Published Human Studies/ Cohort Studies
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| Article | Study objective/ findings |
| The effect of vitamin E (mixed tocotrienol) on the liver stiffness measurement measured by transient elastography (fibroScan) among NAFLD patients
Arguillas M, et al. (June 7th, 2013). APAS Liver Week. Singapore |
In this clinical study, 67 patients with ultrasound-proven NAFLD were enrolled and were assigned to either daily supplementation of 100 mg of EVNol SupraBio™ and lifestyle modification advice group (LMAG) for 3 months or in LMAG only. After 3 months of supplementation, 57% of all patients (n=38) showed decrease in their liver stiffness measurement, but 43% (n=29) did not improve. 79% of those who improved were from the Treatment group and 21% from LMAG alone. This suggested that EVNol SupraBio™ together with positive lifestyle intervention is about 4 times more effective compared to positive lifestyle modification alone in the context of liver stiffness amelioration |
| Tocotrienols for normalisation of hepatic echogenic response in nonalcoholic fatty liver: a randomised placebo-controlled clinical trial.
Magosso, E., et.al (2013). Nutr J.
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The study was to determine the effects of mixed tocotrienols, in normalising the hepatic echogenic response in hypercholesterolaemic patients with ultrasound-proven NAFLD. This is the first clinical trial that showed the hepatoprotective effects of mixed palm tocotrienols in hypercholesterolemic adults with NAFLD. |
| Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients.
Patel, V., et.al (2012). J Nutr. |
The primary objective of this work was to determine the concentrations of tocotrienols (200 mg mixed T3, b.i.d.) and TCP [200 mg α-tocopherol, b.i.d.)] in vital tissues and organs of adults receiving oral supplementation. This work provides, the first evidence demonstrating that orally supplemented tocotrienols are transported to vital organs of adult humans. The findings of this study, in the context of the current literature, lay the foundation for Phase II clinical trials testing the efficacy of tocotrienols against stroke and end-stage liver disease in humans. |
In vivo / Animal Studies |
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| Article | Study objectives/ findings |
| Palm tocotrienol-rich fraction inhibits methionine-induced cystathionine β-synthase in rat liver.
Kamisah, Y., et.al (2015). J Physiol Biochem
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The study investigated the effects of dietary palm tocotrienol-rich fraction on homocysteine metabolism in rats fed a high-methionine diet. In conclusion, palm tocotrienol-rich fraction reduced high-methionine-induced hyperhomocysteinaemia possibly by reducing hepatic oxidative stress in high-methionine-fed rats. It may also exert a direct inhibitory effect on hepatic cystathionine β-synthase. |
| Inhibitory effects of palm tocotrienol-rich fraction supplementation on bilirubin-metabolizing enzymes in hyperbilirubinemic adult rats.
Kamisah, Y, et.al (2014). PLoS One. |
To investigate the effects of palm TRF supplementation on hepatic bilirubin-metabolizing enzymes and oxidative stress status in rats administered phenylhydrazine. Palm tocotrienol-rich fraction was able to afford protection against phenylhydrazine-induced hyperbilirubinemia, possibly by reducing oxidative stress and inhibiting bilirubin-metabolizing enzymes in the liver. |
| Effects of palm oil tocotrienol-rich fraction on biochemical and morphological alterations of liver in fenitrothion-treated rats
Jayusman, P.A., et.al (2014). Pak J Pharm Sci.
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The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT. |
| Gamma-tocotrienol attenuates triglyceride through effect on lipogenic gene expressions in mouse heptacellular carcinoma heap 1-6.
Burdeos, G.C., et.al (2013). J of Nutritional Science & Vitaminology. |
In the present study, we elucidated the effect of γ-T3 on lipid levels and lipogenic gene expressions in mouse hepatocellular carcinoma Hepa 1-6. γ-T3 showed attenuation of TG through effect on fatty acid synthase, sterol regulatory element-binding transcription factor 1, stearoyl CoA desaturase 1, and carnitine palmitoyl transferase 1A gene expression in Hepa 1-6. In contrast, the Cho level remained unchanged. These results expanded our previous finding of lipid-lowering effects of T3, especially for TG. Therefore, T3 is a potential lipid-lowering compound candidate with realistic prospects for its use as a therapy for lipid-related diseases in humans. |
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Yachi, R., et.al (2013). J Clin Biochem Nutr.
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A new rat model of steatohepatitis induced by tumor necrosis factor-α (TNF-α) stimulation and used it to investigate the effects of vitamin E analogs. Findings suggest that tocotrienol species are effective for amelioration of steatohepatitis, and that tocotrienol and α-tocopherol exert a synergistic effect. |
| Gamma-tocotrienol reduces the triacylglycerol level in rat primary hepatocytes through regulation of fatty acid metabolism.
Muto, C., et.al (2013). J Clin Biochem Nutr. |
The present study was carried out to investigate the effect of vitamin E analogs, especially gamma-tocotrienol (γ-T3), on hepatic TG accumulation and enzymes related to fatty acid metabolism in three types of rat primary hepatocytes: (1) normal hepatocytes, (2) hepatocytes incubated in the presence of palmitic acid (PA), and (3) hepatocytes with fat accumulation. Our results showed that γ-T3 significantly reduced the TG content of normal hepatocytes. γ-T3 also increased the expression of carnitine palmitoyltransferase 1 (CPT1A) mRNA, and tended to reduce that of sterol regulatory element binding protein 1c (SREBP-1c) mRNA. In addition, γ-T3 markedly suppressed the gene expression of both C/EBP homologous protein (CHOP) and SREBP-1c induced by PA. As these two genes are located downstream of endoplasmic reticulum (ER) stress, their suppression by γ-T3 might result from a decrease of ER stress. Moreover, γ-T3 suppressed the expression of interleukin 1β (IL-1β), which lies downstream of CHOP signaling. Taken together, our data suggest that γ-T3 might prevent hepatic steatosis and ameliorate ER stress and subsequent inflammation in the liver. |
| Tocotrienols reverse cardiovascular, metabolic and liver changes in high carbohydrate, high fat diet-fed rats.
Wong, W.Y., et.al (2012). Nutrients. |
The effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome. |
| Tocotrienol attenuates triglyceride accumulation in HepG2 cells and F344 rats.
Burdeos, G.C., et.al (2012) Lipids. |
We investigated how T3 decreases TG concentration in cultured cells and animals. In a cell culture study, human hepatoma cells (HepG2) were incubated in a control or a fat (1 mM oleic acid)-loaded medium containing γ-T3 for 24 h. These results provided new information and the mechanism of the TG-lowering effect of T3. The lipid lowering effects of dietary T3 might be mediated by the reduction of TG synthesis. |
| Effects of administration of alpha-tocopherol and tocotrienols on serum lipids and liver HMG CoA reductase activity.
Khor, H.T., et.al (2000). Int J Food Sci Nutr. |
Male hamsters were fed on semi-synthetic diets containing commercial corn oil (CO), isolated corn oil triglycerides (COTG), COTG supplemented with of alpha-tocopherol and COTG supplemented with alpha-tocopherol as the dietary lipid for 45 days. The above results indicate that the alpha-tocopherol is hypercholesterolemic in the hamster and its effect on liver HMGCR is dose-dependent. T3 exhibited inhibitory effect on liver HMGCR and alpha-T attenuated the inhibitory effect of T3 on liver HMGCR (HMG CoA reductase). |
| Tocotrienols form palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes.
Kamat, J.P. et.al (1997). Mol Cell Biochem.
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Tocotrienols from palm oil showed significant ability to inhibit oxidative damage induced by ascorbate-Fe2+ and photosensitization, involving different mechanisms, in rat liver microsomes. The results indicate that this fraction from palm oil can be considered as an effective natural antioxidant supplement capable of protecting cellular membranes against oxidative damage. |
In-vitro Studies |
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| Article | Study objectives/ findings |
| Delta and gamma-tocotrienols suppress human hepatocellular carcinoma cell proliferation via regulation or Ras-Raf-MEK-ERK pathway-associated upstream signaling.
Burdeos, G.C., et.al (2016). Food Funct.
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Tocotrienol (T3) has recently gained increasing interest due to its anti-cancer effect. Here, we investigated the modulating effect of δ and γ T3 on the Ras-Raf-MEK-ERK oncogenic upstream signaling pathway in human hepatocellular carcinoma HepG2 cells. The results indicated that T3 regulated the upstream signaling cascades of this pathway. |
| Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury.
Tan C.Y., et.al (2015). Redox Biol
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This study investigates the protective effect of T3 analogs (α-, δ-, γ-) in comparison with α-TP followed by assessing the underlying mechanisms of the cytoprotective T3 analog(s) in two xenobiotics-induced liver injury models using (1) acetaminophen (APAP)- and (2) hydrogen peroxide (H2O2). In summary, these results suggest that α-TP/α-T3 elicit hepatoprotective effects against toxicants-induced damage mainly through activation of antioxidant responses at an early stage to prevent the exacerbation of injury. |
| Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion.
Zaiden, N., et.al (2010). J Atheroscler Thromb.
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Present study aimed to elucidate the suppression of serum lipids by gamma and delta-tocotrienols (γδT3). Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδT3 in human. |
| Effects of gamma-tocotrienol on ApoB synthesis, degradation, and secretion in HepG2 cells.
Theriault, A., et.al (1999). Arteriosclerosis, Thrombosis & Vascular Biology. |
To define the mechanism of action of γ-T3 on hepatic modulation of apoB production using cultured HepG2 cells as the model system. The data suggest that γ-T3 stimulates apoB degradation possibly as the result of decreased apoB translocation into the endoplasmic reticulum lumen. It is speculated that the lack of cholesterol availability reduces the number of secreted apoB-containing lipoprotein particles by limiting translocation of apoB into the endoplasmic reticulum lumen. |
| Effects of tocotrienol on the intracellular translocation and degradation of apoliporotein B: possible involvement of a proteasome independent pathway.
Wang Q., et.al (1998). Biochem. |
The aim of this study was to explore the effects of gamma-T3 on the proteasome dependent co-translational degradation and the proteasome independent post-translational degradation of apoB in HepG2 cells. Gamma-T3 diverted more apoB to a cytosolic proteasomal dependent and possibly an ER-associated proteasomal independent degradation pathways. |