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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


Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time.

Concepts: Nutrition, Fatty acid, Fatty acids, Essential fatty acid, Fat, Saturated fat, Linoleic acid, Lard


Age-related sarcopenia, composed of myopenia (a decline in muscle mass) and dynapenia (a decline in muscle strength), can compromise physical function, increase risk of disability, and lower quality of life in older adults. There are no available pharmaceutical treatments for this condition, but evidence shows resistance training (RT) is a viable and relatively low-cost treatment with an exceptionally positive side effect profile. Further evidence suggests that RT-induced increases in muscle mass, strength, and function can be enhanced by certain foods, nutrients, or nutritional supplements. This brief review focuses on adjunctive nutritional strategies, which have a reasonable evidence base, to enhance RT-induced gains in outcomes relevant to sarcopenia and to reducing risk of functional declines.

Concepts: Metabolism, Energy, Muscle, Physical exercise, Glycogen, Muscle atrophy, Sarcopenia, Strength training


Since the release of a previous meta-analysis on the effect of whole-grain intake on obesity measures, several clinical trials have been published. Therefore, we aimed to update the previous meta-analysis on the effect of whole-grain intake on obesity measures by including recently published studies, as well as considering the main limitations in that analysis. We searched the online databases of PubMed, Scopus, Clarivate Web of Science, EmBase, and Google Scholar for relevant studies published up to February 2019, using relevant keywords. Randomized clinical trials investigating the effect of whole-grain products or diets high in whole-grain foods, compared with a control diet, on anthropometric measures [including body weight, BMI, waist circumference, and fat mass (FM)] were included. In total, 21 studies with a total sample of 1798 participants, aged ≥18 years, were considered. Based on 22 effect sizes from 19 studies on body weight, with a total sample of 1698 adults, we found no significant effect of whole-grain consumption on body weight. The same findings were obtained for BMIs, such that using 10 effect sizes from 10 clinical trials with a total sample of 769 individuals we did not find any significant effect. With regards to body fat percentage [weighted mean difference (WMD): 0.27; 95% CI: -0.05 to 0.58%; P = 0.09], FM (WMD: 0.45; 95% CI: -0.12 to 1.02 kg; P = 0.12), fat-free mass (WMD: 0.31; 95% CI: -0.67 to 0.06 kg; P = 0.10), and waist circumference (WMD: 0.06; 95% CI: -0.50 to 0.63 cm; P = 0.82), we failed to find any significant effect of whole-grain consumption. In conclusion, our findings did not support current recommendations of whole-grain intake in attempts to control obesity measures. Given the beneficial effects of whole-grain intake on other measures of human health, additional well-designed studies are required to further investigate the effect on obesity. The protocol has been registered with PROSPERO (registration number CRD42018089176).