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Journal: Advances in nutrition (Bethesda, Md.)


Resveratrol is a naturally occurring stilbene endowed with multiple health-promoting effects. It is produced by certain plants including several dietary sources such as grapes, apples, raspberries, blueberries, plums, peanuts, and products derived therefrom (e.g., wine). Resveratrol can be isolated and purified from these biological sources or synthesized in a few steps with an overall high yield. This compound and its glucoside, the trans-polydatin piceid, have received worldwide attention for their beneficial effects on cardiovascular, inflammatory, neurodegenerative, metabolic, and age-related diseases. These health-promoting effects are particularly attractive given the prevalence of resveratrol-based nutraceuticals and the paradoxical epidemiologic observation that wine consumption is inversely correlated to the incidence of coronary heart disease. However, the notion of resveratrol as a “magic bullet” was recently challenged by clinical trials showing that this polyphenol does not have a substantial influence on health status and mortality risk. In the present review, we discuss the proposed therapeutic attributes and the mode of molecular actions of resveratrol. We also cover recent pharmacologic efforts to improve the poor bioavailability of resveratrol and influence the transition between body systems in humans. We conclude with some thoughts about future research directions that might be meaningful for resolving controversies surrounding resveratrol.

Concepts: Medicine, Epidemiology, Disease, Nutrition, Medical statistics, Heart, Incidence, Resveratrol


Recent observational and clinical studies have raised interest in the potential health effects of cranberry consumption, an association that appears to be due to the phytochemical content of this fruit. The profile of cranberry bioactives is distinct from that of other berry fruit, being rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present in most other fruit. Basic research has suggested a number of potential mechanisms of action of cranberry bioactives, although further molecular studies are necessary. Human studies on the health effects of cranberry products have focused principally on urinary tract and cardiovascular health, with some attention also directed to oral health and gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the recurrence of urinary tract infections is important because a nutritional approach to this condition could lower the use of antibiotic treatment and the consequent development of resistance to these drugs. There is encouraging, but limited, evidence of a cardioprotective effect of cranberries mediated via actions on antioxidant capacity and lipoprotein profiles. The mixed outcomes from clinical studies with cranberry products could result from interventions testing a variety of products, often uncharacterized in their composition of bioactives, using different doses and regimens, as well as the absence of a biomarker for compliance to the protocol. Daily consumption of a variety of fruit is necessary to achieve a healthy dietary pattern, meet recommendations for micronutrient intake, and promote the intake of a diversity of phytochemicals. Berry fruit, including cranberries, represent a rich source of phenolic bioactives that may contribute to human health.

Concepts: Health care, Health, Nutrition, Urinary tract infection, Antioxidant, Cranberry, Berry


Recent advances in cranberry research have expanded the evidence for the role of this Vaccinium berry fruit in modulating gut microbiota function and cardiometabolic risk factors. The A-type structure of cranberry proanthocyanidins seems to be responsible for much of this fruit’s efficacy as a natural antimicrobial. Cranberry proanthocyanidins interfere with colonization of the gut by extraintestinal pathogenic Escherichia coli in vitro and attenuate gut barrier dysfunction caused by dietary insults in vivo. Furthermore, new studies indicate synergy between these proanthocyanidins, other cranberry components such as isoprenoids and xyloglucans, and gut microbiota. Together, cranberry constituents and their bioactive catabolites have been found to contribute to mechanisms affecting bacterial adhesion, coaggregation, and biofilm formation that may underlie potential clinical benefits on gastrointestinal and urinary tract infections, as well as on systemic anti-inflammatory actions mediated via the gut microbiome. A limited but growing body of evidence from randomized clinical trials reveals favorable effects of cranberry consumption on measures of cardiometabolic health, including serum lipid profiles, blood pressure, endothelial function, glucoregulation, and a variety of biomarkers of inflammation and oxidative stress. These results warrant further research, particularly studies dedicated to the elucidation of dose-response relations, pharmacokinetic/metabolomics profiles, and relevant biomarkers of action with the use of fully characterized cranberry products. Freeze-dried whole cranberry powder and a matched placebo were recently made available to investigators to facilitate such work, including interlaboratory comparability.

Concepts: Inflammation, Epidemiology, Clinical trial, Bacteria, Gut flora, Urinary tract infection, Escherichia coli, Cranberry


Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD.

Concepts: Alzheimer's disease, DNA, Protein, Nutrition, Peptide, Cortisol, Dementia, Sundowning


A high prevalence of obesity and cardiometabolic conditions has been increasingly recognized in childhood cancer survivors. In particular, survivors of pediatric acute lymphoblastic leukemia have been found to be at risk of becoming overweight or obese early in treatment, with increases in weight maintained throughout treatment and beyond. Nutrition plays an important role in the etiology of obesity and cardiometabolic conditions and is among the few modifiable factors that can prevent or delay the early onset of these chronic conditions. However, nutritional intake in childhood cancer survivors has not been adequately examined and the evidence is built on data from small cohorts of survivors. In addition, the long-term impact of cancer diagnosis and treatment on survivors' nutritional intake as well as how survivors' nutritional intake is associated with chronic health conditions have not been well quantified in large-scale studies. Promoting family-based healthy lifestyles, preferably at a sensitive window of unhealthy weight gain, is a priority for preventing the early onset of obesity and cardiometabolic conditions in childhood cancer survivors.

Concepts: Medicine, Health, Cancer, Nutrition, Obesity, Overweight, Acute lymphoblastic leukemia, Healthy diet


Flavones are a class of flavonoids that are a subject of increasing interest because of their biological activities in vitro and in vivo. This article reviews the major sources of flavones and their concentrations in food and beverages, which vary widely between studies. It also covers the roles of flavones in plants, the influence of growing conditions on their concentrations, and their stability during food processing. The absorption and metabolism of flavones are also reviewed, in particular the intestinal absorption of both O- and C-glycosides. Pharmacokinetic studies in both animals and humans are described, comparing differences between species and the effects of glycosylation on bioavailability. Biological activity in animal models and human dietary intervention studies is also reviewed. A better understanding of flavone sources and bioavailability is needed to understand mechanisms of action and nutritional intervention.

Concepts: Protein, Human, Nutrition, Species, Animal, In vivo, Food, In vitro


The Dietary Reference Intakes set the protein RDA for persons >19 y of age at 0.8 g protein ⋅ kg body weight-1 ⋅ d-1. A growing body of evidence suggests, however, that the protein RDA may be inadequate for older individuals. The evidence for recommending a protein intake greater than the RDA comes from a variety of metabolic approaches. Methodologies centered on skeletal muscle are of paramount importance given the age-related decline in skeletal muscle mass and function (sarcopenia) and the degree to which dietary protein could mitigate these declines. In addition to evidence from short-term experimental trials, observational data show that higher protein intakes are associated with greater muscle mass and, more importantly, better muscle function with aging. We are in dire need of more evidence from longer-term intervention trials showing the efficacy of the consumption of protein intakes that are higher than the RDA in older persons to support skeletal muscle health. We propose that it should be recommended that older individuals consume ≥1.2 g protein · kg-1 · d-1 and that there should be an emphasis on the intake of the amino acid leucine, which plays a central role in stimulating skeletal muscle anabolism. Critically, the often-cited potential negative effects of consuming higher protein intakes on renal and bone health are without a scientific foundation in humans.

Concepts: Scientific method, Protein, Amino acid, Metabolism, Nutrition, Muscle, Myosin, Leucine


There is much emerging information surrounding the impact of sleep duration and quality on food choice and consumption in both children and adults. However, less attention has been paid to the effects of dietary patterns and specific foods on nighttime sleep. Early studies have shown that certain dietary patterns may affect not only daytime alertness but also nighttime sleep. In this review, we surveyed the literature to describe the role of food consumption on sleep. Research has focused on the effects of mixed meal patterns, such as high-carbohydrate plus low-fat or low-carbohydrate diets, over the short term on sleep. Such studies highlight a potential effect of macronutrient intakes on sleep variables, particularly alterations in slow wave sleep and rapid eye movement sleep with changes in carbohydrate and fat intakes. Other studies instead examined the intake of specific foods, consumed at a fixed time relative to sleep, on sleep architecture and quality. Those foods, specifically milk, fatty fish, tart cherry juice, and kiwifruit, are reviewed here. Studies provide some evidence for a role of certain dietary patterns and foods in the promotion of high-quality sleep, but more studies are necessary to confirm those preliminary findings.

Concepts: Nutrition, Fat, Food, Carbohydrate, Rapid eye movement sleep, Seafood, Diets, Low-carbohydrate diet


Dietary guidelines commonly recommend that children aged >2 y consume reduced-fat dairy products rather than regular- or whole-fat dairy. In adults, most studies have not found the consumption of whole-fat dairy products to be associated with increased cardiometabolic or adiposity risk. Associations in children could differ due to growth and development. We systematically reviewed the literature in indexed, peer-reviewed journals to summarize pediatric studies (children aged from 2 to 18 y) assessing associations between whole- and reduced-fat dairy intake and measures of adiposity as well as biomarkers of cardiometabolic disease risk, including the serum lipid profile, blood pressure, low-grade chronic inflammation, oxidative stress, and measures of glucose homeostasis. For the purposes of this review, a “whole-fat” dairy product was defined as a product with the natural fat content, whereas a “reduced-fat” dairy product was defined as a product with some or all of the fat removed (including “low-fat” and “skim” versions). A total of 29 journal articles met our criteria for inclusion. The majority were conducted in the United States and were prospective or cross-sectional observational studies, with only 1 randomized controlled trial. Studies were consistent in reporting that whole-fat dairy products were not associated with increased measures of weight gain or adiposity. Most evidence indicated that consumption of whole-fat dairy was not associated with increased cardiometabolic risk, although a change from whole-fat to reduced-fat dairy improved outcomes for some risk factors in 1 study. Taken as a whole, the limited literature in this field is not consistent with dietary guidelines recommending that children consume preferably reduced-fat dairy products. High-quality randomized controlled trials in children that directly compare the effects of whole-fat compared with reduced-fat dairy intake on measures of adiposity or biomarkers of cardiometabolic disease risk are needed to provide better quality evidence in this area.


There is substantial evidence that the prevalence of vitamin D deficiency is unacceptably high in the population, and this requires action from a public health perspective. Circulating 25-hydroxyvitamin D [25(OH)D] is a robust and reliable marker of vitamin D status and has been used by numerous agencies in the establishment of vitamin D dietary requirements and for population surveillance of vitamin D deficiency or inadequacy. In a wider context, modeling of serum 25(OH)D data and its contributory sources, namely dietary vitamin D supply and UVB availability, can inform our understanding of population vitamin D status. The aim of this review is to provide the current status of knowledge in relation to modeling of such vitamin D-relevant data. We begin by highlighting the importance of the measurement of 25(OH)D and its standardization, both of which have led to new key data on the prevalence of vitamin D deficiency and inadequacy in North America and Europe. We then overview how state-of-the-art modeling can be used to inform our understanding of the potential effect of ergocalciferol and 25(OH)D on vitamin D intake estimates and how meteorological data on UVB availability, when coupled with other key data, can help predict population serum 25(OH)D concentration, even accounting for seasonal fluctuations, and lastly, how these in silico approaches can help inform policymakers on strategic options on addressing low vitamin D status through food-based approaches and supplementation. The potential of exemplar food-based solutions will be highlighted, as will the possibility of synergies between vitamin D and other dairy food-based micronutrients, in relation to vitamin D status and bone health. Lastly, we will briefly consider the interactions between season and vitamin D supplements on vitamin D status and health.

Concepts: Vitamin D, Epidemiology, Nutrition, Vitamins, Knowledge, North America, Vitamin A, The Establishment