Monthly Archives: September 2021

Can Berberine have an impact on height?

I saw berberine as part of a height stack and wanted to see if it could have any impact. Berberine is a part of many plants so it is available to the average population. So I searched if berberine had any impact on bone or cartilage.

Possible therapeutic effects of berberine on bone damage in high-fat diet-induced obese rats

“After treatment with berberine, TNF-α, IL-1β and the number of adipocytes in bone marrow were significantly decreased, and P1NP levels were higher in the HB group than in the HFD group.”<-so berberine could be used to prevent over inflammation. I don’t know if this would have any impact in healthy individuals.

“berberine chloride exerted protective effects on bone in an osteoporotic rat model induced by ovariectomy, and berberine significantly increased femur load and stiffness in glucocorticoid treated animals”

This is the study that indicates that berberine may have a positive result on longitudinal bone growth:

Effects of Huang Bai (Phellodendri Cortex) on bone growth and pubertal development in adolescent female rats

“Female Sprague–Dawley rats (28 days old; n = 72) were divided into six daily treatment groups: control (distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20 μg/kg), estradiol (1 μg/kg), and triptorelin (100 μg).”

“Expression of IGF-1 and BMP-2 in the hypertrophic zone was higher in all experimental groups.”

“Huang Bai promoted GH mRNA and protein in pituitary cells and inhibited GnRH mRNA expression in hypothalamus cells “

“Huang Bai contained one representative component: 24.36 mg/g berberine chloride.”<-Huang Bai contains berberine.

“Longitudinal bone growth rates of the Huang Bai 100 mg/kg, rhGH, and triptorelin groups were significantly higher than that of the control group”

It does not look like higher doses of berberine had a benefit. It is important to note that the mice in these studies do not get as diverse a diet as a normal human so it’s possible that it would have no effect on a human.

“Huang Bai stimulates longitudinal bone growth and chondrocyte proliferation by upregulating BMP-2 and IGF-1 expression in the growth plate. However, it has no effects on pubertal onset and estrogenic activity.”

Berberine for bone regeneration: Therapeutic potential and molecular mechanisms

“Berberine promotes osteogenesis”

“the migration of BMSCs to target organs is also of great significance for repairing the damaged bone tissues. Berberine can promote this process by activating PI3K/AKT pathway”

“berberine can activate the expression of key osteogenic transcription factor Runt-related transcription factor 2 (Runx2) through the p38MAPKs pathway, thereby promoting bone regeneration”

“berberine was confirmed to be able to reduce the apoptosis of BMSCs and promote bone regeneration by up-regulating the expression of anti-apoptotic factor Bcl-2, down-regulating the expression of pro-apoptotic factor bax and cleaving caspase-3 in the apoptosis pathway”

“oral berberine has poor bioavailability due to the first pass effect in the intestine. Currently, there are
some solutions, such as D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), that can increase the absorption of berberine in the intestine to improve the bioavailability”

In one study mentioned by the review “Mice treated with berberine showed better cartilage surfaces
with cracks and less cartilage degradation”

So it’s possible that berberine could be used to effect height but there’s lots of things that increase BMP-2 and IGF-1. It’d have to be studied more.

IL23 inhibition may have niche applications for height growth(Tremfya)

Some questions that have to be answered for Tremfya that have to be answered to see if it influences longitudinal bone growth:

1: Does it inhibit IL-23 in an area that would affect height such as the growth plate, articular cartilage, or intervertebral discs? I don’t think reducing the action of inflammatory cytokines on bone would have any impact on height as we generally want more bone turnover to get more height.

2: Does IL-23 impact height? Is it biphasic where there needs to be an equilibrium amount. In which case Tremfya can help when IL-23 is too high.

According to the study Pro-Inflammatory Cytokines Produced by Growth Plate Chondrocytes May Act Locally to Modulate Longitudinal Bone Growth, inflammatory cytokine inhibition of IL-1Beta and TNF-Alfa increased growth. Inflammatory cytokines can cause chondrocyte apoptosis which too much of is bad but chondrocyte apoptosis is a needed a stage in endochondral ossification. It’s likely that inflammatory cytokines are needed in small quantities so knockout is bad but too much overall decreases height.

IL-23 Inhibits Osteoclastogenesis Indirectly through Lymphocytes and Is Required for the Maintenance of Bone Mass in Mice

“L-23 stimulates the differentiation and function of the Th17 subset of CD4+ T cells and plays a critical role in chronic inflammation. The IL-23 receptor-encoding gene is also an inflammatory disease susceptibility gene. IL-23 shares a common subunit with IL-12, a T cell-dependent osteoclast formation inhibitor, and we found that IL-23 also dose-dependently inhibited osteoclastogenesis in a CD4+ T lymphocyte-dependent manner. When sufficiently enriched, γδ T cells also mediated IL-23 inhibition. Like IL-12, IL-23 acted synergistically with IL-18 to block osteoclastogenesis but, unlike IL-12, IL-23 action depended on T cell GM-CSF production. IL-23 did not mediate IL-12 action although IL-12 induced its expression. Male mice lacking IL-23 (IL-23p19−/−) had ∼30% lower bone mineral density and tibial trabecular bone mass (bone volume (BV)/total volume (TV)) than wild-type littermates at 12 wk and 40% lower BV/TV at 26 wk of age; male heterozygotes also had lower bone mass. Female IL-23p19−/− mice also had reduced BV/TV. IL-23p19−/− mice had no detectable osteoclast defect in trabecular bone but IL-23p19−/− had thinner growth plate hypertrophic and primary spongiosa zones (and, in females, less cartilage remnants) compared with wild type. This suggests increased osteoclast action at and below the growth plate, leading to reduced amounts of mature trabecular bone. Thus, IL-23 inhibits osteoclast formation indirectly via T cells in vitro. Under nonpathological conditions (unlike inflammatory conditions), IL-23 favors higher bone mass in long bones by limiting resorption of immature bone forming below the growth plate.”

IL-23 knockout increases osteoclast action. It’s unclear how this would affect height at skeletal maturity.

“IL-23 is a heterodimeric cytokine structurally related to IL-12.”

“IL-23p19/ male mice develop shorter limb bones than WT:”<-so IL-23 knockout is bad as it reduces height when you’re skeletally immature. The difference in length was 8.6% which is fairly significant.

So if knockout of IL-23 is bad is too much IL-23 good or also bad(and IL-23 is biphasic)?

According to the study Linear growth and bone metabolism in pediatric patients with inflammatory bowel disease, chronic inflammation results in reduced longitudinal bone growth. But there are many inflammatory cytokines involved inflammatory bowel disease, not just IL-23.

According to Bone phenotypes in rheumatology – there is more to bone than just bone, IL-23 can cause bone destruction which may actually be good if you want to grow taller as bone is not capable of interstitial growth. Distraction osteogenesis after all begins with an osteotomy. Also of note in this study is that it’s mentioned that psoriatic osteoarthritis involves ossification of the enthesis. Tremfya is a treatment for psoriatic osteoarthritis. The study also mentions that psoriatic osteoarthritis can result in increased bone formation.

I could not find a direct link between IL-23 and longitudinal bone growth reduction just with inflammation in general. I’m going to conclude that Tremfya if it could be used as a way to increase longitudinal bone growth it is only in very niche cases where inflammation is very high.