TOCOTRIENOLS The Unsaturated Vitamin E Science & Human Clinical Studies CAROTECH INC.
Presentation Outline Introduction to Carotech and Vitamin E Absorption and Pharmacokinetic Self-Emulsifying Delivery System (SEDDS) SUPRABIO System Unique Health Benefits and Human Clinical Studies Cardiovascular Health Cholesterol Managament Arterial Compliance Sustainability & Marketing Take Home Message Product Concept
Carotech 1990 Incorporated in Ipoh, Perak, Malaysia. 1995 Commenced commercial production. First and largest plant to commercially extract palm tocotrienol complex (Tocomin ), mixed carotene complex (Caromin ), phytosterol complex (Stelessterol TM ) from red palm oil / palm fruit. Started by a Pharmaceutical Company Hovid (www.hovid.com) US Patented Technology : 5,157,132 & 7,544,822. Main markets : US, Europe, Japan and Australia. 2007 - cgmp-certified by NPCB (3 rd API company to be GMP in Malaysia). Leader in Tocotrienol Research, Clinical Studies, Registration etc.
Manufacturing Facilities Chemor Carotech s Chemor, Plant A (Phytonutrients Products - Class D HVAC System)
Manufacturing Facilities Lumut Carotech s Lumut Facility, Commissioned in 2009 (Capacity - 120,000MT / year)
Vitamin E : Tocopherol & Tocotrienol Alpha-tocopherol, first discovered in 1922 by Dr. Evans (University of California) Alpha-tocopherol predominant form (human & animal tissue found most abundant in nature synonymous with vitamin E main focus of research in early years Tocotrienols, about 25 years later.
Vitamin E : Molecular Structures Methyl Group R 1 R 2 TOCOPHEROL HO R 1 Alpha- CH 3 CH 3 Beta- CH 3 H Gamma- H CH 3 Delta- H H TOCOTRIENOL R 2 HO CH 3 R 1 R 2 CH 3
Source of Vit. E in Major Veg. Oils
Question - Are Tocotrienols Well Absorbed Orally?????????
Our Pharmacokinetic Studies on Tocotrienols in Human / Rats J Chromatography B, 1999, 735:279-283 J Pharm Pharmacol, 2001, 53:6-71 J Pharm Pharmacol, 2003, 55:53-58 Int J Pharmaceutics, 2004, 281:67-78 J of Clinical Nutrition, 2012
Incomplete/ Erratic Oral Bioavailability 1200 Delta-tocotrienol iv Plasma concentration (ng/ml) 1000 800 600 400 200 Oral absorption < 8.5% oral 0 0 4 8 12 16 20 24 Time (hr)
Absolute Oral Bioavailability Alpha-T3 : 27.7% Gamma-T3 : 9.1% Delta-T3 : 8.5% J Pharm Pharmacol, 2003, 55:53-58 Carotech,
Influenced By Type of Oil Vehicle Used Plasma concentration (ng/ml) 7000 6000 5000 4000 3000 2000 1000 0 M CT Palm Olein Soya Oil 0 2 4 6 8 10 12 Time (h)
Tocotrienols via Oral Route T3 from Regular Tocotrienol Oil Extract Incomplete (Low Absorption) Erratic & Inconsistent Influenced by type of oil vehicle / carrier To be taken with foods HOW TO OVERCOME THESE ABSORPTION ISSUES?
Our Strategy SupraBio System Self-emulsifying Delivery System (SEDS) Food Grade Emulsifies (FDA-Approved) Homogenization / Particle Size 100% NON-GMO, GRAS, Kosher and Halal.
In contact with aqueous environment After gentle agitation Emulsion formed able to undergo lipolysis to form particles of colloidal dimensions ensuring optimal bioavailability
Alpha-Tocotrienol Mean plasma alpha-tocotrienol versus time curves of the conventional preparation and SupraBio System Plasma concentration (ng/ml) 1200 1000 800 600 400 Conventional Preparation SupraBio System Formulation X 300% 200 0 0.0 4.0 8.0 12.0 16.0 20.0 Time (h)
Gamma-Tocotrienol Mean plasma gamma-tocotrienol versus time curves of the conventional preparation and SupraBio System Plasma concentration (ng/ml) 1400 1200 1000 800 600 400 Conventional Preparation SupraBio System Formulation X 290% 200 0 0.0 4.0 8.0 12.0 16.0 20.0 Time (h)
Delta-Tocotrienol Mean plasma delta-tocotrienol versus time curves of the conventional preparation and Suprabio System Plasma concentration (ng/ml) 180 160 140 120 100 80 60 Conventional Preparation SupraBio System Formulation X 260% 40 20 0 0.0 4.0 8.0 12.0 16.0 20.0 Time (h)
Human Tissue Distribution Study
Distribution of Tocotrienols in Vital Organs with TS Conc (ng/ml) 6000 5000 4000 3000 2000 α-t3 γ-t3 α-t3 = 4.5mg γ-t3 = 11.3mg δ-t3 = 3.0mg Control α-t3 Control γ-t3 All T3 well distributed. Control δ-t3 α-t3 High in liver, heart, skin & muscle γ-t3 Tocomin SupraBio - Increased Bioavailability - Assured Bioefficiency δ-t3 1000 δ-t3 0 skin muscle heart liver eyeballs brain
CardioProtection / Cardiovascular Health
Cholesterol-Lowering Activity First studied by Qureshi et al in 1986 (Tocotrienol in barley) Animal study showed 44 & 60% decrease in total serum cholesterol and LDL-cholesterol Similar effects demonstrated in human studies Alpha tocopherol No cholesterol lowering effect Mechanism: Degrading HMG-CoA reductase of the cholesterol biosynthetic pathway
Studies on Cardiovascular Health Gamma-Tocotrienol found to be MOST POTENT cholesterol inhibitor and cardioprotective tocotrienol. Am J Clin Nut 1991; 53(4 Suppl):1021S-1026S. AJP-Heart and Circulatory Physiology, 2008 Gamma-tocotrienol is the most cardioprotective!
Statin inhibits HMG- CoA Reductase via enzyme competitive inhibition mechanism lower cholesterol production. Cholesterol-Lowering Activity of T3 - Mechanism Tocotrienol, inhibits HMG CoA Reductase via farnesol that induces proteolytic degradation of this enzyme. A. Theriault et al., Clinical Biochemistry 1999;Vol 32:309-319
Reducing Arterial Stiffness Arterial Compliance & vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E Rasool et al, Arch Pharm Res 2008, 31:1212-7 Randomized, placebo controlled, blinded end point clinical study Subject: 36 healthy male volunteers Duration: 2 months Dosages: 50, 100, 200mg Tocomin SupraBio daily Assessment of arterial compliance by carotid femoral pulse wave velocity (PWV) and augmentation index (AI) Significant improvement in reducing arterial stiffness after Tocomin SupraBio supplementation!
Significance of Tocomin SupraBio Vs Generic Palm Tocotrienol Oil Extract Result Year Journal No of Subject Material Dosage, mg/ day Period Augmentation index Pulse wave velocity Arterial Compliance 2006 Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E 36 Tocotrienoll (Palm) Oil Extract 80mg, 160mg & 320mg 60Days Not Significant Not Significant No significant effect on arterial compliance 2008 Arterial Compliance & vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E 36 Tocomin SupraBio 50mg, 100mg & 200mg 60Days 50mg, 100mg and 200mg 100mg and 200mg Significant effect arterial compliance
Sustainability?
Take Home Messages Food-Based Tocotrienol from Red Palm Oil Problem : Oral bioavailability of tocotrienol is poor and erratic (with regular tocotrienol oil extracts) Tocomin SupraBio - Improves Bioavailability and Assures BioEfficiency Human Clinical Studies 13 Published and 8 On-Going Trials (Heart, Brain and Liver Health) scientifically substantiated! Assured Sustainability and Marketing/PRs Activities (over 1.0 mil)
Product Concept Synergistic Combination Super Omega plus Tocotrienol SupraBio Bio-enhanced Omega-3 Tocotrienols (SUPER O3T3)
Serving Size - 1 Soft Gels Serving Per Container 60 Each Serving Contains Krill / Fish / Calamari Phospholipids Omega-3 Fatty Acids EPA (Eicosapentaenoic acid) DHA (Docosahexaenoic acid) d-mixed-tocotrienols (Tocomin SupraBio ) d-alpha-tocotrienol d-beta-tocotrienol d-gamma-tocotrienol d-alpha-tocopherol (Vit E Activity) Plant Squalene Phytosterols Complex d-delta-tocotrienol WWWmg XXXmg YYYmg ZZZmg AAAmg 30.0mg 9.3mg 1.7mg 13.9mg 5.2mg 8.2mg / 12..1IU 5.6mg 2.6mg Supplement Facts
THANK YOU