Fat-Soluble Vitamins Can Play Role in Managing Osteoarthritis

As researchers continue to look for factors that may influence the development of osteoarthritis (OA), a recent review published in the Journal of Clinical Rheumatology examined the role of fat-soluble vitamins in managing this condition. The research team looked at the 4 fat-soluble vitamins (A, D, E and K) and gathered all available information about their potential impact on OA’s pathology.

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Perspective: Should Vitamin E Recommendations for Older Adults Be Increased?

Meydani SN, Lewis ED, Wu D

Adv Nutr. 2018 Aug 11. doi: 10.1093/advances/nmy035. [Epub ahead of print]


Current vitamin E requirements are uniformly applied across the population for those >14 y of age. However, aging is associated with alterations in cellular and physiologic functions, which are affected by vitamin E. Therefore, it is questionable whether vitamin E requirements can be uniformly applied to all adult age categories. With aging, there is dysregulation of the immune system in which there are decreased cell-mediated and pathogen defense responses coupled with an overactive, prolonged inflammatory state. Both animal and human studies in the aged suggest that intake above currently recommended levels of vitamin E may improve immune and inflammatory responses and be associated with a reduced risk of infectious disease. We review the evidence that was considered in establishing the current requirements for vitamin E and highlight data that should be considered in determining the vitamin E requirements in older adults, particularly focusing on the evidence suggesting a benefit of increased vitamin E intake on immune function and inflammatory processes and resistance to infection. The main objective of this Perspective is to initiate the discussion of whether the current Dietary Reference Intake for vitamin E should be increased for the older population. We make this suggestion on the basis of mechanistic studies showing biological plausibility, correction of a major cellular dysfunction in older adults, and strong evidence from several animal and a few human studies indicating a reduction in risk and morbidity from infections.

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Vitamin E administration erases an enhanced oxidation in multiple sclerosis

Guan JZ, Guan WP, Maeda T

Can J Physiol Pharmacol. 2018 Aug 9. doi: 10.1139/cjpp-2018-0246. [Epub ahead of print]


Systemic peroxidation status has been reported as a pathogenic factor for multiple sclerosis (MS). Systemically elevated oxidation levels are associated with serum lipid peroxidation and somatic telomere length (TL) shortening. We investigated whether vitamin E (VE) administration suppresses peroxidation and improves clinical symptoms in 34 MS patients. We analyzed serum lipid peroxidation and degree of TL in circulating leukocytes of MS patients before and after VE treatment. The oxidation level was enhanced and TL was shortened in MS. The MS population treated with VE 400 mg/day for 3 months showed significantly reduced serum lipid oxidation level with maintenance of TL. These findings showed that systemic peroxidation is associated with the development of MS. Antioxidants such as vitamin E can be candidates for supplementary therapeutic agents for MS.

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An Evaluation of Crude Palm Oil (CPO) and Tocotrienol Rich Fraction (TRF) of Palm Oil as Percutaneous Permeation Enhancers Using Full-Thickness Human Skin

Singh I, Nair RS, Gan S, Cheong V, Morris A

Pharm Dev Technol. 2018 Aug 7:1-25. doi: 10.1080/10837450.2018.1509347. [Epub ahead of print]


The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright ‘Franz-type’ diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log P values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2.h and 23.0 µg/cm2.h respectively, compared to the control with a flux of 16.2 µg/cm2.h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

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α-Tocopherol transfer protein does not regulate the cellular uptake and intracellular distribution of α- and γ-tocopherols and -tocotrienols in cultured liver cells

Irías-Mata A, Sus N, Flory S, Stock D, Woerner D, Podszun M, Frank J

Redox Biol. 2018 Aug 5;19:28-36. doi: 10.1016/j.redox.2018.07.027. [Epub ahead of print]


Liver cells express a cytosolic α-tocopherol transfer protein (αTTP) with high binding affinity for α-tocopherol (αT) and much lower affinities for the non-αT congeners. The role of αTTP in the intracellular distribution of the different vitamin E forms is currently unknown. We therefore investigated the intracellular localization of αT, γ-tocopherol (γT), α-tocotrienol (αT3), and γ-tocotrienol (γT3) in cultured hepatic cells with and without stable expression of αTTP. We first determined cellular uptake of the four congeners and found the methylation of the chromanol ring and saturation of the sidechain to be important factors, with tocotrienols being taken up more efficiently than tocopherols and the γ-congeners more than the α-congeners, irrespective of the expression of αTTP. This, however, could perhaps also be due to an observed higher stability of tocotrienols, compared to tocopherols, in culture media rather than a higher absorption. We then incubated HepG2 cells and αTTP-expressing HepG2 cells with αT, γT, αT3, or γT3, isolated organelle fractions by density gradient centrifugation, and determined the concentrations of the congeners in the subcellular fractions. All four congeners were primarily associated with the lysosomes, endoplasmic reticulum, and plasma membrane, whereas only αT correlated with mitochondria. Neither the chromanol ring methylation or sidechain saturation, nor the expression of αTTP were important factors for the intracellular distribution of vitamin E. In conclusion, αTTP does not appear to regulate the uptake and intracellular localization of different vitamin E congeners in cultured liver cells.

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Vitamin E status and its determinants in patients with cystic fibrosis

Sapiejka E, Krzyżanowska-Jankowska P, Wenska-Chyży E, Szczepanik M, Walkowiak D, Cofta S, Pogorzelski A, Skorupa W, Walkowiak J

Adv Med Sci. 2018 Aug 3;63(2):341-346. doi: 10.1016/j.advms.2018.04.001. [Epub ahead of print]



The risk of vitamin E deficiency is of primary concern in cystic fibrosis patients. However, early diagnosis and routine vitamin Esupplementation can lead to its normal or even high levels. In the present study, we assessed vitamin E status in a large group of cystic fibrosis patients. Moreover, we also aimed to establish determinants of its body resources in cystic fibrosis patients.


The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography.


Median vitamin E concentration was 9.9 μg/ml (1st-3rd quartile: 7.5-13.5). Vitamin E deficiency was found in 17 (8.0%) and high levels were documented in 24 (11.4%) participants. Patients with and without vitamin E deficiency did not differ significantly with respect to age, standardized body weight and height, FEV1, albumin concentration and vitamin E supplementation dose. However, vitamin E deficiency appeared more frequently in participants without vitamin E supplementation. Moreover, in multiple linear regression analysis pancreatic insufficiency, severe CFTR gene mutation and vitamin E dose, were potentially defined as determinants of vitamin E concentration.


Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn’t documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.

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Proteomic Changes in Mouse Spleen after Radiation-Induced Injury and its Modulation by Gamma-Tocotrienol

Cheema AK, Byrum SD, Sharma NK, Altadill T, Kumar VP, Biswas S, Balgley BM, Hauer-Jensen M, Tackett AJ, Ghosh SP

Radiat Res. 2018 Aug 2. doi: 10.1667/RR15008.1. [Epub ahead of print]


Gamma-tocotrienol (GT3), a naturally occurring vitamin E isomer, a promising radioprotector, has been shown to protect mice against radiation-induced hematopoietic and gastrointestinal injuries. We analyzed changes in protein expression profiles of spleen tissue after GT3 treatment in mice exposed to gamma radiation to gain insights into the molecular mechanism of radioprotective efficacy. Male CD2F1 mice, 12-to-14 weeks old, were treated with either vehicle or GT3 at 24 h prior to 7 Gy total-body irradiation. Nonirradiated vehicle, nonirradiated GT3 and age-matched naïve animals were used as controls. Blood and tissues were harvested on days 0, 1, 2, 4, 7, 10 and 14 postirradiation. High-resolution mass-spectrometry-based radioproteomics was used to identify differentially expressed proteins in spleen tissue with or without drug treatment. Subsequent bioinformatic analyses helped delineate molecular markers of biological pathways and networks regulating the cellular radiation responses in spleen. Our results show a robust alteration in spleen proteomic profiles including upregulation of the Wnt signaling pathway and actin-cytoskeleton linked proteins in mediating the radiation injury response in spleen. Furthermore, we show that 24 h pretreatment with GT3 attenuates radiation-induced hematopoietic injury in the spleen by modulating various cell signaling proteins. Taken together, our results show that the radioprotective effects of GT3 are mediated, via alleviation of radiation-induced alterations in biochemical pathways, with wide implications on overall hematopoietic injury.

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Anticancer properties of tocotrienols: A review of cellular mechanisms and molecular targets

Montagnani Marelli M, Marzagalli M, Fontana F, Raimondi M, Moretti RM, Limonta P

J Cell Physiol. 2018 Aug 1. doi: 10.1002/jcp.27075. [Epub ahead of print]


Vitamin E is composed of two groups of compounds: α-, β-, γ-, and δ-tocopherols (TPs), and the corresponding unsaturated tocotrienols(TTs). TTs are found in natural sources such as red palm oil, annatto seeds, and rice bran. In the last decades, TTs (specifically, γ-TT and δ-TT) have gained interest due to their health benefits in chronic diseases, based on their antioxidant, neuroprotective, cholesterol-lowering, anti-inflammatory activities. Several in vitro and in vivo studies pointed out that TTs also exert a significant antitumor activity in a wide range of cancer cells. Specifically, TTs were shown to exert antiproliferative/proapoptotic effects and to reduce the metastatic or angiogenic properties of different cancer cells; moreover, these compounds were reported to specifically target the subpopulation of cancer stem cells, known to be deeply involved in the development of resistance to standard therapies. Interestingly, recent studies pointed out that TTs exert a synergistic antitumor effect on cancer cells when given in combination with either standard antitumor agents (i.e., chemotherapeutics, statins, “targeted” therapies) or natural compounds with anticancer activity (i.e., sesamin, epigallocatechin gallate (EGCG), resveratrol, ferulic acid). Based on these observations, different TT synthetic derivatives and formulations were recently developed and demonstrated to improve TT water solubility and to reduce TT metabolism in cancer cells, thus increasing their biological activity. These promising results, together with the safety of TT administration in healthy subjects, suggest that these compounds might represent a new chemopreventive or anticancer treatment (i.e., in combination with standard therapies) strategy. Clinical trials aimed at confirming this antitumor activity of TTs are needed.

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Protective Effect of Alpha-Tocopherol in Deltamethrin Induced Immunotoxicity

Kumar A, Sharma R, Rana D, Sharma N

Endocr Metab Immune Disord Drug Targets. 2018 Aug 1. doi: 10.2174/1871530318666180801144822. [Epub ahead of print]



α-Tocopherol is the active form of vitamin E which have various biological functions. However, the exact molecular mechanism of its action is not fully understood. Thus, the main objective of the current study is to determine the contribution of α-tocopherol in counteraction of the apoptogenic signaling pathways induced by deltamethrin in murine thymocytes and splenocytes.


Deltamethrin (25 µM) induces apoptosis at 18 h through activation of reactive oxygen species, caspases and depletion of glutathione in thymocytes and splenocytes. MTT assay results have shown that α-tocopherol (10 and 50 µg/ml) when added along with Deltamethrin (25µM), increases the viability of thymocytes and splenocytes in a concentration-dependent manner. The α-tocopherol treatment reduces the early markers of cell death (ROS and caspase3 activation) significantly. Further, the depleted GSH by deltamethrin, has been also restored by α-tocopherol. At 18 h, α-tocopherol (50 µg/ml) significantly reduced the Deltamethrin induced cell death. In additional, phenotyping and cytokines assay have demonstrated that alpha-tocopherol significantly ameliorated the altered immune functions.


These findings indicate that α-tocopherol shows immunoprotective effects in Deltamethrin induced splenic and thymic apoptosis by inhibiting oxidative stress and caspase-dependent apoptogenic pathways.

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