Abstract
Background: Tocotrienols have hypocholesterolemic, anti-inflammatory, and anti-cancer properties. Clinical studies using tocotrienol-rich fraction (TRF) from palm oil yielded inconsistent results with regards to its efficacy due to presence of tocopherols in TRF mixture. Objectives: The impact of tocopherol-free δ-tocotrienol on inflammatory and oxidative stress biomarkers, plasma cytokines/proteins, their gene expression, and microRNAs was studied in hypercholesterolemic subjects. Design: Hypercholesterolemic (n=31; serum cholesterol >5.2 mmol/L) subjects were enrolled in the study. All hypercholesterolemic subjects were given increasing doses of δ-tocotrienol (125, 250, 500, 750 mg/d) plus AHA Step-1 diet for 4 weeks each during a 30 week study period. Serum nitric oxide (NO), C-reactive protein (CRP), malondialdehyde (MDA), δ-glutamyl-transferase (δ-GT), total antioxidant status (TAS), cytokines/proteins, cDNA, and microRNAs were determined. Results: All concentrations of δ-tocotrienol reduced serum levels of NO, CRP, MDA, δ-GT. The most effective dose (250 mg/d) decreased serum NO (40%), CRP (40%), MDA (34%), δ-GT (22%) significantly (P<0.001), while TAS levels increased 22% (P<0.001). The 500 mg/d and 750 mg/d doses were less effective in improving oxidative stress compared to the 250 mg/d dose. Inflammatory plasma cytokines (resistin, IL-1α, IL-12, IFN-γ) were reduced 15-17% (P<0.05-0.01), while cardiac angiogenic fibroblast growth factor-b (FGF-b) and platelet-derived growth factor (PDGF) were decreased by 11% and 14% (P<0.05-0.01), respectively, with 250 mg/d δ-tocotrienol treatment. Similar results were obtained for cytokine gene expression. Several plasma miRNAs (miRNA-16-1, miRNA-125a, miRNA-133, miRNA-155, miRNA-223, miRNA-372, miRNA-10b, miRNA-18a, miRNA-214) associated with cardiovascular disease and cancer were modulated by δ-tocotrienol treatment. Conclusions: In a dose-dependent study of 125-750 mg/d, δ-tocotrienol maximally reduced inflammation and oxidative stress parameters with a 250 mg/d dose in hypercholesterolemic subjects, and may be a potential therapeutic alternative natural product for the maintenance of health during aging process.
Highlights
It is well-established that low-grade inflammation causes progressive damage to organs in chronic diseases
Our recent studies have demonstrated that serum nitric oxide (NO) levels are significantly increased with aging, and administration of δ-tocotrienol along with other nutritional supplements has beneficial effects in lowering NO, γ-glutamyl-transferase (γ-GT), C-reactive protein (CRP), and uric acid in normalcholesterolemic seniors [1]
The most important aging and inflammatory biomarkers, such as NO and CRP were 2 to 4 times higher compared to normal values in these hypercholesterolemic subjects [2]
Summary
It is well-established that low-grade inflammation causes progressive damage to organs in chronic diseases. Our recent studies have demonstrated that serum nitric oxide (NO) levels are significantly increased with aging, and administration of δ-tocotrienol along with other nutritional supplements (resveratrol, quercetin, and niacin) has beneficial effects in lowering NO, γ-glutamyl-transferase (γ-GT), C-reactive protein (CRP), and uric acid in normalcholesterolemic seniors [1]. Intake of these nutritional supplements in hypercholesterolemic individuals along with AHA Step-1 diet has proved to considerably reduce the serum total cholesterol, LDL-cholesterol and triglyceride levels [2]. Clinical studies using tocotrienol-rich fraction (TRF) from palm oil yielded inconsistent results with regards to its efficacy due to presence of tocopherols in TRF mixture
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