Publications
Egg Consumption Increases Vitamin E Absorption from Co-Consumed Raw Mixed Vegetables in Healthy Young Men.
Kim JE, Ferruzzi MG, Campbell WW.
Nutr. 2016 Nov;146(11):2199-2205. Epub 2016 Sep 21.
Abstract
Most people living in the United States underconsume vitamin E, and dietary approaches to increase the absorption of vitamin E may help individuals to meet their body’s needs. In this study, we assessed the effect of adding cooked whole egg to a raw mixed-vegetable salad on α-tocopherol and γ-tocopherol absorption.
With the use of a randomized-crossover design, 16 healthy young men [mean ± SD age: 24 ± 4 y; mean ± SD body mass index (in kg/m2): 24 ± 2] consumed the same salad (all served with 3 g canola oil) with no egg [control (CON)], with 75 g cooked egg [low egg (LE)], or with 150 g cooked egg [high egg (HE)]; a 1-wk dietary washout period was included between trials. For the first 7 d of each trial, participants consumed a low-vitamin E diet to reduce plasma vitamin E concentrations. Blood was collected hourly for 10 h and the triacylglycerol-rich lipoprotein fractions (TRLs) were isolated. α-Tocopherol and γ-tocopherol concentrations in TRLs were analyzed and composite areas under the curve (AUCs) were calculated.
Results showed that the consumption of cooked whole eggs is an effective way to increase the absorption of α-tocopherol and γ-tocopherol from a co-consumed meal that naturally contains vitamin E, such as a raw mixed-vegetable salad, in healthy young men. This trial was registered at clinicaltrials.gov as NCT01951313.
Role of Noncovalent Sulfur···Oxygen Interactions in Phenoxyl Radical Stabilization: Synthesis of Super Tocopherol-like Antioxidants.
Menichetti S, Amorati R, Meoni V, Tofani L, Caminati G, Viglianisi C.
Org Lett. 2016 Nov 4;18(21):5464-5467. Epub 2016 Oct 18.
Abstract
Noncovalent sulfur···oxygen interactions can increase the stability of chalcogen ortho-substituted phenoxyl radicals. This effect contributes to transforming the 7-hydroxybenzo[b]thiophene moiety in a privileged structural motif to enhance the activity of phenolic antioxidants. A cascade of five consecutive electrophilic reactions occurring in one pot afforded potent and biocompatible α-tocopherol-like antioxidants.
Peroxisome proliferator-activated receptor γ down-regulation mediates the inhibitory effect of d-δ-tocotrienol on the differentiation of murine 3T3-F442A preadipocytes.
Torabi S, Yeganehjoo H, Shen CL, Mo H.
Nutr Res. 2016 Nov 3. pii: S0271-5317(16)30204-4. doi: 10.1016/j.nutres.2016.11.001. [Epub ahead of print]
Abstract
Tocotrienols accelerate the degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that catalyzes the biosynthesis of mevalonate; the latter is essential for preadipocyte differentiation. Tocotrienols also down-regulate peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation. We hypothesized that mevalonate deprivation and PPARγ down-regulation mediate d-δ-tocotrienol-induced inhibition of adipocyte differentiation. The objectives of this study were to determine the effect of d-δ-tocotrienol on 3T3-F442A preadipocyte differentiation and the involvement of PPARγ and mevalonate. Murine 3T3-F442A preadipocytes were incubated with d-δ-tocotrienol (2.5-10 μmol/L) for 8 days. AdipoRed assay and Oil Red O staining showed that d-δ-tocotrienol dose-dependently reduced the intracellular triglyceride content. Concomitantly, d-δ-tocotrienol dose-dependently inhibited glucose uptake by 3T3-F442A cells and the expression of GLUT4, HMG CoA reductase, and p-Akt proteins. The effects of d-δ-tocotrienol on intracellular triglyceride content and glucose uptake were attenuated by rosiglitazone, an agonist of PPARγ, but not supplemental mevalonate (100 μmol/L). In contrast, mevalonate, but not rosiglitazone, reversed the effects of lovastatin, a competitive inhibitor of HMG CoA reductase shown to inhibit adipocyte differentiation via mevalonate deprivation. Trypan blue staining revealed no changes in cell viability after a 48-hour incubation of 3T3-F442A cells with d-δ-tocotrienol (0-80 μmol/L), suggesting that the adipogenesis-suppressive activity of d-δ-tocotrienol was independent of cytotoxicity. In conclusion, these findings demonstrate the antiadipogenic effect of d-δ-tocotrienol via PPARγ down-regulation.
A naturally occurring mixture of tocotrienols inhibits the growth of human prostate tumor, associated with epigenetic modifications of cyclin-dependent kinase inhibitors p21 and p27.
Huang Y, Wu R, Su ZY, Guo Y, Zheng X, Yang CS, Kong AN.
J Nutr Biochem. 2016 Nov 4;40:155-163. doi: 10.1016/j.jnutbio.2016.10.019. [Epub ahead of print]
Abstract
Tocotrienols, members of the vitamin E family, have three unsaturated bonds in their side chains. Recently, it has been suggested that the biological effects of tocotrienols may differ from that of tocopherols. Several in vitro studies have shown that tocotrienols have stronger anticancer effects than tocopherols. VCaP cell line used in this study is from a vertebral bone metastasis from a patient with prostate cancer. Eight-week-old male NCr(-/-) nude mice were subcutaneously injected with VCaP-luc cells in matrigel and then administered a tocotrienol mixture for 8 weeks. The tocotrienol mixture inhibited the growth of human prostate tumor xenografts in a dose-dependent manner. The concentrations of tocotrienols and their metabolites were significantly increased in treatment groups. Tocotrienols inhibited prostate tumor growth by suppressing cell proliferation, which was associated with the induction of the cyclin-dependent kinase (CDK) inhibitors p21 and p27. In addition, tocotrienol treatment was associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27 and with decreased expression of histone deacetylases. Tocotrienols inhibited human prostate tumor growth, associated with up-regulation of the CDK inhibitors p21 and p27. Elevated expression of p21 and p27 could be partly due to the suppressed expression of HDACs.
Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis.
Rahman TA, Hassim NF, Zulkafli N, Muid S, Kornain NK, Nawawi H.
Food Nutr Res. 2016 Oct 28;60:31525. doi: 10.3402/fnr.v60.31525.
Abstract
Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined. This study aims to determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits. The findings suggest the possible atheroprotective role T3 plays as an adjunct supplementation to standard treatment in the prevention of CAD.
Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer’s Disease.
Grimm MO, Regner L, Mett J, Stahlmann CP, Schorr P, Nelke C, Streidenberger O, Stoetzel H, Winkler J, Zaidan SR, Thiel A, Endres K, Grimm HS, Volmer DA, Hartmann T.
Int J Mol Sci. 2016 Oct 29;17(11). pii: E1809.
Abstract
One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienolsinhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD.
Biological Properties of Tocotrienols: Evidence in Human Studies.
Meganathan P, Fu JY.
Int J Mol Sci. 2016 Oct 26;17(11). pii: E1682. Review.
Abstract
Vitamin E has been recognized as an essential vitamin since their discovery in 1922. Although the functions of tocopherols are well established, tocotrienols have been the unsung heroes of vitamin E. Due to their structural differences, tocotrienols were reported to exert distinctive properties compared to tocopherols. While most vegetable oils contain higher amount of tocopherols, tocotrienolswere found abundantly in palm oil. Nature has made palm vitamin E to contain up to 70% of total tocotrienols, among which alpha-, gamma- and delta-tocotrienols are the major constituents. Recent advancements have shown their biological properties in conferring protection against cancer, cardiovascular diseases, neurodegeneration, oxidative stress and immune regulation. Preclinical results of these physiological functions were translated into clinical trials gaining global attention. This review will discuss in detail the evidence in human studies to date in terms of efficacy, population, disease state and bioavailability. The review will serve as a platform to pave the future direction for tocotrienols in clinical settings.
The Impact of Vitamin E and Other Fat-Soluble Vitamins on Alzheimer´s Disease.
Grimm MO, Mett J, Hartmann T.
Int J Mol Sci. 2016 Oct 26;17(11). pii: E1785. Review.
Abstract
Alzheimer’s disease (AD) is the most common cause of dementia in the elderly population, currently affecting 46 million people worldwide. Histopathologically, the disease is characterized by the occurrence of extracellular amyloid plaques composed of aggregated amyloid-β (Aβ) peptides and intracellular neurofibrillary tangles containing the microtubule-associated protein tau. Aβ peptides are derived from the sequential processing of the amyloid precursor protein (APP) by enzymes called secretases, which are strongly influenced by the lipid environment. Several vitamins have been reported to be reduced in the plasma/serum of AD-affected individuals indicating they have an impact on AD pathogenesis. In this review we focus on vitamin E and the other lipophilic vitamins A, D, and K, and summarize the current knowledge about their status in AD patients, their impact on cognitive functions and AD risk, as well as their influence on the molecular mechanisms of AD. The vitamins might affect the generation and clearance of Aβ both by direct effects and indirectly by altering the cellular lipid homeostasis. Additionally, vitamins A, D, E, and K are reported to influence further mechanisms discussed to be involved in AD pathogenesis, e.g., Aβ-aggregation, Aβ-induced neurotoxicity, oxidative stress, and inflammatory processes, as summarized in this article.]
Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas.
Steuber N, Vo K, Wadhwa R, Birch J, Iacoban P, Chavez P, Elbayoumi TA.
Int J Mol Sci. 2016 Oct 26;17(11). pii: E1792.
Abstract
Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted δ-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70:30 wt % surfactant mix of Lutrol F-127:VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-potential = -35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-T3 NE produced superior cytotoxicity profiles, in concentration- and time-dependent manners (p ≤ 0.05), at least three to four folds lower IC50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.