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In rats, δ-tocotrienol improved inflammation, heart structure and function, and liver structure and function, while γ-tocotrienol produced more modest improvements, with minimal changes with α-tocotrienol and α-tocopherol. The most important mechanism of action is likely to be reduction in organ inflammation.

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. 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.

Previous studies have revealed that tocotrienol-rich fractions (TRF) from palm oil inhibit the proliferation and the growth of solid tumors. The anticancer activity of TRF is said to be caused by several mechanisms, one of which is antiangiogenesis. In this study, we looked at the antiangiogenic effects of TRF. In vitro investigations of the antiangiogenic activities of TRF, delta-tocotrienol (deltaT3), and alpha-tocopherol (alphaToc) were carried out in human umbilical vein endothelial cells (HUVEC). TRF and deltaT3 significantly inhibited cell proliferation from 4 microg/ml onward (P < 0.05). Cell migration was inhibited the most by deltaT3 at 12 microg/ml. Anti-angiogenic properties of TRF were carried out further in vivo using the chick embryo chorioallantoic membrane (CAM) assay and BALB/c mice model. TRF at 200 microg/ml reduced the vascular network on CAM. TRF treatment of 1 mg/mouse significantly reduced 4T1 tumor volume in BALB/c mice. TRF significantly reduced serum vascular endothelial growth factor (VEGF) level in BALB/c mice. In conclusion, this study showed that palm tocotrienols exhibit anti-angiogenic properties that may assist in tumor regression.

In this Letter we omitted to cite a relevant paper 1 showing that loss of cerebral cavernous malformation (CCM) signalling confers an increase in KLF2 expression in endothelial cells and in the developing zebrafish heart. We regret this oversight. 1. Renz, M. et al. Regulation of β 1 integrin-Klf2-mediated angiogenesis by CCM proteins. Dev. Cell 32, 181-190 (2015).

Metabolic syndrome is defined as a set of health risk factors that are associated with an increased chance of cardiovascular diseases and type 2 diabetes. These include abdominal obesity, hyperglycemia, impaired glucose tolerance, dyslipidemia, and hypertension. Interventions in metabolic syndrome include lifestyle interventions such as a healthy diet using functional foods together with increased physical activity to induce weight loss as the first aim of treatment. Nutraceuticals such as tocotrienols and tocopherols as members of the vitamin E family may be more targeted interventions. This review evaluates the effects of tocotrienols on the risk factors of metabolic syndrome using data from human, animal and in vitro studies. Tocotrienols improved lipid profiles and reduced atherosclerotic lesions, decreased blood glucose and glycated hemoglobin concentrations, normalized blood pressure, and inhibited adipogenesis. The differences in responses between tocopherols and tocotrienols in preventing obesity, diabetes, hypertension, atherosclerosis, ischemia, and inflammation suggest that different receptors or signaling mechanisms may be involved.

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