A Case Western Reserve University School of Medicine study in the November 22 issue of Journal of Biological Chemistry, explains how vitamin A is generated from beta carotene, its dietary precursors. The discovery sheds new light into how beta carotene’s enzymes are utilized differently contributing to the vitamin’s production. This insight will help guide solutions for vitamin A deficiency, a global public health problem affecting more than half of all countries, according to the World Health Organization.
The study, named a Paper of the Week, led by Johannes von Lintig, PhD, associate professor of pharmacology, demonstrates that beta-carotene is converted to Vitamin A and not other metabolites, which some theorized were toxic compounds.
Vitamin A deficiency is especially prevalent in developing countries of Asia, due to largely rice-based diets which lack beta-carotene, a member of the micronutrient carotenoid family. The deficiency mainly affects pregnant women and children and leads to blindness and increases morbidity.
Understanding how vitamin A is produced in the body is essential to effective public health interventions. Efforts are underway by humanitarian groups to supplement young children and fortify foods, for example in the form of “golden rice,” rice genetically modified to contain beta-carotene. The von Lintig Laboratory’s discovery validates the benefits of fortifying foods to combat the worldwide deficiency problem. Some reports indicate the problem exists in areas of the U.S. where access to fresh fruits and vegetables is scarce.
While the benefit of beta-carotene and fellow carotenoids are widely known, how the body metabolizes beta-carotene has remained a matter of debate. The reason for this controversy is the existence of the micronutrient’s two different metabolizing enzymes, BCO1 and BCO2. Some studies have suggested BCO2 metabolizes beta-carotene differently, thereby inhibiting the beneficial effects of Vitamin A.
The research team provided evidence that BCO1 directly converts beta-carotene to vitamin A. However, they discovered the second enzyme, BCO2, is also significant. It helps prepare carotenoids, other than beta-carotene, for vitamin A production. Specifically, BCO2 removes the part of the carotenoid that cannot be utilized for vitamin A production. The remaining portion of the carotenoid is then further processed by BCO1 to generate vitamin A.
“Our study shows that beta-carotene’s second enzyme does not produce a toxic compound, as had been proposed by some researchers. Rather, the enzyme aids in the metabolizing of carotenoids, aside from beta-carotene, to become vitamin A,” said von Lintig and concluded “that beta-carotene is an important and safe precursor for vitamin A in our diet. Our findings also suggest that golden rice plants are likely very safe for consumption.”
This work was supported, in whole or in part, by grants from the National Institutes of Health’s National Eye Institute, RO1EY019641 and RO1EY020551, and from the Postbaccalaureate Research Education Program (PREP) of CWRU.
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."
The School of Medicine is affiliated with University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. case.edu/medicine.