Surprising Results From New Vitamin E Oxidative Stress Isoprostane Dose Response Study Featured In Presentations at American Heart Association and Oxygen Society Conferences

November 20, 2002: Researchers at Vanderbilt University presented the results of a vitamin E dose response and time course study on oxidative stress at this weeks American Heart Association and Oxygen Society meetings. The American Heart Association meeting is being held in Chicago and the Oxygen Society meeting is being held in San Antonio. The results are being delivered in oral presentations at both conferences by L. Jackson Roberts M.D. and Jason Morrow M.D. from the Department of Clinical Pharmacology at Vanderbilt University Medical School, and published in the proceedings.

The study measured the effects of increasing doses of vitamin E as alpha tocopherol on a patented biomarker for measuring oxidative stress in-vivo called isoprostanes (F2 IsoPs). Isoprostanes are produced in-vivo by oxidation of lipids, and can be measured in blood or non-invasively urine. The isoprostanes have become the gold standard for the in-vivo measurement of free radicals in the body, and over 250 papers per year are being published which use the isoprostanes as an index for measuring oxidative stress in-vivo. The isoprostanes have been correlated with many different diseases including atherosclerosis, diabetes, Alzheimer's disease, environmental pollution, cigarette smoking, homocysteine, alcohol, pesticides, and high blood pressure, in addition to other physiological health issues. For the first time, scientists now have a tool for measuring the effects of oral anti-oxidant supplements and drugs on free radical production in-vivo. Surprisingly, researchers are finding out that anti-oxidants that looked good in-vitro, don't always prove to be effective in-vivo.

The clinical trial involved 35 subjects with elevated cholesterol who were supplemented with either 0, 100, 200, 400, 800, 1600, or 3200 IU/d of alpha tocopherol for 16 weeks. A run in period to establish the time course for the highest dose effect on oxidative stress was conducted in 8 subjects at a dose of 3200 IU/d for 20 weeks prior to commencement of the dose response phase of the study. The time course study indicated that the maximum reduction in oxidative stress as measured by the isoprostanes was not achieved until 16 weeks of dosing and levels remained reduced at 20 weeks. No effect was observed on plasma F2 IsoPs (oxidative stress) at a dose of 400 IU/d or less. At a dose of 800 IU/d, plasma F2IsoPs levels were reduced by 30%, at 1600 IU/d levels were reduced by 35%, and at 3200 IU/d reductions of 49% were achieved. This study may provide an answer for why clinical trials of alpha tocopherol in the prevention of atherosclerotic events have largely failed to show a beneficial effect. Implicit in these trials is the assumption that the doses of alpha tocopherol tested effectively inhibit oxidative stress. This study represents one of the first dose finding studies with commonly used anti-oxidants that enables the selection of the appropriate dose of a particular anti-oxidant ingredient or formula.

Lipoprotein Diagnostics, Inc., a development stage diagnostic company has the exclusive rights to commercialize the isoprostanes as biomarkers for the measurement of oxidative stress in-vivo and in foods as an index of food spoilage. The company is developing an easy to use consumer friendly test that can be used to measure the effects of oral anti-oxidant supplementation on the body by measuring this marker in urine with a simple dipstick. Urine represents a non-invasive means of diagnosing whole body oxidative stress, and is preferred by consumers over blood. Future development includes an electronic device with Internet connectivity that will be able to provide consumers and physicians with quantitative results in minutes. "Now consumers, scientists, and physicians will be able to study and determine the optimum doses for anti-oxidant products, as well as test and screen new anti-oxidant ingredients for efficacy" said Eric Kuhrts, President of Lipoprotein Diagnostics, Inc. "This will result in a radical shift in thinking for supplement marketers in the future, as each formulation will be able to be tested in-vivo, and in-vitro/in-vivo correlation's of anti-oxidants will be subjected to scrutiny" stated Kuhrts. An easy, quick test for food spoilage is also in development by the company, and corporate partners are being sought who have an interest in this application.


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