Early studies identifying vitamin D as an antirachitic factor led to studies in vitamin D-deficient models that resulted in a basic understanding of the mechanism of action of vitamin D. Recent studies using genetically modified mice have provided important new insight into the physiological role of vitamin D at target tissues and the functional significance of vitamin D target proteins, as well as the functional significance of proteins involved in the transport and metabolism of vitamin D. Studies using these mice have played an increasingly important role in elucidating the mechanisms involved in the control of calcium homeostasis and have provided evidence for a role of vitamin D in extraskeletal health. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Concern about the overconsumption of unhealthy foods is growing worldwide. With high global rates of noncommunicable diseases related to poor nutrition and projections of more rapid increases of rates in low- and middle-income countries, it is vital to identify effective but low-cost interventions. Cost-effectiveness studies show that individually targeted dietary interventions can be effective and cost-effective, but a growing number of modeling studies suggest that population-wide approaches may bring larger and more sustained benefits for population health at a lower cost to society. Mandatory regulation of salt in processed foods, in particular, is highly recommended. Future research should focus on lacunae in the current evidence base: effectiveness of interventions addressing the marketing, availability, and price of healthy and unhealthy foods; modeling health impacts of complex dietary changes and multi-intervention strategies; and modeling health implications in diverse subpopulations to identify interventions that will most efficiently and effectively reduce health inequalities. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Iron is a nutritionally essential trace element that functions through incorporation into proteins and enzymes, many of which contribute to physical and neuropsychological performance. Poor iron status, including iron deficiency (ID; diminished iron stores) and iron deficiency anemia (IDA; poor iron stores and diminished hemoglobin), affects billions of people worldwide. This review focuses on physical and neuropsychological outcomes associated with ID and IDA in premenopausal women, as the prevalence of ID and IDA is often greater in premenopausal women than other population demographics. Recent studies addressing the physiological effects of poor iron status on physical performance, including work productivity, voluntary activity, and athletic performance, are addressed. Similarly, the effects of iron status on neurological performance, including cognition, affect, and behavior, are summarized. Nutritional countermeasures for the prevention of poor iron status and the restoration of decrements in performance outcomes are described. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Tea, made from leaves of the plant Camellia sinensis, Theaceae, has been used by humans for thousands of years, first as a medicinal herb and then as a beverage that is consumed widely. For the past 25 years, tea has been studied extensively for its beneficial health effects, including prevention of cancer, reduction of body weight, alleviation of metabolic syndrome, prevention of cardiovascular diseases, and protection against neurodegenerative diseases. Whether these effects can be produced by tea at the levels commonly consumed by humans is an open question. This review examines these topics and elucidates the common mechanisms for these beneficial health effects. It also discusses other health effects and possible side effects of tea consumption. This article provides a critical assessment of the health effects of tea consumption and suggests new directions for research in this area. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Energy homeostasis-ensuring that energy availability matches energy requirements-is essential for survival. One way that energy balance is achieved is through coordinated action of neural and neuroendocrine feeding circuits, which promote energy intake when energy supply is limited. Feeding behavior engages multiple somatic and visceral tissues distributed throughout the body-contraction of skeletal and smooth muscles in the head and along the upper digestive tract required to consume and digest food, as well as stimulation of endocrine and exocrine secretions from a wide range of organs. Accordingly, neurons that contribute to feeding behaviors are localized to central, peripheral, and enteric nervous systems. To promote energy balance, feeding circuits must be able to identify and respond to energy requirements, as well as the amount of energy available from internal and external sources, and then direct appropriate coordinated responses throughout the body. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Our understanding of the mechanism of action of vitamin D has been broadened by the discovery of the extrarenal 1α-hydroxylase (CYP27B1) in various vitamin D target tissues around the body and the implications of this for the putative paracrine actions of 1,25-dihydroxyvitamin D3. This review updates our current knowledge of the cytochrome P450-mediated steps of vitamin D activation (CYP2R1, CYP27B1) and inactivation (CYP24A1, CYP3A4) and the newest physiological roles of vitamin D. The review goes on to examine how well exogenously supplied vitamin D compounds, whether dietary vitamin D2 supplements or prescribed vitamin D analogs, substitute for their natural counterparts; how in some cases vitamin D can be used in conjunction with vitamin D analogs; and the overall impact of these supplements and drugs on the components of the vitamin D signal transduction machinery. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

The field of nutrigenomics shows tremendous promise for improved understanding of the effects of dietary intake on health. The knowledge that metabolic pathways may be altered in individuals with genetic variants in the presence of certain dietary exposures offers great potential for personalized nutrition advice. However, although considerable resources have gone into improving technology for measurement of the genome and biological systems, dietary intake assessment remains inadequate. Each of the methods currently used has limitations that may be exaggerated in the context of gene × nutrient interaction in large multiethnic studies. Because of the specificity of most gene × nutrient interactions, valid data are needed for nutrient intakes at the individual level. Most statistical adjustment efforts are designed to improve estimates of nutrient intake distributions in populations and are unlikely to solve this problem. An improved method of direct measurement of individual usual dietary intake that is unbiased across populations is urgently needed. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Cocoa is a dry, powdered, nonfat component product prepared from the seeds of the Theobroma cacao L. tree and is a common ingredient of many food products, particularly chocolate. Nutritionally, cocoa contains biologically active substances that may affect human health: flavonoids (epicatechin and oligomeric procyanidins), theobromine, and magnesium. Theobromine and epicatechin are absorbed efficiently in the small intestine, and the nature of their conjugates and metabolites are now known. Oligomeric procyanidins are poorly absorbed in the small intestine, but catabolites are very efficiently absorbed after microbial biotransformation in the colon. A significant number of studies, using in vitro and in vivo approaches, on the effects of cocoa and its constituent flavonoids have been conducted. Most human intervention studies have been performed on cocoa as an ingredient, whereas many in vitro studies have been performed on individual components. Approximately 70 human intervention studies have been carried out on cocoa and cocoa-containing products over the past 12 years, with a variety of endpoints. These studies indicate that the most robust biomarkers affected are endothelial function, blood pressure, and cholesterol level. Mechanistically, supporting evidence shows that epicatechin affects nitric oxide synthesis and breakdown (via inhibition of nicotinamide adenine dinucleotide phosphate oxidase) and the substrate arginine (via inhibition of arginase), among other targets. Evidence further supports cocoa as a biologically active ingredient with potential benefits on biomarkers related to cardiovascular disease. However, the calorie and sugar content of chocolate and its contribution to the total diet should be taken into account in intervention studies. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Bariatric surgery, and in particular, gastric bypass is an increasingly utilized and successful approach for long-term treatment of obesity and amelioration of comorbidities. Nutrient deficiencies after surgery are common and have multiple causes. Preoperative factors include obesity, which appears to be associated with risk for several nutrient deficiencies, and preoperative weight loss. Postoperatively, reduced food intake, suboptimal dietary quality, altered digestion and absorption, and nonadherence with supplementation regimens contribute to risk of deficiency. The most common clinically relevant micronutrient deficiencies after gastric bypass include thiamine, vitamin B12, vitamin D, iron, and copper. Reports of deficiencies of many other nutrients, some with severe clinical manifestations, are relatively sporadic. Diet and multivitamin use are unlikely to consistently prevent deficiency, thus supplementation with additional specific nutrients is often needed. Though optimal supplement regimens are not yet defined, most micronutrient deficiencies after gastric bypass currently can be prevented or treated by appropriate supplementation. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.