[Note: A Reader of the site recently contacted me and messaged that they would be interested in helping out with the site, the project, and the endeavor to find a solution to height increase. The help is much appreciated and I find that it makes my job a little easier. I wanted to give the biggest of thanks to this person who seems to not only check up on this site on a regular basis, but is also willing to contribute to the cause. Thank you.]
This is their written post on the possible use of statin to increase height and grow taller. The amount of research and study that went into the writing is very admirable.
Statins has been long said to stimulate bone growth. Statins has also been used for wound healing and fractures. Statins are also used for slowing bone loss. Statins work by blocking the action of an enzyme in the liver that turns fatty foods into cholesterol. Common statins used are lovastatin, simvastatin, pravastatin. Statins have also been used for osteoporosis.
Since statins work by lowering cholesterol , What is the role of cholesterol on the growth plates you must ask? Here it is:
Inborn errors of cholesterol synthesis are associated with multiple systemic abnormalities, including skeletal malformations. The regulatory role of cholesterol during embryogenesis appears to be mediated by Shh, a signaling molecule in which activity depends on molecular events involving cholesterol. Based on this evidence, we hypothesized that cholesterol, by modifying the activity of Ihh (another of the Hedgehog family proteins) in thegrowth plate, regulates longitudinal bone growth. To test this hypothesis, we treated rats with AY 9944, an inhibitor of the final reaction of cholesterol synthesis. After 3 weeks, AY 9944 reduced the cumulative growth, tibial growth, and the tibial growth plate height of the rats. To determine whether cholesterol deficiency affects bone growth directly at the growth plate, we then cultured fetal rat metatarsal bones in the presence of AY 9944. After 4 days, AY 9944 suppressed metatarsal growth and growth plate chondrocyte proliferation and hypertrophy. The inhibitory effect on chondrocyte hypertrophy was confirmed by the AY 9944-mediated decreased expression of collagen X. Lastly, AY 9944 decreased the expression of Ihh in the metatarsal growth plate. We conclude that reduced cholesterol synthesis in the growth plate, possibly by altering the normal activity of Ihh, results in suppressed longitudinal bone growth and growth plate chondrogenesis.
Here is what Dr. Wittfield has to say about statin and its uses:
The statin-and-bone story began when Wang et al. (1995) reported that lovastatin (Mevacor) reduced steroid-induced bone loss in New Zealand rabbits. Further studies showed that atorvastatin (Lipitor), cerivastatin (Baycol [withdrawn from the market August 2001]), fluvastatin (Lescol), lovastatin and simvastatin (Zocor) stimulated cultured bone cells to make the osteogenic bone-morphogenic protein (BMP)-2 (Garrett et al., 2001a, 2001b; Hoffmann and Gross, 2001; Mundy et al., 1999; Sugiyama et al., 2000). Pravastatin (Pravachol), which only targets liver cells, had no such effect (Garrett et al., 2001b). Lovastatin and simvastatin stimulated bone formation in cultured mouse calvariae and orally gavaged simvastatin (5 mg/kg or 10 mg/kg body weight) nearly doubled trabecular bone volume and increased bone formation by 50% in ovary-intact and ovariectomized (OVX) rats (Garrett et al., 2001b; Gasper et al, 2000a, 2000b; Mundy et al., 1999). Lovastatin, either topically applied or seeping continuously from a polylactide scaffold implanted in the skin, was 50 to 80 times more effective in rats than when given orally or injected subcutaneously (Gutierrez et al., 2000; Whang et al., 2000).
Others have reported that topically or systemically administered cerivastatin, fluvastatin and simvastatin did not stimulate bone growth or prevent OVX-induced bone loss in mice and rats (Crawford et al., 2001; Sato et al., 2001; Yao et al., 2001).
Clinical record reviews of the many patients who have taken statins to lower their blood cholesterol level reported the statins did indeed significantly reduce fracturing in postmenopausal women (Bauer et el., 1999; Chan et al., 2000; Chung et al., 2000; Meier et al., 2000). The odds ratios for fracturing ranged between 0.29 and 0.61 for statin users relative to non-users. Chan et al. (2001) reported that giving simvastatin (20 mg/day for four weeks) to 17 hypercholesteremic non-osteoporotic patients increased serum osteocalcin level but not bone-specific alkaline phosphatase activity, both indicators of bone formation.
What Mundy and his research team found:
The research team first applied four different types of statins to bone taken from the skulls of mice and grown in a laboratory culture. Each of the statins increased bone growth in the cultures two to threefold by stimulating the production of osteoblasts, the specialized cells that create new bone.
“The statins build up a team of osteoblasts, but in addition to that, they bring these osteoblasts into maturity, so they can start growing bone,” Mundy said. This is in contrast to most current bone loss therapies, which only increase the number of osteoblasts without encouraging the differentiation and maturity of these bone-building cells.
The researchers tested statins in mice and in two groups of female rats, one group with intact ovaries and the other with the ovaries removed to mimic the effects of menopause. Mice that were directly injected showed an almost 50 percent increase in new bone formation in the skull after only five days of treatment. In the oral dose groups, the statins caused increases in new trabecular bone (the type of bone found at the ends of bones like the femur) ranging from 39 to 94 percent after approximately one month’s treatment.
“It was totally amazing to us,” Mundy said of the amount of bone growth, “especially the effects of it in culture and applied locally.”
He noted that the less dramatic increase in bone growth for the oral dosage groups was probably due to the fact that the orally-administered statins don’t make their way to the targeted bone as well as those that are directly injected. Since statins are designed to zero in on the liver, most of their effects on bone are secondary. For these statins to be really effective as agents against osteoporosis, Mundy said, they need to be the kind of statins that distribute themselves directly to bone or bone marrow.
Although the statins seem to be most effective at building new bone, the researchers could not rule out the possibility that the drugs were also inhibiting the breakdown of bone, which could make them a candidate for osteoporosis prevention as well.
A preliminary analysis that looked back at a group of elderly women taking statins to lower their cholesterol found that these women had higher bone mineral density and less fractures in their hip. However, Mundy cautioned that this retrospective analysis is not definitive, since the overall sample size was small and there were no controls on the length of treatment or the consistency of the statin doses. The real answer to how well these statins contribute to bone formation in humans will come after randomized clinical trials, he said.
Stimvastatin enhances pSMAD1/5/8 expression:
smad1/5/8 Is needed for chondrogenesis.
Statins inhibit 3-hydroxy-3-methylglutarylcoen zyme A reductase, which catalyzes the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a rate-limiting step in cholesterol synthesis. A number of studies have demonstrated bone-promoting effects when simvastatin is applied locally with different carriers in various animal models. In the prsent study, the dose-dependent impact of simvastatin and bone morphogenetic protein-2 (BMP-2) on the cellular proliferation and differentiation of osteopre-cursor cells was evaluated. The alkaline phosphatase activity (ALP) test was performed to assess differentiation, and protein expression related to bone formation, including that of phospho-Smad1/5/8 (pSmad1/5/8), was measured using western blot analysis to evaluate the underlying mechanism(s). Cultures grown in the presence of 0.1 μM simvastatin with 60 ng/ml BMP-2 exhibited the highest value for ALP activity. The results of the western blot analysis indicated that the addition of simvastatin upregulated pSmad1/5/8 expression and the combination of 0.1 μM simvastatin and 60 ng/ml BMP-2 produced a significant increase in protein expression. Based on these findings, it was concluded that the combination of simvastatin and BMP-2 produced positive effects on the differentiation of osteoprecursor cells. The results also suggest that the combination of simvastatin and BMP-2 has synergistic effects that are achieved through the BMP pathway by enhancing the expression of Smad1/5/8 expression.
In vitro experiment to study the effect of simvastatin on rat intervertebral disc (IVD) cells.
Simvastation for invertabral disc cells~ and promotes chondrogenesis.
Hmmm spinal growth?
To evaluate the time-course effect of simvastatin on the gene expression of bone morphogenetic protein-2 (BMP-2), aggrecan, and collagen type II in rat IVD cells cultured in alginate bead. Role of BMP-2 on the simvastatin-induced chondrogenesis of IVD cells was also investigated.
SUMMARY OF BACKGROUND DATA:
Growth factors including BMP-2 have been found to improve anabolism of IVD cells and have shown promise for the treatment of disc degeneration. Statins is known to increase BMP-2 expression in vitro and stimulate bone formation in vivo. However, it is still unknown whether statins can also increase BMP-2 expression and in turn, stimulate matrix synthesis by IVD cells.
Rat IVD cells (harvested from nucleus pulpusos and inner annular fibrosus) cultured in alginate beads were exposed to different doses ofsimvastatin. DMMB, and real-time polymerase chain reaction were used to quantify proteoglycan and gene expression of BMP-2, aggrecan and collagen type II, respectively. Noggin or mevalonate was used to investigate the mechanism of the effect of simvastatin on rat IVD cells.
Simvastatin significantly upregulated BMP-2 mRNA expression, followed by aggrecan and type II collagen gene expression and proteoglycan content in rat IVD cells. Moderate dose (500 ng/mL) of noggin completely hindered the expression of aggrecan and collagen type II induced by simvastatin on day 7, but not on day 14. The upregulated type II collagen expression was blocked with 3 mug/mL of noggin on day 14, whereas aggrecan levels remained unchanged. Lastly, simvastatin appeared to facilitate BMP-2, aggrecan, and type II collagen gene expression by inhibiting the production of mevalonate as evidenced that the anabolic effect was completely reversed with the addition of mevalonate.
Simvastatin drives a mechanism for promoting chondrogenesis of IVD cells partially mediated by upregulated BMP-2 through the inhibition of mevalonate pathway.
Me: I wanted to end this post by stating that after looking through the old boards, the general conclusion by most height seekers on there was that statin does seem to cause bone growth, but not in the way most people would want it. It seems that the bone density increases so technically, there is bone growth but only inside the long bones, at least after the cartilage is gone. The long bones doesn’t seem to grow in the morphological sense of the word and does not actually enlarge in real form size in terms of longer or wider.
Just something to always remember and consider when looking into statin application. Overall, this post was brilliantly researched.