Betaine May Make Muscles and Bones Stronger

Betaine, a bodybuilding supplement, which has been shown in small studies to have an anabolic effect on muscle tissue, may also help to strengthen bones. This is suggested by an in-vitro study that Italian researchers at the San Raffaele Scientific Institute published in the Journal of Translational Medicine.

The Italians exposed human osteoblasts – the bone cells that build new bone tissue – in test tubes to 10 millimoles of betaine. That’s the equivalent of a human taking 6 g betaine. [J Nutr. 2006 Jan;136(1):34-8.]

Administering betaine boosted the osteoblasts’ calcium uptake. In the figure below, each line represents the uptake of calcium by a different group of cells, measured in separate experiments.

Six hours after exposing the osteoblasts to betaine the cells were producing more of the bone-building proteins runt-related transcription factor 2 [RUNX2], osteoblast-specific transcription factor Osterix [OSX], bone sialoprotein [BSP] and bone sialoprotein 1 [OPN].

How betaine activated the bone cells’ anabolic machinery is shown below: by getting the osteoblasts to produce more IGF-1. The increased production is the consequence of activating the ERK/MAPK pathway, according to the Italians. Whether this is indeed the case, we wonder. But never mind: we are not the experts.

“The present study has demonstrated that betaine exerts a stimulatory effect on human osteoblast by acting on synergic pathways leading to osteogenic gene activation and production of bone matrix proteins,” the researchers wrote.

“This study has a translational value in opening the perspective that betaine supplementation, by acting on bone and muscle cells through common pathways, might be effective in counteracting bone and muscle deterioration in the elderly, particularly in those individuals with an age-related proinflammatory state (i.e. obese and diabetic subjects).””

“Betaine could represent an important nutraceutical approach in preventing the loss of muscle and bone with disuse, aging and disease, and in supporting therapies for age-related sarcopenia and osteoporosis, the major determinants of senile frailty and related mortality.”

Betaine promotes cell differentiation of human osteoblasts in primary culture


Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation.

The effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery. Cells were treated with 10 mM BET at 5, 15, 60 min and 3, 6 and 24 h. The possible effects of BET on hObs differentiation were evaluated by real time PCR, western blot and immunofluorescence analysis. Calcium imaging was used to monitor intracellular calcium changes.

Real time PCR results showed that BET stimulated significantly the expression of RUNX2, osterix, bone sialoprotein and osteopontin. Western blot and immunofluorescence confirmed BET stimulation of osteopontin protein synthesis. BET stimulated ERK signaling, key pathway involved in osteoblastogenesis and calcium signaling. BET induced a rise of intracellular calcium by means of the calcium ions influx from the extracellular milieu through the L-type calcium channels and CaMKII signaling activation. A significant rise in IGF-I mRNA at 3 and 6 h and a significant increase of IGF-I protein at 6 and 24 h after BET stimulus was detected. Furthermore, BET was able to increase significantly both SOD2 gene expression and protein content.

Our study showed that three signaling pathways, i.e. cytosolic calcium influx, ERK activation and IGF-I production, are enhanced by BET in human osteoblasts. These pathways could have synergistic effects on osteogenic gene expression and protein synthesis, thus potentially leading to enhanced bone formation. Taken together, these results suggest that BET could be a promising nutraceutical therapeutic agent in the strategy to counteract the concomitant and interacting impact of sarcopenia and osteoporosis, i.e. the major determinants of senile frailty and related mortality.