After having written hundreds of research articles, reviews, and book chapters, I find it awkward to pen an autobiography. I still do use a pen. As stated by others in the nutrition field who have written of their own experiences in a perspective article for the Annual Review of Nutrition, my course through this field of science has been serendipitous. My interest in nutrition developed during my experiences with horses and then Angus cattle and entry into an animal science degree program. As the age of molecular biology was unfolding, I pursued a PhD in nutritional biochemistry with Hamilton Eaton at the University of Connecticut followed by postdoctoral work with Hector DeLuca at the University of Wisconsin, working on vitamins A and D, respectively. At Rutgers University, one of the two institutions where I have served on the faculty, I started my research program on trace elements with a focus on cadmium toxicity but soon thereafter began my research on zinc metabolism and function. I moved to the University of Florida in 1982 for an endowed position and have been a Florida Gator ever since. At the University of Florida, research expanded to include identification of zinc-responsive genes and physiological outcomes of zinc transport influencing health and disease, particularly as related to inflammation. I had the opportunity to contribute national science policy as president of both the Federation of American Societies for Experimental Biology and the American Society for Nutrition. As the time of this writing, I maintain an active laboratory.

Introduction to the thirty-fifth volume of the Annual Review of Nutrition (ARN).

Selenium is regulated in the body to maintain vital selenoproteins and to avoid toxicity. When selenium is limiting, cells utilize it to synthesize the selenoproteins most important to them, creating a selenoprotein hierarchy in the cell. The liver is the central organ for selenium regulation and produces excretory selenium forms to regulate whole-body selenium. It responds to selenium deficiency by curtailing excretion and secreting selenoprotein P (Sepp1) into the plasma at the expense of its intracellular selenoproteins. Plasma Sepp1 is distributed to tissues in relation to their expression of the Sepp1 receptor apolipoprotein E receptor-2, creating a tissue selenium hierarchy. N-terminal Sepp1 forms are taken up in the renal proximal tubule by another receptor, megalin. Thus, the regulated whole-body pool of selenium is shifted to needy cells and then to vital selenoproteins in them to supply selenium where it is needed, creating a whole-body selenoprotein hierarchy.

Emerging evidence suggests that ascorbate, the dominant form of vitamin C under physiological pH conditions, influences activity of the genome via regulating epigenomic processes. Ascorbate serves as a cofactor for Ten-eleven translocation (TET) dioxygenases that catalyze the oxidation of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), and further to 5-formylcytosine (5fC) and to 5-carboxylcytosine (5caC), which are ultimately replaced by unmodified cytosine. The Jumonji C (JmjC)-domain-containing histone demethylases also require ascorbate as a cofactor for histone demethylation. Thus, by primarily participating in the demethylation of both DNA and histones, ascorbate appears to be a mediator of the interface between the genome and environment. Furthermore, redox status has a profound impact on the bioavailability of ascorbate in the nucleus. In order to bridge the gap between redox biology and genomics, we suggest an interdisciplinary research field that can be termed redox genomics to study dynamic redox processes in health and diseases. This review examines the evidence and potential molecular mechanism of ascorbate in the demethylation of the genome, and it highlights potential epigenetic roles of ascorbate in various diseases.

Launching a new food/dietary supplement into the US market can be a confusing process to those unfamiliar with the food industry. Industry capability and product specifications are initial determinants of whether a candidate product can be manufactured in a reproducible manner and whether pilot production can be brought up to the market scale. Regulatory issues determine how a product can be produced and marketed; the primary federal institutions involved in regulations are the US Department of Agriculture, the Food and Drug Administration, and the Federal Trade Commission. A primary distinction is made between food and drugs, and no product may enter the food market if it is in part or whole a drug. Product safety is a major concern, and myriad regulations govern the determination of safety. New foods/dietary supplements are often marketed by health claims or structure/function claims, and there are specific regulations pertaining to claims. Not understanding the regulatory issues involved in developing a new product or failing to comply with associated regulations can have legal and financial repercussions.

Decisions related to a spectrum of nutrition-related public health and clinical concerns must consider many factors and are best informed by evaluating the totality and quality of the evidence. Systematic review (SR) is a structured process to evaluate, compare, and synthesize relevant evidence for the SR-specific question(s). Applications of SR are exemplified here through the discussion of four case studies: research agendas, nutrient reference intakes, dietary guidance, and practice guidelines. Concerns that SR cannot be effectively applied to nutrition evidence because of the lack of an unexposed comparator and the complex homeostasis in nutrition are discussed. Central to understanding the applicability of SR is its flexibility in defining key inclusion criteria and rigorous elements as appropriate for the SR-specific question(s). Through the reduction of bias and random error by explicit, reproducible, comprehensive, and rigorous examination of all of the evidence, SR informs the scientific judgment needed for sound evidence-based public health nutrition.

Although obesity is a well-known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colo-rectal cancer. We note that the evidence overrepresents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors.

Concerns exist about the adequacy of vitamin D in pregnant and lactating women. This review assesses the evidence that maternal vitamin D status influences maternal, fetal, and breast-fed infant bone health; maternal adverse outcomes (preeclampsia, gestational diabetes, obstructed labor, and infectious disease); fetal adverse outcomes (growth, gestational age, and developmental programming); and infant adverse outcomes. The evidence for all of these outcomes is contradictory (except for maternal infectious disease) and lacking causality; thus, it is inconclusive. The 2011 Dietary Reference Intakes for vitamin D and their implications for assessing vitamin D status are discussed. An estimated 5% to 29% of American pregnant women may have inadequate vitamin D status, with the higher prevalence in African Americans. Little is known about the prevalence of inadequacy in American lactating women. Research needs are also identified, especially the need for rigorous and well-designed randomized clinical trials to determine the role of vitamin D in nonbone health outcomes in pregnancy and lactation.

Murine models have made valuable contributions to our understanding of iron metabolism. Investigation of mice with inherited forms of anemia has led to the discovery of novel proteins involved in iron homeostasis. A growing number of murine models are being developed to investigate mitochondrial iron metabolism. Mouse strains are available for the major forms of hereditary hemochromatosis. Findings in murine models support the concept that the pathogenesis of nearly all forms of hereditary hemochromatosis involves inappropriately low expression of hepcidin. The availability of mice with floxed iron-related genes allows the study of the in vivo consequences of cell-selective deletion of these genes.