In a research first, scientists at the Texas Tech University Health Sciences Center published the results of a new clinical study1 showing that tocotrienols from annatto seed may promote bone health in postmenopausal osteopenic women.
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Potential roles of vitamin E in age-related changes in skeletal muscle health.
Chung E, Mo H, Wang S, Zu Y, Elfakhani M, Rios SR, Chyu MC, Yang RS, Shen CL
Nutr Res. 2018 Jan;49:23-36. doi: 10.1016/j.nutres.2017.09.005. Epub 2017 Sep 21.
Abstract
Skeletal muscle disorders including sarcopenia are prevalent during the complex biological process of aging. Loss of muscle mass and strength commonly seen in sarcopenia is induced by impaired neuromuscular innervation, transition of skeletal muscle fiber type, and reduced muscle regenerative capacity, all attributable to chronic inflammation, oxidative stress, and mitochondrial dysfunction. Current literature suggests that vitamin E molecules (α-, β-, γ-, δ-tocopherols and the corresponding tocotrienols) with their antioxidant and anti-inflammatory capabilities may mitigate age-associated skeletal dysfunction and enhance muscle regeneration, thus attenuating sarcopenia. Preclinical and human experimental studies show that vitamin E benefits myoblast proliferation, differentiation, survival, membrane repair, mitochondrial efficiency, muscle mass, muscle contractile properties, and exercise capacity. Limited number of human cross-sectional observational studies reveal positive associations between serum tocopherol level and muscle strength. Several factors, including difficulties in validating vitamin E intake and deficiency, variations in muscle-protective activity and metabolism of diverse forms of vitamin E, and lack of understanding of the mechanisms of action, preclude randomized clinical trials of vitamin E in people with sarcopenia. Future research should consider long-term clinical trials of with adequate sample size, advanced imaging technology and omics approaches to investigate underlying mechanisms and assess clinically meaningful parameters such as muscle strength, physical performance, and muscle mass in sarcopenia prevention and/or treatment.
Development and in-vitro characterization of nanoemulsions loaded with paclitaxel/γ-tocotrienol lipid conjugates.
Abu-Fayyad A, Kamal MM, Carroll JL, Dragoi AM, Cody R, Cardelli J, Nazzal S
Int J Pharm. 2018 Jan 30;536(1):146-157. doi: 10.1016/j.ijpharm.2017.11.062. Epub 2017 Dec 2.
Abstract
Vitamin E TPGS is a tocopherol (α-T) based nonionic surfactant that was used in the formulation of the Tocosol™ paclitaxel nanoemulsion, which was withdrawn from phase III clinical trials. Unlike tocopherols, however, the tocotrienol (T3) isomers of vitamin E were found to have innate anticancer activity and were shown to potentiate the antitumor activity of paclitaxel. The primary objective of the present study was therefore to develop a paclitaxel nanoemulsions by substituting α-T oil core of Tocosol™ with γ-T3 in, and vitamin E TPGS with PEGylated γ-T3 as the shell, and test the nanoemulsions against Bx-PC-3 and PANC-1 pancreatic tumor cells. A secondary objective was to test the activity of paclitaxel when directly conjugated with the γ-T3 isomer of vitamin E. The synthesis of the conjugates was confirmed by NMR and mass spectroscopy. Developed nanoemulsions were loaded with free or lipid conjugated paclitaxel. Nanoemulsions droplets were <300 nm with fastest release observed with formulations loaded with free paclitaxel when γ-T3 was used as the core. Substituting α-T with γ-T3 was also found to potentiate the anticancer activity of the nanoemulsions. Although marginal increase in activity was observed when nanoemulsions were loaded with free paclitaxel, a significant increase in activity was observed when lipid conjugates were used. The results from this study suggest that the developed paclitaxel nanoemulsions with either γ-T3, PEGylated γ-T3, or paclitaxel lipid conjugates may represent a more promising option for paclitaxel delivery in cancer chemotherapy.
Gamma-Tocotrienol Stimulates the Proliferation, Differentiation, and Mineralization in Osteoblastic MC3T3-E1 Cells
Weili Xu, Pan He, Shenghua He, Pengju Cui, Yaqing Mi, Yang Yang, Yang Li, Shaobo Zhou
Journal of Chemistry Volume 2018 (2018), Article ID 3805932, 9 pages
Abstract
Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effects in vivo. However, the effects of γ-tocotrienol on osteoblast cells are still unclear. In this study, the effects of γ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed that γ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (), but it did not affect cell cycle progression. γ-Tocotrienol significantly increased alkaline phosphatase (ALP) activity (), secretion levels of osteocalcin (OC) and osteonectin (ON), and mRNA levels of collagen type I (Col I) of MC3T3-E1 cells. Meanwhile, we found that γ-tocotrienol is promoted in differentiation MC3T3-E1 cells by upregulation of the expression of Runx2 protein. Moreover, the number of bone nodules increased over 2.5-fold in cells treated with γ-tocotrienol (2–8 μmol/L) for 24 d compared to control group. These results indicated that γ-tocotrienol at low dose levels, especially 4 μmol/L, could markedly enhance the osteoblastic function by increasing the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Moreover, our data also indicated that Runx2 protein may be involved in these effects. Further studies are needed to determine the potential of γ-tocotrienol as an antiosteoporotic agent.
Benefits of Palm Tocotrienols in Health and Disease Management
During the recently concluded Palm International Nutra-Cosmeceutical Conference (PINC 2017), speakers highlighted recent breakthroughs in palm tocotrienols research and the current clinical practices of using palm tocotrienols for disease management. Some of the highlights are:
Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms
Hayashi D, Ueda S, Yamanoue M, Ashida H, Shirai Y
Biosci Biotechnol Biochem. 2018 Jan;82(1):65-73. doi: 10.1080/09168451.2017.1411184. Epub 2018 Jan 3.
Abstract
Diabetic nephropathy (DN) is a diabetic vascular complication, and abnormal protein kinase C (PKC) activation from increased diacylglycerol (DG) production in diabetic hyperglycemia is one of the causes of DN. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. In other words, DGK can attenuate PKC activity by reducing the amount of DG. Recently, we reported that intraperitoneally administered d-α-tocopherol (vitamin E, αToc) induces an amelioration of DN in vivo through the activation of DGKα and the prevention of podocyte loss. However, the effect of the oral administration of αToc on DN in mice remains unknown. Here, we evaluated the effect of oral administration of αToc on DN and its molecular mechanism using streptozocin-induced diabetic mice. Consequently, the oral administration of αToc significantly ameliorated the symptoms of DN by preventing the loss of podocytes, and it was revealed that the inhibition of PKCactivity was involved in this amelioration.
Association of Circulating Vitamin E (α- and γ-Tocopherol) Levels with Gallstone Disease.
Waniek S, di Giuseppe R, Esatbeyoglu T, Ratjen I, Enderle J, Jacobs G, Nöthlings U, Koch M, Schlesinger S, Rimbach G, Lieb W
Nutrients. 2018 Jan 27;10(2). pii: E133. doi: 10.3390/nu100201
Abstract
In addition to well-established risk factors like older age, female gender, and adiposity, oxidative stress may play a role in the pathophysiology of gallstone disease. Since vitamin E exerts important anti-oxidative functions, we hypothesized that circulating vitamin E levels might be inversely associated with prevalence of gallstone disease. In a cross-sectional study, we measured plasma levels of α- and γ-tocopherolusing high performance liquid chromatography in a community-based sample (582 individuals; median age 62 years; 38.5% women). Gallstone disease status was assessed by ultrasound. Multivariable-adjusted logistic regression models were used to estimate the association of circulating α- and γ-tocopherol/cholesterol ratio levels with prevalent gallstone disease. Lower probabilities of having gallstone disease were observed in the top (compared to the bottom) tertile of the plasma α-tocopherol/cholesterol ratio in multivariable-adjusted models (OR (Odds Ratio): 0.31; 95% CI (Confidence Interval): 0.13-0.76). A lower probability of having gallstone disease was also observed for the γ-tocopherol/cholesterol ratio, though the association did not reach statistical significance (OR: 0.77; 95% CI: 0.35-1.69 for 3rd vs 1st tertile). In conclusion, our observations are consistent with the concept that higher vitamin E levels might protect from gallstone disease, a premise that needs to be further addressed in longitudinal studies.
New study points to bone health benefits of annatto-derived tocotrienols, a form of vitamin E
Supplementation with annatto-derived tocotrienol decreased bone resorption and improved bone turnover rate in postmenopausal women more than a placebo, according to a new study.
Vitamin E as an Antioxidant in Female Reproductive Health.
Mohd Mutalip SS, Ab-Rahim S, Rajikin MH
Antioxidants (Basel). 2018 Jan 26;7(2). pii: E22. doi: 10.3390/antiox7020022.
Abstract
Vitamin E was first discovered in 1922 as a substance necessary for reproduction. Following this discovery, vitamin E was extensively studied, and it has become widely known as a powerful lipid-soluble antioxidant. There has been increasing interest in the role of vitamin E as an antioxidant, as it has been discovered to lower body cholesterol levels and act as an anticancer agent. Numerous studies have reported that vitamin E exhibits anti-proliferative, anti-survival, pro-apoptotic, and anti-angiogenic effects in cancer, as well as anti-inflammatory activities. There are various reports on the benefits of vitamin E on health in general. However, despite it being initially discovered as a vitamin necessary for reproduction, to date, studies relating to its effects in this area are lacking. Hence, this paper was written with the intention of providing a review of the known roles of vitamin E as an antioxidant in female reproductive health.
Effect of combination of vitamin E and umbilical cord-derived mesenchymal stem cells on inflammation in mice with acute kidney injury
Guo Q, Wang J
Immunopharmacol Immunotoxicol. 2018 Jan 22:1-5. doi: 10.1080/08923973.2018.1424898. [Epub ahead of print]
Abstract
BACKGROUND:
The objective of this study is to investigate the effect of combination of umbilical cord-derived mesenchymal stem cell (UC-MSC) and vitamin E (VitE) on inflammation in mice with acute kidney injury (AKI).
METHODS:
UC-MSCs were isolated from pregnant wistar mice and cultured. A total of 90 female wistar mice were randomly divided into control group, AKI group, AKI + VitE group, AKI + UC-MSC group, and AKI + VitE + UC-MSC group (18 mice in each group) which were given no treatment, normal saline, VitE, UC-MSC, and VitE + UC-MSC, respectively. The renal pedicles on both sides were clipped for 50 min with micro-artery clips to induce AKI. Six mice were sacrificed at days 1, 3, and 7, while blood and kidney tissues were collected to detect levels of blood urea nitrogen (BUN) and creatinine (Scr). Kidney tissues were stained by HE staining to observe pathological changes; levels of interleukin-lβ, TNF-α, interleukin-10, and β-FGF were measured by ELISA.
RESULTS:
Compared with the control group, AKI mice showed higher levels of serum BUN and Scr, tubular swelling and necrosis suggesting that AKI model was successfully established. Mice in AKI + VitE group, AKI + UC-MSC group, and AKI + VitE + UC-MSC presented better renal function than mice of AKI group. Mice from AKI + VitE + UC-MSC group showed the best renal function with the least renal tubular injury (p < .05). ELISA detection revealed that pro-inflammatory cytokines were significantly increased and anti-inflammatory cytokine levels were significantly decreased in all time points (p < .05). VitE, UC-MSC, and VitE + UC-MSC resulted in the increase of anti-inflammatory cytokine levels and reduction of pro-inflammatory cytokine levels and the combination of VitE and UC-MSC performed favorable effect in the suppression of inflammation in AKI mice (p < .05).
CONCLUSIONS:
Combination of UC-MSC and VitE significantly inhibited inflammatory reaction in kidney through the regulation of inflammatory cytokines in the microenvironment of kidney with AKI. Combination of UC-MSC and VitE presented therapeutic effect on AKI than the single use of UC-MSC or VitE.