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Stroke. 2014 May;45(5):1422-8. doi: 10.1161/STROKEAHA.113.004449. Epub 2014 Apr 3.

Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter.

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From the Faculty of Pharmacy, Universiti Teknologi Mara, Selangor, Malaysia (Y.G.); Advanced Medical and Dental Institute, Penang, Malaysia (I.L.S., E.M., M.A.A., M.R.A.B.); School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia (N.A.K.K., K.H.Y.); Hovid Research Sdn Bhd, Ipoh, Malaysia (J.W.W., B.H.N.); Malaysian Palm Oil Council (K.S.); Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia (C.K.); Buckinghamshire Healthcare, NHS Trust, Buckinghamshire, United Kingdom (W.C.L.).



Previous cell-based and animal studies showed mixed tocotrienols are neuroprotective, but the effect is yet to be proven in humans. Thus, the present study aimed to evaluate the protective activity of mixed tocotrienols in humans with white matter lesions (WMLs). WMLs are regarded as manifestations of cerebral small vessel disease, reflecting varying degrees of neurodegeneration and tissue damage with potential as a surrogate end point in clinical trials.


A total of 121 volunteers aged ≥35 years with cardiovascular risk factors and MRI-confirmed WMLs were randomized to receive 200 mg mixed tocotrienols or placebo twice a day for 2 years. The WML volumes were measured from MRI images taken at baseline, 1 year, and 2 years using a validated software and were compared. Fasting blood samples were collected for full blood chemistry investigation.


According to per-protocol (88 volunteers) and intention-to-treat (121 volunteers) analyses, the mean WML volume of the placebo group increased after 2 years, whereas that of the tocotrienol-supplemented group remained essentially unchanged. The mean WML volume change between the 2 groups was not significantly different (P=0.150) at the end of 1 year but was significant at the end of 2 years for both per-protocol and intention-to-treat analyses (P=0.019 and P=0.018). No significant difference was observed in the blood chemistry parameters between the 2 groups.


Mixed tocotrienols were found to attenuate the progression of WMLs.

CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00753532.


magnetic resonance imaging; tocotrienols

[Indexed for MEDLINE]

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