Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial.

Traber MG, Mah E, Leonard SW, Bobe G, Bruno RS.

Am J Clin Nutr. 2017 Jan 11. pii: ajcn138495. doi: 10.3945/ajcn.116.138495. [Epub ahead of print]

Abstract

Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that α-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements. We hypothesized that α-tocopherol catabolites α-carboxyethyl hydroxychromanol (α-CEHC) and α-carboxymethylbutyl hydroxychromanol (α-CMBHC) are useful biomarkers of α-tocopherol status. Adults (healthy or with MetS; n = 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeled RRR-α-tocopherol (d₆-α-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured α-CEHC and α-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma α-tocopherol, α-CEHC, and α-CMBHC concentrations at various times ≤72 h. Conclusion, urinary α-CEHC and α-CMBHC are useful biomarkers to noninvasively assess α-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs α-tocopherol trafficking.

Alias D, Ruiz-Tovar J, Moreno A, Manso B, Diaz G, Duran M, Garcia-Olmo D.

Surg Infect (Larchmt). 2017 Jan 6. doi: 10.1089/sur.2016.199. [Epub ahead of print]

Abstract

Despite several interventions having been adopted to reduce the incidence of incisional surgical site infection (SSI), it still remains a challenge for surgeons, because incisional SSI is a common cause of health-care-associated infection, leading to increased morbidity, prolonged hospital stay, patient discomfort, and increased sanitary costs. The aim of this study was to evaluate the effect on incisional SSI of vitamin E ointment in the subcutaneous tissue of patients undergoing a laparoscopic colorectal surgical procedure. A randomized study was performed. Patients with colorectal neoplasms undergoing an elective laparoscopic surgical procedure were included. The patients were randomized into two groups: Those patients undergoing a subcutaneous vitamin E ointment application (Group 1) and those patients who did not receive it (Group 2). Incisional SSI, post-operative pain, and analytical acute phase reactants were analyzed. There were 108 patients who were assessed for eligibility, and 101 patients were analyzed. The incisional SSI rate was 4% in Group 1 and 17.6% in Group 2 (p = 0.03). Mean post-operative pain, 24 hours after operation, was 17.3 ± 10.5 mm in Group 1 and 31.9 ± 18.9 mm in Group 2 (p < 0.001). Median hospital stay was six days in Group 1 and eight days in Group 2 (p < 0.001). White blood cell count was significantly lower in Group 1 (p < 0.001). Conclusion, the subcutaneous application of sterile vitamin E acetate ointment leads to a reduction in the incisional SSI rate, lower post-operative pain, and decrease in C-reactive protein and white blood cell count.

Georgousopoulou EN, Panagiotakos DB, Mellor DD, Naumovski N.

Maturitas. 2017 Jan;95:55-60. doi: 10.1016/j.maturitas.2016.11.003. Epub 2016 Nov 9.

Abstract

A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage. Following PRISMA guidelines a systematic review of epidemiological observational studies and clinical trials was undertaken. Inclusion criteria included all English language publications in the databases PubMed and Scopus, through to the end of July 2016. Evidence from prospective and case-control studies suggested that increased blood levels of tocotrienols were associated with favorable cognitive function outcomes. A clinical trial of tocotrienol supplementation for 6 months suggested a beneficial effect of intake on DNA damage rates, but only in elderly people. Regarding osteoporosis, only in vitro studies with cultures of human bone cells were identified, and these demonstrated significant inhibition of osteoclast activity and promotion of osteoblast activity. In conclusion, research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects.

Zingg JM, Azzi A, Meydani M.

Toxicol In Vitro. 2017 Jan 3;40:124-133. doi: 10.1016/j.tiv.2016.12.014. [Epub ahead of print]

Abstract

The expression of CYP4F2, a form of cytochrome P-450 with proposed role in α-tocopherol and long-chain fatty acid metabolism, was explored in HepG2 and HepaRG human hepatocytes during ethanol toxicity. Cytotoxicity, ROS production, and JNK and ERK1/2 kinase signaling increased in a dose and time-dependent manner during ethanol treatments; CYP4F2 gene expression decreased, while other CYP4F forms, namely 4F11 and 12, increased along with 3A4 and 2E1 isoforms. α-Tocopherol antagonized the cytotoxicity and CYP4F2 gene repression effect of ethanol in HepG2 cells. Ethanol stimulated the tocopherol-ω-hydroxylase activity and the other steps of vitamin E metabolism, which points to a minor role of CYP4F2 in this metabolism of human hepatocytes. PPAR-γ and SREBP-1c followed the same expression pattern of CYP4F2 in response to ethanol and α-tocopherol treatments. Moreover, the pharmacological inhibition of PPAR-γ synergized with ethanol in decreasing CYP4F2 protein expression, which suggests a role of this nuclear receptor in CYP4F2 transcriptional regulation. In conclusion, ethanol toxicity modifies the CYP expression pattern of human hepatic cells impairing CYP4F2 transcription and protein expression. These changes were associated with a lowered expression of the fatty acid biosynthesis regulators PPAR-γ and SREBP-1c, and with an increased enzymatic catabolism of vitamin E. CYP4F2 gene repression and a sustained vitamin E metabolism appear to be independent effects of ethanol toxicity in human hepatocytes.

Barranco-Ruiz Y, Aragón-Vela J, Casals C, Martínez-Amat A, Casuso RA, Huertas JR.

Nutrition. 2017 Jan;33:278-284. doi: 10.1016/j.nut.2016.06.017. Epub 2016 Jul 28.

Abstract

Controlling antioxidant supplementation in athletes involved in studies related to oxidative stress and muscle damage is the key to ensure results. The aim of this study was to confirm through high-performance liquid chromatography (HPLC) analysis whether well-trained individuals lied during a personal interview when asked if they were taking supplements with antioxidants, and how this could affect oxidative stress, muscle damage, and antioxidant response. A total of 94 men, well trained in endurance sports, volunteered in this study. They denied taking any antioxidant supplementation at initial interview. After a HPLC analysis, abnormal α-tocopherol concentrations were detected, probably due to a hidden antioxidant supplementation. Participants were classified into two groups: no evidence of antioxidant supplementation (NS group = α-tocopherol values <80 nmol/mL; n = 75) and evidence of antioxidant supplementation (S group = α-tocopherol values >80 nmol/mL; n = 19). Lipid peroxidation, muscle damage, antioxidant enzyme activity, and nonenzymatic antioxidant content were analyzed according to this classification. Statistical comparisons were performed using Student’s t test. Data from the present study reveal that 20% of participants lied in the exclusion criteria of antioxidant supplementation in a personal interview, as they showed high plasmatic α-tocopherol concentrations after HPLC verification. Catalase activity seems to be affected by high α-tocopherol plasma levels. Therefore, we strongly recommend the HPLC analysis as a necessary tool to verify the antioxidant intake and preserve results in studies linking oxidative stress and sport.

Gao Y, Qi X, Zheng Y, Ji H, Wu L, Zheng N, Tang J.

Int J Pharm. 2016 Dec 30;515(1-2):506-514. doi: 10.1016/j.ijpharm.2016.10.026. Epub 2016 Oct 13.

Abstract

The vitamin E analogue, α-tocopherol succinate (α-TOS), has a broad anti-tumor effect. α-TOS can induce cancer cells apoptosis and suppress tumor growth by targeting mitochondria. Low bioavailability of α-TOS is the major problem encountered with formulation development. In our study, α-TOS nanoemulsion (α-TOS-NE) was demonstrated as a new drug delivery system of α-TOS to increase the bioavailability. MTT-based cytotoxicity assay and mitochondrial membrane potential (ΔY) were performed on human breast cancer cell lines MCF-7 and human oral epithelial cancer cell lines KB to evaluate in vitro anticancer efficacy of α-TOS-NE. In comparison with free α-TOS, α-TOS-NE exhibited a stronger cytotoxicity and decreased ΔΨ. Pharmacokinetic profiles of I.V. α-TOS-NE group, I.P. α-TOS-NE group, and I.P. free α-TOS group (7% DMSO/93% PEG) were drawn. First of all, nanoemultion (NE) enables the I.V. injection of α-TOS, make it possible to be an I.V. preparation. Second, compare to the I.P. free α-TOS group, I.P. α-TOS-NE group had a higher bioavailability. Thus, NE improved the strong anti-cancer efficacy of α-TOS while increasing its in vivo bioavailability in rats. In conclusion, our laboratory-made NE was a safe drug delivery system for clinical trials and could be a promising formulation for α-TOS by I.V administration.

Ledet GA, Biswas S, Kumar VP, Graves RA, Mitchner DM, Parker TM, Bostanian LA, Ghosh SP, Mandal TK.

Int J Mol Sci. 2016 Dec 24;18(1). pii: E28. doi: 10.3390/ijms18010028.

Abstract

The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at -20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.

Guitard R, Paul JF, Nardello-Rataj V, Aubry JM.

Food Chem. 2016 Dec 15;213:284-95. doi: 10.1016/j.foodchem.2016.06.038. Epub 2016 Jun 15.

Abstract

22 natural polyphenols are compared to 7 synthetic antioxidants including BHT, BHA, TBHQ and PG with regard to their ability to protect omega-3 oils from autoxidation. The antioxidant efficiency of phenols is assessed using the DPPH test and the measurement of oxygen consumption during the autoxidation of oils rich in omega-3 fatty acids. Also, the bond dissociation enthalpies (BDE) of the Ar-OH bonds are calculated and excellent correlations between thermodynamic, kinetic and oxidation data are obtained. It is shown that kinetic rates of hydrogen transfer, number of radicals scavenged per antioxidant molecule, BDE and formation of antioxidant dimers from the primary radicals play an important role regarding the antioxidant activity of phenols. Based on this, it is finally shown that myricetin, rosmarinic and carnosic acids are more efficient than α-tocopherol and synthetic antioxidants for the preservation of omega-3 oils.

Melo PS, Arrivetti Lde O, Alencar SM, Skibsted LH.

Food Chem. 2016 Dec 15;213:440-9. doi: 10.1016/j.foodchem.2016.06.101. Epub 2016 Jun 30.

Abstract

Extracts of açaí seed and of grape rachis alone or in combination with α-tocopherol were evaluated as antioxidants in (i) bulk soybean oil, (ii) soybean oil liposomes and (iii) soybean-oil/water emulsions. The extracts made with 57% aqueous ethanol showed an antioxidant activity not dependent on concentration for grape rachis extracts and a concentration-dependent prooxidative activity for açaí seed extracts in bulk soybean oil. Both the extracts, however, protected liposome suspensions and oil/water emulsions against lipid oxidation. Synergism was demonstrated when extracts were combined with α-tocopherol, effects explained by the solubility of extract components in the water-phase and of α-tocopherol in the lipid-phase. Phenolic profiling of the extracts by U-HPLC-ESI-LTQ-MS was used to identify active antioxidants. Açaí seed and grape rachis extracts served as good sources of procyanidins and flavan-3-ols, imparted high antioxidant activity especially when combined with α-tocopherol and are suggested for protection of food oil/water emulsions.

Tafazoli M, Fazeli E, Nematy M, Bahri N, Dadgar S.

J Obstet Gynaecol. 2016 Dec 7:1-5. [Epub ahead of print]

Abstract

This study aimed to clarify the relationship between functional ovarian cysts and vitamin A, vitamin E, and folate intake. This case-control study evaluated 265 women of reproductive age who presented at gynaecology clinics of three hospitals in Mashhad, Iran. While women in the ovarian cyst group [n = 132] had functional ovarian cysts, control group [n = 133] consisted of women without functional ovarian cysts. The participants’ vitamin A, vitamin E, and folate intake was assessed using the Food Frequency Questionnaire. Results showed that folate intake was significantly higher in the ovarian cyst group [p = .040]. No significant differences in vitamin A and vitamin E intake were observed between the two groups [p = .950 and .230, respectively]. It is concluded that women with functional ovarian cysts had significantly higher folate intake. Vitamin A and vitamin E intake had no significant effects on the incidence of these cysts.