Dose‐response impact of various tocotrienols on serum lipid parameters in 5‐week‐old female chickens

Abstract

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.

Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers

“…In this study we looked to see whether daily supplementation of 400 mg of TRF for 2 months could enhance the immune response in human volunteers challenged with TT vaccine. The dose of TRF (400 mg) chosen for this study is in line with the other vitamin E studies (Meydani et al, 1997a, b;Yusuf et al, 2000;Yu et al, 2006). Recently, we reported that supplementation of a-T or TRF for 2 months did not produce any significant changes on immune parameters in healthy human subjects in the absence of immunogenic challenge (Radhakrishnan et al, 2008).…”

Tocotrienols in health and disease: The other half of the natural vitamin E family

“…Thus, tocotrienols may be viewed as being members of the natural vitamin E family not only structurally but also functionally. Disappointments with outcomes-based studies investigating a-tocopherol (Friedrich, 2004;Greenberg, 2005) need to be cautiously handled recognizing the untapped opportunities offered by the other forms of natural vitamin E. Recently it has been suggested that the safe dose of various tocotrienols for human consumption is 200-1000 mg/d (Yu et al, 2006). Vitamin E represents one of the most fascinating natural resources that have the potential to influence a broad range of mechanisms underlying human health and disease.…”

Combined γ‐tocotrienol and Met inhibitor treatment suppresses mammary cancer cell proliferation, epithelial‐to‐mesenchymal transition and migration

“…Previous findings have shown that combined treatment with subeffective doses of c-tocotrienol and SU11247 significantly inhibited HGFdependent mouse +SA mammary tumour cell growth, and this effect was associated with large reduction in total and phosphorylated (activated) levels of Met (24). Recommended safe dose limit is 200-1000 mg/day in humans for various tocotrienol isoforms (36). Treatment doses of c-tocotrienol in the present study are physiologically relevant based on serum concentrations that were found to range between 2 and 4 lM in human subjects given a single 300 mg oral dose of mixed tocotrienols, under fed or fasting conditions (37).…”