title: Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose-response double-blinded placebo-controlled randomised trial.
abstract: Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women.
  
  
  
  In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2analysis and regression will be used for comparisons.
  
  
  
  This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.
  
  
  
  NCT02058420; results.
authors.affiliation: Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
authors.forename: Chwan-Li
authors.initials: CL
authors.lastname: Shen
authors.affiliation: Department of Nutrition, Byrdine F. Lewis School of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Huanbiao
authors.initials: H
authors.lastname: Mo
authors.affiliation: Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
authors.forename: Shengping
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
authors.forename: Carol K
authors.initials: CK
authors.lastname: Felton
authors.affiliation: Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tomison
authors.affiliation: Department of Pharmacology, Universiti Kebangasaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Ima Nirwana
authors.initials: IN
authors.lastname: Soelaiman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism / Q000517:prevention & control*; D017698:Postmenopause; D012107:Research Design; D024508:Tocotrienols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D024508:Tocotrienols
keywords: bone turnover marker; intervention trial; osteoporosis; oxidative stress; tocotrienols; women