Dose-dependent Modulation of Lipid Parameters, Cytokines and RNA by δ-tocotrienol in Hypercholesterolemic Subjects Restricted to AHA Step-1 Diet

Qureshi, Asaf A.; Khan, Dilshad Ahmad; Mahjabeen, Wajiha; Qureshi, Nilofer

doi:10.9734/bjmmr/2015/13820

Cited by 14 publications

(23 citation statements)

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“…The correlation between plasma levels of several pro-inflammatory and anti-inflammatory cytokines affected by δ-tocotrienol treatment has been reported in our recent publications [4,5,37]. Most of the cytokines (eight out of eleven) were down-regulated in a dosedependent manner by δ-tocotrienol treatment, except adiponectin, tumor growth factor β1 and leptin (Table 6).…”

Section: Discussionsupporting

confidence: 63%

“…We have reported earlier the influence of δ-tocotrienol on several key cytokines/proteins involved in various diseases [5,6]. In the present paper, only those plasma cytokines/proteins are described which are important for inflammation, cardiovascular disease, cancer, and aging.…”

Section: Effects Of δ-Tocotrienol On Human Plasma Cytokines/proteins mentioning

confidence: 82%

“…The phenomena of bioconversion of tocotrienols to tocopherols have been discussed in earlier publications [4][5][6]29]. It was reported that failure of large doses of palm TRF and rice bran TRF25 to lower lipid parameters in hypercholesterolemic subjects maybe due to their conversion to tocopherols, because the plasma concentrations of tocopherols were 2-to 4-fold higher than tocotrienols as compared to placebo group.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported the antioxidant, anti-inflammatory, anticancer, hypocholesterolemic and neuroprotective properties of tocotrienols in different cell lines, animal models, and in humans [1][2][3][4][5][6][7][8]. However, question on the bioavailability of pure tocotrienols remained unanswered.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, high doses of tocotrienols may be useful for cancer chemoprevention and treatment. Large doses of δ-tocotrienol up to 3200 mg/d have been used to treat patients suffering from resectable pancreatic cancer [23].The biological properties of tocotrienols have been underestimated despite several studies showing their positive effects on physiological and biological functions [1][2][3][4][5][6][7][8]. The scientific recognition for tocotrienols remains limited as compared to tocopherols due to their low concentrations in most food products.…”

mentioning

confidence: 99%

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

Qureshi¹,

Khan²,

Saleem³

et al. 2015

J Clin Exp Cardiolog

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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...

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Section: Discussionsupporting

confidence: 63%

Section: Effects Of δ-Tocotrienol On Human Plasma Cytokines/proteins mentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Qureshi¹,

Khan²,

Saleem³

et al. 2015

J Clin Exp Cardiolog

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Effects of delta‐tocotrienol supplementation on Glycemic Control, oxidative stress, inflammatory biomarkers and miRNA expression in type 2 diabetes mellitus: A randomized control trial

Mahjabeen

Khan

Mirza

et al. 2021

Phytotherapy Research

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The study aimed to ascertain the effects of delta-tocotrienol (δT3) supplementation on glycemic control, oxidative stress, inflammation and related micro-ribonucleic acid (miRNA) expression in patients with type 2 diabetes mellitus (T2DM). Total 110 patients of T2DM on oral hypoglycemic agents, were randomly divided into tocotrienol and placebo groups and given 250 mg δT3 or cellulose soft gel capsule once daily respectively for 24 weeks. Glycemic control, oxidative stress, inflammatory biomarkers, and miRNAs expression were measured in serum at baseline and end of the intervention by using standard laboratory methods. Compared to the placebo, δT3 supplementation resulted in a significant (p ≤ .05) reduction [mean difference (95% confidence interval)] in plasma glucose [−0.48 (−0.65, −0.30)], insulin [−1.19 (−1.51, −0.87)], homeostatic model assessment of insulin resistance [−0.67 (−0.86, −0.49)], glycosylated hemoglobin [−0.53 (−0.79, −0.28)], malondialdehyde [−0.34 (−0.45, −0.22)], high sensitive-Creactive protein[−0.35 (−0.54, −0.16)], tumor necrosis factor-alpha [−1.22 (−1.62, −0.83)], and interleukin-6[−2.30 (−2.91, −1.68)]. More than twofold downregulation in miRNA expression was observed in the δT3 group compared to the placebo. The study demonstrated that δT3 supplementation in addition to oral hypoglycemic agents, improved glycemic control, inflammation, oxidative stress, and miRNA expression in T2DM without any adverse effect. Thus, δT3 might be considered as an effective dietary supplement to prevent long-term diabetic complications.

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Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial

et al. 2018

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Dose-dependent Modulation of Lipid Parameters, Cytokines and RNA by δ-tocotrienol in Hypercholesterolemic Subjects Restricted to AHA Step-1 Diet

Cited by 14 publications

References 0 publications

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

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

Effects of delta‐tocotrienol supplementation on Glycemic Control, oxidative stress, inflammatory biomarkers and miRNA expression in type 2 diabetes mellitus: A randomized control trial

Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial

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