Oregon State University - Comment

Docket No. 2006N-0168 Food and Drug Administration, HHS 21 CFR Part 101 Food Labeling: Revision of Reference Values and Mandatory Nutrients. Remarks concerning vitamin E units and amounts to define the Daily Value My name is Maret G. Traber, PhD, and I am a Professor in the Department of Nutrition and Exercise Sciences and in the Linus Pauling Institute at Oregon State University. I was a member of the Food and Nutrition Board?s Antioxidant Panel that made recommendations concerning the dietary reference intakes for Vitamin E (Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington: National Academy Press, 2000). I have published more than 200 scientific articles, most relating to my research on vitamin E. I believe that it is critical for the consumer to understand that changes concerning vitamin E are being made to labels because of new scientific discoveries in the last 20 years. We now know that: 1) only one form of vitamin E, alpha-tocopherol, is preferentially retained and used by the human body; 2) a specific liver protein, the alpha-tocopherol transfer protein, regulates the human body?s vitamin E concentrations; and 3) genetic defects in this protein cause severe vitamin E deficiency in humans. Vitamin E is confusing because there are many forms, names and units to describe this antioxidant family. Plants make eight different vitamin E forms but only one, alpha-tocopherol, is retained and used by the human body, the others are rapidly metabolized and excreted. Importantly, chemically synthesized alpha-tocopherol is not identical to the plant-made alpha- tocopherol. Chemically synthesized alpha-tocopherol contains eight different molecular forms (indicated by the stereochemistry at positions 2, 4? and 8? on the molecule: RRR, RSR, RSS, RRS, SRR, SSR, SRS, SSS) but only half of these (those in the R-conformation at position 2) the ?2R-forms? are recognized by the alpha-tocopherol transfer protein and only one, RRR-alpha- tocopherol, is identical to the form synthesized by plants. Vitamin E manufacturers and nutritionists for decades have used the vitamin E international unit (IU) to attempt to correct for the activities of the various molecular forms in chemically synthesized alpha-tocopherol and the seven other non-alpha-tocopherols made by plants. The intention for the use of the IU was to correct for the lower activities of the various vitamin E forms compared with the natural RRR-alpha-tocopherol. However, the IU was defined by how much vitamin E pregnant rats require, not based on what is currently known regarding the amount and specific form of vitamin E required by humans. The current vitamin E daily value (DV) is set at 30 IU based on 1968 dietary recommendations. The IU is defined as equivalent to 1 mg dl-alpha-tocopheryl acetate. This latter form of synthetic alpha tocopherol (RRR- and SRR-, made with naturally occurring phytol) is no longer commercially available, instead the commercial form of synthetic vitamin E is all racemic-alpha tocopherol (an entirely synthetic molecule). All racemic-alpha tocopherol contains eight molecular forms of alpha tocopherol (RRR, RSR, RSS, RRS, SRR, SSR, SRS, SSS) in equal amounts, is usually sold as the acetate ester, and is called dl-alpha-tocopheryl acetate. This name is allowed because dl and all racemic-alpha tocopherols were shown to have equivalent activities in rats. The current vitamin E DV definition (30 IU) underestimates the amount of alpha tocopherol naturally present in food. The new definition would allow the consumer to easily determine that a food with natural vitamin E has twice as much as that fortified with synthetic vitamin E. For example, in a food with 5 mg vitamin E per serving, if the food is fortified with synthetic vitamin E, 5 mg equals 5 IU or 16.7% DV. If the food naturally contains 5 mg RRR-alpha-tocopherol, this equals 6.8 IU or 22.7% DV by the current definition. However, if as proposed, the DV is defined as 15 mg 2R-alpha tocopherol, then the food with 5 mg synthetic vitamin E would still be 16.7% DV (2.5 mg/15 mg), while the naturally present vitamin E would be 33% DV (5 mg/15 mg). These ?differences? in food vitamin E are due to the currently incorrect definition of the IU and overestimated DV. This example shows the impact that the definition of both the form and the amount of vitamin E will have in clarifying for the consumer what constitutes a good source of vitamin E. Based on the available scientific information for humans, I believe that the DV for vitamin E should be defined as 15 mg 2R-alpha-tocopherol. The natural, plant-derived RRR-alpha- tocopherol has twice the activity of chemically synthesized all racemic-alpha-tocopherol that contains eight molecular forms of which half have the activity of the natural. The synthetic forms that are useful to the body are the 2R-alpha-tocopherol forms. I also believe that the incorrect terms, d and dl, should be changed to the scientifically accurate, RRR and all racemic (or all rac) terms, to indicate to the consumer that there are structural differences between ?natural? and synthetic vitamin E. In summary, in my view there are four aspects that need to be redefined by the FDA: 1) Name: change from d and dl, to RRR and all racemic, respectively, alpha-tocopherol 2) Reference material: change from all racemic-alpha-tocopheryl acetate to RRR-alpha- tocopherol as the reference standard 3) Activity: change from units based on rodent data to mg based on activity in humans (1 mg RRR-alpha-tocopherol has twice the activity of 1 mg all racemic- alpha-tocopherol because all racemic-alpha-tocopherol contains 0.5 mg 2R-alpha-tocopherols) 4) DV (change units from IU to mg 2R-alpha-tocopherol), the amount should be 15 mg 2R- alpha-tocopherol Respectfully submitted, Maret G. Traber, Ph.D. Professor, Dept Nutrition & Exercise Sciences Oregon State University PS Attachment is a pdf of this letter Maret Traber, Oregon State University -Remarks concerning vitamin E units and amounts to define the Daily Value