There's a patent pending on free patents online for a new height increase product called a "composition for increasing body height":
"This invention provides a composition for increasing a body height of a patient with short stature or an individual other than patients with short stature. More specifically, the invention provides: a composition for increasing the body height of an individual comprising a guanyl cyclase B (GC-B) activator as an active ingredient, the composition being to be administered to an individual free from FGFR3 abnormality; a method for increasing the body height of an individual free from FGFR3 abnormality which comprises activating GC-B[I don't know if GC-B will increase height on it's own without additional cGMP]; a method for screening an agent for increasing the body height of an individual which comprises selecting an agent for increasing the body height using GC-B activity as an indication; and a method for extending a cartilage bone free from FGFR3 abnormality which comprises activating GC-B in an individual."
"Guanyl cyclase (GC) is a membrane protein belonging to the enzyme family that catalyzes the synthesis of the second messenger cGMP from GTP. GC-B is found mainly in vascular endothelial cells, and thought to be involved in relaxation of the smooth muscle."
"Natriuretic peptides (NPs) are divided into ANP (atrial sodium peptide), BNP (brain natriuretic peptide) and CNP (type c natriuretic peptide), and they are thought to elevate an intracellular cGMP level through two guanyl cyclase conjugated receptors (NPR-A for ANP and BNP, and NPR-B for CNP) and to perform intracellular signal transduction mediated by a plurality of cGMP effecter molecules. NPs have been reported to play an important role in the control of humoral homeostasis and blood pressure, and their expression and biological activity in various tissues other than the cardiovascular system are known. Concerning cartilage bones, effectiveness of overexpression of BNP or CNP in the joints on the treatment of achondrogenesis resulting from mutation of a fibroblast growth factor receptor 3 (FGFR3) gene has been reported."
"We have prepared a C-type natriuretic peptide (CNP) transgenic mouse, which expresses CNP, a guanyl cyclase B (GC-B) activator, systemically with elevated blood level of CNP, and then studied the effect of CNP on body height or on growth cartilage. As a result, we have now found that in the CNP transgenic mouse the increase in body height is accelerated, that the femoral growth plate cartilage becomes significantly thickened, and that, through the property analyses of such CNP transgenic mice, the increase in body height is accelerated by the effect of CNP on hematogenously in the absence of an abnormality in FGFR3."
Now remember an acceleration of height gain does not necessarily mean an increase in final adult height.
"The thickness of the growth cartilage of CNP Tgm(CNP transgenic mice) was histologically analyzed using the mean thickness of the resting layer, proliferating layer and hypertrophy layer of the growth cartilage on the patellar surface femur, and the total of the three layers (as the thickness of growth cartilage). As a result, it was confirmed that each thickness of the resting layer, proliferating layer and hypertrophy layer, and the total thickness thereof for CNP Tgm were greater with statistical significance than those of the wild type. It was also demonstrated that CNP accelerates the increase in body height in animals by increasing each thickness of the resting layer, proliferating layers and hypertrophy layer of other cartilage bones, such as the tibiae, radiuses or ulnae, in addition to those of the cartilage bone of femora."
Now C-type natriuretic peptide affects the resting layer which might be the limiting factor in terms of height growth. Therefore, this supplement does have potential to increase height since it does act locally on the growth plate and affects the starting stage of growth.
"In the present invention, the term “FGFR3 abnormality” refers to achondrogenesis or achondroplasia, which is caused by growth inhibition of cartilage bones resulting from mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, or achondrogenesis or achondroplasia caused by function control failure of FGFR3 or overexpression of FGFR3 gene resulting from mutations in the FGFR3 gene."
I don't get what a cartilage bone is. Maybe it refers to a long bone which has cartilage in the growth plate.
There are lots of studies that state that C-type natruiretic peptides are essential in growth and can account for growth variation like this one:
A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation.
"Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (P(combined) = 3.4 x 10(-9)). Notably, a second SNP (rs6718438) located approximately 450 bp away and in strong LD (r(2) = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (P(combined) = 2.1 x 10(-7)). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height."
So yes maybe guanyl cyclase activator could increase height. In adults it's unclear if manipulation of the C-type natriuretic peptide signaling pathway could "re-awaken the growth plates". Someone like alkoclar claims that enhancing CNP expression has the ability to increase adult height.
Here's a study that shows that CNP causes skeletal overgrowth during development but I don't have access to the full study:
C-Type Natriuretic Peptide and Overgrowth
"Natriuretic peptides are a family of structurally related peptides with different distinct biological effects. C-type natriuretic peptide (CNP)-mediated signaling is important for endochondral ossifica-tion and intervenes in the control of chondrocyte maturation by regulating the balance between proliferation and terminal differentiation[there's no proliferating chondrocytes in adults so how would CNP increase adult height? Unless you cause the differentiation of stem cells into chondrocytes with LSJL]. CNP is encoded by the NPPC gene on human chromosome 2 for which, so far, no mutations have been described in humans. Recently, two independent articles reported the description of 3 patients with a similar clinical phenotype characterized by the pres-ence of skeletal anomalies and overgrowth. In all 3 cases, the clinical picture was associated with the presence of a balanced translocation involving chromosome 2 and causing overexpression of the NPPC gene and an increased plasma concentration of its product, CNP[to cause skeletal overgrowth in development increase plasma concentration of CNP]. Transcriptional dysregulation of NPPC has been ascribed to the separation of the gene unit from the long-range regulatory element with a transcriptional silencing effect on its expression and CNP overproduction has been correlated to the skeletal overgrowth phenotype observed."
In the study "Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and boneanomalies in an individual with balanced t(2;7) translocation" overexpression of CNP in osteoblastic cells in mice resulted in skeletal overgrowth this supports the theory that increasing CNP plasma levels can increase skeletal size as adults definitely have osteoblastic cells.
Here's an article about achondroplasia(dwarfism) and how CNP may be a possible cure:
"[CNP acts by inducing intracellular cGMP through Guanylyl Cyclase B]"
"genetically engineered mice have short bones when null for CNP and long bones when CNP is overexpressed"<-is this dose dependent however? Would more CNP increase height indefinitely at higher and higher levels?
"growth plates in these mice are shortened and widened [in CNP over- and -under expression] in a manner similar to that detected in mice with loss- and gain-of-function mutations for FGFR3"<-FGFR3 gain-of-function causes dwarfism.
"transgenic mice [were generated] in which CNP was overexpressed in the growth plate; expression of the gene encoding CNP, designated Nppc, was driven by the type II collagen cartilage-specific promoter (Col2). The Col2-Nppc transgenic mice displayed excessive skeletal growth that was mainly postnatal[after birth]."<-So more Type II Collagen more CNP?
"Offspring of the mating that carried both the Col2-Nppc and Col2-FGFR3 transgenes had near normal body lengths when measured over 10 weeks"
"the over-expression of CNP did not appear to rescue the reduced proliferation of growth plate chondrocytes detected in the Col2-FGFR3"<-meaning that possibly the amount of proliferation of growth plate chondrocytes does not have much affect on height. Or, it's possible that the positive benefits of CNP overexpression are greater than the effects of FGFR3 overexpression.
"[cultured tibias were treated] from Col2-FGFR3 ach mice with different doses of CNP. Bone length showed a dose response to the CNP"<-But we can't be sure that this dose response occurs forever.
"The dose that restored bone length to normal also restored synthesis of 2 markers of cartilage matrix biosynthesis(glycosaminoglycan and collagen),which were reduced in the Col2-FGFR3 mice, to near normal"<-so cartilage matrix is likely the best determinant of height and not chondrocyte proliferation. That means that something like High Molecular Weight Hyaluronic Acid could possibly increase height during puberty.
"FGFR3 signals through STAT1 to down regulate chondrocyte proliferation and differentiation and through the MAP kinase-ERK pathway to negatively control matrix synthesis in the growth plate. They propose that CNP blocks the MAP kinase inhibitory signals of FGFR3 to increase matrix synthesis and thereby counters the restraining consequences of FGFR3 on bone growth"<-So other possible target proteins for height increase are STAT1 and MAPK inhibitory signals.
Dose dependent effect of C-type natriuretic peptide signaling in glycosaminoglycan synthesis during TGF-β1 induced chondrogenic differentiation of mesenchymal stem cells.
"Recent investigations credited important roles to C-type natriuretic peptide (CNP) signaling during chondrogenesis. This study investigated the role of CNP in transforming growth factor (TGF)-β1 induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs) in pellet culture. MSCs were derived from human trabecular bone and were characterized on the basis of their cell surface antigens and adipogenic, osteogenic, and chondrogenic differentiation potential. TGF-β1 induced chondrogenic differentiation[our goal is to induce mesenchymal chondrogenesis in the trabecular bone, so it's good news that TGF-Beta1 induced chondrogenic differentiation there] and glycosaminoglycan (GAG) synthesis was analyzed on the basis of basic histology, collagen type II, Sox 9 and aggrecan expressions, and Alcian blue staining. Results revealed that human trabecular bone-derived MSCs express CNP and NPR-B analyzed on the basis of RT-PCR and immunohistochemistry. In pellet cultures of MSCs TGF-β1 successfully induced chondrogenic differentiation and GAG synthesis. RT-PCR analyses of both CNP and NPR-B during this process revealed an activation of this signaling pathway in response to TGF-β1. Similar cultures induced with TGF-β1 and treated with different doses of CNP showed that CNP supplementation at 10(-8) and 10(-7) M concentrations significantly increased GAG synthesis in a dose dependent manner, whereas at 10(-6) M concentration this stimulatory effect was diminished. In conclusion, CNP/NPR-B signaling pathway is activated during TGF-β1 induced chondrogenic differentiation of human trabecular bone-derived MSCs and may strongly be involved in GAG synthesis during this process. This effect is likely to be a dose-dependent effect."
CNP should only help during development. After development, you would need to induce a new cartilagenous matrix followed by endochondral ossification.
