You might be saying to yourself, “who cares about natural versus synthetic alpha-tocopherol.” But the small change in stereochemistry makes a big difference in how alpha-tocopherol is maintained in the body.

All forms of vitamin E (tocopherols, tocotrienols) are absorbed equally. Fat-soluble vitamins are handled like lipids and thus are incorporated into chylomicrons that have triglycerides removed by lipoprotein lipase. The chylomicron remnants containing the different forms of vitamin E are then taken up by the liver. The figure below shows the absorption, metabolism, and excretion of vitamin E.

Figure 9.221 The absorption, metabolism, and excretion of vitamin E

The liver contains a protein called alpha-tocopherol transfer protein (alpha-TTP), which is responsible for maintaining higher levels of alpha-tocopherol in the body. Alpha-TTP preferentially binds to 2R alpha-tocopherol and helps facilitate its incorporation into VLDL. 2R means any form of alpha-tocopherol in which the 2 position is in the R conformation. The following table summarizes the forms of alpha-tocopherol that bind well to alpha-TTP, and those that don’t bind well to alpha-TTP.

Table 9.221 Alpha-tocopherol isomers and binding to alpha-TTP

Other forms of vitamin E (gamma-tocopherol, tocotrienols) also don’t bind well to alpha-TTP and thus, are found in lower levels than alpha-tocopherol in the body. The following graph shows plasma vitamin E levels from a study in which subjects were given 150 mg each of RRR-alpha-tocopherol, all-rac-alpha-tocopherol, or gamma-tocopherol¹.

Figure 9.222 Plasma vitamin E concentrations in response to a 150 mg dose of RRR-alpha-tocopherol, all-rac-alpha-tocopherol, or gamma-tocopherol. Adapted from reference 1

As you can see in the figure, there was a greater rise in the plasma alpha-tocopherol levels after receiving RRR-alpha-tocopherol vs. all-rac-alpha-tocopherol. This is not a surprise because approximately 50% of all-rac-alpha-tocopherol is 2R alpha-tocopherol that binds well with alpha-TTP. You can also see that the plasma gamma-tocopherol concentration is much lower than either natural or synthetic alpha-tocopherol.

From VLDL and subsequent lipoproteins, vitamin E reaches tissues, with most vitamin E in the body being found in the adipose tissue. There are two main routes of vitamin E excretion. The major route of excretion is through bile that is then excreted in feces. The second route is in the urine after vitamin E is chain-shortened in a process similar to beta-oxidation to make them more water-soluble.

Reference

1. Traber MG, Elsner A, Brigelius-Floh R. (1998) Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: Studies using deuterated alpha-tocopheryl acetates. FEBS Lett 437(1-2): 145-148.