Increase your Height with Calcium

Calcium supplements are very popular amonst people who want to grow taller.  If you can achieve the activation of surface osteoblasts to deposit new bone along the subchondral plate then you will increase your height.  High levels of dietary calcium increases levels of calcitonin which encourage osteoblast deposition of new bone.  An increase in bone mineral content should also increase height as long as the bone mineral is deposited along the longitudinal ends of the bones.  The study Inhibition of chondrogenesis and endochondral mineralization in vitro by different calcium channel blockers. showed that chondrogenesis did not occur when calcium channels were blocked.

Calcium is of course easily available such as here: Schiff Super Calcium 1200 mg with Vitamin D, 120 Softgels.  Calcium is usually paired with Vitamin D.  However, the active metabolite of Vitamin D may increase levels of VEGF(which causes epiphyseal fusion).  Inhibition of Cyp27b1 resulted in more growth and Cyp27b1 converts Vitamin D to it's active metabolite.  You'd have to find a way to specifically inhibit Cyp27b1 only in the hyaline cartilage growth plate. 

Still, possible future applications of inhibiting Cyp27b1 aside, supplementing with Calcium may be a way to increase height on the longitudinal ends of your bones by subchondral plate apposition.

[Effects of calcitonin on osteoblast cell proliferation and OPG/RANKL expression: experiment with mouse osteoblasts]

"Osteoblasts were separated by enzyme digestion methods from the cranial bones of 30 newborn mice, cultured, and inoculated in 96-well plate. Calcitonin of the concentrations of 10, 40, and 80 IU/L was administrated into the culture medium for 24, 48, and 72 hours. The proliferation of osteoblasts was detected by MTT method. Flow cytometry was used to analyze the cell cycle. The mRNA expression of osteoprotegerin (OPG) and RANKL and protein expression of OPG were examined by RT-PCR and ELISA respectively.
The proliferation rates of the osteoblasts exposed to the calcitonin of the concentrations of 40 and 80 IU/L for 24. 48, and 72 hours cell were all significantly higher than those of the blank control group. The index of osteoblasts at the G1 phase was significantly lower and the indexes of the osteoblasts at the S phase and G2-M phase were significantly increased after exposure to calcitonin. The OPG mRNA expression of the osteoblasts exposed to 80 IU/L calcitonin was significantly higher and the RANKL mRNA expression was significantly lower compared with the control group. The OPG protein expression of the osteoblasts exposed to 80 IU/L calcitonin was significantly higher than that of the control group at different time points.
Calcitonin increases the osteoblast proliferation and the OPG mRNA expression in the osteoblasts while RANKL mRNA expression in the osteoblasts is inhibited"

High levels of blood calcium increases Calcitonin levels. RANKL expression was reduced which essentially means that osteoclasts were inhibited.  Now remember this study was performed outside a live subject so homeostatic mechanisms were not in effect.

Reducing fracture risk with calcium and vitamin D.

"Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50-75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in successful fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits."

Manipulation of calcium balance may have applications in height increase.  Calcium is toxic in high quantities.  OPG's main purpose is to inhibit osteoclasts.  The anabolic purpose of calcium(and thereby calcitonin) is an increase in osteoblast proliferation.

The catbolic prevention effects took place at 80 IU/L.  The increase in osteoblast proliferation occurred at 40 IU/L.  I'm not sure how IU converts to mg for Calcium and the measurement occurred for Calcitonin so we also have to know how blood calcium levels correlate with calcitonin.  But it seems like the increase in IU from 40 to 80 did not increase osteoblast proliferation.  Calcium's effects seem to be based on certain thresholds and may not be amplified by supranormal levels.  Also, parathyroid hormone may have a positive effect on bone growth by preventing chondrocytes from hypertrophying too soon in the growth plate(high calcium levels in the blood stream inhibit parathyroid hormone).

Effect of Parathyroid Hormone on Type X and Type II Collagen Expression in Mesenchymal Stem Cells from Osteoarthritic Patients.

"Human mesenchymal stem cells (MSCs) from osteoarthritic (OA) patients express type X collagen (COL10), a marker of late-stage chondrocyte hypertrophy (associated with endochondral ossification). Parathyroid hormone (PTH) regulates endochondral ossification by inhibiting chondrocyte differentiation toward hypertrophy. In this study, we investigated the effect of PTH on expression of COL10 in MSCs from OA patients and analyzed the potential mechanisms related to its effect. MSCs were obtained from aspirates from the intramedullary canal of donors undergoing total hip replacement for OA. Expanded cells were then incubated for 0-48 h without (control) or with 100 nM PTH (1-34). Protein expression and phosphorylation were measured by Western blot. Results showed that PTH (1-34) inhibited expression of COL10 in MSCs from OA patients in a time-dependent manner. In parallel, PTH (1-34) stimulated expression of COL2, a marker of chondrogenic differentiation. Results also showed that PTH (1-34) inhibited in a sustained manner the phosphorylation of p38, [JNK], and AKT protein kinase signaling pathways. Interestingly, the modulation of COL2 and COL10 gene expression was significant as rapidly as after 1 h in the presence of PTH (1-34); changes in the phosphorylation of p38 and AKT were significant only after 6 h. This suggests that while p38 and AKT protein kinase signaling pathways may not be required to initiate the regulation of expression of COL2 and COL10 by PTH (1-34), these pathways may modulate later events necessary for preventing precocious MSC hypertrophy."

Parathyroid Hormone interacts with Indian Hedgehog in the Growth Plate.  Parathyroid Hormone prevents chondrocytes from hypertrophying giving chondrocytes more time to proliferate and differentiate.  High blood levels of calcium inhibit Parathyroid Hormone.  So high levels of calcium may increase type X collagen levels(although that may not necessarily be a bad thing).  Calcium and Vitamin D may be catabolic for the growth plate but anabolic for other parts of bone.  You may not want to supplement with Calcium and Vitamin D during normal development.

"PTH (1–34) induced the expression of COL2 in a time-dependent manner (Fig. 4). The stimulation was significant after 1 h (5.9 times control; p = 0.03) and maximal after 48 h (17 times control; p = 0.01). This suggests that the regulation of both COL2 and COL10 may be linked in MSCs from OA patients."<-This would be a huge fact for normal cells as it would mean that you can increase COL2 levels by inhibiting COL10 levels but this may only be true for people with OA.

"suppression of ERK signaling [may enhance] in vitro chondrogenesis."

Here's a study linking calcium metabolism directly to human height:

Associations between polymorphisms related to calcium metabolism and human height: the Tromsø Study.

"A number of single nucleotide polymorphisms (SNPs) related to height have been detected. Calcium metabolism is important for the skeleton and accordingly also for adult height. Therefore, in the present study, nine SNPs related to the vitamin D receptor (VDR) gene and serum levels of 25-hydroxyvitamin D (25(OH)D), calcium, phosphate and parathyroid hormone (PTH) were related to height in 9471 subjects[Thus vitamin D, calcium, phosphate, and PTH are important to height directly as well]. Relation with height was evaluated with linear regression for trend across SNP genotypes with age and gender as covariates. After correcting for multiple testing, significant associations with height were found for two SNPs related to the VDR gene (rs1544410 (Bsml) and rs7975232 (Apal)), one SNP related to serum 25(OH)D (rs3829251 at the DHCR7/NADSYN1 gene), one SNP related to serum calcium (rs1459015 at the PTH gene) and one SNP related to serum phosphate (rs1697421 at the ALPL gene). For rs3829251, the mean differences in height between major and minor homozygotes were 1.5-2.0 cm (P < 0.01) and were seen in both genders and all age groups tested, whereas for the other SNPs, the differences were less than 1 cm[So Vitamin D receptors have the most impact on height]. In conclusion, several SNPs related to calcium metabolism are associated with height, in particular rs3829251 at the DHCR7/NADSYN1 gene."

"Both dietary and solar vitamin D undergo a hydroxylation in the liver to 25-hydroxyvitamin D (25(OH)D) which is the biochemical marker that best reflects the vitamin D status of the body. 25(OH)D serves as a substrate for 1-α-hydroxylase in the kidneys, which under tight regulation forms the active form of the vitamin, namely 1,25-dihydroxyvitamin D (1,25(OH)2 D). The main regulator is parathyroid hormone (PTH), which increases the formation of 1,25(OH)2 D as a response to low serum calcium levels. The formation of 1,25(OH)2 D is also affected by serum phosphate where elevated phosphate levels have an inhibitory effect"<-So PTH and phhosphate all impact Vitamin D so it could be mainly Vitamin D that has the effect on height.

"The DHCR7/NADSYN1 gene where rs3829251 is located encodes the enzyme 7-DHC reductase. This enzyme converts 7-DHC to cholesterol, and as 7-DHC is a precursor of 25(OH)D, it is plausible that removal of 7-DHC could affect the individual's vitamin D status as was confirmed in our study. Mutations in the DHCR7/NADSYN1 gene cause Smith–Lemli–Opitz syndrome which is accompanied by reduced serum cholesterol levels and elevated serum 7-DHC levels."

Here's a patent studying the effects of calcium on height growth:

CALCIUM-SENSING RECEPTORS AND GROWTH PLATE DEVELOPMENT

"Delayed cell differentiation in the growth plate can produce growth retardation. The orderly progression of chondrocyte differentiation is maintained by hormones, nutritional components, and autocrine and paracrine factors produced by chondrocytes. The concentration of Ca2+ in the extracellular fluid ([Ca2+]e) plays a key role in growth plate cartilage development. Certain forms of childhood rickets are due to extremely low Ca2+ intakes. The bones and cartilage in rickets are soft and deformed and growth is stunted. We found that raising the [Ca2+]e directly promotes the terminal differentiation and mineralization of cultured mouse growth plate chondrocytes (mGPCs). Like Ca2+, insulin-like growth factor-1 (IGF1) promotes GPC differentiation. High Ca2+ also increases IGF1/IGF1R signaling capacity in mGPCs, suggesting that IGF1R-mediated signaling may be involved in the high [Ca2+]e-induces cell differentiation.  The Ca2+-sensing receptor (CaR) is strongly expressed in mGPCs. Altering CaR expression and function profoundly impacts the differentiation of these cells[so how much CaR is expressed may effect your height more than serum levels of calcium]. To determine whether the CaR is responsible for extracellular Ca2+-sensing by cartilage in vivo, we generated mice [CartCaR(-/-)] with tissue-specific knockout of the CaR in chondrocytes by a Cre-lox recombination technique. These mice die in gestation with malformed skeletons. We also developed a tamoxifen-inducible, chondrocyte-specific CaR knockout mouse [(Tam-CartCaR(-/-)]. These mice grow poorly during their postnatal life and have abnormally expanded growth plates with delayed mineralization in their hypertrophic zones -- features seen in rickets. These data strongly support a role for the CaR in growth plate development. We will use these models to address the hypothesis that a high [Ca2+]e by activating CaRs stimulates ERK1/2 and PLC activity, increases the intracellular [Ca2+], enhances the expression of and signaling by IGF1 and the IGF1R, and promotes the terminal differentiation of GPCs. We propose the following AIMs: (1) to determine the role of the CaR at specific stages of growth plate development by inducing CaR gene deletion with Tam at timed intervals before and after birth; (2) to determine whether a high [Ca2+]e alters chondrocyte function by regulating the expression of and signaling by IGF1 and the IGF1R in chondrocytes; (3) to assess the contribution of IGF1 and IGF1R-mediated signaling to the responses of GPCs to changes in the [Ca2+]e; and (4) to identify the high [Ca2+]e-induced signaling responses that are mediated by the CaR and are responsible for changes in the growth, survival, and differentiation of chondrocytes. Successful completion of these studies will provide insights into how the CaR interacts with local IGF1/IGF1R signaling pathway to modulate GPC differentiation and growth plate development[so this study will help people learn how to grow taller].  Growth plate cartilage, which is located at the ends of the bones, allows them to grow bigger. Chondrocytes from growth plate cartilage are capable of sensing changes in the concentrations of Ca2+ in their surroundings and adjusting their activities accordingly[so serum levels of Ca2+ may definitely have an effect on height growth]. Changes in the concentrations of Ca2+ near growth plate chondrocytes influence their whole program of gene expression, matrix protein synthesis, and mineral deposition."

Ex vivo real-time observation of Ca2 + signaling in living bone in response to shear stress applied on the bone surface

"Bone cells respond to mechanical stimuli by producing a variety of biological signals, and one of the earliest events is intracellular calcium ([Ca2 +]i) mobilization. Our recently developed ex vivo live [Ca2 +]i imaging system revealed that bone cells in intact bone explants showed autonomous [Ca2 +]i oscillations, and osteocytes specifically modulated these oscillations through gap junctions. We herein introduce a novel fluid-flow platform for probing cellular signaling networks in live intact bone, which allows the application of capillary-driven flow just on the bone explant surface while performing real-time fluorogenic monitoring of the [Ca2 +]i changes. In response to the flow, the percentage of responsive cells was increased in both osteoblasts and osteocytes, together with upregulation of c-fos{up in LSJL} expression in the explants. Treatment with 18 α-GA, a reversible inhibitor of gap junction, significantly blocked the [Ca2 +]i responsiveness in osteocytes without exerting any major effect in osteoblasts. On the contrary, such treatment significantly decreased the flow-activated oscillatory response frequency in both osteoblasts and osteocytes. The stretch-activated membrane channel, when blocked by Gd3 +, is less affected in the flow-induced [Ca2 +]i response. These findings indicated that flow-induced mechanical stimuli accompanied the activation of the autonomous [Ca2 +]i oscillations in both osteoblasts and osteocytes via gap junction-mediated cell–cell communication and hemichannel. Cell-cell signaling via augmented gap junction and hemichannel-mediated [Ca2 +]i mobilization could be involved as an early signaling event in mechanotransduction."

"The GJIC mediated by connexin43 (Cx43) plays an important role in the bone cell response to mechanical stimulation"

"The Ca2 + ionophore dose- and time-dependently activated c-fos mRNA expression in the chick calvarial bone cells"<-increases in C-Fos were coupled with increases in Ca2+

"mechanical stress did not affect the fluid flow in porous lacunar–canalicular tissue in this experimental model."

"removal of the periosteum and subsequent experiments on intact bone explants did not damage the osteoblast layer."

C-Fos expression increased with time under flow and intensity of flow.


Endochondral bone growth, bone calcium accretion, and bone mineral density: how are they related?

"in lactating rats with enhanced trabecular bone resorption, bone elongation is inversely correlated with BMD."

"Vitamin D deficiency can induce abnormal bone growth known as rickets in the young and osteomalacia in adults. In rickets, failure of two separate processes are evident: (1) the growth plate chondrocytes fail to complete a sequential process of proliferation, differentiation and degeneration; and (2) the matured chondrocytes persist in the hypertrophic state without undergoing degeneration; therefore, there is no capillary invasion and matrix mineralization"

"The growth plate of VDR knockout mice showed extensive disorganization of the chondrocyte column with an increase in the growth plate thickness"

"8-day-old vitamin D-deficient chick showed an absence of PTH/PTHrP receptor expression in the growth plate chondrocytes"

"Chondrocyte-specific inactivation of Cyp27b1 which is the 1,25(OH)2D3-synthesizing enzyme in mice led to decreased mRNA expression of vascular endothelial growth factor (VEGF), an essential growth factor for vascular invasion"

"Deficiency of vitamin A suppresses all stages of growth plate chondrocyte development, resulting in thin bony trabeculae formed across the face of the growth plate"

" femoral and tibial lengths of pregnant and lactating rats were increased from mid-pregnancy until the end of lactation. This elongation of the long bones was inversely correlated with the thickness of the total growth plate and the hypertrophic zone"

"Besides prolactin, PTHrP secreted from the mammary gland during lactation and suckling may also contribute to the lactation-induced growth plate changes, since PTHrP can modulate Ihh production"

"prolactin stimulates intestinal calcium absorption and trabecular bone resorption"

"prolactin stimulated differentiation of [human mesenchymal stem] cells into chondrocytes "  However for men elevated prolactin levels can lead to erectile dysfunction.

" no difference in femoral lengths of PRKO[Progesterone Receptor] versus wild-type littermates."

"swimming [increases] bone length and body height"

Is Calcium Signaling Relevant for Long Bone Growth?

"Neonatal severe hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis, more often induced by homozygous inactivating mutations of the Calcium-sensing receptor gene.
We report the clinical case of a male patient, son of consanguineous hypercalcemic parents, with clinical and biochemical features of NSHPT, followed until the age of twenty-one years. The patient underwent total parathyroidectomy, and then, due to the low compliance to calcium and calcitriol supplementation, an attempt was made with recombinant human parathyroid hormone [rhPTH (1-84)]. The patient did not reach the predicted height with an increased ratio of the upper and lower segments."

"persisting bilateral curvature of the tibia and fibula [was present]"