Clinical Application of Palm-Tocotrienols: Challenges and - - PowerPoint PPT Presentation
Clinical Application of Palm-Tocotrienols: Challenges and Opportunities Dr. Fu Ju Yen Ms. Puvaneswari Meganathan Ms. Doryn Tan Meam Yee Dr. Zaida Zainal fujuyen@mpob.gov.my / fujuyen@gmail.com WHY FUNCTIONAL INGREDIENTS? (Department of
fujuyen@mpob.gov.my / fujuyen@gmail.com
(Department of Statistics, Malaysia)
Tocotrienol Tocopherol
R1 R2 α CH3 CH3 β CH3 H γ H CH3 δ H H
Vitamin E
(Aggarwal et al., Biochem Pharmacol. , 2010)
Tocopherols α + β Tocotrienols γ + δ Tocotrienols
Tocotrienol is now intended for use in the following foods:
power bars
Mangialasche et al. 2010, 2012, 2013
Higher tocotrienol levels in blood had lower risk of developing Alzheimer’s disease. Higher gamma-tocotrienol levels in their blood had lower risk of developing cognitive impairment. 2 years supplementation
volume change in white matter lesion.
Gopalan et al., Stroke. 2014
ALZHEIMER’S DISEASE WHITE MATTER LESION PERIPHERAL NEUROPATHY
1 year supplementation
lancinating pain in diabetic patients with peripheral neuropathy.
The Vitamin E in Neuroprotection Study (VENUS) Investigators, JAMA
Khanna et al., J. Neurochem. 2010
T3 supplementation reduced
brain injury.
Park et al., Stroke, 2011
NEURAL CELL DAMAGE INFARC SIZE ARTERIOGENESIS
T3 improved cerebrovascular circulation and fiber connectivity after ischemic stroke
Rink et al., J Cereb Blood Flow Metab. 2011
Nanomolar of tocotrienol prevented glutamate induced damage neural cells.
(Zhao et al., Int. J. Obesity. 2014)
OBESITY INSULIN SENSITIVITY
and weight of adipose tissue with T3 supplementation
fasting glucose and insulin with T3 supplementation
HF: high fat; LF: low fat; T3: tocotrienol; Epi: epididymal; Peri: perirenal; Mes: mesenteric (Mes) fat.
HF: high fat; LF: low fat; T3: tocotrienol.
(Zhao et al., Int. J. Obesity. 2014)
macrophage recruitment in adipose tissue.
arrest
(Kanchi et al., Drug Discovery Today, 2017)
SMOKE-INDUCED COPD
Peh et al., Free Rad Biology and Medicine, 2017
ASTHMA
Zainal et al., IJMS, 2019
(Meganathan et al., 2015. Sci. Reports.) Gamma-tocotrienol from TRF 300 mg (Yap et al., 2001. Journal of Pharm and Pharmacol.)
Oral bioavailability in rat α-Tocotrienol: 27.7 ± 9.2% γ-Tocotrienol: 9.1 ± 2.4% δ-Tocotrienol: 8.5 ± 3.5%
Affected by
(Yap et al., 2003) (Fu et al., 2014) Gamma-tocotrienol from TRF 800 mg
Solubility: Low
DMSO Permeability: High
permeability across epithelium cell membranes if its log P value is greater than 1.
reaches the systemic circulation in an active form.
Lipid bilayer Hydrophilic polymer Tocotrienols
efficiency
ionic surfactants
nanoemulsion
207 nm PDI < 0.3 (Maniam et al., Front. Pharmacol. 2018; Tan et al., Nanomedicine. 2017)
(Fu et al., J Controlled Release. 2009)
days
Tumour-targeted nano T3 Non-targeted nano T3 Free T3 Untreated
A431 xenograft models
Free T3 Non-targeted nano-T3 Targeted nano-T3 Untreated
MDA-MB-231 breast cancer models
Day 11 Day 20
treated with nano-T3
20
(Tan et al., Nanomedicine. 2017)
Francesca Mangialasche and team, Karolinska Institutet, Stockholm, Sweden
Year Subject / Cohort Findings 2010 Kungsholmen Project 232 advance-aged subjects High plasma total vitamin E content reduced the risk of developing Alzheimer’s disease 2012 AddNeuroMed-Project 168 Alzheimer disease 166 mild cognitive impairement 187 cognitively normal people AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD. 2013 AddNeuroMed-Project 81 Alzheimer disease 86 mild cognitive impairement 86 cognitively normal people Plasma tocopherol and tocotrienol levels + MRI are sensitive indicators of Alzheimer’s disease. 2013 Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study 140 elderly subjects High levels of serum tocopherol and tocotrienol are associated with reduced risk of cognitive impairment. 2019 Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) Database of 2654 elderly subjects On-going
Study Site:
Tocotrienols Conventional Medicine
mechanism
therapeutic level in tissues
toxicity
(Meganathan and Fu, IJMS, 2016)
Poster Puvaneswari Meganathan Health Properties of Tocotrienols: Evidence in Human Studies