The evolving role of carotenoids in human biochemistry

Abstract

The growth of our knowledge of carotenoid biochemistry has opened new and divergent paths for research. The earliest role established for β-carotene in animals was as a vitamin A precursor, a role it shares with several other pro–vitamin A carotenoids. Additional studies have continued to refine our understanding of this function. Because carotenoids are excellent scavengers of singlet oxygen and respectable scavengers for other reactive oxygen species, substantial work was done concerning their potential role as antioxidants. In an unexpected twist, the ability of radicals in cigarette smoke to degrade carotenoids might be responsible for the finding that high-dose dietary β-carotene increased the incidence of lung cancer in smokers. A new role for the polar carotenoids lutein and zeaxanthin was identified, when those carotenoids were found to constitute the macular pigment (the yellow spot at the center of the human retina). Many different carotenoids can be metabolized to products with retinoid activity, which might affect gene expression and cell differentiation. The formation of retinoids from diverse carotenoids might account for a portion of their activities as anticancer agents. Studies of lycopene in prostate cancer prevention have been very promising, and clinical studies of lycopene are underway. Carotenoids have emerged as the best single tissue marker for a diet rich in fruits and vegetables, and measurements of plasma and tissue carotenoids have an important role in defining the optimal diets for humans.

Introduction

My collaboration with Larry Machlin began with studies of the role of antioxidants in the prevention of age-related macular degeneration (ARM). Those investigations ultimately led me to studies of the carotenoids in the macula, but at that time our focus was on vitamin E and selenium. At the start of the 1980s, Larry, Ed Dratz, and I hypothesized that the photoreceptors of the human retina were vulnerable to injury from dietary antioxidant deficiency. Because the rod outer segments are very rich in 22:6ω3 fatty acids, with high oxygen tension and exposure to light, we hypothesized that dietary antioxidant intake might play a role in development of ARM.1 Larry provided support for our investigations of the role of vitamin E and selenium nutrition status in the occurrence of ARM. These studies led to our observation that high-dose dietary α-tocopherol supplements led to lower plasma levels of γ-tocopherol2, 3; ultimately, we observed that dietary α-tocopherol supplements also decreased adipose γ-tocopherol levels.4 One chief finding was that the α-tocopherol:γ-tocopherol ratio in adipose tissue is a useful means of identifying persons who use large doses of α-tocopherol supplements for extended periods.4

Collaborations with Larry were always distinguished by his attention to the core science of each research question. We owe him a great debt for his contributions to our knowledge of the biochemistry of antioxidants in human health.