Thursday, February 21, 2013

Grow taller by eating deer antlers?

Deer antler extract is available for sale: 3 Pack Deer Antler Velvet 2 oz. Liquid Extract.

Deer antler has been reported to have anecdotal uses on dogs. I'm bumping this study due to this topic being a possible field of interest for an upcoming Natural Height Growth Podcast.  Deer Antler has had positive effects on chondrogenesis but only in vitro(in cell cultures).  So it's unknown whether digestion ruins the pro-chondrogenic stimulatory effects.  Only few in vivo(in live animals) studies have been done on bones and deer antler but found that bone and deer antler did have a stimulatory effect on bone formation.  So deer antler can affect the bone but it's still unclear whether the chondrogenic effects can remain unmolested.

So Deer Antler could possibly play a role in inducing ectopic chondrogenesis or enhancing the growth plate in the developing.  But it may not do anything at all but it shouldn't hurt or inhibit any pro-chondrogenic actiions.

Pilose antler polypeptides promote chondrocyte proliferation via the tyrosine kinase signaling pathway.

"Pilose antler polypeptides (PAP) have been reported to promote chondrocyte proliferation.  [We] investigate the effects of PAP on the proliferation of chondrocytes.
Chondrocytes isolated from the knee of Zealand white rabbits were cultured. The second generation chondrocytes were collected. The chondrocytes were divided into the following 4 groups including serum-free, PAP, genistein (an inhibitor of tyrosine kinases), and PAP plus genistein group. Cell viability was analyzed. The cell cycle distribution of the chondrocytes was analyzed. The expression levels of cyclin A was detected.
No significant difference was observed between serum-free and genistein group. Treatment of the cultures with PAP produced a significant dose-dependent increase in cell viability, the percentage proportion of chondrocytes in the S phase and Cyclin A expression as well. However, the promoting effect of PAP on chondrocyte proliferation were dose-dependently inhibited by genistein, whereas genistein alone had no effect on proliferation of isolated chondrocytes.
PAP promotes chondrocyte proliferation with the increased cell number, percentage proportion of chondrocytes in S phase and expression of protein cyclin A via the TK signaling pathway."

"Genistein (4,7,4'-trihydroxyisoflavone), a major isoflavone from soybean, has been proven as a specific inhibitor of TK. Genistein, which block kinase ATP-binding sites, specifically inhibit phosphorylation of tyrosine residues, thereby inhibiting cells growth"

"The higher concentration of PAP added the [higher the] number of cultured chondrocytes".  Genistein inhibited this increase in proliferation.

"Compared to control group, the mean proportion of cells in S phase increased sharply from 6.4% to 35.2% after adding PAP."<-The S phase is the DNA replication phase of the cell cycle.

"cyclin A expression increased to 50% after adding PAP"

"level of cyclin A correlates directly with the proliferative state of cells"

It should be noted that this may only increase growth rate in growth plates and may not increase adult height.  It should also be noted that the PAP was added directly to the cartilage so it doesn't show whether or not deer antler supplemenation can bypass digestion.

[Role of pilose antler polypeptides on replicative senescence of rat chondrocyte].

"3rd generation chondrocytes were divided into blank group, and PAP groups with three different concentration of PAP which were passaged to the 4th generation. Meanwhile, the 2nd generation of chontrocytes were used as control group. The chondrocytes in different groups were detected with the method of histochemistry for S-A-beta-gal, flow cytometry for cell life cycle and proliferation index, alcian blue test for the content and structure of GAG of ECM, and RT-PCR for type II collagen and Aggrecan. Then PAP's function was observed regarding the appearance and functional status in the process of chondrocyte's senescence.
PAP significantly inhibited chondrocyte's express of S-A-beta-gal, promoted chondrocyte's proliferation, reduced cell content on G1 phase, enhanced the content of GAG, type II collagen and Aggrecan of ECM."

So deer antlers are pro chondrogenic but the study was not done on live rats so no idea whether it gets past digestion.  This was a chinese study so couldn't get access to the full version.

Effect of Pilose Antler Polypeptides on Cataplasia and Senescence of Rat Chondrocyte in Vitro

" 1. The rat articularchondrocytes were isolated with the method of enzyme digestion.The 3rdpassage chondrocytes were divided into blank group, different concentration PAP groups,different concentration glucosaminsalfate groups and were sequently passaged to 4thgeneration. The 2nd passage chondrocytes was contrasted as young cells group. Thechondrocytes of different groups were detected with the methods of histochemistry forS-A-β-gal, and with alcian blue test for the content and constructure of GAG of ECM,immuocytochemistry for typeⅡcollagen and PCNA, MTT assay for proliferation, RT-PCRfor typeⅡcollagen and Aggrecan, flow cytometry for cell life cycle and proliferationindex,by which to observe PAP’s function regarding to the appearance and functional status inthe process of chondrocyte’s cataplasia and senescence. 4. The successive tert-generation (2ndpassage, 3rd passage, 4th passage) chondrocytes and the 4th passage cells intervented by PAPwere studied for senenscence mechanism. In this course, immuocytochemistry was applied for p16, pRb, E2F, CyclinD, CDK4 and TRAP-ELISA was applied for telomerase activation toobserve targets’ changing regarding to cataplasia and senescence. The function of PAP wasdetected too. Results: 1. The method of enzyme digestion is practicable for harvesting considerable and better activity cells, which were identified that had good phenotype anddifferentiation. 2. From 4th passage, the chondrocytes emerging some cataplasia-senescence changes such as the expression of S-A-β-gal raising to large extent, cell life cycle being detented on G1 phase, dedifferentiation and so on. 3. PAP has better anti-senenscence function than GS on several respect such as inhibiting express of S-A-β-gal, promoting chontrocyte proliferating, reducing cell content on G1 phase, promoting cell energy metabolism, makingcell growth active, enhancing chondrocyte differentiating and so on. 4. In the course ofchondrocyte’s cataplasia and senescence, factors controlling cell life cycle and cell growth changes as follow: p16↑—pRb↑—E2F↓—CyclinD↑—CDK4↓—telemorase"

Effect of pilose antler polypeptides on chondrogenic phenotype differentiation of bone marrow-derived mesenchymal stem cells in vitro

"third passage BMSCs from [6-month old] rabbits were randomly divided into control group cultured in ordinary medium, induced group cultured in defined medium, and PAP group cultured in defined medium containing 10 mg/L PAP. An equal volume of articular chondrocytes were selected from rabbits as articular cartilage group. The cellular morphological and functional characteristics were observed after 1, 2, 3 weeks in centrifuge tubes by histological, biochemical and reverse transcription-polymerase chain reaction (RT-PCR) technique.  Cell masses in the control group gradually crumbled after 2 weeks, and hematoxylin-eosin staining could not be done. Cell masses in the induced and PAP groups were semitransparent, but slightly contracted. A part of these cells were round or oval with a high density distribution at the surface. The content of GAG and mRNA expression of typeⅡ collagen in the induced and PAP groups were increased with culture time, and higher than those in the control group at different time points. The content of GAG and mRNA expression of type Ⅱ collagen in the PAP group were higher than those in the induced group, but lower than those in the articular cartilage group. BMSCs can differentiate into chondrogenic phenotype in the defined medium, and PAP can significantly enhance chondrogenic phenotype differentiation of BMSCs."

TGFB1 was present in the serum.

[The initial mechanism's investigation of pilose antler polypeptides resisting replicative senescence of rat chondrocyte].

"The successive tert-generation (2nd passage, 3rd passage, 4th passage) chondrocytes and the 4th passage cells intervented by PAP were studied for senenscence mechanism. In this course, immunocytochemistry was applied for pl6, pRb, E2F, CyclinD, CDK4 and TRAP-ELISA (telomerase repeat amplification protocol assay-enzyme linked immunosorbent assay) was applied for telomerase activation to observe targets' changing regarding to senescence and the function of PAP.
Along with cell's replicative senescence, pl6, pRb and Cyclin D express significantly rised, while E2F, CDK4 and telomerase express significantly lowerd. Meanwhile, in PAP interfered group compared with which in 4th passage group, pl6, pRb and Cyclin D express significantly lowered, while E2F, CDK4 and telomerase express significantly increased.
PAP postpones chondrocyte senenscence{thus it could possibly keep growth plates open longer}."

[Comparison of protein composition and activities of pilose antler processed by different methods].

"To elucidate the influence of processing conditions on pilose antlerś therapic effects, the protein composition and activities were compared on three kinds of pilose antler processed by lyophilization, freezing and traditional short-time heating, respectively. The concentration of the water soluble protein in freeze-dried pilose antler was 126.54 mg/g (Folin-Phenol assay), which was 13.1 times higher than that of heating processed antler. These proteins distributed widely in SDS-PAGE electrophoresis and the protein band between 50.0 kDa approximately 60.0 kDa achieved the highest concentration. The water extract of freeze-dried antler promoted the proliferation and IGF-I secretion of rat osteogenic-like cell UMR-106 by 245.25% ( MTT assay) and 66.36 ng/ml, which was respectively 2.2 times and 1.2 times of those of heating processed antler. The same candidate inhibited the growth of human hepatic carcinoma cell BEL-7402 by the highest rate of 47.64% , which was 1.4 times of heating processed antler. The activities of frozen fresh pilose antler were lower than those of its freeze-dried counterpart, but were much higher than those of heating processed antler. The results indicated that lyophilization help to remain the activity of pilose antlerś proteins as much as possible and improve its efficacy."

This study could be informative but can't get access.

[Effect of pilose antler polypeptides on the apoptosis of rabbit marrow mesenchymal stem cells differentiated into chondrogenic phenotype in vitro].

"The MSCs were separated from the nucleated cells fraction of autologous bone marrow by density gradient centrifuge and cultured in vitro. The MSCs were induced into chondrogenic phenotype by transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF). According to different medias, the MSCs were randomly divided into four groups: group A as black control group, group B (100 ng IL-1beta), group C (10 microg/ml PAP + 100 ng IL-1beta) and group D (100 ng/ml TGF-beta1 + 100 ng IL-1beta). The samples were harvested at 24, 48 and 72 hours.
The intranuclear chromatin agglutinated into lump and located under nuclear membranes which changed into irregular shape at 24 hours. The intranuclear chromatin agglutinated intensified at 48 hours. Then the nuclear fragments agglutinated into apoptosis corpuscles at 72 hours in group B. The structure change of cells in groups C and D was later than that in group B, and the number of cells changed shape was fewer than that in group B. The structure change of cells in group A was not significant. The apoptosis rate of cells, the mRNA expression of Caspase-3 and the enzymatic activity of Caspase-3 gradually increased in group B, and there were significant differences compared with groups A, C and D.
Caspase-3 is involved in apoptosis of the MSCs differentiated into chondrogenic phenotype cultured in vitro. PAP could prevent from or reverse apoptosis of these MSCs by decreasing the expression of Caspase-3 and inhibiting the activity of Caspase-3."

Adult stem cells and mammalian epimorphic regeneration-insights from studying annual renewal of deer antlers.

"[Some] animals have the ability to reprogram phenotypically committed cells at the amputation plane toward an embryonic-like cell phenotype (dedifferentiation). Deer antlers are the only mammalian appendages capable of full renewal. Following casting of old hard antlers, new antlers regenerate from permanent bony protuberances, known as pedicles. Antler renewal is markedly different from that of amphibian limb regeneration (dedifferentiation-based), being a stem cell-based epimorphic process. Antler stem cells reside in the pedicle periosteum. We envisage that epimorphic regeneration of mammalian appendages, other than antler, could be made possible by recreating comparable milieu to that which supports the elaboration of that structure from the pedicle "

Deer antler regeneration: a stem cell-based epimorphic process.

"Antler regeneration takes place in yearly cycles from its pedicle, a permanent protuberance on the frontal bone. Both growing antlers and pedicles consist of internal (cartilage and bone) and external components (skin, blood vessels, and nerves). The regeneration of both internal and external components relies on the presence of pedicle periosteum (PP){the properties of the pedicle periosteum can provide insight into how to grow taller}. PP cells express key embryonic stem cell markers (Oct4, Nanog, and SOX2) and are multipotent, so are termed antler stem cells. Now it is clear that proliferation and differentiation of PP cells directly forms internal antler components. The full regenerative ability of external antler tissue components is achieved through PP-derived chemical induction and PP-derived mechanical stimulation: the former triggers the regeneration of these external components, whereas the latter drives their rapid elongation."

"Antlers, despite being called head pieces, do not regenerate directly from the head of a deer but instead from the permanent cranial bony outgrowths, known as pedicles. Deer are not born with pedicles; instead, these start to develop from frontal crests (behind and above the eye sockets) when deer approach puberty"

" Initially, the developing pedicles are covered by typical scalp skin. When they have grown to their species-specific height (around 5–6 cm in red deer), first antlers begin to generate spontaneously from the apices of these pedicles. This development can be seen externally by a change in the appearance of the skin from the typical scalp skin to a velvet-like soft pelage, called velvet skin or velvet. When the rutting season approaches, the antlers become fully calcified and the blood supply is occluded, which causes the demise of the velvet skin. The dead velvet is subsequently shed to expose the bare bone of the hard antlers. These are cast in the following spring, and regeneration of the second set antlers from their living pedicle stumps is immediately initiated. From then on, annual renewal of subsequent antlers enters a well-defined cycle: casting of previous hard antler and regeneration of a new soft antler in spring, with rapid antler growth (up to 2 cm/day) and maturation in summer, then full antler calcification and velvet shedding in autumn, followed by the bare bony antler phase in winter"

" Immediately after a hard antler falls off, the rim of pedicle skin surrounding the distal end of a pedicle stump encroaches upon the bone margin, the space that was formerly occupied by the periphery of the antler base. This rim of skin is shiny, only sparsely populated by hair, and it possesses the peculiar features of velvet skin, specifically a thicker epidermis and the de novo formation of hair follicles, which distinguishes it from the more proximal pedicle skin, typical of the scalp skin. Within days of hard antler casting, wound healing nears completion by centripetal growth of velvet skin over the cast plane of a pedicle. At the same time, the distal part of pedicle periosteum (PP) becomes thickened through the active division of cells resident within it. Toward the late wound healing stage, two crescent-shaped growth centers are formed directly from the thickening distal PP, one of which is located anteriorly and the other posteriorly. Each center is made up of cartilaginous clusters that are capped by a layer of hyperplastic PP/perichondrium. Further augmentation of each growth center pushes up the anterior and posterior portions of the pedicle stump and leaves the central region behind. These posterior and anterior growth centers are the centers for the formation of the antler “main beam” and “first tine”"

"both PP and antlerogenic periosteum, from which PP is derived, express the stem cell marker CD9 antigen [and have elevated telomerase and nucleostemin activity]"

"stretching the skin stimulates epidermal proliferation only sufficiently to relieve tension. "<-Maybe such a concept would work for the one if osteoblast proliferation was stimulated to relieve stretching tension in the bone.

"direct proliferation and differentiation of the PP cells cause the internal tissue components (cartilage and bone) of a regenerating antler to form, whereas close association with PP or PP-derived tissue is the prerequisite for regeneration of external pedicle components (including skin, blood vessels, and nerves) to take place."

Deer antler supplements could certainly be a source of embryonic-like stem cells.

Histological studies of bone formation during pedicle restoration and early antler regeneration in roe deer and fallow deer

"Initially, [during antler regeneration], bone formation occurs by intramembranous ossification, but early during the regeneration process cartilage is formed at the tips of the cranial appendages, and is subsequently replaced by bone in a process of endochodral ossification"

"the periosteum serves as a cell source for the bone-forming tissue covering the exposed pedicle bone."

"The early onset of chondrogenesis in the regeneration process is regarded as an adaptation to the necessity of producing a huge volume of bone within a short period. This parallels the situation in other cases of chondrogenesis in membrane bones."

"antler casting can be postponed by administration of testosterone or estradiol to deer carrying hard antlers"

"administration of compounds that inhibit LH and thus testosterone release (medroxyprogesterone acetate), or interfere with both the release of testosterone and its action at the receptor level (cyproterone acetate) [can cause premature antler casting]"

"Early regenerating antler of a roe buck. a: Middle portion of regenerated antler. The cartilage (asterisks) is lined by a perichondrium consisting of an inner cellular (C) and an outer fibrous layer (F). D, dermis; E, epidermis; H, hair follicle; S, sebaceous gland; arrows, vascular spaces. Specimen R4: Heidenhain's azan (×26, bar = 500 μm). b: Vertical columns of cartilage (C) separated by highly vascularized mesenchymal tissue. Arrowheads, vascular spaces. Specimen R4: Heidenhain's azan (×80, bar = 100 μm). c: Zone of cartilage resorption and replacement by bone. Asterisk, cartilage; arrows, newly formed bone; arrowheads, multinucleated chondro-/osteoclasts; I, intertrabecular tissue. Specimen R4: Heidenhain's azan (×160, bar = 50 μm)."

"Cells from the cellular condensations in the fibrous mesenchymal tissue of the fallow deer pedicle distal to the newly formed osseous trabeculae. The cells contain numerous mitochondria (M) and a prominent rough endoplasmic reticulum (ER). N, nucleus; asterisks, bundles of collagen fibers in the extracellular matrix cut at different angles (×4,800, bar = 2 μm)."

"Advanced stage of pedicle restoration in a fallow buck. a: Overview of regenerated cranial appendage. Newly formed slender osseous trabeculae (T) distal to the pedicle stump (asterisk). The zone of the slender trabeculae is capped by mesenchymal tissue (M). D, dermis; E, epidermis. The rectangles indicate the regions shown in b, c, and e. Specimen F: Heidenhain's azan (×6.4, bar = 1.25 mm). b: Higher magnification of the transition zone between the pedicle stump (asterisk) and the newly formed osseous trabeculae (T). The mesenchymal tissue (M) overlying the trabecular bone is seen in the upper left corner of the figure. Specimen F, Heidenhain's azan (×13.2, bar = 600 μm). c: Newly formed, mostly vertically oriented osseous trabeculae (T) lined by osteoblasts (arrow). Note the presence of numerous capillaries (asterisk) in the intertrabecular mesenchymal tissue. Specimen F: Heidenhain's azan (×53, bar = 150 μm). d: Higher magnification of a newly formed osseous trabecula with some recently incorporated cells (osteocytes, black arrow). White arrows, osteoblasts; asterisk, mineralized bone matrix. Specimen F: semithin section, toluidine blue-borax (×211, bar = 38 μm). e: Cellular condensations and accompanying reticular bundles of collagen fibers (arrow) in the richly vascularized mesenchymal tissue overlying the zone of the newly formed osseous trabeculae. Asterisk, vascular space. Specimen F: Heidenhain's azan (×53, bar = 150 μm)."

Evidence that the canonical Wnt signalling pathway regulates deer antler regeneration

"Immunocytochemistry was used to map the distribution of the activated form of β-catenin (aβCAT). A low level of aβCAT staining was detected in chondrocytes and in osteoblasts at sites of endochondral bone formation{Thus perhaps inhibiting Beta-Catenin activation can be a possible way to form ectopic growth plates]. However, aβCAT was localised in cellular periosteum and in osteoblasts in intramembranous bone, where it co-localised with osteocalcin. The most intense aβCAT staining was in dividing undifferentiated cells in the mesenchymal growth zone. Antler progenitor cells (APCs) were cultured from this region and when the canonical Wnt pathway was inhibited at the level of Lef/TCF by epigallocatechin gallate (EGCG), the cell number decreased. TUNEL staining revealed that this was as a result of increased apoptosis. Activation of the pathway by lithium chloride (LiCl) had no effect on cell number but inhibited alkaline phosphate activity (ALP), a marker of APC differentiation, whereas EGCG increased ALP activity."

"targeted deletion of β-catenin in head and limb mesenchyme prevents the trans-differentiation of osteoblasts into chondrocytes"

Localization and characterization of STRO-1 cells in the deer pedicle and regenerating antler.

"Cells positive for the mesenchymal stem cell marker STRO-1 [were present] in the chondrogenic growth zone and the perivascular tissue of the cartilaginous zone in primary and regenerating antlers as well as in the pedicle of fallow deer (Dama dama). In addition, cells positive for the stem cell/progenitor cell markers STRO-1, CD133 and CD271 (LNGFR) were isolated from the growth zones of regenerating fallow deer antlers as well as the pedicle periosteum and cultivated for extended periods of time. STRO-1(+) cells isolated from the different locations are able to differentiate in vitro along the osteogenic and adipogenic lineages."

"the growing tip of the deer antler contains proliferating perivascular cells and possible angioblastic precursors"

"In contrast to long bones, adipogenesis does not occur in regenerating antlers."

Exploring the mechanisms regulating regeneration of deer antlers.

" Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues."

"The first set of antlers are shed in the spring when testosterone levels fall, a process known as ‘casting’. A blastema then forms on the exposed surface of the pedicle bone and from this the first set of ‘mature’ branched antlers regenerate"

"RXRB expression increases as cells differentiate from chondroprogenitors into mature chondrocytes."

"significant amounts of vitamin A (retinol) are present in antler tissues at all stages of differentiation."

"IGF-I and IGF-II receptors [are present] in the antler tip"

"[regenerating antlers express] Wnt 3a and the active form of Beta-catenin, leptin, the beta isoform of the leptin receptor, Msx-1 and Msx-2, FGF-4, cbfa1 and osterix"

Lentiviral-mediated RNAi knockdown of Cbfa1 gene inhibits endochondral ossification of antler stem cells in micromass culture.

"we silenced expression of Cbfa1 [in antler cartilage] , a key factor regulating endochondral ossification, using RNAi, and showed that expression of the downstream genes type I collagen and osteocalcin were suppressed which, in turn, inhibited endochondral ossification process taking place in the antler stem cell-formed nodules."

Neither chondrogenesis or osteogenesis occured in the Runx2(Cbfa1) knock down culture.

Gene expression dynamics in deer antler: mesenchymal differentiation toward chondrogenesis.

"To identify novel genes involved either in early events of mesenchymal cell specialization or in robust bone development, we have introduced a 3 K heterologous microarray set-up (deer cDNA versus mouse template). Fifteen genes were differentially expressed; genes for housekeeping, regulatory functions (components of different signaling pathways, including FGF, TGFbeta, Wnt), and genes encoding members of the Polycomb group were represented. Expression dynamics for genes are visualized by an expression logo. The expression profile of the gene C21orf70 of unknown function is described along with the effects when over-expressed; furthermore the nuclear localization of the cognate protein is shown. In this report, we demonstrate the particular advantage of the velvet antler model in bone research for: (1) identification of mesenchymal and precartilaginous genes and (2) targeting genes upregulated in robust cartilage development."

Skeletal development genes upregulated in gene antlers:
Sprouty 1 homolog
Glypican 3

Detailed comparison to LSJL genes to be done.

"unlike in the growth plate cartilage, the antler cartilage is densely vascularized. Expression of p311 may keep under control the proliferation of the myofibroblast-like cells surrounding the blood vessels "

Identification of differentially expressed genes in the developing antler of red deer Cervus elaphus.

"we have identified the expression patterns for 36 genes that were characteristic or dominant in the consecutive cell differentiation zones (mesenchyme, precartilage, cartilage) of the tip section of the developing velvet antler of red deer Cervus elaphus. Two major functional groups of these genes clearly outlined: six genes linked to high metabolic demand and other five to tumor biology. Our study demonstrates the advantages of the antler as a source of mesenchymal markers, for distinguishing precartilage and cartilage by different gene expression patterns and for identifying genes involved in the robust bone development, a striking feature of the growing antler. Putative roles for "antler" genes that encode alpha-tropomyosine (tpm1), transgelin (tagln), annexin 2 (anxa2), phosphatidylethanolamine-binding protein (pebp) and apolipoprotein D (apoD) in intense but still controlled tissue proliferation are discussed."

"In the antler mesenchyme, α-tropomyosin (tpm1) and less profoundly, transgelin, (tagln) slow down the vigorous cell proliferation and make conditions favorable toward differentiation. Downstream of this pathway, annexin 2 (anxa2) acts by channeling the cells toward chondrogenesis."

Comparison to LSJL genes to be done.

Deer antler base as a traditional Chinese medicine: A review of its traditional uses, chemistry and pharmacology.

 "Both in vitro and in vivo pharmacological studies have demonstrated that deer antler base possess immunomodulatory, anti-cancer, anti-fatigue, anti-osteoporosis, anti-inflammatory, analgesic, anti-bacterial, anti-viral, anti-stress, anti-oxidant, hypoglycemic, hematopoietic modulatory activities and the therapeutic effect on mammary hyperplasia."

"Based on animal studies and clinical trials, deer antler base causes no severe side effects."

The Table summary of chemical constituients reveals no unusual compositions but those would not reveal things like the embryonic-like stem cells.  And there may be some unique proteins.

"Deer antler base collagens (800 mg/kg/day, i.g., for 90 days)" had a stimulatory effect on bone formation parameters on rats in vivo(Therapeutic effects of collagen of antler base on osteoporosis in ovariectomized rats).

Effects of Velvet Antler with Blood on Bone in Ovariectomized Rats

" In traditional Chinese medicine (TCM), both velvet antlers (VA) and VA blood can tonify qi, essence, and marrow, nourish the blood, and invigorate bones and tendons. In TCM, the combination of VA and VA blood is believed to have superior pharmacological effects. The effectiveness of the combination therapy of VA middle sections (VAMs) and VA blood (VAM-B) was first examined in promoting proliferation of mouse osteoblastic cells (MC3T3-E1). The anti-osteoporotic activity of VAM-B (ratio of VAM:VA blood = 1:0.2) was evaluated with ovariectomized (OVX) rats at a dose of 0.2 g/kg. In VAM-B-treated OVX rats, the body weight decreased 10.7%, and the strength of vertebrae and the femur respectively increased 18.1% and 15.4%, compared to the control. VAM-B treatment also recovered the estrogen-related loss of the right tibial trabecular bone microarchitecture. Alkaline phosphatase (ALP) significantly decreased, but estradiol did not significantly change in serum of VAM-B-treated OVX rats."

"[In another study], long-term antler administration (13 months) moderated decreased plasma phosphorus and calcitonin levels and femoral bone density and calcium content, and increased plasma parathyroid hormone (PTH) and alkaline phosphates (ALP) activity levels associated with an ovariectomy (OVX) in 2 month-old senescence-accelerated mouse (prone-8, SAMP8)"

"VAM-B contained testosterone, estradiol, and IGF-1. The top three amino acids in VAM-B were in the order glutamic acid, glycine, and aspartic acid."

The effect of sambar velvet antler suplement on femur bone, body growth, and physical endurance in rat. 

"Antlers are deer's bony organ that follows a cycle of growing, hardening, casting and regrouping within a certain period. The effect of consuming velvet antler from temperate origin has been known scientifically to have positive effect for rheumatism and metabolic disorder sickness therapy. However, the role of velvet antler originated from tropical deer has not yet been explored. This study aimed to assess the potential of the velvet antler of sambar deer (Rusa unicolor) which was experimentally fed to laboratory rats. The assessment was made based on the animals growth rate (i.e. femur length, weight of testicle, body eight) and physical endurance (i.e. swimming test). Laboratory rats at 21 days old were allocated into four different groups and each group consisted of five rats were fed with powder of soft and hard parts of velvet antler at dose of 0, 1, 2, and 3 g/kg body weight, respectively. Animals were examined for eight weeks the body weight was examined weekly and the dose at velvet antler supplement was adjusted accordingly. At the end of the study the rat were put on endurance swimming test and then euthanized, for measurement of femur bone length and weight of testis. The results showed that there were no differences in the body weight. However at dose of 2 g soft part/kg BW indicating a consistently higher live weight gains across the observation time. Testis weight showed no significant differences between the treatments, but the length of femur bone showed a significant effect (p<0.05) with the doses level, with the highest score being at 3 g hard part / kg BW. Physical endurance showed a significant effect (p<0.05) with the doses level, with the level of 1 g soft part/kg BW gave the best performance."

Couldn't get full study.

Wednesday, February 6, 2013

Growing Taller with Swimming?

Got a full study ctrl-F (*NEW*)

Swimming to increase height has been a theory that has been bounced around for a while now within the grow taller community because of this guy:

Much has been made of Michael Phelps' long torso and has led many to investigate the possibility that swimming may increase height in the torso.  And, it is true that since the bones of the spine are irregular an increase in periosteal width of these bones would increase overall body height.  Swimming does put shearing forces on the spinal bones especially the freestyle stroke.  It is possible therefore that swimming did increase Michael Phelps' spinal height.  But, one thing that contraindicates that is that Michael Phelps has a long wingspan.  Now there are some short and irregular bones in the hands that contribute to wingspan but Michael Phelps' hand size could not possibly account for his large wingspan(6'7").

Michael Phelps has large feet too(size 14) and the feet are made largely of irregular and short bones(the long bones of the feet do not account for a large amount of shoe size).

It entirely makes sense for certain individuals to have long torsos, large hands, and large feet but short arms and legs.  The bones that make up the former are largely short and irregular bones and the bones of the latter are long bones.  It does not make sense to have long arms and short legs.  The explanation for this paradox could be key for height seekers.  Their could be something unique in the growth plate histology of people with long arms and short legs that is essential to extending the growth phase.

Dear Michael Phelps,

Stop swimming and donate your body to science.

These next two studies were based on citations from the study "Endochondral bone growth, bone calcium accretion, and bone mineral density: how are they related?" which flat out stated that swimming and other non-impact exercises increase body height.  I have also emailed that author for clarification and got this response "Thank you for your e-mail. Our opinion regarding the effect of swimming on bone length (mentioned in the perspective section of our review) is based on the previous study in young rats by Swissa-Sivan et al. (Bone Miner. 1989;7(2):91-105). Therein, rats were randomly divided into swimming (experimental) and sedentary (control) groups, and bone length was found to increase by approx. 3% after 20-week swimming. In our opinion, swimming did cause bone elongation (i.e., not correlational)."

Differential effects of swimming versus weight-bearing activity on bone mineral status of eumenorrheic athletes.

"To examine the role of skeletal loading patterns on bone mineral density (BMD), we compared eumenorrheic athletes who chronically trained by opposite forms of skeletal loading, intensive weight-bearing activity (gymnastics), and nonweightbearing activity (swimming) and 19 nonathletic controls. BMD (g/cm2) of the lumbar spine, femoral neck, trochanter, and whole body was assessed by dual energy X-ray absorptiometry (DXA). Subregion analysis of the whole body scan permitted BMD evaluation of diverse regions. Swimmers were taller, heavier, and had a greater bone-free lean mass than gymnasts and nonathletic controls. When adjusted for body surface area, there was no difference in lean mass between swimmers and gymnasts, and both were higher than controls. Gymnasts had a lower fat mass than swimmers and controls. There were no group differences for spine or whole body BMD, but gymnasts had higher spine BMD corrected for body mass than either swimmers or controls. Gymnasts had higher femoral neck BMD than controls, who were higher than swimmers (0.875 +/- 0.105). This result still applied when BMD was normalized for body weight and bone size. Trochanter BMD of gymnasts (0.898 +/- 0.130) was also higher than controls (0.784 +/- 0.097) and swimmers (0.748 +/- 0.085), and remained higher when corrected for body mass."

Unfortunately, I couldn't get the full study.  So we can't analyze the parameters to see how much was the swimming causal for height growth versus correlational.

Effect of swimming on bone growth and development in young rats.

"The effect of chronic swimming on bone modelling was studied. Forty female Sabra rats (5 weeks old) were randomly assigned to the following experimental groups: 30 rats were trained to swim (water bath 35 +/- 1 degree C, one h daily, five times a week) for 20 weeks--20 of them loaded with lead weights (1% body weight) while the rest (10 animals) swam load free. Ten sedentary rats matched for age and weight served as controls. At the end of the twenty-week swimming period, all rats were sacrificed, both humeri bones were dissected and prepared for the following examinations: morphometric, bone density (BD), bone mineral content (BMC), compression tests and cross-sectional geometrical parameters, histomorphometry and biochemical analysis of minerals (Ca, Pi, Mg, Zn). All measured parameters were found to be significantly higher (P less than 0.05) in the swimming rats irrespective of load, as compared with the controls. Bone weight was higher by 19%, bone volume by 11%, bone length by 2.8%, cortical area by 16%, BD by 7% and BMC by 15%. The compression breaking force at the distal shaft of the humerus was higher by 24% in the trained group, while the ultimate compressive stress was not significantly different. Maximal and minimal moment of inertia at the distal diaphysis were 33.4 and 40% higher, respectively, for the swimming groups than the controls. Ca, Pi, Mg and Zn levels per total humeral bone were significantly higher in the exercising rats. The histomorphometry and cross-sectional data emphasize longitudinal and transversal growth. These data indicate that swimming exercise exerts a positive effect on bone growth and development in young rats."

"The forces applied on the limbs during any moment of running can reach values of 6-12 times body weight"

"During swimming no limb-ground pounding is exerted and body weight-bearing action is reduced signiticantly. The gravitational forces acting on the body are counteracted by buoyancy. Thus. the changes that might occur in the long bones could be attributed solely to the stresses applied by muscle contractions during intensive treading water action of the animal, trying to stay afloat."

Humeral Length: "30.34(Control)  30.852(Groups that swam unloaded) 31.20(groups loaded with 1% bodyweight)" So the groups with the extra load grew longer arms.

"The longitudinal growth of the humerus of trained animals was faster compared to controls. Bone length increased by 1.7 and 2.8% for [unloaded swimmers] and [loaded swimmer] groups, respectively, compared to control groups."

Calcium, Phosphate, Magnesium, and Zinc content was higher with increasing load to control group per bone volume and total bone but not per bone dry weight.

Exercising group has the larger growth plate.  Note that this exercising rat growth plate is different from the LSJL growth plate.  But note that the control growth plates are similar in both groups.  So LSJL increases bone length in a different manner from swimming.  The main difference being that LSJL growth plate is less straight and that the area surrounding the growth plate is more porous with LSJL.

Here's a study that uses similar variables as the above study:

Swimming Training Increases the Post-Yield Energy of Bone in Young Male Rats

"Male Wistar rats (7 week-old) were assigned to one baseline control group, one control group and two swimming training groups, which were trained with 2(LOW) and 4(HIGH)% body-weight mass added, respectively."

"Femoral length, mm
31.5 ± 0.1(BCON)

39.4 ± 0.2(CON)

37.6 ± 0.4(LOW)

38.4 ± 0.3(HIGH)"

"Femoral length (mm)[when adjusting for bodyweight]

38.2 ± 0.3(CON)

38.1 ± 0.2(LOW)

38.7 ± 0.2(HIGH)"

In this study, versus the other study there was a baseline control group in this group whereas in the other group the control group was rats matched for age and weight.

Statement by Narattaphol Charoenphandhu "I agree that these two papers used different method for choosing baseline control. In addition, the duration of swimming protocol in Swissa-Sivan et al. (20 weeks) was much longer than that in Huang et al. (8 weeks)." The duration was longer in the study that found growth.

I couldn't get the study The Sabra rat: definition of a laboratory animal.  This study would help us learn when female Sabra rats tend to stop growing.  The rats would be 25 weeks old at the end of the experiment.  Which is about 6 months which is at the point where mouse rats reach growth plate senesence and stop growing which leads credence to the possibility that swimming increased rats adult bone length and didn't just increase growth rate.

Here's another study that while not cited by the author who claims that swimming can make you taller may provide insight:

Histomorphometry of long bone growth plate in swimming rats.

" We performed a histomorphometric study on the effect of swimming on the growth plate and subepiphyseal area of young adult rats. The experiments were carried out on 28 12-week-old albino Sabra rats. One group of 14 rats was trained to swim 1 hour/day, 5 days a week, for 12 weeks. Another group of 14 rats served as controls. The proximal femur and humerus of each animal were examined histomorphometrically. There was an increase in the subepiphyseal cancellous bone trabecullae of the femur. In the growth plate there was an increase in the number of column cells and proliferative cells. These changes were more pronounced in the femur than the humerus. Swimming induces an increase in subepiphyseal cancellous bone in young adult rats by enhancing growth plate activity."

Note in this study swimming did not increase the proximal length of the rat femur.  In fact the rat femur was slightly shorter in length than the control group.

Effect of a five-week swimming program on rat bone: a histomorphometric study.

"To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swim training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2-6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. "Normal" gravity would be an important cofactor in the osteogenic effects of exercise."

The effects of exercise mode, swimming vs. running, upon bone growth in the rapidly growing female rat.

"The purpose of this study was to compare the effects of two programs of endurance training, of equal duration and intensity, on bone development in female rats. Thirty-eight female Wistar rats were randomly assigned to one of three groups: run-trained (RUN), swim-trained (SWIM) or control (CON). The RUN group ran at a speed of 27 m/min up an 8 degrees incline. Swim trained animals swam with 2% of body weight attached to their tails. Training sessions were 2 h/day, 5 days/week and were conducted over a 10-week period. Hindlimb and forelimb muscles were removed upon sacrifice and analyzed for citrate synthase (CS) activity, liver (LG) and muscle (MG) glycogen. The parametrial fat pads were removed, digested with collagenase, and 2-deoxy-D-[3H]glucose uptake measured in isolated cells. Bone weight, length, diameter, ponderal index and bone mineral content (BMC) were measured in the femur and humerus of each animal. The LG, MG, fat cell volume, glucose uptake of the adipocyte and adrenal weight data indicate that the training response was identical. The CS activity of the muscles indicated that mechanical and recruitment patterns of the upper and lower body differ and could be responsible for bone development patterns found in this study. Exercise had a minimal effect on bone growth in the run-trained animals but did stimulate development in the swim-trained animals. The humerus of the SWIM was significantly (P < 0.05) heavier, wider and had a greater BMC when compared with those of the RUN and CON rats. The results of this study indicate that the muscular forces applied by the swim training protocol produced greater bone adaptations than the forces applied by a running protocol of equal duration and intensity."

Both running and swimming increased the glycogen levels of muscles and increased glucose uptake by adipocytes.  Running increased citrate synthesis activity more than swimming which is stilll more than control. Swimming caused a minor, statistically insignificant increase in femur and humerus length.  Running was statistically insignificantly shorter in femur and humerus length than control.

The age of the rats wasn't specified.

Physical activity and bone mass: exercises in futility?

"In Frost's CGFR[chondral/growth force response curve], increasing compression to the right of the curve increases growth to a peak, after which loads begin to decrease growth (with large enough loads being sufficient to arrest it)."<-although LSJL has been proven effective on mice at 4 months old which are close to the four month senescence point but this theory could explain swimming induced longitudinal growth.

"When growing mice from 14 days of age up to 22 weeks were run at a speed of 18 m/rain for 80 rain each day for 12 weeks, larger and heavier femora were found. But when the duration was increased to 21 weeks, or for a duration of 120 min/day, femora were shorter and lighter than those in the control group."

High-impact exercise strengthens bone in osteopenic ovariectomized rats with the same outcome as Sham rats

"Forty-two 9-mo-old female rats were either sham-operated (Sham) or ovariectomized (OVX). Three months after surgery, the rats were divided into the following groups: Sham sedentary, Sham exercised, OVX sedentary, and OVX exercised. Rats in the exercise groups jumped 10 times/day, 5 days/wk, for 8 wk, with a jumping height of 40 cm. Less than 1 min was required for the jump training. "

"jump exercise generates high-impact loading before the rats leave the ground."

"OVX and training did not affect tibial length."

Physical Exercise Improves Properties of Bone and Its Collagen Network in Growing and Maturing Mice

" male C57BL/6J mice"

Running mice had access to running wheels in cages.  The length of the femur began to decrease in the running group between 4-6 months of age.  Bone length was the same for control and running groups between 1-4 months of age.


"male Swiss Albino mice (4 weeks old)"

"The mice within their cage in the running training group were placed on the flat bed treadmill, the speed of which was constant at 15 m/min, on a plain floor. An electric grid at the rear of the belt was used to create a stimulus for the mice to run. All mice ran 5 days/week for 12 weeks. Each running training period lasted 30 minutes."

"The lengths of the femur and the tibia were significantly greater for mice in the running training group"  The exercise group increased 50% more in femur length than the sedentary group.

Effects of exercise on bone growth mechanical and physical properties studied in the rat.

"Thirty-four pubescent male rats were divided into exercise and control groups to examine the effects of a 1-month intensive exercise programme on the mechanical, physical (group 1) and histological properties (group 2) of the tibia and femur. At the completion of training, rats were sacrificed and the right hind-limbs dissected and stored at -60°C prior to torsional-testing at a speed of 180/s. Left tibiae and femora were measured for length and weight' Values for the width of the epiphyseal plate were also obtained from animals in group 2. Following the exercise programme the tibiae showed significant reductions in energy absorbed to failure, bone length and width of the proximal epiphyseal plate. No change was observed for the mechanical properties of the femora, but significant reductions occurred in bone length and weight. "

"The training schedule consisted of a l-month intensive exercise programme of treadmill-running (1 h/day) and swimming (1 h/day) 5 days per week"

It's possible that exercise merely slowed down growth and did not decrease height potential.