Saturday, November 3, 2012

Gain Height with Harmine?

Harmine is available for sale: Peganum Harmala (Syrian Rue) Extract 10x 5 Gram

Novel chondrogenic and chondroprotective effects of the natural compound harmine.

"CCN2/connective tissue growth factor (CTGF) [has] essential roles in cartilage development, chondrocyte proliferation and differentiation, [and regulates] extracellular matrix metabolism. CCN2 [can help] regenerate surgical defects in articular cartilage of rat knee. Transgenic mice over-expressing cartilage-specific CCN2 [are] more resistant to aging-related cartilage degradation. Small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. The β-carboline alkaloid harmine [is] a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and type II collagen, as well as that of the master regulator of chondrogenesis, Sox-9. Harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine [ameliorates] TNFα-induced decrease in expression of CCN2 and cartilage markers."

"CCN family protein 2 (CCN2) or connective tissue growth factor (CTGF) promotes proliferation and maturation, but not hypertrophic differentiation of articular chondrocytes. CCN2 [regulates] ECM metabolism, by interacting with a number of growth factors including bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β); and ECM components such as aggrecan, perlecan and fibronectin"

"Harmine, compared with other β-carboline alkaloid derivatives, yielded the highest increase in mRNA levels of CCN2 and chondrocytic markers (aggrecan, type II collagen)."

"low doses (1, 2 and 5 μM) of harmine slightly increased cell viability after 24 h, whereas a dose-dependent decrease was observed therein"<-So harmine is likely only anabolic up to a certain point in chondrogenesis which is consistent to it's upregulation of Sox9.

"Concentrations of harmine above 10 μM decreased cell viability and were toxic to HCS-2/8[human chondrocytic cell line] cells."

"CCN2 [enhances] the adhesion and migration of bone marrow stromal cells (BMSCs)"

"harmine is a very small molecule that does not chemically bind to carriers that enable sustained supply of this compound to chondrocytes."

I can't guarantee that this'll help with existing growth plates as in existing growth plates there's the hypertrophic chondrocyte stage to consider in which Sox9 is not beneficial for height gain.

But for chondroinduction or to induce new growth plates Harmine seems very promising.  However in this study Harmine wasn't tested directly on MSCs.

Here's some information on Harmine on a mesenchymal stem cell line:

Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling.

"β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. We investigated the effects of harmine on osteoblast proliferation, differentiation and mineralization. Harmine promoted alkaline phosphatase (ALP) activity in MC3T3-E1 cells without affecting their proliferation. Harmine also increased the mRNA expressions of the osteoblast marker genes ALP and Osteocalcin. The mineralization of MC3T3-E1 cells was enhanced by treatment with harmine. Harmine also induced osteoblast differentiation in primary calvarial osteoblasts and mesenchymal stem cell line C3H10T1/2 cells{this cell line has been successfully differentiated into chondrocytes as well but it has fibroblast characteristics}. Structure-activity relationship studies using harmine-related β-carboline alkaloids revealed that the C3-C4 double bond and 7-hydroxy or 7-methoxy group of harmine were important for its osteogenic activity. The bone morphogenetic protein (BMP) antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated harmine-promoted ALP activity. In addition, harmine increased the mRNA expressions of Bmp-2, Bmp-4, Bmp-6, Bmp-7{these are all pro chondrogenic} and its target gene Id1. Harmine also enhanced the mRNA expressions of Runx2 and Osterix, which are key transcription factors in osteoblast differentiation. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by harmine treatment. Taken together, these results indicate that harmine enhances osteoblast differentiation probably by inducing the expressions of BMPs and activating BMP and Runx2 pathways."

"Harmine is a naturally occurring β-carboline alkaloid compound found in various plants including Peganum harmala (Syrian Rue) and Passiflora incarnata (Passionflower)"


  1. Hi Tyler, I am new to your blog and find all this information very interesting. I was wondering if kettle bells could be used instead of dumbells to load the bones? I am going to give the LSJL approach a try.

    Also, I saw your supplement guide and your reccomendation of folic acid. You might be interested in reading this article:


  2. So thiscould be beneficial even if your growth plates are closed/inactive when doing lsjl?

  3. what about selectin: One extract, which contains an L-selectin ligand, supports the natural release of stem cells (CD34+ cells) from the bone marrow

  4. there is also Ostinol

  5. I wonder if you can increase the size of your growth plate you can gain more height. Sorry if that sounded cavemanish to anyone.

  6. Petroleum ether extract of Cissus quadrangularis (Linn.) enhances bone marrow mesenchymal stem cell proliferation and facilitates osteoblastogenesis.