Clinical Investigation of the Protective Effects of Palm Vitamin E Tocotrienols on Brain White Matter

Gopalan, Yogheswaran; Shuaib, Ibrahim Lutfi; Magosso, Enrico; Ansari, Mumtaz Ahmad; Bakar, Mohd Rizal Abu; Wong, Jeannie Hsiu Ding; Khan, Nurzalina Abdul Karim; Liong, Wei Chuen; Sundram, Kalyana; Ng, Bee Hong; Chinna, Karuthan; Yuen, Kah Hay

doi:10.1161/strokeaha.113.004449

Cited by 79 publications

(68 citation statements)

References 48 publications

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“…TRF at the dose of 200 mg twice daily for two years was reported to be beneficial in attenuating the progression of brain white matter lesion in volunteers with cardiovascular risk factors and MRI-confirmed white matter lesion. This lesion is regarded as manifestations of cerebral small vessel disease [118]. In a study cohort consisting of 50 patients with cerebrovascular disease, apparent carotid atherosclerotic regression was found in the TRF-supplemented subjects while some controls showed progression [77].…”

Section: Effects Of Tocotrienol On Cerebrovascular Diseasesmentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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Tocotrienol (T3) is a subfamily of vitamin E known for its wide array of medicinal properties. This review aimed to summarize the health benefits of T3, particularly in prevention or treatment of non-communicable diseases (NCDs), including cardiovascular, musculoskeletal, metabolic, gastric, and skin disorders, as well as cancers. Studies showed that T3 could prevent various NCDs, by suppressing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the mevalonate pathway, inflammatory response, oxidative stress, and alternating hormones. The efficacy of T3 in preventing/treating these NCDs is similar or greater compared to tocopherol (TF). TF may lower the efficacy of T3 because the efficacy of the combination of TF and T3 was lower than T3 alone in some studies. Data investigating the effects of T3 on osteoporosis, arthritis, and peptic ulcers in human are limited. The positive outcomes of T3 treatment obtained from the preclinical studies warrant further validation from clinical trials.Nutrients 2020, 12, 259 2 of 84 Nutrients 2020, 12, 259 4 of 84 the order δ > γ > β > α [45]. Using HepG2 cells, γT3 was shown to stimulate apolipoprotein B (Apo-B) degradation by decreasing its translocation into the endoplasmic reticulum (ER) lumen. This action eventually caused a reduction in the number of Apo-B in lipoprotein particles [46]. Other reports showed that γT3 and δT3 had the potential to reduce the hepatic TG synthesis and very-low-density lipoprotein (VLDL) secretion by suppressing expression of genes involved in lipid homeostasis, particularly the TG, cholesterol, and VLDL biosynthesis. Moreover, δT3 also promoted the efflux of LDL through LDL receptor expression [47]. A summary of the literature on effect of T3 supplementation on lipid profile of hypercholesterolemic model in vitro is shown in Table 1.Animal models of dyslipidemia have been used to investigate the effects of T3 on lipid profile. Several animals have been tested, including chicken, swine and rodents (rats, hamsters, guinea pigs). In chickens fed with a varying level of αTF and γT3, Qureshi et al. (1996) showed that αTF enhanced the inhibition of HMGCR by γT3. They further stipulated that the vitamin E mixture should contain 15-20% of αTF and approximately 60% of γT3 or δT3 for optimal anti-cholesterol effects [48]. In the subsequent study, demonstrated that combination of 50 ppm T3-rich fraction (TRF) and 50 ppm lovastatin was more effective in suppressing HMGCR activity compared to lovastatin alone in chickens. The combination also reduced serum TC and LDL-C, TG, Apo-B, thromboxane B 2 , and platelet factor 4 in contrast to individual treatment [49]. Using chicken supplemented with 50 ppm of δT3, Qureshi et al. (2011) further revealed that δT3 reduced TC and LDL-C besides suppressing the lipid elevating effects of dexamethasone and potentiated the TG-lowering effect of riboflavin [50]. Using genetically hypercholesterolemic swine, Qureshi et al. (1991) demonstrated the significant effect of TRF in lowering serum TC, LDL-C, Apo-B, thrombo...

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Section: Effects Of Tocotrienol On Cerebrovascular Diseasesmentioning

confidence: 99%

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

et al. 2020

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“…Khanna et al demonstrated that tocotrienols blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-Lox [120]. Gopalan et al demonstrated that mixed tocotrienols attenuated the progression of white matter lesions, indicating cerebral small vessel disease [121]. Ibrahim et al demonstrated that treatment with a tocotrienol-rich fraction (TRF) dose-dependently inhibited the formation of Aβ formation fibrils and Aβ oligomers in vitro, and that daily TRF supplementation to AβPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aβ immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain and eventually improved cognitive function [122,123].…”

Section: Tocotrienolsmentioning

confidence: 99%

Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements

Tadokoro

Ohta

Inufusa

et al. 2020

IJMS

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Oxidative stress plays a crucial role in Alzheimer's disease (AD) from its prodromal stage of mild cognitive impairment. There is an interplay between oxidative stress and the amyloid β (Aβ) cascade via various mechanisms including mitochondrial dysfunction, lipid peroxidation, protein oxidation, glycoxidation, deoxyribonucleotide acid damage, altered antioxidant defense, impaired amyloid clearance, inflammation and chronic cerebral hypoperfusion. Based on findings that indicate that oxidative stress plays a major role in AD, oxidative stress has been considered as a therapeutic target of AD. In spite of favorable preclinical study outcomes, previous antioxidative components, including a single antioxidative supplement such as vitamin C, vitamin E or their mixtures, did not clearly show any therapeutic effect on cognitive decline in AD. However, novel antioxidative supplements can be beneficial for AD patients. In this review, we summarize the interplay between oxidative stress and the Aβ cascade, and introduce novel antioxidative supplements expected to prevent cognitive decline in AD.

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“…High dietary intake of the combination of all natural vitamin E congeners has been shown to exhibit protection against AD [68]. Dietary intake of mixed tocotrienols in subjects with cardiovascular risk factors and white matter lesions (WMLs) also revealed neuroprotective properties by reducing the progression of WMLs [69]. However, supplementing AD patients with vitamin E showed no clear beneficial effect on disease progress [70,71,72].…”

Section: Discussionmentioning

confidence: 99%

Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer’s Disease

Grimm

Regner

Mett

et al. 2016

IJMS

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One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienols inhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD.

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Clinical Investigation of the Protective Effects of Palm Vitamin E Tocotrienols on Brain White Matter

Abstract: http://www.clinicaltrials.gov. Unique identifier: NCT00753532.

Cited by 79 publications

References 48 publications

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence

Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Antioxidative Supplements

Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer’s Disease

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