Advances in Nutrition: An International Review Journal current issue

Perspective: What Makes It So Difficult to Mitigate Worldwide Anemia Prevalence?

Anemia can be related to decreased production or increased loss of erythrocytes, or both, leading to many underlying and often overlapping causes. A largely cereal-based diet with plenty of phytates, polyphenols, and other ligands that inhibit intestinal iron absorption predominated in preindustrial Europe and predominates in present-day developing countries alike. In both situations, we find poor hygienic conditions, which frequently lead to anemia of inflammation. The large number of possible causes and their interaction shows why it is so difficult to mitigate anemia prevalence. Diagnostic biomarkers are required to differentiate the different types of anemia and to treat them appropriately. Some of them are well established in adults [e.g., concentrations of serum ferritin, soluble transferrin receptor (sTfR), and serum iron or the ratio of sTfR to log ferritin]. Others, such as serum hepcidin, hold considerable promise, although they are not yet widely used. A particular issue is to establish reference values for biomarkers in infants and children at different ages. The fact that resource-rich postindustrial societies have a very low prevalence of iron-deficiency anemia offers hope that common types of anemia can be eliminated. In contrast, inborn forms of anemia, such as thalassemia, and anemias related to underlying diseases (e.g., bleeding tumors or peptic ulcers, gynecologic blood losses, or renal diseases) require an operational health system to be addressed appropriately.

Perspective: A Historical and Scientific Perspective of Sugar and Its Relation with Obesity and Diabetes

Fructose-containing added sugars, such as sucrose and high-fructose corn syrup, have been experimentally, epidemiologically, and clinically shown to be involved in the current epidemics of obesity and diabetes. Here we track this history of intake of sugar as it relates to these epidemics. Key experimental studies that have identified mechanisms by which fructose causes obesity and diabetes are reviewed, as well as the evidence that the uricase mutation that occurred in the mid-Miocene in ancestral humans acted as a "thrifty gene" that increases our susceptibility for fructose-associated obesity today. We briefly review recent evidence that obesity can also be induced by nondietary sources of fructose, such as from the metabolism of glucose (from high-glycemic carbohydrates) through the polyol pathway. These studies suggest that fructose-induced obesity is driven by engagement of a "fat switch" and provide novel insights into new approaches for the prevention and treatment of these important diseases.

Flavones: Food Sources, Bioavailability, Metabolism, and Bioactivity

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.

A Systematic Examination of the Association between Parental and Child Obesity across Countries

Childhood obesity has become a global epidemic. Parents can have an important influence on their children’s health behaviors and weight status. Many studies have examined the association between parental and childhood weight status. However, much heterogeneity between studies exists, and the parent-child (P-C) association in obesity has varied. The purpose of this systematic examination and meta-analysis was to examine the strength and variation of the P-C association in obesity and to identify factors (e.g., demographic characteristics and country’s economic level) that may influence this association. PubMed was searched for relevant studies published between January 2000 and July 2015. Thirty-two studies from 21 countries met inclusion criteria; 27 reported ORs for the P-C obesity association and were included in a meta-analysis. The meta-analysis showed a strong P-C obesity association (pooled OR: 2.22; 95% CI: 2.09, 2.36), which varied by type of P-C pair (i.e., parents-child, father-child, and mother-child), child age, parent and child weight status, and the country’s economic level. Stronger associations were shown in older children than in younger children (β ± SE: 0.02 ± 0.01), in both parents than in father only (β ± SE: 0.51 ± 0.11) or mother only (β ± SE: 0.38 ± 0.11), in parental obesity (β ± SE: 0.26 ± 0.10) and child obesity (β ± SE: 0.28 ± 0.12) than in parental and child overweight, and in high- than in middle-income countries (β ± SE: 0.23 ± 0.08). Thus, research from multiple countries shows significant P-C associations in weight status, but this association varies by child age, type of P-C pair, weight status, and the country’s economic level. Results suggest that families and parents should be a key target for obesity intervention efforts.

A Systematic Review of Application and Effectiveness of mHealth Interventions for Obesity and Diabetes Treatment and Self-Management

The use of mobile and wireless technologies and wearable devices for improving health care processes and outcomes (mHealth) is promising for health promotion among patients with chronic diseases such as obesity and diabetes. This study comprehensively examined published mHealth intervention studies for obesity and diabetes treatment and management to assess their effectiveness and provide recommendations for future research. We systematically searched PubMed for mHealth-related studies on diabetes and obesity treatment and management published during 2000–2016. Relevant information was extracted and analyzed. Twenty-four studies met inclusion criteria and varied in terms of sample size, ethnicity, gender, and age of the participating patients and length of follow-up. The mHealth interventions were categorized into 3 types: mobile phone text messaging, wearable or portable monitoring devices, and applications running on smartphones. Primary outcomes included weight loss (an average loss ranging from –1.97 kg in 16 wk to –7.1 kg in 5 wk) or maintenance and blood glucose reduction (an average decrease of glycated hemoglobin ranging from –0.4% in 10 mo to –1.9% in 12 mo); main secondary outcomes included behavior changes and patient perceptions such as self-efficacy and acceptability of the intervention programs. More than 50% of studies reported positive effects of interventions based on primary outcomes. The duration or length of intervention ranged from 1 wk to 24 mo. However, most studies included small samples and short intervention periods and did not use rigorous data collection or analytic approaches. Although some studies suggest that mHealth interventions are effective and promising, most are pilot studies or have limitations in their study designs. There is an essential need for future studies that use larger study samples, longer intervention (≥ 6 mo) and follow-up periods (≥ 6 mo), and integrative and personalized innovative mobile technologies to provide comprehensive and sustainable support for patients and health service providers.

Influence of Diet in Multiple Sclerosis: A Systematic Review

Nutrition is considered to be a possible factor in the pathogenesis of the neurological disease multiple sclerosis (MS). Nutrition intervention studies suggest that diet may be considered as a complementary treatment to control the progression of the disease; a systematic review of the literature on the influence of diet on MS was therefore conducted. The literature search was conducted by using Medlars Online International Literature (MEDLINE) via PubMed and Scopus. Forty-seven articles met the inclusion criteria. The reviewed articles assessed the relations between macro- and micronutrient intakes and MS incidence. The patients involved used alternative therapies (homeopathy), protocolized diets that included particular foods (herbal products such as grape seed extract, ginseng, blueberries, green tea, etc.), or dietary supplements such as vitamin D, carnitine, melatonin, or coenzyme Q10. Current studies suggest that high serum concentrations of vitamin D, a potent immunomodulator, may decrease the risk of MS and the risk of relapse and new lesions, while improving brain lesions and timed tandem walking. Experimental evidence suggests that serum vitamin D concentration is lower during MS relapses than in remission and is associated with a greater degree of disability [Expanded Disability Status Scale (EDSS) score >3]. The findings suggest that circulating vitamin D concentrations can be considered a biomarker of MS and supplemental vitamin D can be used therapeutically. Other studies point to a negative correlation between serum vitamin B-12 concentrations and EDSS score. Vitamin B-12 has fundamental roles in central nervous system function, especially in the methionine synthase–mediated conversion of homocysteine to methionine, which is essential for DNA and RNA synthesis. Therefore, vitamin B-12 deficiency may lead to an increase in the concentration of homocysteine. Further research is clearly necessary to determine whether treatment with vitamin B-12 supplements delays MS progression.

Dietary Factors Promoting Brown and Beige Fat Development and Thermogenesis

Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes. Despite advances in knowledge regarding the developmental lineage and transcriptional regulators of brown and beige adipocytes, our current understanding of environmental modifiers of BAT thermogenesis, such as diet, is limited. In this review, we consolidated the latest research on dietary molecules that may serve to promote BAT thermogenesis. Here, we summarized the thermogenic function of selected phytochemicals (e.g., capsaicin, resveratrol, curcumin, green tea, and berberine), dietary fatty acids (e.g., fish oil and conjugated linoleic acids), and all-trans retinoic acid, a vitamin A metabolite. We also delineated the proposed mechanisms whereby these dietary molecules promote BAT activity and/or browning of white adipose tissue. Characterizing thermogenic dietary factors may offer novel insight into revising nutritional intervention strategies aimed at obesity and diabetes prevention and management.

Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation

Constipation is a common and burdensome gastrointestinal disorder that may result from altered gastrointestinal motility. The effect of probiotics on constipation has been increasingly investigated in both animal and human studies, showing promising results. However, there is still uncertainty regarding the mechanisms of action of probiotics on gut motility and constipation. Several factors are vital to normal gut motility, including immune and nervous system function, bile acid metabolism and mucus secretion, and the gastrointestinal microbiota and fermentation; an imbalance or dysfunction in any of these components may contribute to aberrant gut motility and, consequently, symptoms of constipation. For example, adults with functional constipation have significantly decreased numbers of bifidobacteria (with one study showing a mean difference of 1 log10/g) and lactobacilli (mean difference, 1.4 log10/g) in stool samples, as well as higher breath methane, compared with control subjects. Modifying the gut luminal environment with certain probiotic strains may affect motility and secretion in the gut and, hence, provide a benefit for patients with constipation. Therefore, this review explores the mechanisms through which probiotics may exert an effect on gut motility and constipation. Nevertheless, the majority of current evidence is derived from animal studies, and therefore, further human studies are needed to determine the mechanisms through specific probiotic strains that might be effective in constipation.

Associations between Breastfeeding and Maternal Responsiveness: A Systematic Review of the Literature

Recent recommendations and prevention programs have focused on the promotion of responsive feeding during infancy, but more research is needed to understand best practices for fostering responsive feeding during early life. The objective of this systematic review was to synthesize the accumulating bodies of evidence aimed at understanding associations between mothers’ feeding experiences and responsive feeding in an attempt to clarify the nature of associations between feeding mode and responsive feeding. A literature search was conducted between January and October 2016; articles were collected from PsychINFO, Medline, and CINAHL, as well as from references in published research and reviews. Article inclusion criteria were as follows: 1) empirical research, 2) included a measure of infant feeding, 3) included a measure of maternal responsiveness, 4) study conducted in human participants, 5) available in English, and 6) study conducted in a developed and/or high-income country. Forty-three studies were identified. Cross-sectional observational studies consistently reported greater responsiveness among breastfeeding mothers than among formula-/bottle-feeding mothers. In addition, longitudinal studies showed that longer breastfeeding durations predicted lower use of nonresponsive feeding practices during later childhood, and some, but not all, found that breastfeeding mothers showed greater increases in responsiveness across infancy than did formula-/bottle-feeding mothers. However, a limited number of longitudinal studies also reported that greater responsiveness during early infancy predicted longer breastfeeding durations. A common limitation among these studies is the correlational nature of their designs and lack of prenatal measures of maternal responsiveness, which hinders our understanding of causal mechanisms. Although 2 randomized clinical trials aimed at promoting maternal responsiveness did not find effects of the intervention on breastfeeding outcomes, these findings were limited by the way in which breastfeeding outcomes were assessed. In sum, although there is consistent evidence for an association between breastfeeding and responsive feeding, more research is needed to better understand the mechanisms underlying this association.

Preserving Healthy Muscle during Weight Loss

Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers. The potential health benefits of diet-induced weight loss are thought to be compromised by the weight-loss–associated loss of lean body mass, which could increase the risk of sarcopenia (low muscle mass and impaired muscle function). The objective of this review is to provide an overview of what is known about weight-loss–induced muscle loss and its implications for overall physical function (e.g., ability to lift items, walk, and climb stairs). The currently available data in the literature show the following: 1) compared with persons with normal weight, those with obesity have more muscle mass but poor muscle quality; 2) diet-induced weight loss reduces muscle mass without adversely affecting muscle strength; 3) weight loss improves global physical function, most likely because of reduced fat mass; 4) high protein intake helps preserve lean body and muscle mass during weight loss but does not improve muscle strength and could have adverse effects on metabolic function; 5) both endurance- and resistance-type exercise help preserve muscle mass during weight loss, and resistance-type exercise also improves muscle strength. We therefore conclude that weight-loss therapy, including a hypocaloric diet with adequate (but not excessive) protein intake and increased physical activity (particularly resistance-type exercise), should be promoted to maintain muscle mass and improve muscle strength and physical function in persons with obesity.

Metabolic Effects of Inflammation on Vitamin A and Carotenoids in Humans and Animal Models

The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency. On the other hand, inflammation causes impaired VA absorption and urinary losses that can precipitate VA deficiency in at-risk groups of children. Many epidemiologic studies have suggested that high dietary carotenoid intake and elevated plasma concentrations are correlated with a decreased risk of several chronic diseases; however, large-scale carotenoid supplementation trials have been unable to confirm the health benefits and in some cases resulted in controversial results. However, it has been documented that dietary carotenoids and retinoids play important roles in innate and acquired immunity and in the body’s response to inflammation. Although animal models have been useful in investigating retinoid effects on developmental immunity, it is more challenging to tease out the effects of carotenoids because of differences in the absorption, kinetics, and metabolism between humans and animal models. The current understanding of the relations between inflammation and retinoid and carotenoid metabolism and status are the topics of this review.

Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review

Research findings over the past several decades have shown that inflammation is a prominent feature of many chronic diseases, with poor diet being one likely inflammatory stimulus. Specifically, a single high-fat meal (HFM) has been suggested to increase inflammation, although there is currently no consensus with regard to the specific changes in many of the proinflammatory markers that are frequently assessed after an HFM. The aim of this systematic review was to objectively describe the postprandial timing and magnitude of changes in 5 common inflammatory markers: interleukin (IL) 6, C-reactive protein (CRP), tumor necrosis factor (TNF) α, IL-1β, and IL-8. Ten relevant databases were searched, yielding 494 results, of which 47 articles met the pre-established inclusion criteria: 1) healthy men and women aged 18–60 y, 2) consuming a single HFM (≥30% fat, ≥500 kcal), and 3) assessing relevant inflammatory markers postmeal for ≥2 h. The only marker found to consistently change in the postprandial period was IL-6: on average, from a baseline of ~1.4 pg/mL, it peaked at ~2.9 pg/mL ~6 h post-HFM (an average relative change of ~100%). CRP, TNF-α, IL-1β, and IL-8 did not change significantly in 79% (23 of 29), 68% (19 of 28), 67% (2 of 3), and 75% (3 of 4) of included studies, respectively. We conclude that there is strong evidence that CRP and TNF-α are not responsive at the usual time scale observed in postprandial studies in healthy humans younger than age 60 y. However, future research should further investigate the role of IL-6 in the postprandial period, because it routinely increases even in healthy participants. We assert that the findings of this systematic review on markers of inflammation in the postprandial period will considerably aid in informing future research and advancing clinical knowledge.

Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function

Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function.

Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the world, yet the pathogenesis of the disease is not well elucidated. Due to the close anatomic and functional association between the intestinal lumen and the liver through the portal system, it is speculated that the gut microbiome may play a pivotal role in the pathogenesis of NAFLD. Furthermore, diet, which can modulate the gut microbiome and several metabolic pathways involved in NAFLD development, shows a potential tripartite relation between the gut, diet, and the liver. In this review, we summarize the current evidence that supports the association between NAFLD, the gut microbiome, and the role of diet.

Nutritional Approaches to Achieve Weight Loss in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5–10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches to Stop Hypertension diet, a sodium-restricted diet, has been associated with less prevalence of NAFLD and has been shown to improve NAFLD. In addition, the Mediterranean diet has been promising in improving hepatic steatosis, and a larger randomized controlled trial is currently enrolling subjects. For those who are unable to pursue weight loss through dietary approaches, bariatric surgery has been shown to improve hepatic steatosis and steatohepatitis. This method has been variable in improving hepatic fibrosis. In conclusion, weight loss is crucial to the improvement of NAFLD and NASH, and patients should attempt various diets in an attempt to achieve weight loss.

Optimizing Protein Intake in Adults: Interpretation and Application of the Recommended Dietary Allowance Compared with the Acceptable Macronutrient Distribution Range

The adult RDA is defined as the average daily level of intake sufficient to meet the nutrient requirements of nearly all healthy people. The RDA for protein for adults ≥18 y of age (0.8 g/kg) has been essentially unchanged for >70 y. In practice, the RDA for protein was derived to estimate the minimum amount of protein that must be eaten to avoid a loss of body nitrogen. The Acceptable Macronutrient Distribution Range (AMDR) (10–35% of calories as protein) was developed to express dietary recommendations in the context of a complete diet. It is noteworthy that the lowest level of protein intake reflected in the AMDR is higher than that of the RDA. Furthermore, recent studies, particularly in older individuals, suggest specific health benefits at levels of protein intake that significantly exceed the RDA. Translation of protein intake recommendations for the general adult population into dietary guidance for individuals requires an understanding of the derivation and intended use of both the protein RDA and AMDR. The following discussion will describe limitations to the derivation and practical application of the RDA compared with the use of the AMDR to help maximize health benefits associated with higher protein intake by using flexible calories inherent in different dietary patterns.

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