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Metabolism of Tocopherols and Tocotrienols

The metabolism of tocotrienols is different from that of -tocopherol.  -Tocopherol is almost exclusively secreted into chylomicrons by the enterocytes in the intestine, whereas tocotrienols are secreted into both chylomicrons and small high-density lipoproteins (HDL).  The ratio of tocotrienols secreted into chylomicrons and HDL varies greatly amongst individual human subjects.


Uptake of tocotrienols in newly formed chylomicrons at peripheral tissues does not occur because the truncated apoprotein B-48 in the chylomicrons does not have the required domains for the uptake receptors.  Newly formed chylomicrons deliver lipids to muscles and adipose tissue via lipoprotein lipase actions and the chylomicron remnants are transported to the liver.  Vitamin E is subjected to discrimination by the -tocopherol transfer protein (-TTP) in the liver before they are re-secreted into nascent very low-density lipoproteins (VLDLs).  The extent of discrimination depends on the relative binding affinity of individual forms of vitamin E with -TTP.  -Tocotrienol has 12.4% binding affinity of -tocopherol.  In layman term, for every 100 molecules of -tocopherol sequestered by -TTP, the corresponding amount for -tocotrienol is 12.4 molecules, whereas the balance 87.6 molecules are unprotected, and subjected to catabolism.  The relative binding affinity for - and -tocotrienols has not been reported.  From literature data, these binding affinities may be very low.  In other words, most of the tocotrienols secreted into chylomicrons are not re-secreted into nascent VLDLs and they undergo catabolism leading to secretion of metabolites in the urine.


Nascent VLDL has apo B-100 with docking domains for the receptors.  It also delivers lipids to muscles and adipose tissue via lipoprotein lipase actions and become intermediate-density lipoproteins (IDL).  Further lipoprotein lipase action on IDL forms low-density lipoprotein (LDL).  IDL and LDL deliver vitamin E to peripheral tissues via LDL-receptors mediated endocytosis.


Tocotrienols secreted into small HDL are independent of -TTP action and can be delivered directly for uptake into selective peripheral tissues via scavenger receptor-mediated selective vitamin E uptake.  Unlike LDL-receptors, scavenger receptors are not evenly distributed in the peripheral tissues, they are more abundant in the fatty tissues.  Therefore tocotrienols uptake via direct vitamin E uptake is concentrated in selective tissues whereas vitamin E uptake via LDL-receptors is more evenly distributed in the peripheral tissues.


For maximum tocotrienols absorption, the -tocopherol content should be minimized in order to enable tocotrienols to have a chance for -TTP sequestering.  Hepatic re-circulation of -tocopherol and also -tocopherol from dietary intake will jeopardize the absorption of tocotrienols via chylomicrons absorption pathway.  Natural -tocopherol is more harmful than the synthetic counterpart due to its high binding affinity with -TTP and therefore suppresses the absorption of tocotrienols more drastically.

For further details, kindly refer to "Unleashing the untold and misunderstood observations on vitamin E" doi: 10.1007/s12263-010-0180-z.  Genes & Nutrition, 2010 published online first. 

Link: http://www.springerlink.com/content/64g13t7525504205/


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