that IGF2 significantly lengthened the treated femur, with an elevation of bone mineral density (BMD) as well as bone mineral content (BMC). The increase in the femoral length of the IGF2-treated left limb was 1.6% (p < 0.05) to the vehicle control, and 1.7% (p < 0.05) to the contralateral control. However, the length, BMD, and BMC of the tibiae were not affected by administration of IGF2 or saline. Western blotting analysis demonstrated that this administration of IGF2 upregulated phosphorylation of an extracellular signal-regulated kinase in the treated femur.

CONCLUSION:

The current study supports for the first time the potential effectiveness of administration of IGF2 in adjusting limb length discrepancy.

Copyright © 2012. Published by Elsevier B.V.

PMID: 23089400    [PubMed – in process]

Evidence That The LSJL Method Or Loading Is Ineffective In Post-Pubertal Adult Humans? (Important)

Me: I think this study that I somehow found seems to bring up evidence that the LSJL method that some height increase seekers have  been using might not be effective in generating the gains they have been hoping for. While the study never states at face value that there was at metaphysis lengthening form loading in prepubertal girls as compared to post pubertal girls, it seems to suggestively imply that.

The issue is that with the study, I couldn’t find where they said what actual type of loading was done. Did they use the same type of device as the stuff used on mice with Yokota and Zhang?

Analysis: The thing about this study was that length was never measured but only cortical diameter. As stated from the results section “Growth itself, as reflected by structural changes in the nonloaded arm, resulted in a 14% increase in cortical area of the mid- and distal humerus from the pre- to peripubertal years because of greater periosteal expansion than medullary expansion“. That could correlate to length increase assuming proportional size increase. For my final interpretation, I am of course assuming that the periosteal appositional growth we see in prepubertal females don’t just affect in the radial direction leading to bone thickening but also the limb ends of the epiphysis which leads to long bone lengthening too. For the post pubertal females the endocortical surface is what is begin affected, which means nothing to the outer surface of the bone which means neither lengthening to shortening.

Main Points: “Cortical areas of the mid- and distal humerus were ∼14% greater in the peripubertal players than in the prepubertal players because of greater periosteal expansion than medullary expansion. Cortical areas of the mid- and distal humerus were ∼20% greater in the postpubertal players than in the peripubertal players. At the midhumerus, this was the result of periosteal expansion alone, whereas at the distal humerus, medullary contraction contributed to the larger cortical area”

Before puberty, periosteal apposition accounts for most of the increase in cortical area. Endocortical resorption creates an enlarging marrow cavity and partly offsets the increase in cortical area produced by periosteal apposition. The net result is an enlarged cortical area located further from the neutral axis, which has the effect of increasing its resistance to bending.(3) Late in puberty, periosteal apposition continues with a contribution from endocortical apposition(7); particularly at the distal humerus, where, in this study, the increase in cortical area was the result of equal contributions from periosteal and endocortical apposition.

Before puberty, loading magnified periosteal apposition. During the postpubertal period, loading magnified the effect of endocortical apposition, which makes an important contribution to cortical thickness in females. Indeed, endocortical apposition accounted for most of the greater side-to-side difference attained in the postpubertal years.

Thus, loading affects both the periosteal and the endocortical surfaces but the magnitude of the effects vary according to whether the surface is anterior, posterior, medial, or lateral and according to whether the region is proximal, central, or distal along the bone’s length. 

In conclusion, loading before puberty increases bone size and its resistance to bending. After puberty, loading increases the acquisition of bone on the endocortical surface with little benefit in the bone’s resistance to bending. Growth and the effects of loading were surface specific and varied along the length of the bone depending on the maturation of the region as well as the intensity and direction of loading. Increasing the bone’s resistance to bending and torsion is achieved by modifying the shape and mass of bone but not necessarily its density.

Conclusion: What might be the smartest thing to do is actually try to contact the people who originally did this experiment and try to ask them whether they ever tried to collect length data for the unloaded/loaded differences.

From PubMed Source link HERE…

J Bone Miner Res. 2002 Dec;17(12):2274-80.

The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players.

Bass SL, Saxon L, Daly RM, Turner CH, Robling AG, Seeman E, Stuckey S.

Source

School of Health Sciences, Deakin University, Melbourne, Australia.

Abstract

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8-17 years. Periosteal (external) cross-sectional area (CSA), cortical area, medullary area, and the polar second moments of area (I(P), mm4) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and I(P) of the humerus were 11-14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri- or postpubertal players despite longer duration of loading (both, p < 0.01). The higher BMC was the result of a 7-11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone’s resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone’s resistance to torsion is achieved by modifying bone shape and mass, not necessarily bone density.

PMID: 12469922    [PubMed – indexed for MEDLINE] 

This source link HERE is the full article.

Keywords:

  • exercise; growth and development; bone strength; rigidity

Abstract

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8–17 years. Periosteal (external) cross-sectional area (CSA), cortical area, medullary area, and the polar second moments of area (IP, mm4) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and IP of the humerus were 11–14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri- or postpubertal players despite longer duration of loading (both, p < 0.01). The higher BMC was the result of a 7–11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone’s resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone’s resistance to torsion is achieved by modifying bone shape and mass, not necessarily bone density.

INTRODUCTION

Exercise during growth results in biologically important increases in bone mass. Growth in bone width and cortical thickness before puberty occurs by greater periosteal (outer surface) apposition than by endocortical (inner surface) resorption. During puberty, estrogen production inhibits periosteal apposition but stimulates the acquisition of bone on the endocortical surface.(1)

It has been proposed that exercise will enhance formation at the surfaces of bone undergoing bone apposition.(2) Because apposition of bone on the periosteal surface is a more effective means of increasing the bending and torsional strength of bone than acquisition of bone on the inner surface,(3) exercise regimens may be more effective when undertaken at a time when the growth of bone is dominated by periosteal rather than endocortical growth.

Exercise has been reported to enhance periosteal expansion in young animals and endocortical contraction in mature animals. Thus, to determine whether the effects of exercise depend on the maturational stage of the region exposed to loading as well as the intensity and duration of the loading, we tested the following hypotheses: (i) loading of bone during tennis playing will result in increased cortical area of the playing humerus because of periosteal expansion with no endocortical apposition in the pre- and peripubertal years; (ii) during the postpubertal years, loading will increase cortical area by endocortical apposition with less contribution from periosteal apposition; and (iii) the exercise-induced increase in cortical area and bending strength of the humerus will be caused by greater periosteal apposition with little or no contribution from endocortical bone acquisition.

MATERIALS AND METHODS

Subjects

Forty-seven pre-, peri-, and postpubertal competitive female tennis players aged 8–17 years were recruited from tennis clubs in Melbourne, Australia. Players were included if they had been playing competitive tennis for a minimum of 2 years and were currently playing at least 3 h/week (Table 1). Forty girls were right-handed, and 41 girls used a double-handed backhand. Longitudinal data were collected in 37 subjects after 1.1 ± 0.01 years (range, 0.8–1.5 years); 6 subjects remained prepubertal, 6 subjects became peripubertal, 9 subjects remained peripubertal, and 16 subjects remained postpubertal during the observation period. Ten subjects were not included because they were either no longer playing (n = 2), not willing to participate (n = 4), or relocated (n = 4).

Table Table 1.. Age, Age of Menarche, and Training History of Pre-, Peri-, and Postpubertal Female Tennis Players (Mean ± SEM)

All girls were healthy and received no medication known to affect the skeleton. The Deakin University and Alfred Hospital ethics committees approved the study, and written consent was obtained from all participants and their parents. Sexual maturation was self-assessed with parental guidance using the standard five-scale Tanner stages for breast development. Subjects were classified as prepubertal (Tanner stage 1), peripubertal (Tanner stage 2–4), or postpubertal (postmenarche).

 

Bone geometry, mass, and strength

Magnetic resonance imaging (MRI) was used to determine bone dimensions (1.5 T whole-body unit; with a commercial transit-receive torso coil; Signa Advantage GE Medical Systems, Milwaukee, WI, USA). T1-weighted spin-echo images at a repetition time (TR) of 600 ms and an echo time (TE) of 14 ms were acquired in the axial plane. Field of view was 200 mm2 and the matrix size was 512 × 192. The region of interest (ROI) was 30–60% from the distal end of the humerus and was divided into thirds. Areas of the proximal third of the ROI representing the midportion of the humerus were compared with the distal third. Five-millimeter slices (with 5-mm gaps between slices) were scanned along the ROI. Each axial image was analyzed using the OSIRIS imaging software program (Digital Imaging Unit, Center of Medical Informatics, University Hospital of Geneva, Geneva, Switzerland). Periosteal area was the external size of the bone (i.e., periosteal border) and cortical area was periosteal minus the medullary area (Fig. 1).

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Figure FIG. 1.. Typical MRI transverse slices of cortical bone (black) and medullary area (white) of the playing and nonplaying humerus of a postpubertal female tennis player. ROIs were analyzed at the mid- and distal humerus, each representing 10% of the total arm length (30–40% and 50–60%, measured from the distal condyles).

Summing the cross-sectional areas of each slice in the ROI divided by the total number of slices in the ROI determined average periosteal, cortical, and medullary areas. The short-term precision (CV) was 1.02% and 0.21% for periosteal and cortical bone areas, respectively. In vivo studies using bovine bones have shown that MRI provides accurate estimates of bone cross-sectional areas, and these data correlate well with quantitative computed tomography (QCT) measurements of the same bone (r2 = 0.98).(4) Bone mineral content (BMC) of the playing and nonplaying arm was measured using DXA (CV for BMC was 3.6%; Lunar DPX-L, version 1.3b; Lunar Corp., Madison, WI, USA).

To assess the bones resistance to bending (rigidity), each image was imported into Scion Image 4.0.2 (Scion Corp., Frederick, MD, USA). The maximum (IMAX, mm4) minimum (IMIN, mm4), and polar (IP, mm4) second moments of area were calculated using a custom macro. The second moment of area (I) reflects a structure’s resistance to bending and is calculated by dividing the section into small areas (pixels), and multiplying each (dA) by its squared distance from the neutral plane. This procedure is integrated over the entire cross-section. The macro calculates I about all possible neutral planes and reports the largest value as IMAX and the smallest value as IMIN, which are perpendicular to one another. The polar second moment of area (IP) reflects a long bones resistance to torsion and equals the sum of the maximum and minimum moments of area (IP = IMAX + IMIN).

Statistical analysis

Data were expressed in absolute terms and as a percentage of the nonplaying arm. Within each pubertal group, side-to-side differences were assessed using paired t-tests. ANOVA, with Tukey post hoc comparisons, was used to detect differences between pubertal groups. In the longitudinal analysis, subjects were divided according to pubertal status: prepuberty to prepuberty (n = 16), peripuberty to peripuberty (n = 15, includes prepuberty to peripuberty and peripuberty to peripuberty), and postpuberty to postpuberty (n = 16). Repeated measures ANOVA and analysis of covariance (ANCOVA) were used to determine changes over time in bone strength adjusted for bone size. Significance is reported as p < 0.05; borderline significances are reported at p < 0.1. All data are reported as mean ± SE unless otherwise stated.

RESULTS

Growth itself, as reflected by structural changes in the nonloaded arm, resulted in a 14% increase in cortical area of the mid- and distal humerus from the pre- to peripubertal years because of greater periosteal expansion than medullary expansion (Table 2 and Fig. 2). Cortical area of the mid- and distal humerus were both ∼20% greater in the postpubertal players than in the peripubertal players (Table 2and Fig. 2). At the midhumerus, this was the result of periosteal expansion alone, whereas at the distal humerus, medullary contraction contributed to the larger cortical area.

Table Table 2.. Cross-Sectional Analyses of the Change in Cortical, Periosteal, and Medullary Bone Areas and the Second Polar Moment of Area (Ip) in the Nonloaded Humerus With Advancing Maturation (Mean ± SEM)

 

 

 

 

Figure FIG. 2.. Schematic scaled representation of structural changes in the nonloaded arm. Cortical areas of the mid- and distal humerus were ∼14% greater in the peripubertal players than in the prepubertal players because of greater periosteal expansion than medullary expansion. Cortical areas of the mid- and distal humerus were ∼20% greater in the postpubertal players than in the peripubertal players. At the midhumerus, this was the result of periosteal expansion alone, whereas at the distal humerus, medullary contraction contributed to the larger cortical area.

The effect of loading was reflected in the side-to-side trait differences. BMC and resistance to torsion (IP) of the humerus were 11–14% greater in the loaded arm than in the nonloaded arm in the prepubertal players (both p < 0.01) and did not increase further in peri- or postpubertal players despite longer duration of loading (Tables 1 and 3). The higher BMC was the result of a 7–11% greater cortical area in the prepubertal players, which was the result of greater periosteal expansion than medullary expansion at the midhumerus but greater periosteal expansion alone at the distal humerus (Table 3 and Fig. 3). Loading during the peri- to postpubertal years resulted in medullary contraction at both sites; however, this did not lead to a significant increase in the side-to-side difference in cortical area (Table 3 and Fig.3).

Table Table 3.. Average Bone Areas of the Mid- and Distal Regions of the Humeral Shaft in the Loaded and Nonloaded Humerus of Pre-, Peri-, and Postpubertal Female Tennis Players (Mean ± SEM)

 

Figure FIG. 3.. The change in cortical area caused by loading ([box with slashes]) is the net effect of changes in the medullary (□) and periosteal areas ([box with horizontal slashes]). The 7–11% greater cortical area in the prepubertal players was the result of greater periosteal expansion than medullary expansion at the midhumerus but greater periosteal expansion alone at the distal humerus. Loading during the peri- to postpubertal years resulted in medullary contraction at both sites; however, this did not lead to a significant increase in the side-to-side difference in cortical area. †p < 0.08 and ‡p < 0.01 verus zero; **p < 0.06 and *p < 0.05 versus postpubertal players relative to bone size.

Similar observations were made in the 37 girls followed during the 12 months of follow-up. In particular, cortical area at the distal site increased 4% more in the loaded arm than in the nonloaded arm in the postpubertal players because of contraction of medullary area (2%,p < 0.05) and increased periosteal expansion (2%, NS).

DISCUSSION

Growth in the external size of a long bone, its cortical thickness, and the distribution of cortical bone about the neutral axis are determined by the absolute and relative behavior of the periosteal and endocortical bone surfaces along the length of the bone.(5, 6) Before puberty, periosteal apposition accounts for most of the increase in cortical area. Endocortical resorption creates an enlarging marrow cavity and partly offsets the increase in cortical area produced by periosteal apposition. The net result is an enlarged cortical area located further from the neutral axis, which has the effect of increasing its resistance to bending.(3) Late in puberty, periosteal apposition continues with a contribution from endocortical apposition(7); particularly at the distal humerus, where, in this study, the increase in cortical area was the result of equal contributions from periosteal and endocortical apposition.

In addition to surface specificity, growth is also region specific with more rapid maturation of distal regions than proximal regions. Distal segments of the appendicular skeleton mature before the proximal segments.(1,7,8) The longitudinal data indicate that when the subjects were older, endocortical contraction was detected at the midhumerus but not at the distal humerus.

Loading magnifies the structural changes produced during growth and this was detected by comparing the trait differences in the loaded and nonloaded arms. The data suggest that during growth the effect of exercise, like the effect of risk factors, is determined not only by the intensity of exercise or severity of illness, but also by the timing of exposure.(7, 9) Before puberty, loading magnified periosteal apposition. During the postpubertal period, loading magnified the effect of endocortical apposition, which makes an important contribution to cortical thickness in females. Indeed, endocortical apposition accounted for most of the greater side-to-side difference attained in the postpubertal years.

Most of the structural changes occurred early in the prepubertal years because adaptive changes in response to loading were sufficient to reduce the strains in bone that may lead to microdamage if not decreased.(10, 11) The only additional benefit achieved from tennis training later in puberty was contraction of the medullary cavity, which did not confer any additional increase in the structural rigidity of the bone. Similar effects have been reported in soccer players in whom increased duration of training beyond 6 h/week had no benefit on bone mass.(12) To further modify bone mass or architecture, other components of loading other than duration (i.e., magnitude or strain patterns) would have to increase, as reported in elite gymnasts.(13)

Heterogeneity in the response to loading has been reported in several studies.(14–17) The relative contributions of periosteal and endocortical modeling and remodeling varies along the whole length of a limb.(18) Local loading will modify each part of the geometry of the bone in accordance with the imposed load. In racquet sports, the greater humeral cortical area of the loaded versus the nonloaded arm is the result of both greater periosteal expansion and greater endocortical contraction; for instance, the relative contributions of periosteal expansion and endocortical contraction to the greater cortical thickness in the loaded arm than in the nonloaded arm in a study by Haapasalo et al. were 75:25 at the proximal humerus and 10:90 at both mid- and distal humerus.(15) In the study by Jones et al., the respective relative contributions of greater periosteal expansion and greater endosteal contraction to the greater cortical thickness were 60:40 in the anteroposterior dimension and 80:20 in the mediolateral dimension in male and female tennis players.(16)

Thus, loading affects both the periosteal and the endocortical surfaces but the magnitude of the effects vary according to whether the surface is anterior, posterior, medial, or lateral and according to whether the region is proximal, central, or distal along the bone’s length. Measurements of bone geometry in two dimensions using densitometry or X-rays cannot adequately describe this heterogeneity. Bone is not a cylinder with a circular perimeter and the assumption that loading will produce homogenous changes is flawed.

In conclusion, loading before puberty increases bone size and its resistance to bending. After puberty, loading increases the acquisition of bone on the endocortical surface with little benefit in the bone’s resistance to bending. Growth and the effects of loading were surface specific and varied along the length of the bone depending on the maturation of the region as well as the intensity and direction of loading. Increasing the bone’s resistance to bending and torsion is achieved by modifying the shape and mass of bone but not necessarily its density.

Acknowledgements

The authors thank radiographers Amanda Hunt and Glenn Rush for their technical assistance. They also thank the players and their parents for their time given to this study. This study was funded by grants from the Australian Research Council Grant and the School of Health Sciences, Deakin University.

REFERENCES

  • 1. Garn S 1970 The Earlier Gain and Later Loss of Cortical Bone. Charles C Thomas, Springfield, IL, USA.
  • 2. Ruff CB, Walker A, Trinkaus E 1994 Postcranial Robusticity in Homo. III: Ontogeny. Am J Phys Anthrop 93: 35–54.
  • 3. Turner CH, Burr DB 1993 Basic biomechanical measurements of bone: A tutorial. Bone 14: 595–608.
  • 4. Woodhead HJ, Kemp AF, Blimkie CJR, Briddy JN, Duncan CS, Thompson M, Lam A, Howman-Giles R, Cowell CT 2001Measurement of midfemoral shaft geometry: Repeatability and accuracy using magnetic resonance imaging and dual-energy X-ray absorptiometry. J Bone Miner Res 16: 2251–2259.
  • 5. Seeman E 2002 An exercise in geometry. J Bone Miner Res 17: 373–380.
  • 6. Seeman E 2001 Clinical review 137: Sexual dimorphism in skeletal size, density, and strength. J Clin Endocrinol Metab 86:4576–4584.
  • 7. Bass S, Delmas PD, Pearce G, Hendrich E, Tabensky A, Seeman E 1999 The differing tempo of growth in bone size, mass and density in girls is region-specific. J Clin Invest 104: 795–804.
  • 8. Preece MA, Hendrich I 1981 Mathematical modelling of individual growth curves. Br Med Bull 37: 247–252.
  • 9. Seeman E, Karlsson M, Duan Y 2000 On exposure to anorexia nervosa, the temporal variation in axial and appendicular skeletal development predisposes to site-specific deficits in bone size and density: A cross-sectional study. J Bone Miner Res 15:2259–2265.
  • 10. Frost H 1987 The mechanostat: A proposed pathogenic mechanism of osteoporosis and the bone mass effects of mechanical and nonmechanical agents. Bone Miner 2: 73–86.
  • 11. Lanyon LE 1987 Functional strain in bone tissue as an objective and controlling stimulus for adaptive remodelling. J Biomech 20:1083–1093.
  • 12. Karlsson MK, Magnusson H, Karlsson C, Seeman E 2001 The duration of exercise as a regulator of bone mass. Bone 28:128–132.
  • 13. Bass S, Pearce G, Bradney M, Hendrick E, Delmas P, Harding A, Seeman E 1998 Exercise before puberty may confer residual benefits in bone density in adulthood: Studies in active prepubertal and retired female gymnasts. J Bone Miner Res 13: 500–507.
  • 14. Haapasalo H, Sievanen H, Kannus P, Heinonen A, Oja P, Vuori I 1996 Dimensions and estimated mechanical characteristics of the humerus after long-term tennis loading. J Bone Miner Res 11: 864–872.
  • 15. Haapasalo H, Kontulainen S, Sievanen H, Kannus P, Jarvinen M, Vuori I 2000 Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: A peripheral quantitative computed tomography study of the upper arms of male tennis players. Bone 27: 351–357.
  • 16. Jones HH, Priest JD, Hayes WC, Tichenor CC, Nagel DA 1977 Humeral hypertrophy in response to exercise. J Bone Joint Surg Am 59A: 204–208.
  • 17. Huddleston A, Rockwell D, Kulund DN, Harrison B 1980 Bone mass in lifetime tennis athletes. JAMA 244: 1107–1109.
  • 18. Hsieh YF, Robling AG, Ambrosius WT, Burr DB, Turner CH 2001 Mechanical loading of diaphyseal bone in vivo: The strain threshold for an osteogenic response varies with location. J Bone Miner Res 16: 2291–2297.

From an old link on P. Zhangs’s article on joint loading on hindlegs of pre-pubescent mice HERE…. For the Full Text of the study click HERE.

J Bone Miner Metab. 2010 May;28(3):268-75. Epub 2009 Nov 5.

Lengthening of mouse hindlimbs with joint loading.

Zhang P, Hamamura K, Turner CH, Yokota H.

Source

Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.

Abstract

For devising clinical approaches to treating limb length discrepancies, strategies that will generate differential longitudinal growth need to be improved. This report addresses the following question: does knee loading increase bone length of the loaded hindlimb? Knee loading has been shown to induce anabolic responses on the periosteal and endosteal surfaces, but its effects on longitudinal bone growth have not yet been examined. In the present studies, loads were applied to the left hindlimb (5-min bouts at 0.5 N) of C57/BL/6 mice (21 mice, ~8 weeks old). Compared to the contralateral and age-matched control groups, knee loading increased the length of the femur by 2.3 and 3.5%, together with the tibia by 2.3 and 3.7% (all P < 0.001), respectively. In accordance with the length measurements, knee loading elevated BMD and BMC in both the femur and the tibia. Histological analysis of the proximal tibia revealed that the loaded growth plate elevated its height by 19.5% (P < 0.001) and the cross-sectional area by 30.7% (P < 0.05). Particularly in the hypertrophic zone, knee loading increased the number of chondrocytes (P < 0.01) as well as their cellular height (P < 0.001) along the length of the tibia. Taken together, this study demonstrates for the first time the potential effectiveness of knee loading in adjusting limb length discrepancy.

PMID: 19890688       [PubMed – indexed for MEDLINE]

How To Build A Personal LSJL Automatic Device For Less Than $600

One of Tyler’s comments which was posted to me got me wondering whether there might be a easier way to possibly do the Lateral Synovial Joint Loading. The clamps we might buy operates on a rather easily understood principle. Two blunt, rather flat surfaces is compressive down upon bone tissue to try to create bone modification. Most people have legs that are about 3-4 inches in diameter and the knee is often slightly smaller in width.

[The exact location we are supposed to load the clamp is the protruding bumps on the side of our limb synovial joints. There are 5 locations that I can think of from the top of my head, the wrist area, the elbow area of the forearm, above the knee where the distal femur epiphysis is, below the knee where the proximal tibia and fibula are, and the ankle area where the tibia is connected to the feet bones.]

This means that any device that is build must be able to at least clamp around 4 inches of material. We know that we can try using weights/ dumbbell but that is hard to aim and really compress/load in the right area. Plus, the other side using a dumbbell would have the hard floor to load on.

What I propose in this post is to build an automatic LSJL device for less than $600 in cost, using material one can find from EBay and speciality shops on the internet.

When I first started on the idea, I envisioned in my head a device that was similar to a piston that push in a axial direction with sinusoidal behavior. When I called and around and did some research, most people at a hardware store or electronic store could not even give a name what such a device would look like.

I have worked in building robots before so I know that if the device could not be bought as an intact device, then it could be built, because I know exactly which parts are needed. Eventually I found the right suppliers and parts to make the device.

These are the parts needed

1. We need to buy two linear actuators. The two types I would suggest is get either the electro-mechanical or the linear motor, which can give one some speed. The actuators are what would allow one to control the stroke action, where one stroke compresses and load, while the alternate stroke releases the loading. A website to use is Progressive Automations. For the actual thing to buy, we would be looking for the strongest ones since I am almost positive to scale up the loading from the original experiments done on mice hindleg bone, we might have to multiple the loading force by at least 10,000X.

Note three factors of the actuators,

  • 1. stroke size – this is the maximum stroke or actual length that can happen. This also determines the both the size of the actual device and the range one can put the actuators apart from each other.
  • 2. force – the amount of loading that is being exerted.
  • 3. speed – the amount of change that the stroke can change by per second.
We have to remember the actual values of the loading (in Newtons) , the frequency, and the frequency each week the loading was done on the mice legs and keep the frequency the same, but increase the loading amount. I personally would suggest trying at a force of around 100X to start with.
I do note that most of the stuff on the Progressive Automations website are either fast and light or slow and strong. Go with the actuators that only have a stroke size of 4″ or less since you want to make this device at least small enough and portable to move it rather easily. I would go with the Tubular High Speed models first which can go up to 9-3″/sec but relatively weak at 33-11 lb at $160 each. If the loading is not strong enough, move on towards the heavy duty ones with 2000 lb force, 2 or 4 ” stroke size, and 0.24″/sec speed. These cost about $300 each.

2. We need to buy a field-programmable gate array (FPGA). FPGAs are integrated circuits which you can plug to your own computer and program to send specific signals out. For more information on FPGA check out the wikipedia article on it HERE. For a company where you can buy a very nice easy to use FPGA board you can try Digilent Inc HERE. You can get a Nexys-3 Spartan-6 for $200 but also discount it for $120 if you are a student. This should handle simultaenous devices. Remember that if you are using the board to control the stroking movement, you have to get the digital actuators which I haven’t looked into.

3. You need a board and a mounting bracket sold HERE to hold the electro-mechanical actuators in place, at about 6 inches apart from each other in their standard resting distance. depending on what size of stroke you buy, you may have to put the devices either further apart or closer together to account for both the stroke size and your leg width.

4. You need a computer with knowledge on embedded systems to program the FPGA board. This part I have no knowledge on. It would take me at least 3 months to learn how to program using the original language I used which was Assembly. Most people seem to suggest using C or Java these days. Almost any Electrical Engineering major in university would know how to do this part.

5. It might be helpful if on the ends you put some types of plastic plug or covering to avoid skin chafing or stretching when the loading is happening.

Alternatively, if you don’t want to get the stuff for 2 and 4, you can get the control box for the actuators HERE. There is a nice video on the website to show how easy it is to just use the control box. You want to buy the one AC controller with 2 motors with simultaneous function which costs $186. However, the issue is that they seem to only have one speed, but we would need to test the leg bone’s response to different frequencies and speeds. That is why we can modulate the speed of the actuator with the FPGA board.

Actual construction: So you basically just mount the two linear actuators facing each other, screw or bolt the devices on a board or plane which will not be moving, plug the actuator cord into the board, and program the board to send specific wave function signals to the actuator to either stoke in or out. The simpler method would be to remove the Board completely and just go with a controller board but one might have to replace and switch actuators if the speed and force are not right for the bone lengthening effect we desire. No matter what, you need at least 4 parts, the two actuators, something to control it, and the mounting parts to hold the actuators down to a flat solid surface. The combined total is around the $600 range for the weaker loading devices and around $800 for the stronger loading devices.

 

A Final Message On The InstaHEIGHT Products And Any Other Height Increase E-Products Out There, For You Rafael

Note: This is a message for Rafael and any other future and new readers who come to this website asking about E-Products found on the internet dealing with Height Increase.

I was planning on not writing any new posts for at least 7 days while I change a few things on the website but this new recent development has to be resolved.

In my last post I had done a product review on the E-Books from the InstaHEIGHT.com website since a regular reader of the website Rafael informed me and another regular reader that there was another E-Book for Height Increase out there. I looked at the website, read the links and citations, and had concluded that the book is part of a scam.

Maybe I was not clear on what I mean. What I meant to say is that the E-product will not work for a person who is already a physically mature adult, with no growth plates available. If you are still young and can still grow, the advice might help. If your bones are set, I would suggest trying something else.

I have looked through the 2 main products, the E-Book “HGH Explained, Understanding InstaHEIGHT Super Massing” and the E-Book “Inch Adding, Get Taller Today” both by authors Deavon Stollar & Harry Pope.

A Slightly Deeper Analysis: First of all, the 1st PDF/Book is only 41 pages of actual PDF writing with 4 of those pages with pictures of only ads. The other book/PDF is 21 pages with 5 of the pages having no information. All the information in the E Books I can reproduce at a higher level of detail. Of course I have been researching and studying this stuff for a few months though. On the first Doc there is suppose to be a chapter #7 which is entitled ” The instaHeight super massing procedure ” and that on pg. 34 is completely missing. Why is that entire chapter missing?  There is also no actual steps or actions the Book tells me to actually take in the entire PDF. I could not find any steps on what I should be actually doing. The chapter that is supposed to be of actual use and action is missing. 

All the 3 E-Book PDFs  you have given me I have already uploaded to the “Downloads” section of the website. I want to show and give it to the other people in the world who wish to look at it, analyze it, and see if it is real or not. If you are upset at me over this since they did not have to pay that type of money, then I will pay you the money back for it. Just contact me on the website email, sent me your Bank account Real Name, routing #, account #, and which bank you use (need bank transit #) and I will transfer you the $67 you paid through my Bank Of America checking account if you should desire. All that I ask is that you come along this website and write a message which will be posted saying that I have given you my own money to help you out so that at least you won’t be hurt financially by this.

[Note: Since you are the first reader of this website to be so adamant and believe in an E-Product that I have not seen before, I will only do this ONE time and never again. I will be giving you my own money just to cover you if you so should wish but this will not happen again for anyone else after this event.]

If you happened to be a internet marketer who is selling the InstaHEIGHT product and trying to trick me by coming to this website to promote the product then I can only say that I am sorry about that. We all have to make our own decisions on how we choose to live our lives. Rafael, I am going to ask that you try to use the Refund policy on the InstaHEIGHT website and get your money back.   The internet is full of huckster and sometimes we get tricked. I have been tricked myself when I didn’t know better.

I have not revealed who I am at this time yet but I think it is time that I at least reveal my first name to the readers of this website/blog to  make myself more transparent. I am really hear to inform, help others, and do research for this endeavor.

My name is Michael. I am 28 years old. And I want to help myself and others possibly get taller and gain extra height. Honestly, legitimately, with real scientific evidence and facts.