Advances in Nutrition




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Plant-Based Eating Pattern for Type 2 Diabetes Prevention and Treatment: Efficacy, Mechanisms, and Practical Considerations 

Meghan A Jardine, Hana Kahleova, Susan M Levin, Zeeshan Ali, Caroline B Trapp, Neal D Barnard

doi : 10.1093/advances/nmab063

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2045–2055

A plant-based eating pattern is associated with a reduced risk of developing type 2 diabetes and is highly effective in its treatment. Diets that emphasize whole grains, vegetables, fruits, and legumes and exclude animal products improve blood glucose concentrations, body weight, plasma lipid concentrations, and blood pressure and play an important role in reducing the risk of cardiovascular and microvascular complications. This article reviews scientific evidence on the effects of plant-based diets for the prevention and treatment of type 2 diabetes. The mechanisms by which plant-based diets improve body weight, insulin sensitivity, and ?-cell function are described. Practical considerations including education, nutrition adequacy, and adjusting medications will enhance the success of patients who have diabetes.

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Plant-based Whole-Grain Foods for Chronic Kidney Disease: The Phytate-Phosphorus Conundrum

Mona S Calvo, Jaime Uribarri

doi : 10.1093/advances/nmab066

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2056–2067

Restriction of dietary phosphorus intake is an important component of good clinical practice in kidney failure patients, particularly after dialysis initiation. Greater consumption of predominantly plant-based diets, including phytate-rich foods, is increasingly recommended for health maintenance/disease prevention in this population, with the implicit assumption that phytate-phosphorus in whole-grain cereals, legumes, pulses, and nuts is poorly absorbed. Review of human interventions with diets high in phytate-phosphorus indeed suggests an absorption of at least 50%, still less than animal protein–bound phosphorus, but higher than the generally believed 10–30%. Factors largely ignored up to now, but of potential influence on phytate-phosphorus bioavailability, include effect of food processing in releasing phosphorus, action of colonic bacteria that are able to release inorganic phosphorus, and capacity of the colon to absorb phosphorus. These issues may become increasingly important as new plant-based alternatives to meats, all containing phytate, are being rapidly introduced in the market.

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Identifying Ultra-Processed Plant-Based Milk Alternatives in the USDA Branded Food Products Database

Adam Drewnowski

doi : 10.1093/advances/nmab089

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2068–2075

This study explored the characteristics of plant-based beverages (PBBs) that are marketed as “milks” in the United States. First, machine searches of product names and ingredients in the USDA Branded Food Products Database (BFPDB) yielded 641 nondairy PBBs that included almond, soy, coconut, cashew, other tree nut, flax/hemp, pea, and quinoa and rice “milks.” The products varied in energy density and the majority of PBBs contained added salt (69%) and added sugar (53%). Scores on nutrient density metrics [Nutri-Score, Choices, and the Nutrient Rich Food index 7.3 (NRF7.3)] were higher for almond and pea products and lower for coconut PBBs, which contained saturated fat. Ingredient lists were searched further for added flavors, stabilizers, or preservatives said to be characteristic of the NOVA food classification system's ultra-processed group. Most PBBs (90.1%) and 95% of almond milks met the NOVA criteria for ultra-processed foods, because they were created from food components and contained multiple substances not used in normal cooking. Replacing milk and dairy products with plant-based alternatives will necessarily involve the use of ultra-processed foods.

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Does Glycemic Index Matter for Weight Loss and Obesity Prevention? Examination of the Evidence on “Fast” Compared with “Slow” Carbs 

Glenn A Gaesser, Julie Miller Jones, Siddhartha S Angadi

doi : 10.1093/advances/nmab093

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2076–2084

High-glycemic index (high-GI) foods (so-called fast carbs) have been hypothesized to promote fat storage and increase risk of obesity. To clarify whether dietary GI impacts body weight, we searched PubMed and the Cochrane Database of Systematic Reviews for observational studies reporting associations between BMI and dietary GI, and for meta-analyses of randomized controlled trials (RCTs) comparing low-GI and high-GI diets for weight loss. Data on 43 cohorts from 34 publications, totaling 1,940,968 adults, revealed no consistent differences in BMI when comparing the highest with the lowest dietary GI groups. In the 27 cohort studies that reported results of statistical comparisons, 70% showed that BMI was either not different between the highest and lowest dietary GI groups (12 of 27 cohorts) or that BMI was lower in the highest dietary GI group (7 of 27 cohorts). Results of 30 meta-analyses of RCTs from 8 publications demonstrated that low-GI diets were generally no better than high-GI diets for reducing body weight or body fat. One notable exception is that low-GI diets with a dietary GI at least 20 units lower than the comparison diet resulted in greater weight loss in adults with normal glucose tolerance but not in adults with impaired glucose tolerance. While carbohydrate quality, including GI, impacts many health outcomes, GI as a measure of carbohydrate quality appears to be relatively unimportant as a determinant of BMI or diet-induced weight loss. Based on results from observational cohort studies and meta-analyses of RCTs, we conclude that there is scant scientific evidence that low-GI diets are superior to high-GI diets for weight loss and obesity prevention.

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Moving Toward Desirable Linoleic Acid Content in Infant Formula 

Susan E Carlson, Lidewij Schipper, J Thomas Brenna, Carlo Agostoni, Philip C Calder, Stewart Forsyth, Philippe Legrand, Marieke Abrahamse-Berkeveld, Bert J M van de Heijning, Eline M van der Beek, Berthold V Koletzko, Beverly Muhlhausler

doi : 10.1093/advances/nmab076

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2085–2098

Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes.

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The Impact of Protein Type on Phosphorus Intake, Serum Phosphate Concentrations, and Nutrition Status in Adults with Chronic Kidney Disease: A Critical Review

Kelly Picard, Diana R Mager, Caroline Richard

doi : 10.1093/advances/nmab062

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2099–2111

Lower phosphorus intake to prevent hyperphosphatemia for those with chronic kidney disease (CKD) is often recommended. Plant proteins are frequently restricted for their high phosphorus content despite having lower bioavailability. To summarize the evidence on protein type and dietary phosphorus intake, serum phosphate concentrations, and nutritional adequacy in adults with CKD, a search in MEDLINE via Ovid was conducted. Citation lists were reviewed to identify any additional articles. Sixteen articles were included—7 intervention (n = 290) and 9 observational (n = 4933). All intervention trials reported high-plant-protein diets provided adequate protein and adhered to low phosphorus diet guidelines. All intervention trials reported higher plant-protein intake was associated with lower serum phosphate; however, only 2 achieved statistical significance. For observational studies, 2 reported that higher proportions of plant to animal protein resulted in lower phosphorus intake but equivalent serum phosphate concentrations. Two reported that plant protein and animal protein had equivalent correlation values to phosphorus intake and no correlation to serum phosphate concentrations. One trial reported lower total phosphorus and protein intake among those who consumed more plant proteins but did not examine serum concentrations. Four reported lower serum phosphate concentrations among those who consumed more plant proteins but did not report dietary phosphorus intake. Of the observational studies that reported on protein intake, all reported lower protein intake among those with higher versus lower plant-protein intake. BMI tended to be lower among those consuming more plant protein. There was not a consistent relation between protein type and albumin concentrations. Routine restriction of plant-protein foods to prevent hyperphosphatemia in CKD would likely benefit from re-evaluation, as evidence does not suggest that higher plant-protein intake leads to higher serum phosphate concentrations or worse nutritional status, although longer-duration intervention trials with larger sample sizes appear to be warranted.

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A Scoping Review: Metabolomics Signatures Associated with Animal and Plant Protein Intake and Their Potential Relation with Cardiometabolic Risk

Gaïa Lépine, Hélène Fouillet, Didier Rémond, Jean-François Huneau, François Mariotti, Sergio Polakof

doi : 10.1093/advances/nmab073

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2112–2131

The dietary shift from animal protein (AP) to plant protein (PP) sources is encouraged for both environmental and health reasons. For instance, PPs are associated with lower cardiovascular and diabetes risks compared with APs, although the underlying mechanisms mostly remain unknown. Metabolomics is a valuable tool for globally and mechanistically characterizing the impact of AP and PP intake, given its unique ability to provide integrated signatures and specific biomarkers of metabolic effects through a comprehensive snapshot of metabolic status. This scoping review is aimed at gathering and analyzing the available metabolomics data associated with PP- and AP-rich diets, and discusses the metabolic effects underlying these metabolomics signatures and their potential implication for cardiometabolic health. We selected 24 human studies comparing the urine, plasma, or serum metabolomes associated with diets with contrasted AP and PP intakes. Among the 439 metabolites reported in those studies as able to discriminate AP- and PP-rich diets, 46 were considered to provide a robust level of evidence, according to a scoring system, especially amino acids (AAs) and AA-related products. Branched-chain amino acids, aromatic amino acids (AAAs), glutamate, short-chain acylcarnitines, and trimethylamine-N-oxide, which are known to be related to an increased cardiometabolic risk, were associated with AP-rich diets, whereas glycine (rather related to a reduced risk) was associated with PP-rich diets. Tricarboxylic acid (TCA) cycle intermediates and products from gut microbiota AAA degradation were also often reported, but the direction of their associations differed across studies. Overall, AP- and PP-rich diets result in different metabolomics signatures, with several metabolites being plausible candidates to explain some of their differential associations with cardiometabolic risk. Additional studies specifically focusing on protein type, with rigorous intake control, are needed to better characterize the associated metabolic phenotypes and understand how they could mediate differential AP and PP effects on cardiometabolic risk.

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What Role Do Plant-Based Diets Play in Supporting the Optimal Health and Well-being of Canadians? A Scoping Review

Zoe L Bye, Pardis Keshavarz, Ginny L Lane, Hassan Vatanparast

doi : 10.1093/advances/nmab061

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2132–2146

In Canada, unhealthy diets are associated with several chronic conditions, such as type 2 diabetes, cardiovascular disease, and obesity, and thus negatively impact the health and well-being of Canadians. Consequently, unhealthy diets are associated with an increased risk of morbidity and mortality in Canada. Recently, plant-based diets have gained in popularity due to their ability to provide a diet that is nutritionally adequate and health-conscious in addition to supporting environmental sustainability. The adoption of plant-based diets may address the substantial need to improve the health and well-being of Canadians, while also having a positive global environmental impact such as reducing greenhouse gas emissions. The aim of this scoping review was to identify current knowledge on the nutritional adequacy of plant-based diets and their relation with chronic conditions to support improved health and well-being of Canadians while identifying gaps in knowledge. Canadian peer-reviewed literature on diet, nutritional quality, and chronic conditions published between the years 2010 and 2020 were systematically examined. Sixteen articles met the inclusion criteria, with the majority pertaining to the relation between animal- or plant-based nutrition and cancer. Epidemiological studies support the practice of plant-based diets, in comparison to omnivore diets, as a strategy to improve nutritional adequacy and reduce the development of chronic conditions such as obesity, type 2 diabetes, cardiovascular diseases, osteoporosis, and select cancers such as endometrial, colorectal, and breast cancers. Overall, plant-based diets offer an opportunity to improve the health and well-being of Canadians while simultaneously working to counteract climate change, which may have a global reach. Gaps in knowledge were identified and mainly pertained to the lack of valid Canadian quantitative assessments of the long-term health impacts of plant-based diets. Further research should be completed to quantify the long-term health effects of the practice of a plant-based diet across all demographics of the Canadian population.

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Activation of Brown Adipose Tissue and Promotion of White Adipose Tissue Browning by Plant-based Dietary Components in Rodents: A Systematic Review

Francisco J Osuna-Prieto, Borja Martinez-Tellez, Antonio Segura-Carretero, Jonatan R Ruiz

doi : 10.1093/advances/nmab084

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2147–2156

Activation of brown adipose tissue (BAT) and promotion of white adipose tissue (WAT) browning is considered a potential tool to combat obesity and cardiometabolic disorders. The use of plant-based dietary components has become one of the most used strategies for activating BAT and promoting WAT browning in rodents. The main reason is because plant-based dietary components are usually recognized as safe when the dose is properly adjusted, and they can easily be administrated by being added to the diet or dissolved in water. The present systematic review aimed to study the effects of plant-based dietary components on activation of BAT and promotion of WAT browning in rodents. A systematic search of PubMed and Scopus (from 1978 to 2019) identified eligible studies. Studies assessing the effects of plant-based dietary components added to diet and/or water on uncoupling protein 1 (UCP1) expression in BAT and/or WAT were included. Studies that used dietary components of animal origin, did not specify the effects on UCP1, or were conducted in other species different from mice or rats were excluded. Of 3919 studies identified in the initial screening, 146 studies were finally included in the review. We found that tea extract catechins, resveratrol, capsaicin and capsinoids, cacao extract flavanols, and quercetin were the most studied components. Scientific evidence suggests that some of these dietary components activate BAT and promote WAT browning via activation of the AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) pathways. These findings reveal that there is strong scientific evidence supporting the use of plant-based dietary components to activate BAT and promote WAT browning in rodents and thus to potentially combat obesity and cardiometabolic disorders.

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Circulating Advanced Glycation End Products and Their Soluble Receptors in Relation to All-Cause and Cardiovascular Mortality: A Systematic Review and Meta-analysis of Prospective Observational Studies

Elham Sharifi-Zahabi, Fatemeh Hajizadeh Sharafabad, Hadi Abdollahzad, Mahsa Malekahmadi, Nadya Bahari Rad

doi : 10.1093/advances/nmab072

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2157–2171

Advanced glycation end products (AGEs) are involved in the development of several age-related complications. The protective role of soluble receptors for AGEs (sRAGE) against deleterious effects of AGEs has been indicated in several studies. However, findings on the association of AGEs or sRAGE with mortality are equivocal. In this meta-analysis we aimed to present a quantitative estimation of the association between circulating AGEs or sRAGE and all-cause or cardiovascular disease (CVD) mortality. A comprehensive literature search was performed to determine relevant publications through the online databases including PubMed, Scopus, and Web of Science up to 29 November 2020. Prospective observational studies assessing the association between circulating AGEs or sRAGE and all-cause or CVD mortality were included. Seven studies with a total of 3718 participants and 733 mortality cases (345 CVD deaths) were included in the meta-analysis for assessing the association between circulating AGEs and mortality. Our results showed that higher circulating AGEs were associated with increased risk of all-cause (pooled effect measure: 1.05; 95% CI: 1.01, 1.09; P = 0.018, I2 = 77.7%) and CVD mortality (pooled effect measure: 1.08; 95% CI: 1.01, 1.14; P = 0.015, I2 = 80.2%), respectively. The association between sRAGE and mortality was assessed in 14 studies with a total of 16,335 participants and 2844 mortality cases (419 CVD deaths). Serum concentrations of sRAGE were not associated with the risk of all-cause mortality (pooled effect measure: 1.01; 95% CI: 1.00, 1.01; P = 0.205, I2 = 75.5%), whereas there was a significant link between sRAGE and the risk of CVD mortality (pooled effect measure: 1.02; 95% CI: 1.00, 1.04; P = 0.02, I2 = 78.9%). Our findings showed that a higher serum AGE concentration was associated with increased risk of all-cause and CVD mortality. In addition, higher circulating sRAGE was related to increased risk of CVD mortality. This review was registered at PROSPERO as CRD42021236559.

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Contribution of Biotransformations Carried Out by the Microbiota, Drug-Metabolizing Enzymes, and Transport Proteins to the Biological Activities of Phytochemicals Found in the Diet

Anna Boronat, Jose Rodriguez-Morató, Gabriele Serreli, Montserrat Fitó, Rachel F Tyndale, Monica Deiana, Rafael de la Torre

doi : 10.1093/advances/nmab085

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2172–2189

The consumption of dietary phytochemicals has been associated with several health benefits and relevant biological activities. It is postulated that biotransformations of these compounds regulated by the microbiota, Phase I/II reactions, transport proteins, and deconjugating enzymes contribute not only to their metabolic clearance but also, in some cases, to their bioactivation. A number of factors (age, genetics, sex, physiopathological conditions, and the interplay with other dietary phytochemicals) modulating metabolic activities are important sources and contributors to the interindividual variability observed in clinical studies evaluating the biological activities of phytochemicals. In this review, we discuss all the processes that can affect the bioaccessibility and beneficial effects of these bioactive compounds. Herein, we argue that the role of these factors must be further studied to correctly understand and predict the effects observed following the intake of phytochemicals. This is, in particular, with regard to in vitro investigations, which have shown great inconsistency with preclinical and clinical studies. The complexity of in vivo metabolic activity and biotransformation should therefore be considered in the interpretation of results in vitro and their translation to human physiopathology.

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Fueling Gut Microbes: A Review of the Interaction between Diet, Exercise, and the Gut Microbiota in Athletes 

Riley L Hughes, Hannah D Holscher

doi : 10.1093/advances/nmab077

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2190–2215

The athlete's goal is to optimize their performance. Towards this end, nutrition has been used to improve the health of athletes’ brains, bones, muscles, and cardiovascular system. However, recent research suggests that the gut and its resident microbiota may also play a role in athlete health and performance. Therefore, athletes should consider dietary strategies in the context of their potential effects on the gut microbiota, including the impact of sports-centric dietary strategies (e.g., protein supplements, carbohydrate loading) on the gut microbiota as well as the effects of gut-centric dietary strategies (e.g., probiotics, prebiotics) on performance. This review provides an overview of the interaction between diet, exercise, and the gut microbiota, focusing on dietary strategies that may impact both the gut microbiota and athletic performance. Current evidence suggests that the gut microbiota could, in theory, contribute to the effects of dietary intake on athletic performance by influencing microbial metabolite production, gastrointestinal physiology, and immune modulation. Common dietary strategies such as high protein and simple carbohydrate intake, low fiber intake, and food avoidance may adversely impact the gut microbiota and, in turn, performance. Conversely, intake of adequate dietary fiber, a variety of protein sources, and emphasis on unsaturated fats, especially omega-3 (?-3) fatty acids, in addition to consumption of prebiotics, probiotics, and synbiotics, have shown promising results in optimizing athlete health and performance. Ultimately, while this is an emerging and promising area of research, more studies are needed that incorporate, control, and manipulate all 3 of these elements (i.e., diet, exercise, and gut microbiome) to provide recommendations for athletes on how to “fuel their microbes.”

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Effect of Carnosine or ?-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis 

Joseph J Matthews, Eimear Dolan, Paul A Swinton, Lívia Santos, Guilherme G Artioli, Mark D Turner, Kirsty J Elliott-Sale, Craig Sale

doi : 10.1093/advances/nmab087

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2216–2231

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor ?-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or ?-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of ?-cell function (HOMA-?) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random-effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-?, and HOMA-IR). The model provides evidence that supplementation decreases fasting glucose [humans: mean difference (MD)0.5 = –0.95 mmol · L–1 (90% CrI: –2.1, 0.08); rodent: MD0.5 = –2.26 mmol · L–1 (90% CrI: –4.03, –0.44)], HbA1c [humans: MD0.5 = –0.91% (90% CrI: –1.46, –0.39); rodents: MD0.5 = –1.05% (90% CrI: –1.64, –0.52)], HOMA-IR [humans: standardized mean difference (SMD)0.5 = –0.41 (90% CrI: –0.82, –0.07); rodents: SMD0.5 = –0.63 (90% CrI: –1.98, 0.65)], and fasting insulin [humans: SMD0.5 = –0.41 (90% CrI: –0.77, –0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or ?-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. This review was registered at PROSPERO as CRD42020191588.

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Signaling Targets Related to Antiobesity Effects of Capsaicin: A Scoping Review

Danielle L Ávila, Núbia A M Nunes, Paulo H R F Almeida, Juliana A S Gomes, Carla O B Rosa, Jacqueline I Alvarez-Leite

doi : 10.1093/advances/nmab064

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2232–2243

The search for new antiobesogenic agents is increasing because of the current obesity pandemic. Capsaicin (Caps), an exogenous agonist of the vanilloid receptor of transient potential type 1 (TRPV1), has shown promising results in the treatment of obesity. This scoping review aims to verify the pathways mediating the effects of Caps in obesity and the different methods adopted to identify these pathways. The search was carried out using data from the EMBASE, MEDLINE (PubMed), Web of Science, and SCOPUS databases. Studies considered eligible evaluated the mechanisms of action of Caps in obesity models or cell types involved in obesity. Nine studies were included and 100% (n = 6) of the in vivo studies showed a high risk of bias. Of the 9 studies, 66.6% (n = 6) administered Caps orally in the diet and 55.5% (n = 5) used a concentration of Caps of 0.01% in the diet. In vitro, the most tested concentration was 1 ?M (88.9%; n = 8). Capsazepine was the antagonist chosen by 66.6% (n = 6) of the studies. Seven studies (77.8%) linked the antiobesogenic effects of Caps to TRPV1 activation and 3 (33.3%) indicated peroxisome proliferator-activated receptor (PPAR) involvement as an upstream connection to TRPV1, rather than a direct metabolic target of Caps. The main secondary effects of Caps were lower weight gain (33.3%; n = 3) or loss (22.2%; n = 2), greater improvement in lipid profile (33.3%; n = 3), lower white adipocyte adipogenesis (33.3%; n = 3), browning process activation (44.4%; n = 4), and higher brown adipocyte activity (33.3%; n = 3) compared with those of the control treatment. Some studies have shown that PPAR agonists modulate TRPV1 activity, and no study has evaluated the simultaneous antagonism of these 2 receptors. Consequently, further studies are necessary to elucidate the role of each of these signaling molecules in the antiobesogenic effects of Caps.

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The Effect of Lutein/Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis 

Lisa M Wilson, Saraniya Tharmarajah, Yuanxi Jia, Richard D Semba, Debra A Schaumberg, Karen A Robinson

doi : 10.1093/advances/nmab071

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2244–2254

Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating <5 mg/d of total lutein/zeaxanthin intake which primarily assessed dietary interventions for 3–6 mo (pooled mean difference, 0.02; 95% CI: –0.01 to 0.05). The pooled mean increase in MPOD was 0.04 units (95% CI: 0.02 to 0.07) among studies evaluating 5 to <20 mg/d of lutein/zeaxanthin and was 0.11 units (95% CI: 0.06 to 0.16) among studies evaluating ?20 mg/d of lutein/zeaxanthin for 3–12 mo. MPOD increased with lutein/zeaxanthin intake, particularly at higher doses, among adults with healthy eyes. The effects of lutein/zeaxanthin intake at doses <5 mg/d or from dietary sources is less clear. Increased lutein/zeaxanthin intake can help with maintaining ocular health. Future research is needed to determine the minimum dose and duration of lutein/zeaxanthin intake that is associated with a clinically important change in MPOD or visual function.

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Vitamin D Receptor Gene Polymorphisms and Risk of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Nanyang Liu, Tingting Zhang, Lina Ma, Wei Wei, Zehui Li, Xuefan Jiang, Jiahui Sun, Hui Pei, Hao Li

doi : 10.1093/advances/nmab074

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2255–2264

The results from epidemiologic studies suggest that vitamin D receptor (VDR) gene polymorphisms are potentially associated with Alzheimer disease (AD) and mild cognitive impairment (MCI), but this association has yet to be confirmed. Here, we conducted a meta-analysis based on a larger sample size to clarify the contribution of VDR gene polymorphisms to MCI and AD susceptibility. The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were searched to obtain studies published before 30 October, 2020. The case group includes MCI and AD patients, and the matched controls were without any cognitive complaints. ORs and 95% CIs were used to assess the strength of the association. Ten case–control studies with 3573 participants and 4 loci of ApaI rs7975232, BsmI rs1544410, FokI rs10735810, and TaqI rs731236 were included in the meta-analysis. The global assessment indicated an association between the BsmI polymorphism and increased odds of MCI in the allelic model (b compared with B; OR: 1.77; 95% CI: 1.24, 2.54), the dominant model (bb + Bb compared with BB; OR: 2.04; 95% CI: 1.32, 3.16), and the heterozygote model (Bb compared with BB; OR: 1.97; 95% CI: 1.26, 3.09). In contrast, the ApaI polymorphism was protective against MCI in all models. The dominant model (tt + Tt compared with TT; OR: 1.44; 95% CI: 1.17, 1.79) and the homozygous model (tt compared with TT; OR: 1.43; 95% CI: 1.02, 2.00) revealed an association between the TaqI polymorphism of the VDR gene and increased odds of AD, particularly for Caucasian subjects. Egger's linear regression test found no publication bias. This meta-analysis indicated that VDR ApaI and BsmI, and TaqI gene polymorphisms may be important predictors of MCI and AD, respectively, with population discrepancies. More research is needed to further confirm these associations, especially considering gene–gene interactions, gene–environment interactions, and other confounding factors.

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Dietary Approaches to Improve Efficacy and Control Side Effects of Levodopa Therapy in Parkinson's Disease: A Systematic Review 

Jikke T Boelens Keun, Ilse Ac Arnoldussen, Chris Vriend, Ondine van de Rest

doi : 10.1093/advances/nmab060

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2265–2287

Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise unpredictable motor fluctuations and other complications. Counteracting these complications with other pharmacological therapies may prompt a vicious circle of side effects, and here, nutritional therapy may have great potential. Knowledge about the role of diet in PD is emerging and multiple studies have investigated nutritional support specifically with respect to levodopa therapy. With this systematic review, we aim to give a comprehensive overview of dietary approaches to optimize levodopa treatment in PD. A systematic search was performed using the databases of PubMed and Scopus between January 1985 and September 2020. Nutritional interventions with the rationale to optimize levodopa therapy in human PD patients were eligible for this study and their quality was assessed with the Cochrane risk-of-bias tool. In total, we included 22 papers that addressed the effects of dietary proteins (n = 10), vitamins (n = 7), fiber (n = 2), soybeans (n = 1), caffeine (n = 1), and ketogenic diets (n = 1) on levodopa therapy. Interventions with protein redistribution diets (PRDs), dietary fiber, vitamin C, and caffeine improved levodopa absorption, thereby enhancing clinical response and reducing motor fluctuations. Furthermore, supplementation of vitamin B-12, vitamin B-6, and folic acid successfully reduced high homocysteine concentrations that emerged from levodopa metabolism and promoted many metabolic and clinical complications, such as neuropathology and osteoporosis. In conclusion, dietary interventions have the potential to optimize levodopa efficacy and control side effects. Nutrition that improves levodopa absorption, including PRDs, fiber, vitamin C, and caffeine, is specifically recommended when fluctuating clinical responses appear. Supplements of vitamin B-12, vitamin B-6, and folic acid are advised along with levodopa initiation to attenuate hyperhomocysteinemia, and importantly, their potential to treat consequent metabolic and clinical complications warrants future research.

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Index-Based Dietary Patterns and Inflammatory Bowel Disease: A Systematic Review of Observational Studies

Zhenyi Tian, Xiaojun Zhuang, Min Zhao, Shuyu Zhuo, Xiaozhi Li, Ruiqi Ma, Na Li, Caiguang Liu, Yijun Zhu, Ce Tang,Rui Feng, Minhu Chen

doi : 10.1093/advances/nmab069

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2288–2300

Diet is one of the most critical factors for inflammatory bowel disease (IBD). A whole dietary pattern should be considered when doing nutrient-based research to preserve the potential for synergism between nutrients. Dietary indices are important tools to evaluate diet quality, and we investigated the associations of it with IBD. Fourteen studies on the relation between index-based dietary patterns and IBD were included. 6 studies showed the relation between index-based dietary patterns and IBD risk, 7 studies explored the dietary indices and progression of IBD, and 1 study investigated the relationship between index and all-cause mortality in IBD patients. These results implied that a high score on the Mediterranean diet was negatively associated with risk and progression of IBD. However, a diet with high inflammatory potential could increase risk and aggravate disease activity in IBD. Dietary scores have the potential to evaluate the association between overall diet quality and risk and progression of IBD. Future randomized controlled trials are required to confirm the effect of the change in dietary score.

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The Effects of Natural and Synthetic Blue Dyes on Human Health: A Review of Current Knowledge and Therapeutic Perspectives

Beata Olas, Jacek Bia?ecki, Karina Urba?ska, Magdalena Bry?

doi : 10.1093/advances/nmab081

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2301–2311

Blue synthetic dyes are widely used in many industries. Although they are approved for use as food dyes and in cosmetics and some medicines, their impacts on consumer health remain unknown. Some studies indicate that 2 synthetic dyes, Blue No. 1 and Blue No. 2, may have toxic effects. It has therefore been suggested that these should be replaced with natural dyes; however, despite being nontoxic and arguably healthier than synthetic dyes, these compounds are often unsuitable for use in food or drugs due to their instability. Nevertheless, among the natural blue pigments, anthocyanins and genipin offer particular health benefits, as they are associated with the prevention of cardiovascular disease and have anticancer, neuroprotective, anti-inflammatory, and antidiabetic properties. This review summarizes the effects of blue food and drug colorings on health and proposes that synthetic colors should be replaced with natural ones.

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Opportunities for Adding Undernutrition and Frailty Screening Measures in US National Surveys 

Jaime J Gahche, Mary B Arensberg, Mary Weiler, Johanna T Dwyer

doi : 10.1093/advances/nmab056

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2312–2320

Both undernutrition and frailty adversely affect the health and functional outcomes of the older adult population. Timely and accurate national data are necessary to assess those at risk of these debilitating but often preventable conditions, to correct them and support healthy aging. The objective was to identify relevant measures in undernutrition and frailty screening tools and determine if these measures are collected in recent protocols for US national surveys sampling older adults and which measures could be added to be able to better assess risk of undernutrition and frailty. Commonly used undernutrition and frailty screening tools were evaluated to identify measures that were unique or common to both. US national surveys were examined to determine whether they included older adults in their survey sample, collected health measures from participants, in what form, and whether they were functional indexes or survey questions. A comparative analysis of survey protocols was performed to determine which surveys collected data related to the measures of undernutrition and frailty. Of the 8 national surveys, only 3 provided ?1 physical measurement (i.e., height/weight, grip strength, balance). Most surveys included self-reported data on height/weight, physical functioning/mobility, disability, and psychological components. Whereas 6 included questions on food security/food program participation, only 1 collected data on dietary intake. Currently national surveys include only limited health measures that can be used to identify undernutrition and frailty risk in older adults. Adding a few simple screening measures already included in popular screening tools, such as grip strength, unintentional weight loss, and loss of appetite, to national surveys which monitor older Americans would facilitate estimation of the prevalence of undernutrition and frailty risk, better estimate those at risk, provide an opportunity to set national goals to reduce their risk, and help implement strategies for improved health outcomes.

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A Systematic Review and Meta-Analysis of Validation Studies Performed on Dietary Record Apps 

Liangzi Zhang, Andreja Misir, Hendriek Boshuizen, Marga Ocké

doi : 10.1093/advances/nmab058

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2321–2332

Mobile dietary record apps have been increasingly validated by studies with various study designs. This review aims to evaluate the overall accuracy of dietary record apps in measuring the intake of energy, macro- and micronutrients, and food groups in real-life settings and the designs of validation studies. We systematically searched mobile dietary record validation studies published during the period from 2013 to 2019. We identified 14 studies for the systematic review, of which 11 studies were suitable for meta-analyses on energy intake and 8 studies on macronutrient intake. Mean differences and SDs of nutrient estimations between the app and the reference method from studies were pooled using a random-effects model. All apps underestimated energy intake when compared with their reference methods, with a pooled effect of ?202 kcal/d (95% CI: ?319, ?85 kcal/d); the heterogeneity of studies was 72%. After stratification, studies that used the same food-composition table for both the app and the reference method had a lower level of heterogeneity (0%) and a pooled effect of ?57 kcal/d (95% CI: ?116, 2 kcal/d). The heterogeneity of studies in the differences in carbohydrate, fat, and protein intake was 54%, 73%, and 80%, with the pooled effect of ?18.8 g/d, ?12.7 g/d, and ?12.2 g/d, respectively, after excluding outliers. The intakes of micronutrients and food groups were statistically nonsignificantly underestimated by the apps in most cases. In conclusion, dietary record apps underestimated food consumption compared with traditional dietary assessment methods. Moreover, varying study designs have been found across studies. Recommended practices for conducting validation studies were formulated including considering biomarkers as the reference, testing in a larger and more representative study population for a longer period, avoiding the learning effect of each method, and comparing food group or food item consumption in addition to comparing energy and nutrient intakes.

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Nutritional Metabolomics and the Classification of Dietary Biomarker Candidates: A Critical Review

Talha Rafiq, Sandi M Azab, Koon K Teo, Lehana Thabane, Sonia S Anand, Katherine M Morrison, Russell J de Souza, Philip Britz-McKibbin

doi : 10.1093/advances/nmab054

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2333–2357

Recent advances in metabolomics allow for more objective assessment of contemporary food exposures, which have been proposed as an alternative or complement to self-reporting of food intake. However, the quality of evidence supporting the utility of dietary biomarkers as valid measures of habitual intake of foods or complex dietary patterns in diverse populations has not been systematically evaluated. We reviewed nutritional metabolomics studies reporting metabolites associated with specific foods or food groups; evaluated the interstudy repeatability of dietary biomarker candidates; and reported study design, metabolomic approach, analytical technique(s), and type of biofluid analyzed. A comprehensive literature search of 5 databases (PubMed, EMBASE, Web of Science, BIOSIS, and CINAHL) was conducted from inception through December 2020. This review included 244 studies, 169 (69%) of which were interventional studies (9 of these were replicated in free-living participants) and 151 (62%) of which measured the metabolomic profile of serum and/or plasma. Food-based metabolites identified in ?1 study and/or biofluid were associated with 11 food-specific categories or dietary patterns: 1) fruits; 2) vegetables; 3) high-fiber foods (grain-rich); 4) meats; 5) seafood; 6) pulses, legumes, and nuts; 7) alcohol; 8) caffeinated beverages, teas, and cocoas; 9) dairy and soya; 10) sweet and sugary foods; and 11) complex dietary patterns and other foods. We conclude that 69 metabolites represent good candidate biomarkers of food intake. Quantitative measurement of these metabolites will advance our understanding of the relation between diet and chronic disease risk and support evidence-based dietary guidelines for global health.

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Finding the Sweet Spot: Measurement, Modification, and Application of Sweet Hedonics in Humans 

Eunjin Cheon, Evan J Reister, Stephanie R Hunter, Richard D Mattes

doi : 10.1093/advances/nmab055

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2358–2371

Sweetness is a sensation that contributes to the palatability of foods, which is the primary driver of food choice. Thus, understanding how to measure the appeal (hedonics) of sweetness and how to modify it are key to effecting dietary change for health. Sweet hedonics is multidimensional so can only be captured by multiple approaches including assessment of elements such as liking, preference, and consumption intent. There are both innate and learned components to the appeal of sweet foods and beverages. These are responsive to various behavioral and biological factors, suggesting the opportunity to modify intake. Given the high amount of added sugar intake in the United States and recommendations from many groups to reduce this, further exploration of current hypothesized approaches to moderate sugar intake (e.g., induced hedonic shift, use of low-calorie sweeteners) is warranted.

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Female Fertility and the Nutritional Approach: The Most Essential Aspects 

Kinga Skoracka, Alicja Ewa Ratajczak, Anna Maria Rychter, Agnieszka Dobrowolska, Iwona Krela-Ka?mierczak

doi : 10.1093/advances/nmab068

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2372–2386

Infertility is an increasing problem that affects couples attempting pregnancy. A growing body of evidence points to a link between diet and female fertility. In fact, data show that a diet high in trans fats, refined carbohydrates, and added sugars can negatively affect fertility. Conversely, a diet based on the Mediterranean dietary patterns, i.e., rich in dietary fiber, omega-3 (?-3) fatty acids, plant-based protein, and vitamins and minerals, has a positive impact on female fertility. An unhealthy diet can disrupt microbiota composition, and it is worth investigating whether the composition of the gut microbiota correlates with the frequency of infertility. There is a lack of evidence to exclude gluten from the diet of every woman trying to become pregnant in the absence of celiac disease. Furthermore, there are no data concerning adverse effects of alcohol on female fertility, and caffeine consumption in the recommended amounts also does not seem to affect fertility. On the other hand, phytoestrogens presumably have a positive influence on female fertility. Nevertheless, there are many unanswered questions with regard to supplementation in order to enhance fertility. It has been established that women of childbearing age should supplement folic acid. Moreover, most people experience vitamin D and iodine deficiency; thus, it is vital to control their blood concentrations and consider supplementation if necessary. Therefore, since diet and lifestyle seem to be significant factors influencing fertility, it is valid to expand knowledge in this area.

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Maternal Dietary Patterns and Pregnancy Hypertension in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

Mai-Lei Woo Kinshella, Shazmeen Omar, Kerri Scherbinsky, Marianne Vidler, Laura A Magee, Peter von Dadelszen, Sophie E Moore, Rajavel Elango

doi : 10.1093/advances/nmab057

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2387–2400

Healthy maternal diets can lower the odds of developing pre-eclampsia, a direct and second leading cause of maternal death, globally. However, there is a research gap in low- and middle-income countries (LMIC), which bear a disproportionate burden of these deaths. The objectives of this systematic review were to: 1) evaluate the association between dietary patterns in pregnancy and hypertensive disorders, including pre-eclampsia for pregnant and postpartum women in LMIC, and 2) compile barriers and facilitators to an adequate maternal diet. A systematic search was performed on MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health, Web of Science, Cochrane Central Register of Controlled Trials, African Journals Online, the WHO Regional Databases, 2 trial registries, Google Scholar, and reference lists. Included in the analysis were primary research studies of dietary patterns during pregnancy, with pregnancy hypertension outcome(s), and conducted in LMIC. Included studies were assessed using ROBINS-I risk of bias. Thirteen studies were included, of which 5 studies were included in a meta-analysis (Review Manager 5). Lower odds of pre-eclampsia were associated with adequate (compared with no or low) consumption of vegetables (OR: 0.38; 95% CI: 0.18, 0.80; I2 = 85%; P = 0.01) and adequate (compared with no or low) consumption of fruit (OR: 0.42; 95% CI: 0.24, 0.71; I2 = 79%; P = 0.008). No firm conclusions could be drawn about the impact on pre-eclampsia odds of any of the following during pregnancy: high consumption of meat or grains; a “Western” diet; or alcohol consumption. More LMIC-based research is needed to explore whether the apparent beneficial effects of fruits and vegetables on pre-eclampsia incidence might be enhanced when maternal malnutrition is prevalent, and/or whether other sociodemographic factors might contribute.

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Review of Existing Models to Predict Reductions in Neural Tube Defects Due to Folic Acid Fortification and Model Results Using Data from Cameroon 

Hanqi Luo, Kenneth H Brown, Christine P Stewart, Laurel A Beckett, Adrienne Clermont, Stephen A Vosti, Jules M Guintang Assiene, Reina Engle-Stone

doi : 10.1093/advances/nmab083

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2401–2414

Several models have been developed to predict the effects of folic acid fortification programs on prevention of neural tube defects (NTDs), but each relies on different assumptions and data inputs. We identified and reviewed 7 models that predict the effects of folic acid intake or status on NTD risk. We applied 4 of these models [the original and a modified version of the Lives Saved Tool (LiST) and models developed by Arth et al. and Wald et al.] to predict the effect of folic acid fortification of wheat flour on reduction of NTDs using national survey data from Cameroon. The estimated percentage of NTDs averted due to fortified wheat flour (5.0 ?g folic acid/g flour) varied by predictive model, with a 21–31% reduction in LiST to 83% in Arth's model, and 15% in Wald's model. As the simulated fortification level was increased from 1.0 to 7.0 ?g folic acid/g flour, the pattern of change in estimated numbers of NTDs averted differed due to different model assumptions: the number of NTDs averted increased and then reached a plateau in the modified LiST model (as would be expected in real-world conditions), increased sharply in Arth's model, and increased continuously in Wald's model. This wide variation in predicted effects, and implausible results in some cases, undermines the models’ utility for users of model outputs. Concurrent collection of dietary and biomarker data, including plasma and RBC folate concentrations, and NTD outcomes, is necessary to validate these models and monitor change in folic acid intake, folate-related biomarkers, and reduced NTD risk due to fortification. In the meantime, models based on erythrocyte folate concentration are recommended, based on biological plausibility and consistency with empirical evidence. Where erythrocyte folate data are unavailable, sensitivity analyses (using several models) could be conducted to examine the range of possible outcomes.

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Placental Angiogenesis in Mammals: A Review of the Regulatory Effects of Signaling Pathways and Functional Nutrients

Zihao Huang, Shuangbo Huang, Tongxing Song, Yulong Yin, Chengquan Tan

doi : 10.1093/advances/nmab070

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2415–2434

Normal placental development and proper angiogenesis are essential for fetal growth during pregnancy. Angiogenesis involves the regulatory action of many angiogenic factors and a series of signal transduction processes inside and outside the cell. The obstruction of placental angiogenesis causes fetal growth restriction and serious pregnancy complications, even leading to fetal loss and pregnancy cessation. In this review, the effects of placental angiogenesis on fetal development are described, and several signaling pathways related to placental angiogenesis and their key regulatory mediators are summarized. These factors, which include vascular endothelial growth factor (VEGF)-VEGF receptor, delta-like ligand 4 (DLL-4)-Notch, Wnt, and Hedgehog, may affect the placental angiogenesis process. Moreover, the degree of vascularization depends on cell proliferation, migration, and differentiation, which is affected by the synthesis and secretion of metabolites or intermediates and mutual coordination or inhibition in these pathways. Furthermore, we discuss recent advances regarding the role of functional nutrients (including amino acids and fatty acids) in regulating placental angiogenesis. Understanding the specific mechanism of placental angiogenesis and its influence on fetal development may facilitate the establishment of new therapeutic strategies for the treatment of preterm birth, pre-eclampsia, or intrauterine growth restriction, and provide a theoretical basis for formulating nutritional regulation strategies during pregnancy.

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Methodological Aspects of Diet Quality Indicators in Childhood: A Mapping Review

Ángela Hernández-Ruiz, Liza Alejandra Díaz-Jereda, Casandra Madrigal, María José Soto-Méndez, Anneleen Kuijsten, Ángel Gil

doi : 10.1093/advances/nmab053

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2435–2494

Diet quality indicators (DQIns) are tools that aim to assess an individual's overall diet quality. Previous reviews focused mainly on health-related outcomes but did not provide detailed information about components, assessment variables, or important methodological issues for the development and application of DQIns in the pediatric age. The current mapping review aims to provide comprehensive guidance regarding DQIns developed through a priori methodology in children aged ?14 y that have been applied worldwide. A mapping review was conducted, whereby 1665 original articles describing the development, modifications, and updates of DQIns, published up to June 26, 2020, in English and Spanish, were retrieved. A total of 139 articles were identified and classified into 13 subgroups. There were 10 overall DQIns: Healthy Eating Indexes (n = 25), Dietary Diversity Scores (n = 20), Diet Quality Indexes (n = 16), Food Variety Scores (n = 11), Healthy and Unhealthy Scores (n = 11), Feeding and Eating Indexes (n = 10), Diet Quality Scores (n = 5), Nutritional Adequacy and Micronutrients Indexes (n = 5), Dietary Guidelines Indexes (n = 5), and Other Healthy Diet Indexes (n = 13). Three additional subgroups of dietary and lifestyle indicators found were Mediterranean Diet Indexes (n = 10), Diet–Lifestyle Indexes (n = 5), and Breakfast Quality Indexes (n = 3). This compilation of DQIns will help researchers select the most appropriate tool for future epidemiological studies by considering a careful selection of information about the assessment components, scoring methods, and key methodological issues. The main limitations of this review are that, due to its nature, a risk-of-bias assessment was not performed and the article screening was completed in 2 databases (PubMed/MEDLINE and Scopus). More research is needed to identify health-related outcomes associated with DQIns in the pediatric population, using clearer and more standardized methodological criteria.

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Do Healthy Dietary Interventions Improve Pediatric Depressive Symptoms? A Systematic Review and Meta-Analysis

Susan C Campisi, Clare Zasowski, Shailja Shah, Glyneva Bradley-Ridout, Sheri Madigan, Peter Szatmari, Daphne J Korczak

doi : 10.1093/advances/nmab088

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2495–2507

Dietary recommendations have been proposed as a way of impacting current and future mental health. There exists a limited body of conflicting literature related to pediatric nutritional interventions and depression. This meta-analysis aims to determine the efficacy of child and adolescent dietary interventions on depression. Systematic searches in electronic databases and gray literature were conducted. After screening 6725 citations, 17 studies were included in this systematic review. Quality assessment was performed using the Cochrane risk-of-bias tool and the Joanna Briggs Institute Critical Appraisal Tool for Quasi-Experimental Studies. A meta-analysis of Hedges g values was calculated using the Hartung–Knapp–Sidik–Jonkman method. Publication bias was assessed with funnel plots and the Egger test. The results of the meta-analysis of the RCTs (k = 7) demonstrated a nonsignificant effect of dietary intervention (g = 0.05; 95% CI: –0.25, 0.35; P = 0.70) whereas the results of the pre-post intervention studies (k = 9) demonstrated a significant small-to-medium effect favoring dietary intervention for reducing depression (g = –0.45; 95% CI: –0.64, –0.27; P = 0.001). Publication bias was not detected by the Egger test or by funnel plot asymmetry. The current meta-analysis demonstrates that “healthy” dietary interventions for children or adolescents in the community have little impact on nonclinical depression. Confusion will persist until better-designed studies in pediatric nutritional psychiatry research focusing on adolescents with depressive illness are conducted.

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A Scoping Review and Assessing the Evidence for Nutrition Education Delivery Strategies for Refugees in High-Income Countries

Habiba A Nur, Abiodun T Atoloye, Heidi Wengreen, Martha Archuleta, Mateja R Savoie-Roskos, Celina Wille, Melanie Jewkes

doi : 10.1093/advances/nmab080

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2508–2524

Upon resettlement, refugees face many challenges, including limited knowledge of available food and food insecurity, that increase their risks of diet-related diseases. Nutrition education may help them better navigate the challenges of their new food environments and help them live healthier lives. This review assesses the evidence on nutrition education delivery strategies and outcomes among refugees in the United States and other high-income countries using Levac review guidelines. Multiple electronic databases were searched using combinations of the following terms: nutrition, food, cooking, or gardening; education, workshop, curriculum, class, literacy, or program; and refugee. The quality of the peer-reviewed papers was assessed using the Medical Education Research Study Quality Instrument (MERSQI) scoring method. A total of 1930 studies were identified, and 17 met the inclusion criteria. The mean MERSQI score of the peer-reviewed studies was 9.02 (SD, 3.3; range, 1–14). The key nutrition education delivery strategies included conducting a needs assessment and providing client-centered education, a collaborative approach in program design, and hands-on activities such as cooking and store visits. A refugee's literacy level, cultural, and language barriers are common challenges to nutrition education delivery. Because there is limited evidence regarding the efficacy of programs regarding changes in refugees’ nutrition knowledge and diet-related behaviors, future research should include rigorously designed studies and the development and implementation of standardized assessment and training tools. The adoption of a context-specific and flexible model is important for effective nutrition education delivery among the refugee population.

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Water Security and Nutrition: Current Knowledge and Research Opportunities 

Joshua D Miller, Cassandra L Workman, Sarita V Panchang, Gretchen Sneegas, Ellis A Adams, Sera L Young, Amanda L Thompson

doi : 10.1093/advances/nmab075

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2525–2539

Water is an essential nutrient that has primarily been considered in terms of its physiological necessity. But reliable access to water in sufficient quantities and quality is also critical for many nutrition-related behaviors and activities, including growing and cooking diverse foods. Given growing challenges to water availability and safety, including climate change, pollution, and infrastructure degradation, a broader conceptualization of water and its diverse uses is needed to sustainably achieve global nutrition targets. Therefore, we review empirical and qualitative evidence describing the linkages between water security (the reliable availability, accessibility, and quality of water for all household uses) and nutrition. Primary linkages include water security for drinking, food production and preparation, infant and young child feeding, and limiting exposure to pathogens and environmental toxins. We then identify knowledge gaps within each linkage and propose a research agenda for studying water security and nutrition going forward, including the concurrent quantification of both food and water availability, accessibility, use, and stability. By making explicit the connections between water security and nutritional well-being, we aim to promote greater collaboration between the nutrition and water, sanitation, and hygiene sectors. Interdisciplinary policies and programs that holistically address the water–nutrition nexus, versus those that focus on water and nutrition independently, are likely to significantly advance our ability to ensure equitable access to healthy foods and safe water for all.

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Protein- and Calcium-Mediated GLP-1 Secretion: A Narrative Review 

Jonathan D Watkins, Françoise Koumanov, Javier T Gonzalez

doi : 10.1093/advances/nmab078

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2540–2552

Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced in the intestine that is secreted in response to nutrient exposure. GLP-1 potentiates glucose-dependent insulin secretion from the pancreatic ? cells and promotes satiety. These important actions on glucose metabolism and appetite have led to widespread interest in GLP-1 receptor agonism. Typically, this involves pharmacological GLP-1 mimetics or targeted inhibition of dipeptidyl peptidase-IV, the enzyme responsible for GLP-1 degradation. However, nutritional strategies provide a widely available, cost-effective alternative to pharmacological strategies for enhancing hormone release. Recent advances in nutritional research have implicated the combined ingestion of protein and calcium with enhanced endogenous GLP-1 release, which is likely due to activation of receptors with high affinity and/or sensitivity for amino acids and calcium. Specifically targeting these receptors could enhance gut hormone secretion, thus providing a new therapeutic option. This narrative review provides an overview of the latest research on protein- and calcium-mediated GLP-1 release with an emphasis on human data, and a perspective on potential mechanisms that link potent GLP-1 release to the co-ingestion of protein and calcium. In light of these recent findings, potential future research directions are also presented.

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Dietary Fiber

Nancy D Turner, Joanne R Lupton

doi : 10.1093/advances/nmab116

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2553–2555

Dietary fiber is derived from plant material and is composed of complex, nonstarch carbohydrates and lignin. Dietary fiber is not digestible within the small intestine because mammals do not produce enzymes capable of hydrolyzing the polymers into their constituent monomers. As a result, these compounds make it to the colon intact, where they are available for fermentation by the resident microbiota. Dietary fiber is considered to contribute no calories to our diet, yet the metabolites released by the bacteria in the colon are used by humans and other mammals to meet their energy requirements. Variability among the microbiota present in the intestines influences the host's ability to acquire and utilize this source of energy, which precludes assigning a caloric value to dietary fiber. In contrast, ruminants (e.g., cattle) acquire much of their energy requirements from indigestible plant fibers because they have microbiota in their rumen (a forestomach) that can hydrolyze...

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Call for Emergency Action to Limit Global Temperature Increases, Restore Biodiversity, and Protect Health: Wealthy nations must do much more, much faster* 

Laurie Laybourn-Langton, Richard Smith

doi : 10.1093/advances/nmab098

Advances in Nutrition, Volume 12, Issue 6, November 2021, Pages 2556–2558

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