No abstract

No 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 (AUC t0 -t10 , ng/ml) 2464, 5412, 14986; (b) maximum concentration (C max , ng/ml) 829, 1920, 3278 (P<0.001); (c) time to achieve maximum peak (T max ; h) 3, 3, 6; (d) elimination of half-life (t 1/2 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. Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects IntroductionSeveral studies have reported the antioxidant, anti-inflammatory, anticancer, hypocholesterolemic and neuroprotec...

The cholesterol-suppressive action of the tocotrienol-rich-fraction (TRF) of palm oil may be due to the effect of its constituent tocotrienols on beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase activity. The tocotrienols, modulate HMG-CoA reductase activity via a post-transcriptional mechanism. As a consequence small doses (5-200 ppm) of TRF-supplemented diets fed to experimental animals lower serum cholesterol levels. These findings led us to evaluate the safety and efficacy of large supplements of TRF and its constituents. Diets supplemented with 50, 100, 250, 500, 1000, or 2000 ppm of TRF, alpha-tocopherol, alpha-tocotrienol, gamma-tocotrienol, or 6-tocotrienol were fed to chickens for 4 wk. There were no differences between groups or within groups in weight gain, or in feed consumption at the termination of the feeding period. Supplemental TRF produced a dose-response (50-2000 ppm) lowering of serum total and LDL cholesterol levels of 22% and 52% (P < 0.05), respectively, compared with the control group. alpha-Tocopherol did not affect total or LDL-cholesterol levels. Supplemental alpha-tocotrienol within the 50-500 ppm range produced a dose-response lowering of total (17%) and LDL (33%) cholesterol levels. The more potent gamma and delta isomers yielded dose-response (50-2,000 ppm) reductions of serum total (32%) and LDL (66%) cholesterol levels. HDL cholesterol levels were minimally impacted by the tocotrienols; as a result, the HDL/LDL cholesterol ratios were markedly improved (123-150%) by the supplements. Serum triglyceride levels were significantly lower in sera of pullets receiving the higher supplements. The safe dose of various tocotrienols for human consumption might be 200-1000 mg/d based on this study.

The aim of this paper is to use qualitative aspects of UV-vis spectrophotometry to understand structural behavior of these plyenic pi systems.