alexa Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects
ISSN: 2155-9880

Journal of Clinical & Experimental Cardiology
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Research Article

Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects

Asaf A Qureshi1*, Dilshad A Khan2, Shahid Saleem3, Neerupma Silswal1, Anne M Trias4, Barrie Tan4 and Nilofer Qureshi1,5
1Department of Basic Medical Sciences, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA
2Department of Chemical Pathology & Endocrinology, Armed Forces Institute of Pathology, and National University of Medical Science, Rawalpindi, 64000, Pakistan
3Pakistan Ordinance Factory Hospital, Wah Cantt, Rawalpindi, 64000, Pakistan
4American River Nutrition, Inc. Hadley, MA, USA
5Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA
Corresponding Author : Asaf A Qureshi
Department of Basic Medical Sciences
2411 Holmes Street, School of Medicine
University of Missouri, Kansas City, MO 64108. USA
Tel: 816-235-5789
E-mail: [email protected]
Received November 18, 2015; Accepted November 26, 2015; Published November 30, 2015
Citation: Qureshi AA, Khan DA, Saleem S, Silswal N, Trias AM, et al. (2015) Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects. J Clin Exp Cardiolog 6:411. doi:10.4172/2155-9880.1000411
Copyright: © 2015 Qureshi AA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Background: Although, α-tocopherol is the most bioavailable form of vitamin E, but several animal and clinical studies have demonstrated tocotrienol bioavailability to various tissues. There are few reports on bioavailability of tocotrienols in humans. Most studies were carried out with mixtures of tocotrienols + tocopherols rather than pure tocotrienols. Moreover, dietary α-tocopherol interferes with the bioavailability of tocotrienols, and prevents absorption and delivery to organs and tissues. Aim: Pharmacokinetics and bioavailability of annatto-based δ-tocotrienol, plasma levels of α-, β-, γ-, δ-tocotrienol and tocopherols were quantified. In addition, several cytokines and microRNAs were examined. Study design: An open-label, randomized study evaluated pharmacokinetics and bioavailability of δ-tocotrienol in 33 healthy fed subjects. All subjects (11/dose) were randomly assigned to doses of 125, 250, or 500 mg/d. Plasma samples collected at 0, 1, 2, 3, 4, 6, 8, 10 h intervals were estimated by HPLC for tocols (tocotrienols and tocopherols). Results: The present study describes the effects of δ-tocotrienol on pharmacokinetic parameters of all eight tocol isomers. Supplementation of 125, 250 and 500 mg/d doses resulted in dose- dependent increases of (a) area under concentration-time curve (AUCt0 - t10 ng/ml) 2464, 5412, 14986; (b) maximum concentration (Cmax, ng/ml) 829, 1920, 3278 (P<0.001); (c) time to achieve maximum peak (Tmax; h) 3, 3, 6; (d) elimination of half-life (t1/2 h) 1.74, 1.39, 2.54; (e) time of clearance (Cl-T, h-1) 0.049, 0.045, 0.030; (f) volume of distribution (Vd/f, mg/h) 0.119, 0.114, 0.113; and (g) elimination rate constant (Ke; h-1) 0.412, 0.401, 0.265. Similar results were reported for the other tocols. Maximum plasma levels of δ-tocotrienol were observed at 3 h with doses of 125 and 250 mg/d, and 6 h with 500 mg/d. γ-tocotrienol, β-tocotrienol, α-tocotrienol, δ-tocopherol, γ-tocopherol β-tocopherol and α-tocopherol were appeared in the plasma after 2 h. Moreover, δ-tocotrienol treatment resulted in down-regulation of eight cytokines and upregulation of adiponectin, TGF-β1, and leptin. The expression of miR-34a (increased in bipolar disorder) was down-regulated, but expression of miR-107, miR-122a, and miR-132 (decreased in Alzheimer’s disease) was upregulated by δ-tocotrienol treatment. Conclusion: This is the first study describing the effect of δ-tocotrienol on pharmacokinetics and bioavailability of all eight tocol isomers. When tocotrienols are supplemented in absence of tocopherols, δ-tocotrienol has better bioavailability, and δ-tocotrienol is converted stepwise to other tocotrienols/tocopherols. These results support that tocotrienol, particularly δ-tocotrienol, as a dietary supplement might be useful in the prevention of age-related and chronic ailments.

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