Neuroprotective and Cardioprotective Effects Of Palm Vitamin E Tocotrienols

Completed

Phase 2 Results N/A

Trial Description

The purpose of the study is to assess the neuroprotective, anti atherogenic and hepatoprotective properties of tocotrienols (palm vitamin E) supplementation as determined by white matter lesion load on serial magnetic resonance imaging (MRI), carotid artery magnetic resonance angiography (MRA) and liver ultrasound (US) as well as lipid profile analysis.

Detailed Description

Stroke is the third largest cause of death after heart disease and cancer in Malaysia. It is estimated that 52,000 Malaysians suffer stroke annually. In 2005, 3245 cases of stroke were fatal. It is projected that the number of fatal stoke cases will exceed 25,000 in 2020.
It was found that at nanomolar concentrations, α-tocotrienol but not α-tocopherol prevent glutamate-induced neuron cell death in mice through inhibition of c-Src kinase and 12-lipoxygenase. Tocotrienol-supplemented rats showed more protection against stroke-induced injury compared with matched controls.
White matter lesion as detected on magnetic resonance imaging (MRI) is closely related to vascular events of the brain. MRI and histopathological study has shown that the larger white matter lesions not usually conforming to usual areas infarcts can actually represent areas of subclinical infarct. In addition there is positive correlation between white matter lesions with established vascular risk factors.
The Rotterdam Scan Study showed that elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of clinical stroke, which could not be explained by the major stroke risk factors alone.
Several recent studies showed that white matter lesions may be an independent prognostic measure of future stroke risk.
White matter hyperintensities as detected on MRI is closely related to vascular events of the brain and in some instances represent subclinical infarcts.
It is therefore conceivable to study the neuroprotective properties of tocotrienol supplementation in humans by looking at serial changes of white matter disease load.
Tocotrienol supplementation brings about various favourable effects including improving lipid profiles, lowering of thromboxane B2 and platelet factor 4 and reduced LDL oxidation. Carotid artery MR angiography is an established and robust technique in the evaluation of carotid artery stenosis. Therefore, to study the anti-atherogenic effects of tocotrienols supplementation, serial MR angiography of the carotid arteries are done.
Non-alcoholic fatty liver disease (NAFLD) is emerging as a not fully understood, both in aetiology and significance, liver disorder. FLD is reported to be the most common cause of chronic liver disease in the U.S.A. and other western countries with a prevalence rate ranging between 15% to 30% of the adult population. However, limited data are available for Malaysia.
US imaging provides valuable information of the liver condition with a sensitivity of 93-100%. Frequently NAFLD is associated with dyslipidemia, obesity, insulin resistance and type II diabetes and it represents the liver component of the metabolic syndrome (MetS). Patients with NAFLD are reported to have low levels of serum vitamin E. NAFLD patients present a significant increase in cardiovascular (CV) risk, thus linking NAFLD, MetS and accelerated atherosclerosis.

Conditions

Interventions

  • Palm vitamin E (tocotrienol) or placebo Dietary Supplement
    Other Names: Tocovid 200mg
    Intervention Desc: 200 mg softgel tocotrienol or placebo to be taken orally twice a day.
    ARM 1: Kind: Experimental
    Label: MRI(+ve), MRI(-ve)
    Description: Volunteers in MRI(+ve) group will be randomized into two groups to receive either palm vitamin E (tocotrienol)or placebo. The same goes to the volunteers in the MRI(-ve) group as well.
    ARM 2: Kind: Experimental
    Label: Tocotrienol
    Description: Tocovid
  • 200mg of Palm vitamin E (tocotrienols) or placebo Dietary Supplement
    Other Names: Tocovid 200mg
    Intervention Desc: Individuals randomized in the (MRI+ve) and (MRI -ve) cohort received either 200 mg softgels of Palm Vitamin E (tocotrienols) or placebo taken orally twice a day.
    ARM 1: Kind: Experimental
    Label: MRI(+ve),
    Description: 121 volunteers in MRI(+ve) cohort were randomized into two groups to receive either 200mg palm vitamin E (tocotrienols) softgel capsules or a identical looking placebo twice daily. 62 volunteers received 200mg palm vitamin E (tocotrienols) and the remaining 59 received placebo. They were followed up every 3 months for a period of 2 years for their blood biochemistry profile and MRI of the brain was conducted at baseline, 12 months and 24 months..
    ARM 2: Kind: Experimental
    Label: MRI(-ve)
    Description: 120 volunteers in MRI(-ve) cohort were randomized into two groups to receive either 200mg palm vitamin E (tocotrienols) softgel capsules or a identical looking placebo twice daily. 63 volunteers received 200mg palm vitamin E (tocotrienols) and the remaining 57 received placebo. They were followed up every 3 months for a period of 1 year for their blood biochemistry profile and MRI of the brain was conducted at baseline and 12 months.

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Prevention
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Regression of white matter lesion load in terms of numbers and size in the brain 1 to 2 years No
Secondary Regression of the carotid artery stenoses in terms of percentage 1 to 2 years No
Secondary The improvement in the lipid profile other markers associated with increased cardiovascular risk 1 to 2 years No
Secondary Improvement in liver echogenicity. 1 to 2 years No

Sponsors