Osteoporosis International

, Volume 29, Issue 4, pp 881–891 | Cite as

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

  • C.-L. ShenEmail author
  • S. Yang
  • M. D. Tomison
  • A. W. Romero
  • C. K. Felton
  • H. Mo
Original Article



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.


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.


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.


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.


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.


Antioxidant Bone metabolism Osteoporosis Tocotrienols Women 8-OHdG 



This study was supported by American River Nutrition, Inc., Hadley, MA.

Funding information

This study is funded by American River Nutrition, Inc.

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • C.-L. Shen
    • 1
    Email author
  • S. Yang
    • 1
  • M. D. Tomison
    • 1
  • A. W. Romero
    • 2
  • C. K. Felton
    • 3
  • H. Mo
    • 4
  1. 1.Department of Pathology, School of MedicineTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Clinical Research InstituteTexas Tech University Health Sciences CenterLubbockUSA
  3. 3.Department of Obstetrics and Gynecology, School of MedicineTexas Tech University Health Sciences CenterLubbockUSA
  4. 4.Department of Nutrition, Byrdine F. Lewis College of Nursing and Health ProfessionsGeorgia State UniversityAtlantaUSA

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