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by Carl P. Verdon, Ph.D. Have you ever noticed that the label on that bottle of "natural" vitamin E in your kitchen pantry lists it as "a mixture of alpha, gama and beta tocopherols" while the older bottle you found in your medicine cabinet lists it as d l-alpha tocopherol"? Yet each promises that every capsule delivers 400 international units (I.U.) of vitamin E. What's an I.U. of vitamin E? Is one I.U. of 'natural' vitamin E better than an I.U. of the other? What do the prefixs "d" and "l" designate, anyway? An adequate explanation can perhaps be best begun by first contrasting vitamin E to its nutritional cousin, vitamin C. The name "Vitamin C", chemically speaking, refers to a single chemical. Whether the vitamin was synthesized in a fermentation factory or extracted from natural plant sources, a molecule of vitamin C, (ascorbic acid, as it is known to chemists) is the same chemical regardless of its source. Thus a pill containing 250 milligrams of vitamin C does contain just that, 250 milligrams (excluding binders and fillers that make a pill possible). It is simple. No need for international units. The reason why vitamin C prepared from one source may differ from another is due to the presence of added or copurified nutritional factors, e.g. vitamin C with bioflavanoids. In this case, however, we are dealing with a chemical mixture, not a pure substance. The case for vitamin E is more complicated and often confuses people. This is in part because the common name "Vitamin E" is not a name for a pure substance but instead is an umbrella term for a family of compounds, known as the tocopherols. It should be appreciated that the name "Vitamin E" is a nutrition term and not a strict chemical designation. Some people are aware from the label on the vitamin E bottle they buy that more than one form of vitamin E exists, e.g. alpha-tocopherol, beta-tocopherol, delta- tocopherol, gama- tocopherol, and others. These are all naturally synthesized by plants and therefore are often extracted and sold together. They are all biological active to varying degrees and while they are chemically related, they are not identical! In fact, chemically speaking, they differ in significant ways (for instance, in the number of carbon atoms and how they are arranged). The prefix "alpha", "beta", "gama" indicates these differences. Since there are so many different tocopherols with different nutritional potencies, nutritional scientists agreed that standard was needed and hence came up with the "international unit" which is really a biological activity unit (i.e. potency). Within the tocopherol family, it is accepted that alpha-tocopherol has the highest biologic activity. More on that later. Consider just for now alpha-tocopherol since the following explanations will apply to the other tocopherols. In a bottle of chemically synthesized alpha-tocopherol, not every molecule of alpha-tocopherol is identical to the next. This is because the chemical process used to synthesize alpha-tocopherol leads to 50% production of molecules whose atoms are arranged in one direction ("right handed") while the other 50% has its atoms arranged as an exact mirror image ("left handed"). Chemists call these "sterioisomers" (a related term is "enatiomer"--same thing). Alpha-tocopherol is not unique to this quirk in chemical synthesis that is subject to the physical laws of chemistry. Though "left-handed" molecules are chemically alike to "right handed" molecules, they may or may not be biologically similar. But from a pharmaceutical point-of-view, the biological dissimilarity between "left-handed" and "right-handed" molcules does not really matter. Even if it turns out that only one of the steroisomers has all the biologic activity, as long as the other one does not get in the way it doesn't make economic sense to separate them. This is the reason that synthetic vitamin E is labeled as "dl-alpha-tocopherol". The "d" is for the 50% of those alpha-tocopherol molecules with "right" handedness and the "l" for the remainder that are "left" handed. [Note that small caps for "d" and "l" are used--upper caps as often seen is not according to proper chemical nomenclature.] Often a pharmaceutical company will purposely make chemical changes to the drug or vitamin to improve some property. It could be to improve its absorption in the digestive tract, to limit side-effects during absorption and metabolism, or simply to improve its manufacturing properties and shelf life. Alpha-tocopherol is an antioxidant (meaning that it reacts readily with reactive forms of oxygen) and therefore its shelf life is limited. If the business-end of the molecule is chemically altered (i.e. "capped") so that the net effect is to limit its chemical reactivity, it follows that its shelf life is improved as well. The problem here is that it could also loses its biologic potency. In the case of alpha-tocopherol, pharmaceutical companies get around potency loss by 'capping' in such a way so that the body's digestive enzymes can readily cleave off the protective cap. Presto! The active form is regenerated. Shelf life is gained and potency is retained. Very clever. In the case of alpha-tocopherol, the common capping groups are "acetate" and "succinate"--by themselves, very harmless substances. The chemical bonds that these capping groups make are known as "ester" bonds. Hence, these derivatives of alpha-tocopherol are sometimes referred to as the ester forms of tocopherol or vitamin E. These are formally named tocopheryl acetate and tocopheryl succinate (sometimes called "vitamin E acetate" or "vitamin E succinate"). Notice the change in spelling for these esters: tocopherol to tocopheryl. The ester forms can be synthesized not only from alpha-tocopherol but also from beta-, gama, and delta-tocopherol. And the capping process does not care whether the molecule is "d" or "l". Both get derivatized to form an ester, hence one gets a 50-50 mixture called "dl-tocopheryl acetate". Research has shown that dl-tocopheryl acetate (or succinate) yields much of the biologic potency that consumers are looking for, therefore, it is not surprising that it is used in many vitamin preparations. In fact, the international committee that devised the International Unit standardized it on dl-alpha-tocopheryl acetate (1 I.U. = 1 milligram), not because it was the most biologically active but because it was the vitamin E form most widely available on store shelves. Let us return the discussion to 'natural' vitamin E which by definition is extracted from plant sources. Plants are brilliant chemists because they have the ability to make only the one sterioisomer of any chemical that they need. Since most biological enzymes work on a "lock and key" principle that just utilizes one of the sterioisomers, plants have proven to be amazingly economical as they have been for millions of years. Plants do make the alpha, beta, delta, and gama forms of tocopherol but they make only the "d" sterioisomer of each! This chemical paradigm of sticking to "one side of the road" also applies to animals. Recent research has demonstrated that the functioning liver in rats and mice preferentially recognizes and stores the "d" form of alpha-tocopherol. It appears that "l" form is ignored. While there is no proof that the "l" form of alpha-tocopherol is functionless, it is clear that the body has evolved a mechanism for picking out its favorite form of vitamin E, d-alpha-tocopherol, out of a digested meal. It is likely that the forementioned reasons explains a known fact to researchers- molecule for molecule, natural vitamin E (d-alpha-tocopherol) has 1.5 times more biological activity than its synthetic counterpart (dl-alpha-tocopheryl acetate). Even if d-alpha-tocopherol is esterified to its acetate form, it still has 1.4 times more potency compared to the dl- mixture of sterioisomers. When considering the oral potency of the different forms of tocopherol, the "right handed" factor is very important. There is no controversy among nutritional scientists that alpha-tocopherol is the member of the tocopherol family with the greatest biological activity. Add to that the fact that nature always holds up the "d" form of tocopherol as the molecule with the "right" configuration. Among the many molecular forms of vitamin E, d-alpha-tocopherol is the most biologically natural form of vitamin E. |
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