An Investigation Of The Neuroprotective Effects Of Palm Vitamin E Tocotrienols Using White Matter Lesions As The Human Study Model
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Date
2014-09
Authors
Gopalan, Yogheswaran
Journal Title
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Publisher
Universiti Sains Malaysia
Abstract
A study was conducted to evaluate the neuroprotective activity of mixed tocotrienols using human volunteers with white matter lesion (WML). WMLs are regarded as manifestations of cerebral small vessel disease. Initially, the anti atherogenic effect of mixed tocotrienols was also evaluated in mildly hypercholesterolemic volunteers via imaging the carotid arteries using Magnetic Resonance Angiography (MRA). Of the first 50 consecutive volunteers who undergone the carotid artery imaging, none of them were detected having carotid artery stenosis and hence this part of the study was discontinued. In the next phase of the study, the prevalence of white matter lesion (WML) in a local hypercholesterolemic population in north –west peninsular Malaysia was determined. Of the 350 research volunteers who were imaged, 161 (46%) of them had WMLs, of which 65 (18.6%) were males and 96 (27.4%) females. The study also demonstrated that the chances of developing WMLs doubled (30.6%) in the age group of above 50 compared to 15.4% in the age group of below 50.
In the neuroprotective part of the study, a randomized double-blind placebo-controlled trial was conducted. Volunteers recruited were ≥ 35 years with cardiovascular risk factors and undergo Magnetic Resonance Imaging (MRI) of the brain. They were categorized as WML positive (MRI +ve) if they were present with WML at baseline. Volunteers without WMLs at baseline were classified as (MRI -ve). In the MRI –ve cohort, 120 volunteers were randomized to receive either 200 mg mixed tocotrienols or placebo twice daily and were followed up for 1 year. Out of 113 volunteers who completed the study, 19 in the mixed tocotrienols and 9 in the placebo group developed new WMLs. However, the mean volume of the WMLs developed after 1 year was lesser in the mixed tocotrienol treated group (8%) compared to placebo (47%) with a statistical significance of p = 0.048. In the final part of the study, 121 volunteers with MRI confirmed WMLs (MRI +ve) were randomized to receive 200 mg mixed tocotrienols or placebo twice daily and were followed up for 2 years. 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 mixed tocotrienol supplemented group remained essentially unchanged. The mean WML volume change between the two 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). Thus, the present study found that mixed tocotrienols can attenuate the progression of WMLs.
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Keywords
The neuroprotective activity of mixed tocotrienols using human volunteers with white matter lesion