Carotenoid Depletion Studies

Carotenoid depletion trials, where well-fed people are fed foods low in lycopene and other carotenoids, should give a clearer picture of whether, and when, carotenoids such as lycopene might have important physiological functions. Unfortunately, there have only been a few studies of carotenoid depletion on oxida-tive damage, and none on gap-junction formation or cholesterol metabolism. All of these studies have shown deleterious increases in oxidative damage during depletion (Burri, 1997; Burri et al., 1999; Dixon et al., 1998; Lin et al., 1998).

We used the information from a well-controlled double-blind placebo-controlled carotenoid-depletion study to estimate the effective range of beta-carotene in the antioxidant defense system. The study population was healthy adult women who lived on our metabolic unit for 120 days. They ate foods low in carotenoids, but that provided adequate nutrients and energy. We measured serum retinol and carotenoid concentrations, and conducted several tests to assess oxidative damage (malondi-aldehyde-thiobarbituric acid concentrations and reactive carbonyls). We analyzed results by fitting a random regression coefficient model to the data. The saturation point was extrapolated similarly to a low-dose extrapolation in dose-response analysis. The maximal protection of low-density lipoproteins from oxidative damage occurred at serum concentrations of 2.3 ±1.6 micromoles/L. These serum concentrations are provided by intakes of 10 to 18 micromoles/day of carotenoid (Lin et al., 1998). Thus, maximal protection from oxidative damage occurs at relatively low carotenoid concentrations that are easily attained by eating the recommended number of servings of fruits and vegetables per day. Higher dosages of carotenoids (15 mg/day, about half the dosage used in the Phase III trials) normalized oxidative damage in depleted subjects but did not improve it over baseline values.

Our results suggest that maximal protection against oxidative damage is provided by relatively modest intakes of carotenoids. It follows that carotenoid trials that feed small amounts of beta-carotene to people who eat diets low in fruits and vegetables (similar to the Linxian trial; Blot et al., 1995) may be more successful than the clinical trials that fed large amounts of beta-carotene to well-fed people.

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