Tocotrienols in Bone Protection: Evidence from Preclinical Studies

Abstract

Osteoporosis is a degenerative bone disease affecting millions, mostly the aging population. Osteoblasts and osteoclasts maintain the balance in bone resorption and formation. Changes occurring in the differentiation, proliferation and activity of these two cell types result in lower bone mass and microarchitecture deterioration, leading to compromised bone strength. Chronic inflammation and oxidative stress disrupt the balance between osteoblasts and osteoclasts. Tocotrienols, vitamin E isoforms with an unsaturated hydrophobic tridecyl chain, reduce oxidative stress and inflammation by downregulating reactive oxygen species, nuclear factor-κB activation and pro-inflammatory cytokines and upregulating the expression of antioxidant enzyme in bone cells. Consequently, tocotrienols increase bone mineralization, promote osteoblast differentiation, and suppress osteoclast formation and differentiation. In vivo studies using various animal models of osteoporosis show improved biomarkers of bone formation and bone strength with tocotrienol supplementation. Tocotrienol-mediated downregulation of the mevalonate pathway that provides substrates for the biological activities of small guanosine triphosphate-binding proteins may also contribute to the regulation of osteoblasts and osteoclasts. Clinical studies are needed to confirm the bone-protection offered by tocotrienols that are found in abundance in plant foods such as fruits, vegetables, nuts, seeds and oils, which are also known for their antioxidant and anti-inflammatory effects.