Antioxidant levels under the microscope

US researchers reported findings this week from a vitamin E dose response and time course study which some believe may help supplement manufacturers to select the appropriate dose of a particular antioxidant ingredient or formula.

The study, which examined vitamin E doses using isoprostanes, widely used to measure in-vivo free radicals in the body, may show why clinical trials of alpha tocopherol have largely failed to show a beneficial effect on the prevention of atherosclerotic events. This is the claim of Lipoprotein Diagnostics, a development stage diagnostic company which has the exclusive rights to commercialise the isoprostanes as biomarkers for the measurement of oxidative stress in-vivo and in foods as an index of food spoilage.

Researchers at Vanderbilt University presented the results of the vitamin E dose response and time course study on oxidative stress at this week's American Heart Association and Oxygen Society meetings, being held in Chicago and San Antonio respectively.

The study measured the effects of increasing doses of vitamin E as alpha tocopherol on isoprostanes (F2 IsoPs), a patented biomarker for measuring oxidative stress in-vivo. Isoprostanes are produced in-vivo by oxidation of lipids, and can be measured in blood or urine. They have become the gold standard for the in-vivo measurement of free radicals in the body, and over 250 papers published each year use the isoprostanes as an index for measuring oxidative stress in-vivo, claims Lipoprotein Diagnostics.

The company added that as scientists now have a tool for measuring the effects of oral antioxidant supplements and drugs on free radical production in-vivo, many are finding out that antioxidants that looked good in-vitro do not always prove to be effective in-vivo.

The clinical trial, presented this week at the American Heart Association and Oxygen Society Conferences, involved 35 subjects with elevated cholesterol who were supplemented with either zero, 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 eight subjects at a dose of 3200 IU/d for 20 weeks prior to starting 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 per cent, at 1600 IU/d levels were reduced by 35 per cent, and at 3200 IU/d reductions of 49 per cent were achieved.

Lipoprotein Diagnostics suggests that clinical trials of alpha tocopherol on the prevention of atherosclerotic events may have failed to show a beneficial effect, because implicit in these trials is the assumption that the doses of alpha tocopherol tested effectively inhibit oxidative stress. The new study enables the selection of the appropriate dose of a particular antioxidant ingredient or formula.

Lipoprotein Diagnostics is currently developing an easy-to-use consumer-friendly test to measure the effects of oral antioxidant supplementation on the body by gauging levels of this marker in urine with a simple dipstick. Future development could also lead to an electronic device with Internet connectivity that will be able to provide consumers and physicians with quantitative results in minutes, said the company.

"Now consumers, scientists, and physicians will be able to study and determine the optimum doses for antioxidant products, as well as test and screen new antioxidant ingredients for efficacy,"​ said Eric Kuhrts, president of Lipoprotein Diagnostics. "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 antioxidants will be subjected to scrutiny,"​ he added.

An easy, quick test for food spoilage is also in development by the company. It is seeking corporate partners for the application.