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[ Feature ]Tocomin Tocotrienols ComplexA Potent Natural Neuroprotective Vitaminby Dr. Sharon Ling (B.Pharm, Ph.D.)Different StrokesAccording to statistics from theWorld Health Organization, 15million people worldwide suffer astroke every year. 10% or 5.5 millionof the global causes of death weredue to stroke (3 million women and2.5 million men). It is the third mostcommon cause of death in developedcountries. Ischemic stroke happenswhen the artery supplying blood tothe brain is blocked. On the otherhand, hemorrhagic stroke happenswhen the artery ruptures, causingbleeding in the brain.Stroke is the main cause ofdeath and permanent disability thataffects 6.5 million people in the US(Lloyd-Jones, D et al., 2009). In theUSA, someone dies of a stroke everythree minutes and on average, every40 seconds someone will have astroke (Lloyd-Jones, D et al., 2009),(Mackay, J., Mensah, G., 2004).Among Asians aged 18 andabove, 2% have had a stroke. In2004, the death rate of strokewas 44.2% for Asian males and38.9% for females (American HeartAssociation., 2008). In the EU, strokeis the second single most commoncause of death, accounting for 1.24million deaths in Europe each year.The incidence of death caused bystroke is higher for women (17%)than in men (11%) (European HeartNetwork, 2008).Smoking and high bloodpressure are important modifiablerisks of stroke. Atrial fibrillationincreases the risk of stroke by five22 Volume 13 Number 9 2009times (Wolf, 1991). Heart failureand heart attack are other importantrisk factors (Mackay, J., Mensah, G.,2004). The Economic BurdenStroke is a major global public healthconcern that prematurely claimsproductive lives and burdens thehealthcare systems, as many of thestroke survivors become disabledand require long term care andrehabilitation. Stroke survivorsoften suffer from loss of speech, coordination, mobility and cognitionphysically. A majority of them alsohave to deal with emotional stressand depression resulting from theloss of self-dependence.The economic costs of stroke arestaggering, as shown by some majorstatistics: The World Health Organization(WHO) estimated that globaldisability-adjusted life years(DALYs) lost to stroke (ameasure of the burden ofdisease) will rise from 38 millionin 1990 to 61 million in 2020(Mackay, J., Mensah, G., 2004). The American HeartAssociation estimated in 2004that stroke cost the nation atotal of US 53.6 billion in directhealthcare cost and productivityloss. In 2001, the NationalStroke Association estimatedt h a t t h e av e ra g e c o s t p e rpatient for the first 90 days after astroke was US 15,000, although10% of cases cost more than US 35,000 (Mackay, J., Mensah,G., 2004).I n S i n g a p o r e, t h e av e ra g ehospital costs for stroke werereported in 2000 as US 5000per patient (Mackay, J., Mensah,G., 2004).According to the EuropeanHeart Network, stroke isestimated to cost the EUeconomy over 38 billion ayear. Around 49% is due todirect healthcare costs, 23% toproductivity losses and 29%to the informal care of peoplewith stroke (European HeartNetwork, 2008).The BrainThe central nervous system consists ofthe brain and spinal cord. The humanbrain (Figure 1.) is the control centerof the nervous system. The nervoussystem is made up of billions of nervecells called neurons.A neuron transmits electricalsignals called nerve impulses. Theaxon will carry these impulses toFigure 1. The human brainwww.asiabiotech.com

[ Feature ]dendrites which deliver them to thereceiving cells or fibers.The central nervous system doesnot regenerate. Therefore, neuronalloss from stroke is permanentalthough limited function can beregained by transferring the tasks toother neurons – a slow process whichhappens in stroke rehabilitation.Glutamate is a neurotransmitter– a group of molecules that allowneurons to communicate with eachother (Figure 2.). When there isexcessive concentration of glutamate,neuronal death results. Ischemia,hypoxia (oxygen deprivation), braintrauma, seizures, various forms ofdementia are all potential causes ofglutamate toxicity.it is a natural vitamin E that isneuroprotective. The efficacy isproven by extensive research.Tocomin Tocotrienols asNeuroprotective VitaminThe vitamin E family compriseseight chemically distinct compounds:4 tocopherols and 4 tocotrienols(alpha, beta, gamma and delta).Tocotrienols differ from tocopherolsby having an unsaturated side tailthat results in significantly differentbiological activities (Figure 3).Tocomin is a natural tocotrienolcomplex concentrated from virgincrude palm oil through a patentedmild extraction process whichFigure 2. Diagrammatic representation of how electrical impulses are transmitted betweenneurons.ensures maximum preservationof phytonutrients. It containspredominantly full spectrumtocotrienols and other phytonutrientssuch as tocopherols, plant squalene,phytosterols, co-enzyme Q10and mixed carotenoids that arenaturally extracted together withtocotrienols.The EvidenceTo c o t r i e n o l c o n f e r sneuroprotection through 2 mainfunctions: its powerful antioxidantactivity and mechanisms other thanantioxidant function. Deficiency ofvitamin E is a cause of neurologicaldysfunction. The brain is highlysusceptible to oxidative damage dueto high oxygen consumption which iscontinuous and independent of degreeof physical activity. Furthermore, thehigh lipid content of the brain makesit susceptible to lipid peroxidation inan antioxidant poor environment.Tocotrienol is 40 – 60 timesmore potent than α-tocopherolin protecting brain cells fromperoxidation (Kamat JP, 1995).Treatments AvailableStroke is best prevented forneuron loss is irreversible. Currently,available medical treatment forthe prevention of stroke includesc h o l e s t e r o l l o w e r i n g d r u g s,antihypertensives and anticoagulantagents such as aspirin. However, thesedrugs often produce undesirable sideeffects and require strict monitoringon the dosage.There are very few compoundsthat have neuroprotective properties.Although quite a number ofhomeopathic treatments and herbsclaim to be protective against stroke,the documented efficacy of thesecompounds remains controversial.To c o t r i e n o l i s u n i q u e a swww.asiabiotech.comFigure 3. Chemical structures of Tocopherol and Tocotrienol. Note the 3 double bonds inthe tocotrienol side tail.Volume 13 Number 9 2009 23

[ Feature ]The higher efficiency ofα-tocotrienol in protecting braincells from oxidative damage couldbe due to the unsaturated side chain oftocotrienol allows for moreefficient penetration into tissuesthat have saturated fatty layers,such as the brain and liver tocotrienols are recycled /regenerated more effectively tobe used again tocotrienols interact betterwith lipid radicals due to strongerdisordering of cell membrane andhigher mobilityTocotrienol prevents neurondeath by other mechanisms unrelatedto its antioxidant activity. In a numberof NIH-sponsored studies, Researchersat the Ohio State Medical Centershowed that α-tocotrienol, but notα-tocopherol, prevented neuron’sdeath at extremely low concentration(nanomolar, 10-9) by regulating specificmediators of cell death (Sen CKet al., 2000). Tocotrienol-treatedneurons maintained healthy growthand motility even in the presenceof excess neurotoxic agent. Theneuroprotective property seen atsuch low concentration of tocotrienolis independent of its antioxidantactivity, as tocotrienols do not exhibitantioxidant properties at nanomolarconcentrations. Tocotrienols onlybegin to show their antioxidanteffects at micromolar concentrations(Khanna et al., 2006).The same researchers wento n t o d e m o n s t ra t e t h a t o ra lsupplementation of tocotrienols(Tocomin , Carotech Inc.) reachesrats’ brain in concentration thatprotected against stroke. There isreduced volume of cerebral infarctin tocotrienol-supplemented ratscompared with un-supplementedcontrols (Khanna S et al., 2005).A further study showed that24 Volume 13 Number 9 2009Tocomin SupraBio (CarotechInc.) supplementation in healthywomen achieved plasma levels oftocotrienols 12 to 30 times more thanthe concentration of α-tocotrienolrequired to completely preventstroke-related neurodegeneration(Khosla P et al., 2006).The patented SupraBio system is a self-emulsifying deliverysystem that provides more consistentand enhanced oral absorption oftocotrienols. It contains a mixtureof oil and surfactants at an optimumratio that will self-emulsify in thegastrointestinal tract. Further reactionswill generate conditions essential foroptimal absorption of tocotrienols.This novel delivery system results inrapid and consistent absorption oftocotrienols independent of dietaryfat or food intake. Clinical study onhealthy human volunteers confirmedthe efficacy of SupraBio system,which increases the rate and extentof tocotrienol absorption by up to300% (Figure 4) (Ho D et al. USPatent 6596306).Looking at NeuroprotectiveEffects of TocotrienolsA collaborative work betweenresearchers from the Malaysian PalmOil Board, University of ScienceMalaysia and Hovid Berhad, thisrandomized double blind placebocontrolled human study is on courseto recruit some 400 participantsover the next few years to study theneuroprotective effects of tocotrienolsby looking at white matter changesusing magnetic resonance imaging(MRI) (ClinicalTrials.gov, 2008).This allows the researchers to lookinto early changes of the brainwithout having to wait for an overtclinical endpoint such as a clinicalstroke.The secondary objectives ofthis human study include evaluatingthe effects of tocotrienols on bloodparameters such as total lipidprofile, Apo-B, C-reactive protein,antioxidant profile, Lp(a) and lipidperoxidation.White matter lesionsWorld’s Largest Clinical TrialFigure 4. Mean plasma alpha-tocotrienol versus time curve of the conventional preparationand SupraBio system.www.asiabiotech.com