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Neuroprotective and Cardioprotective Effects Of Palm Vitamin E Tocotrienols

A Double Blind Placebo Controlled Study On The Neuroprotective And Anti-Atherogenic Effects Of Palm TocotrienolRich Fraction(Palm Vitamin E)

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00753532
Enrollment
241
Registered
2008-09-16
Start date
2007-11-30
Completion date
2012-03-31
Last updated
2022-05-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cerebrovascular Disorders

Keywords

Carotid artery stenoses, Brain ischaemia, stroke, Lipid abnormalities, Fatty Liver

Brief summary

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.

Interventions

DIETARY_SUPPLEMENT200mg of Palm vitamin E (tocotrienols) or placebo

Individuals randomized in the (MRI+ve) and (MRI -ve) cohort respectively. In the MRI(+ve) cohort, 62 subjects received 200 mg softgels of Palm Vitamin E (tocotrienols) and 59 were assigned to placebo, taken orally twice a day for a study period of two years. In the MRI(-ve) cohort, 63 subjects received 200 mg softgels of Palm Vitamin E (tocotrienols) and 57 consumed placebo, taken twice a day for a follow up period of 1 year.

Sponsors

Malaysia Palm Oil Board
CollaboratorOTHER_GOV
Universiti Sains Malaysia
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* Participant able to understand and has signed and dated the Informed Consent Form * Participant can be either a male or female * Participant is more than 35 years of age * Participant has total cholesterol between 5.2 - 6.2 mmol/L and LDL cholesterol between 2.6 - 4.2 mmol/L * Participant is able to comply with visits and medications * Participant has normal liver function (total protein, total albumin, total globulin, total bilirubin, SGOT and SGPT) Participants who satisfy the Inclusion and

Exclusion criteria

for Study in General with one or more of the following conditions will be eligible for MRI screening: * More than 40 years of age * Stable hypertension requiring only out-patient management * Diabetes mellitus requiring only out-patient management * Ischaemic heart disease requiring only out-patient management * Body mass index more than 25 (overweight or obese)

Design outcomes

Primary

MeasureTime frame
Regression of white matter lesion load in terms of numbers and size in the brain1 to 2 years

Secondary

MeasureTime frame
Regression of the carotid artery stenoses in terms of percentage1 to 2 years
The improvement in the lipid profile other markers associated with increased cardiovascular risk1 to 2 years
Improvement in liver echogenicity.1 to 2 years

Countries

Malaysia

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026