Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial

Osteoporos Int. 2018 Apr;29(4):881-891. doi: 10.1007/s00198-017-4356-x. Epub 2018 Jan 12.


Tocotrienols have shown bone-protective effect in animals. This study showed that a 12-week tocotrienol supplementation decreased concentrations of bone resorption biomarker and bone remodeling regulators via suppressing oxidative stress in postmenopausal osteopenic women.

Introduction: Tocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia.

Methods: Eighty-nine postmenopausal osteopenic women (59.7 ± 6.8 year, BMI 28.7 ± 5.7 kg/m2) were randomly assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12 weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study.

Results: Relative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups.

Conclusions: Twelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT's effects may be, in part, mediated by an inhibition of oxidative stress.

Trial registration: identifier: NCT02058420.

Title: Tocotrienols and bone health of postmenopausal women.

Keywords: 8-OHdG; Antioxidant; Bone metabolism; Osteoporosis; Tocotrienols; Women.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Biomarkers / metabolism
  • Bone Diseases, Metabolic / drug therapy
  • Bone Diseases, Metabolic / physiopathology
  • Bone Remodeling / drug effects
  • Bone Resorption / prevention & control*
  • Calcium / urine
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Oxidative Stress / drug effects*
  • Tocotrienols / pharmacology
  • Tocotrienols / therapeutic use*


  • Antioxidants
  • Biomarkers
  • Tocotrienols
  • Calcium

Associated data