Monthly Archives: May 2023

Tachypleus tridentatus potential height increase supplement

Tachypleus tridentatus is also known as horshoe crab. According to The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab (Tachypleus tridentatus) on Obesity, Hyperlipidemia, and Gut Microbiota in High-Fat Diet-Fed Mice, compounds like Kyurenic acid could be beneficial effects of horshe crab.

Proteomic Identification of Plasma Components in Tachypleus tridentatus and Their Effects on the Longitudinal Bone Growth Rate in Rats

“Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.“

The fact that they think that horshoe clab has clinical use is promising but we have to see what unique benefits it has over other compounds. Lots of things stimulate the PI3K-AKT pathway. We have to see if there’s anything the plasma does that is unique or superior in promoting growth.

“T. tridentatus possesses anti-inflammatory, analgesic, hemostatic, and antidysentery medicinal effects. It is also worth noting that T. tridentatus blood that contains hemocyanin possesses important medical application value. The blood extract can be made into a Limulus-reagent (LR), which is widely used for the purposes of endotoxin detection and quantification in injections, as well as in radiopharmaceuticals, vaccines, and other biological products”

“T. tridentatus plasma can promote the growth and development of Wistar rats by increasing body weight, body length, and tail length in adolescent Wistar rats; in addition, despite this range of growth, the rats do not appear obese.”

” IGF-1, BMP2, and ALP are applied to monitor bone growth indicators.”<-lots of things can increase those things. The question is does Horshoe Crab does anything that is unique?

“the plasma group showed macroscopic changes in total longitudinal bone length after 14 days of treatment. In addition, morphological changes were observed, such as the increased height of the growth plate area and an increased number of proliferating cells. Furthermore, T. tridentatus plasma treatment significantly increased the total serum levels of BMP-2, IGF-1R, and IGF-1, as well as induced the upregulated expression of IGF-1 and IGF-1R in the growth plate region.”

So the fact that scientists like that this compound can enhance longitudinal bone growth is interesting but the question is is whether it is really better than say other things in the diet?

Study mentions that bone length is plastic and mentions nutrition and mechanical loading as two potential means by which bone length can be manipulated

The below study suggests that growth is manituable not only be nutrition but also by mechanical loading(tool use). It states that growth of some elements of the body is prioritized over others in times of nutrient restriction(“the thrity phenotype” hypothesis). Although this study is more geared to that nutrition can alter body height and skeletal length growth. Proving the plasticity(ability of bone to change in length) of bone is essential in proving that bone can change in response to mechanical loading.

Plasticity in the growth of body segments in relation to height-for-age and maternal education in Guatemala

“Plasticity in the growth of body segments between populations has been researched in relation to migration, temporal change and high-altitude studies{height seekers could potentially manipulate altitude or temperature}. We study the within population variation in body segments, thus controlling for some of the environmental and genetic differences that could be at play in between populations studies. We test a version of the thrifty phenotype hypothesis, where the growth of head-trunk and hand are prioritized due to their functional significance over height and leg growth.

A total of 3913 Guatemalan, rural, semi-urban and urban, Maya and Ladino children 6 to 15 years old were studied. Height, sitting height, leg length, and metacarpal length were studied in relation to three proxies for living conditions: height- and leg length-for-age, and maternal education. Estimation statistics and null hypothesis significance testing were used to analyze the data.

Metatarsal length and sitting height values were higher than height and leg length respectively. Relative metacarpal length was conserved across height-for-age groups. Females were less affected than males for metacarpal length and sitting height, but more affected for leg length.

Our results agree with the thrifty phenotype hypothesis, where metacarpal and sitting height growth would be prioritized over height and leg length due to greater functional significance.“

“Plasticity refers to the ability of an organism to modify its biology to respond to changes in the environment, particularly when these changes are physiologically stressful”<-plasticity in height is a very promising idea for height as it means height and bone length can be manipulated.

“in conditions of environmental stress, leg length is often more sensitive than is the head-trunk segment, and that tibia and ulna lengths are also more sensitive than humerus, hand and foot lengths. A proximate reason for this sensitivity is due to the allometry of skeletal growth, where the more proximal body segments grow fastest prenatally and are less exposed to extra-uterine environmental stress, but more distal segments grow most rapidly after birth and are more exposed to environmental stress. The thrifty phenotype hypothesis offers an ultimate evolutionary explanation; the growth of human body segments with greater functional significance, such as “head-brain,” “trunk-major organs,” and “hands-tools” will be prioritized over forearms and legs.”

“the thrifty phenotype hypothesis over the predictions of the distal blood flow and cold adaptation models in the growth of different body segments in living populations “

“According to this hypothesis, the growth of the head-trunk segment would be prioritized due to the important organs that it houses (brain, heart, lungs), and the growth of the hand would be prioritized due to its manipulative function in human tool technology, thus offering an ultimate evolutionary explanation for the differential plasticity in the growth of body segments under different conditions of stress.”

the thrifty phenotype hypothesis is basically that growth is conserved based on nutrients with some bones being prioritized over others in times of nutrient restriction.

Infigratinib is another potential FGFR3 inhibitor to increase height

Infigatinib is a potential alternative to Vosoritide to increase height during development. FGFR3 reduces growth in everyone it just does so in a greater manner in people with dwarfism as they have a mutation. CNP may have other beneficial effects on top of inhibiting FGFR3 but this just seems to be an FGFR3 inhibitor.

PMON30 Low-dose Infigratinib, an Oral Selective Fibroblast Growth Factor Receptor Tyrosine Kinase Inhibitor, Demonstrates Activity in a Preclinical Model of Hypochondroplasia 

“Fibroblast growth factor receptor 3 (FGFR3) gain-of-function mutations play a crucial role in achondroplasia (ACH), thanatophoric dysplasia (TD), and hypochondroplasia (HCH).{But FGFR3 may decrease height in everyone during development just to a lesser degree if you have the mutation}. HCH is a less severe form of dwarfism than ACH, but similarly is caused by gain-of-function mutations in the FGFR3 gene. HCH is characterized by a disproportionate short stature and a growth deficit affecting both endochondral and intramembranous ossification. While multiple therapeutic strategies are being tested for ACH, currently there are no approved therapeutic options for individuals with HCH. We tested the hypothesis that the oral, selective FGFR tyrosine kinase inhibitor (TKI) infigratinib (BGJ398) could improve the HCH phenotype and improve endochondral and intramembranous ossification in a preclinical mouse model of HCH Fgfr3N534K/+.

The first Hch mouse model studied expresses the most frequent human mutation p.Asn540Lys (Fgfr3Asn534Lys/+), and exhibits a mild dwarfism and most of the hallmarks of the human pathology. Fgfr3N534K/+ mice received subcutaneous injections of infigratinib or vehicle control every 3 days (1 mg/kg) or daily (1 mg/kg) for 15 days (post-natal day [PND] 4–19) or 21 days (PND 3–24), respectively.

Fgfr3N534K/+ mice treated with 1 mg/kg infigratinib every 3 days did not show obvious and significant modification of the dwarf phenotype. In contrast, Fgfr3N534K/+ mice treated with 1 mg/kg infigratinib daily for a total of 21 days showed a statistically significant increase in appendicular and axial skeletal measures. Length of the long bones was statistically significantly increased in Fgfr3N534K/+ mice compared with Fgfr3+/+ mice (tibia +3.18%, femur +3.16%, humerus +3.04%, ulna +2.94%, radius +3.01%). Treatment also modified the skull shape (skull width, skull height, nasal bone length and naso-occipital length), the length of the mandible and skull base, as demonstrated by measurement of the foramen magnum (foramen magnum length +3.72%). Infigratinib treatment modified the cartilage growth plate organization, in particular the hypertrophic chondrocyte area. Finally, the high activation of the MAP kinase pathway due to the HCH missense FGFR3 mutation was reduced by treatment, as revealed by the immunolabelling of phosphorylated Erk1/2 proteins.

Treatment with daily 1 mg/kg infigratinib improved the length and weight of Fgfr3N534K/+ mice and significantly modified the skull and the axial and appendicular skeleton. We demonstrated in Fgfr3N534K/+ mice that infigratinib is able to counteract the constitutive activation of FGFR3 due to the heterozygous N540K mutation localized in the tyrosine kinase 1 domain of the protein. These results provide a rationale for targeting FGFR3 with a specific TKI for the treatment of children with HCH.”

So basically infigratinib works to increase height in people with dwarfism but given everyone has FGFR3 receptors it could help increase height in anyone with growth plates to a lesser degree.

bridgebio announces positive phase 2 cohort 5 results of infigratinib in achondroplasia demonstrating mean increase in annualized height velocity of 3.03 cm/year with no treatment-related adverse events

“– In the highest dose level (Cohort 5, 0.25 mg/kg once daily), the mean change from baseline in annualized height velocity (AHV) at six months was +3.03 cm/yr (p = 0.0022) for the first 10 children with at least six months of follow-up in Cohort 5. The two remaining children who have not yet had six months of follow-up have a mean change from baseline in AHV of +8.8 cm/yr based on three months data“<-this is huge but again for normal children the gain will be smaller.

“80% of children at six months were responders, as defined by an increase from baseline AHV of at least 25%. The mean change from baseline in AHV of responders was 3.81 cm/yr“<-but that does not mean the 20% who weren’t responders didn’t get additional height at all.

” Infigratinib is an oral small molecule designed to inhibit FGFR3 and target achondroplasia at its source”

“Combined with the previously reported Cohort 4 change from baseline in AHV value of +1.52 cm/yr, the Cohort 5 data demonstrate a strong dose response for infigratinib”<-meaning the more of it you take the better but there is usually a better of diminishing returns…