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

Shen, Chwan Li; Yang, Shengping; Tomison, Michael D.; Romero, Amanda W.; Felton, Carol K; Mo, Huanbiao

doi:10.1007/s00198-017-4356-x

Cited by 39 publications

(48 citation statements)

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“…Supplementation of annatto T3 (430 or 860 mg/day) for 12 weeks decreased bone marker levels (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble RANKL and RANKL/OPG ratio) and oxidative stress biomarker (urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia relative to the placebo group. These findings suggested that T3 exerted osteoprotective effects by suppressing bone remodeling regulators in postmenopausal women with osteopenia, which might be in part mediated by the inhibition of oxidative stress [168].…”

Section: Effects Of Tocotrienol On Osteoporosismentioning

confidence: 88%

“…Recently, a double-blinded placebo-controlled trial involving 89 postmenopausal women with osteopenia was conducted to investigate the effects of T3 on bone [168]. Supplementation of annatto T3 (430 or 860 mg/day) for 12 weeks decreased bone marker levels (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble RANKL and RANKL/OPG ratio) and oxidative stress biomarker (urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia relative to the placebo group.…”

Section: Effects Of Tocotrienol On Osteoporosismentioning

confidence: 99%

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Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

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Section: Effects Of Tocotrienol On Osteoporosismentioning

confidence: 88%

Section: Effects Of Tocotrienol On Osteoporosismentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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“…This δ-TT concentration was employed in the subsequent experiments. Since dietary supplementation of annatto seeds (consisting of 90% δ-TT and 10% γ-TT) exerted bone protective effects in postmenopausal women [24], we examined the ability of increasing γ-TT concentrations to counteract t-BHP-induced cytotoxicity. We found that γ-TT protects MC3T3-E1 cells against oxidative damage even if at a lesser extent than δ-TT ( Fig.…”

Section: Effects Of δ-Tt On Counteracting T-bhp-induced Oxidative Strmentioning

confidence: 99%

“…Clinical studies have reported that dietary supplementation of TTs extracted from annatto seeds (consisting of 90% δ-TT and 10% γ-TT) exerts a beneficial action on bone turnover in postmenopausal women. Interestingly, the positive action of TTs on bone is at least in part due to a suppression of oxidative stress [24].…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of δ-tocotrienol against oxidative stress in osteoblastic cells: studies on the mechanisms of action

et al. 2019

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Purpose Natural antioxidants are considered as promising compounds in the prevention/treatment of osteoporosis. We studied the ability of purified δ-tocotrienol (δ-TT) isolated from a commercial palm oil (Elaeis guineensis) fraction to protect osteoblast MC3T3-E1 and osteocyte MLO-Y4 cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage and the mechanisms involved in its protective action in MC3T3-E1. Methods MC3T3-E1 and MLO-Y4 cells were treated with δ-TT (1.25-20 µg/ml for 2 h) followed by t-BHP at 250 µM or 125 µM for 3 h, respectively. MTT test was used to measure cell viability. Apoptotic cells were stained with Hoechst-33258 dye. Intracellular ROS levels were measured by dichlorofluorescein CM-DCFA. The OPT fluorimetric assay was used to detect the reduced glutathione to oxidized glutathione ratio (GSH/GSSG) contents. Results δ-TT significantly prevented the effects of t-BHP on cell viability and apoptosis reaching a maximum protective activity at 10 and 5 µg/ml in MC3T3-E1 and MLO-Y4 cells, respectively. This protective effect was due to a reduction of intracellular ROS levels and an increase in the defense systems shown by the increase in the GSH/GSSG. GSH loss induced by an inhibitor of GSH synthesis significantly reduced the δ-TT-positive effect on ROS levels. δ-TT prevention of oxidative damage was completely removed by combined treatment with the specific inhibitors of PI3K/AKT (LY294002) and Nrf2 (ML385). Conclusions The δ-TT protective effect against oxidative damage in MC3T3-E1 cells is due to a reduction of intracellular ROS levels and an increase of the GSH/GSSG ratio, and involves an interaction between the PI3K/Akt-Nrf2 signaling pathways. Keywords Tocotrienol • Oxidative stress • MC3T3-E1 cells • MLO-Y4 cells • Signaling pathways Abbreviations δ-TT δ-Tocotrienol γ-TT γ-Tocotrienol ROS Reactive oxygen species t-BHP Tert-butyl hydroperoxide FPP Farnesylpyrophosphate GGPP Geranylgeranylpyrophosphate CM-DCFA 5(6)-Carboxy-2′:7-dichlorofluorescein diacetate GSH Glutathione GSSG Glutathione disulfide Nrf2 Nuclear factor-erythroid-2-related factor 2 PI3K/Akt Phosphatidyl-inositol-3-kinase BSO l-Buthionine-sulfoximine

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“…Additionally, there is not a single study yet to evaluate how TT supplementation affects gut microbiome in humans, particularly obese PMW. We previously reported that 12-week annatto-extracted TT supplementation suppressed bone resorption and oxidative stress in PMW with low bone mass 35. However, there is no study to evaluate how TT supplementation would affect obese PMW.…”

Section: Introductionmentioning

confidence: 99%

Actions of annatto-extracted tocotrienol supplementation on obese postmenopausal women: study protocol for a double-blinded, placebo-controlled, randomised trial

et al. 2020

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IntroductionObesity is a major health concern in postmenopausal women, and chronic low-grade inflammation contributes to the development of obesity. Cellular studies and high-fat-diet-induced obese mouse model mimicking obesity show the antiobesity effect of annatto-extracted tocotrienols (TT) with antioxidant capability. We aim to assess the safety and efficacy of TT consumption for lipid-related parameters in obese postmenopausal women.Methods and analysisEligible obese postmenopausal women will be randomly assigned to placebo group (430 mg olive oil) and TT group (DeltaGold Tocotrienol 70%) for 24 weeks. In the present study, the primary outcome is total/regional fat mass and visceral adipose tissue. The secondary outcomes include lipid profile in serum, mRNA expression of fatty acid synthase and carnitine palmitoyltransferase 1A in fat tissue, oxylipins and endocannabinoids in plasma and adipose tissue, abundance and composition of intestinal microbiome in faeces, high-sensitivity C-reactive protein (hs-CRP) in serum and leptin in serum. Every participant will be evaluated at 0 (prior to starting intervention) and 24 weeks of intervention, except for serum lipid profile and hs-CRP at 0, 12 and 24 weeks. ‘Intent-to-treat’ principle is employed for data analysis. Hierarchical linear modelling is used to estimate the effects of dietary TT supplementation while properly accounting for dependency of data and identified covariates. To our knowledge, this is the first randomised, placebo-controlled, double-blinded study to determine dietary TT supplementation on an obese population. If successful, this study will guide the future efficacy TT interventions and TT can be implemented as an alternative for obese population in antiobesity management.Ethics and disseminationThis study has been approved by the Bioethics Committee of the Texas Tech University Health Sciences Center, Lubbock. An informed consent form will be signed by a participant before enrolling in the study. The results from this trial will be actively disseminated through academic conference presentation and peer-reviewed journals.Trial registration numberNCT03705845.

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

Abstract: Tocotrienols and bone health of postmenopausal women.

Cited by 39 publications

References 39 publications

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Beneficial effects of δ-tocotrienol against oxidative stress in osteoblastic cells: studies on the mechanisms of action

Actions of annatto-extracted tocotrienol supplementation on obese postmenopausal women: study protocol for a double-blinded, placebo-controlled, randomised trial

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