Advances in Nutrition: An International Review Journal current issue

Food Groups and Risk of Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies

The aim of this systematic review and meta-analysis was to summarize the evidence on the relation of the intakes of 12 major food groups, including whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSBs) with the risk of hypertension. PubMed, Scopus, and Web of Science were searched systematically until June 2017 for prospective studies having quantitatively investigated the above-mentioned foods. We conducted meta-analysis on the highest compared with the lowest intake categories and linear and nonlinear dose-response meta-analyses to analyze the association. Summary RRs and 95% CIs were estimated by using a random-effects model. Overall, 28 reports were included in the meta-analysis. An inverse association for the risk of hypertension was observed for 30 g whole grains/d (RR: 0.92; 95% CI: 0.87, 0.98), 100 g fruits/d (RR: 0.97; 95% CI: 0.96, 0.99), 28 g nuts/d (RR: 0.70; 95% CI: 0.45, 1.08), and 200 g dairy/d (RR: 0.95; 95% CI: 0.94, 0.97), whereas a positive association for 100 g red meat/d (RR: 1.14; 95% CI: 1.02, 1.28), 50 g processed meat/d (RR: 1.12; 95% CI: 1.00, 1.26), and 250 mL SSB/d (RR: 1.07; 95% CI: 1.04, 1.10) was seen in the linear dose-response meta-analysis. Indication for nonlinear relations of the intakes of whole grains, fruits, fish, and processed meats with the risk of hypertension was detected. In summary, this comprehensive dose-response meta-analysis of 28 reports identified optimal intakes of whole grains, fruits, nuts, legumes, dairy, red and processed meats, and SSBs related to the risk of hypertension. These findings need to be seen under the light of very-low to low quality of meta-evidence. However, the findings support the current dietary guidelines in the prevention of hypertension.

Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function

Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging.

Yogurt and Cardiometabolic Diseases: A Critical Review of Potential Mechanisms

Associations between yogurt intake and risk of diet-related cardiometabolic diseases (CMDs) have been the subject of recent research in epidemiologic nutrition. A healthy dietary pattern has been identified as a pillar for the prevention of weight gain and CMDs. Epidemiologic studies suggest that yogurt consumption is linked to healthy dietary patterns, lifestyles, and reduced risk of CMDs, particularly type 2 diabetes. However, to our knowledge, few to no randomized controlled trials have investigated yogurt intake in relation to cardiometabolic clinical outcomes. Furthermore, there has been little attempt to clarify the mechanisms that underlie the potential beneficial effects of yogurt consumption on CMDs. Yogurt is a nutrient-dense dairy food and has been suggested to reduce weight gain and prevent CMDs by contributing to intakes of protein, calcium, bioactive lipids, and several other micronutrients. In addition, fermentation with bacterial strains generates bioactive peptides, resulting in a potentially greater beneficial effect of yogurt on metabolic health than nonfermented dairy products such as milk. To date, there is little concrete evidence that the mechanisms proposed in observational studies to explain positive results of yogurt on CMDs or parameters are valid. Many proposed mechanisms are based on assumptions that commercial yogurts contain strain-specific probiotics, that viable yogurt cultures are present in adequate quantities, and that yogurt provides a minimum threshold dose of nutrients or bioactive components capable of exerting a physiologic effect. Therefore, the primary objective of this review is to investigate the plausibility of potential mechanisms commonly cited in the literature in order to shed light on the inverse associations reported between yogurt intake and various cardiometabolic health parameters that are related to its nutrient profile, bacterial constituents, and food matrix. This article reviews current gaps and challenges in identifying such mechanisms and provides a perspective on the research agenda to validate the proposed role of yogurt in protecting against CMDs.

The Nitrate-Independent Blood Pressure-Lowering Effect of Beetroot Juice: A Systematic Review and Meta-Analysis

Beetroot is considered a complementary treatment for hypertension because of its high content of inorganic NO3. This systematic review and meta-analysis aimed to clarify several aspects of beetroot juice supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP). We searched PubMed, Scopus, and Embase databases, and the reference lists of previous reviews. Randomized clinical trials that investigated the effects of beetroot juice on resting blood pressure in humans were recruited for quality assessment, meta-analyses, subgroup analyses, and meta-regressions; of these, 22 were conducted between 2009 and 2017 and included a total of 47 intervention (n = 650) and 43 control (n = 598) groups. Overall, SBP (–3.55 mm Hg; 95% CI: –4.55, –2.54 mm Hg) and DBP (–1.32 mm Hg; 95% CI: –1.97, –0.68 mm Hg) were significantly lower in the beetroot juice–supplemented groups than in the control groups. The mean difference of SBP was larger between beetroot juice–supplemented and control groups in the longer than in the shorter (≥14 compared with <14 d) study durations (–5.11 compared with –2.67 mm Hg) and the highest compared with the lowest (500 compared with 70 and 140 mL/d) doses of beetroot juice (–4.78 compared with –2.37 mm Hg). A positive correlation was observed between beetroot juice doses and the mean differences of blood pressures. In contrast, a smaller effect size of blood pressures was observed after supplementation with higher NO3 (milligrams per 100 mL beetroot juice). A weak effect size was observed in a meta-analysis of trials that used NO3-depleted beetroot juice as a placebo compared with other interventions (–3.09 compared with –4.51 mm Hg for SBP and –0.81 compared with –2.01 mm Hg for DBP). Our results demonstrate the blood pressure–lowering effects of beetroot juice and highlight its potential NO3-independent effects.

Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N-oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans.

Natural Forms of Vitamin E as Effective Agents for Cancer Prevention and Therapy

Initial research on vitamin E and cancer has focused on α-tocopherol (αT), but recent clinical studies on cancer-preventive effects of αT supplementation have shown disappointing results, which has led to doubts about the role of vitamin E, including different vitamin E forms, in cancer prevention. However, accumulating mechanistic and preclinical animal studies show that other forms of vitamin E, such as -tocopherol (T), -tocopherol (T), -tocotrienol (TE), and -tocotrienol (TE), have far superior cancer-preventive activities than does αT. These vitamin E forms are much stronger than αT in inhibiting multiple cancer-promoting pathways, including cyclo-oxygenase (COX)– and 5-lipoxygenase (5-LOX)–catalyzed eicosanoids, and transcription factors such as nuclear transcription factor B (NF-B) and signal transducer and activator of transcription factor 3 (STAT3). These vitamin E forms, but not αT, cause pro-death or antiproliferation effects in cancer cells via modulating various signaling pathways, including sphingolipid metabolism. Unlike αT, these vitamin E forms are quickly metabolized to various carboxychromanols including 13'-carboxychromanols, which have even stronger anti-inflammatory and anticancer effects than some vitamin precursors. Consistent with mechanistic findings, T, T, TE, and TE, but not αT, have been shown to be effective for preventing the progression of various types of cancer in preclinical animal models. This review focuses on cancer-preventive effects and mechanisms of T, T, TE, and TE in cells and preclinical models and discusses current progress in clinical trials. The existing evidence strongly indicates that these lesser-known vitamin E forms are effective agents for cancer prevention or as adjuvants for improving prevention, therapy, and control of cancer.

Role of MicroRNA Regulation in Obesity-Associated Breast Cancer: Nutritional Perspectives

Breast cancer is the most common malignancy diagnosed in women, and the incidence of breast cancer is increasing every year. Obesity has been identified as one of the major risk factors for breast cancer progression. The mechanisms by which obesity contributes to breast cancer development is not yet understood; however, there are a few mechanisms counted as potential producers of breast cancer in obesity, including insulin resistance, chronic inflammation and inflammatory cytokines, adipokines, and sex hormones. Recent emerging evidence suggests that alterations in microRNA (miRNA) expressions are found in several diseases, including breast cancer and obesity; however, miRNA roles in obesity-linked breast cancer are beginning to unravel. miRNAs are thought to be potential noninvasive biomarkers for diagnosis and prognosis of cancer patients with comorbid conditions of obesity as well as therapeutic targets. Recent studies have evidenced that nutrients and other dietary factors protect against cancer and obesity through modulation of miRNA expressions. Herein, we summarize a comprehensive overview of up-to-date information related to miRNAs and their molecular targets involved in obesity-associated breast cancer. We also address the mechanisms by which dietary factors modulate miRNA expression and its protective roles in obesity-associated breast cancer. It is hoped that this review would provide new therapeutic strategies for the treatment of obesity-associated breast cancer to reduce the burden of breast cancer.

Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors

The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation. In the current review, we will discuss the events that lead to micronucleus formation and centromeric and pericentromeric chromatin instability, as well transcripts emanating from these regions, which were previously thought to be inactive. Studies were selected in PubMed if they reported the effects of nutritional status (macro- and micronutrients) or environmental toxicant exposure on micronucleus frequency or any other chromosomal abnormality in humans, animals, or cell models. Mounting evidence from epidemiologic, environmental, and nutritional studies provides a novel perspective on the origination of aneuploidic events. Although substantial evidence exists describing the role that nutritional status and environmental toxicants have on the generation of micronuclei and other nuclear aberrations, limited information is available to describe the importance of macro- and micronutrients on centromeric and pericentromeric chromatin stability. Moving forward, studies that specifically address the direct link between nutritional status, excess, or deficiency and the epigenetic regulation of the centromere will provide much needed insight into the nutritional and environmental regulation of this chromosomal region and the initiation of aneuploidy.

Energy Metabolism Profile in Individuals with Prader-Willi Syndrome and Implications for Clinical Management: A Systematic Review

Prader-Willi syndrome (PWS) is a rare genetic disorder associated with excessive weight gain. Hyperphagia associated with PWS may result in higher energy intake, but alterations in energy expenditure may also contribute to energy imbalance. The purpose of this critical literature review is to determine the presence of alterations in energy expenditure in individuals with PWS. Ten studies that measured total energy expenditure (TEE), resting energy expenditure (REE), sleep energy expenditure (SEE), activity energy expenditure (AEE), and diet induced thermogenesis (DIT) were included in this review. The studies provided evidence that absolute TEE, REE, SEE, and AEE are lower in individuals with PWS than in age-, sex-, and body mass index–matched individuals without the syndrome. Alterations in lean body mass and lower physical activity amounts appear to be responsible for the lower energy expenditure in PWS rather than metabolic differences. Regardless of the underlying mechanism for lower TEE, the estimation of energy requirements with the use of equations derived for the general population would result in weight gain in individuals with PWS. The determination of energy requirements for weight management in individuals with PWS requires a more comprehensive understanding of energy metabolism. Future studies should aim to comprehensively profile all specific components of energy expenditure in individuals with PWS with the use of appropriately matched controls and gold standard methods to measure energy metabolism and body composition. One component of energy expenditure that is yet to be explored in detail in PWS is DIT. A reduced DIT (despite differences in fat free mass), secondary to hormonal dysregulation, may be present in PWS individuals, leading to a reduced overall energy expenditure. Further research exploring DIT in PWS needs to be conducted. Dietary energy recommendations for weight management in PWS have not yet been clearly established.

Scaling up Dietary Data for Decision-Making in Low-Income Countries: New Technological Frontiers

Dietary surveys in low-income countries (LICs) are hindered by low investment in the necessary research infrastructure, including a lack of basic technology for data collection, links to food composition information, and data processing. The result has been a dearth of dietary data in many LICs because of the high cost and time burden associated with dietary surveys, which are typically carried out by interviewers using pencil and paper. This study reviewed innovative dietary assessment technologies and gauged their suitability to improve the quality and time required to collect dietary data in LICs. Predefined search terms were used to identify technologies from peer-reviewed and gray literature. A total of 78 technologies were identified and grouped into 6 categories: 1) computer- and tablet-based, 2) mobile-based, 3) camera-enabled, 4) scale-based, 5) wearable, and 6) handheld spectrometers. For each technology, information was extracted on a number of overarching factors, including the primary purpose, mode of administration, and data processing capabilities. Each technology was then assessed against predetermined criteria, including requirements for respondent literacy, battery life, requirements for connectivity, ability to measure macro- and micronutrients, and overall appropriateness for use in LICs. Few technologies reviewed met all the criteria, exhibiting both practical constraints and a lack of demonstrated feasibility for use in LICs, particularly for large-scale, population-based surveys. To increase collection of dietary data in LICs, development of a contextually adaptable, interviewer-administered dietary assessment platform is recommended. Additional investments in the research infrastructure are equally important to ensure time and cost savings for the user.

Dietary Strategies to Reduce Environmental Impact: A Critical Review of the Evidence Base

The food system is a major source of environmental impact, and dietary change has been recommended as an important and necessary strategy to reduce this impact. However, assessing the environmental performance of diets is complex due to the many types of foods eaten and the diversity of agricultural production systems and local environmental settings. To assess the state of science and identify knowledge gaps, an integrative review of the broad topic of environment and diet was undertaken, with particular focus on the completeness of coverage of environmental concerns and the metrics used. Compared with the 14 discrete environmental areas of concern identified in the United Nations Sustainable Development Goals, the located journal literature mainly addressed greenhouse gas (GHG) emissions and, to a lesser extent, land and water use. Some relevant concerns were rarely addressed or not addressed at all. In the case of GHG emissions, changes in land use and soil carbon stocks were seldom considered. This represents a disconnect between the science informing strategic climate action in the agricultural sector and the science informing public health nutrition. In the case of land and water use, few studies used metrics that are appropriate in a life-cycle context. Some metrics produce inherently biased results, which misinform about environmental impact. The limited evidence generally points to recommended diets having lower environmental impacts than typical diets, although not in every case. This is largely explained by the overconsumption of food energy associated with average diets, which is also a major driver of obesity. A shared-knowledge framework is identified as being needed to guide future research on this topic. Until the evidence base becomes more complete, commentators on sustainable diets should not be quick to assume that a dietary strategy to reduce overall environmental impact can be readily defined or recommended.

25-Hydroxyvitamin D as a Biomarker of Vitamin D Status and Its Modeling to Inform Strategies for Prevention of Vitamin D Deficiency within the Population

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

Vitamins Associated with Brain Aging, Mild Cognitive Impairment, and Alzheimer Disease: Biomarkers, Epidemiological and Experimental Evidence, Plausible Mechanisms, and Knowledge Gaps

The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies. Current evidence suggests that all known vitamins and some "quasi-vitamins" are involved as cofactors or influence ≥1 of the 6 key sets of pathways or pathologies associated with MCI or AD, relating to 1) 1-carbon metabolism, 2) DNA damage and repair, 3) mitochondrial function and glucose metabolism, 4) lipid and phospholipid metabolism and myelination, 5) neurotransmitter synthesis and synaptogenesis, and 6) amyloidosis and Tau protein phosphorylation. The contemporary level of evidence for each of the vitamins varies considerably, but it is notable that B vitamins are involved as cofactors in all of the core pathways or pathologies and, together with vitamins C and E, are consistently associated with a protective role against dementia. Outcomes from recent studies indicate that the efficacy and safety of supplementation with vitamins to prevent MCI and the early stages of AD will most likely depend on 1) which pathways are defective, 2) which vitamins are deficient and could correct the relevant metabolic defects, and 3) the modulating impact of nutrient-nutrient and nutrient-genotype interaction. More focus on a precision nutrition approach is required to realize the full potential of vitamin therapy in preventing dementia and to avoid causing harm.

Cobalamin Status from Pregnancy to Early Childhood: Lessons from Global Experience

Low cobalamin intake and status during pregnancy or lactation have been linked to adverse maternal and perinatal health outcomes, whereas low cobalamin status during early childhood is associated with impaired development in children. Women who begin pregnancy with depleted stores (low or very low plasma cobalamin) will give birth to depleted infants who are likely to develop deficiency symptoms during the first few weeks or months postpartum. Newly ingested cobalamin during pregnancy and lactation (from diet or supplements) is transferred to the child and is not likely to correct cobalamin status in depleted women. The prevalence of low cobalamin status is high especially in low-income settings or in populations with a low intake of animal products. Folate and cobalamin play interdependent roles in one-carbon metabolism. Although folic acid supplementation during early pregnancy is widely recommended and practiced, cobalamin supplementation during pregnancy and lactation has received little attention. Furthermore, the intake recommendations for pregnant and lactating women and in early life need reevaluation in the light of newly available evidence in the field.

Measurement Errors in Dietary Assessment Using Self-Reported 24-Hour Recalls in Low-Income Countries and Strategies for Their Prevention

Securing accurate measurements of dietary intake across populations is challenging. Of the methods, self-reported 24-h recalls are often used in low-income countries (LICs) because they are quick, culturally sensitive, do not require high cognitive ability, and provide quantitative data on both foods and nutrients. Measuring intakes via 24-h recalls involves 1) collecting data on food intakes, 2) the appropriate use of relevant food-composition data for calculating nutrient intakes, and 3) statistically converting observed intakes to "usual intakes" for evaluating nutrient adequacy or relations between foods and nutrients and health outcomes. Like all dietary methods, 24-h recalls are subject to random errors that lower the precision and systematic errors that can reduce accuracy at each stage of the measurement protocol. Research has identified the potential sources of measurement errors in 24-h recall protocols and emphasized that sources of random error can be reduced by incorporating standardized quality-control procedures and collecting more than one 24-h recall per person, with the number depending on the study objective. Careful design of the initial 24-h recall protocol can take into account potential sources of systematic error, such as day of the week, season, age, etc. Other sources of systematic error (e.g., energy underreporting) can best be detected by including a reference measure (e.g., doubly labeled water to measure energy expenditure). Alternatively, 24-h recall intakes of energy can be compared with same-day weighed intakes. Nevertheless, very few studies in LICs have assessed the validity of 24-h recalls in their study settings or adopted recommended standardized protocols to mitigate random errors. Hence, efforts should be made to improve the assessment, analysis, and interpretation of self-reported 24-h recall data for population studies in LICs. Accurate and precise dietary intake data at the national level can play an essential role in informing food, nutrition, and agricultural policies; food fortification planning; and compliance to food-based dietary guidelines.

Perspective: Essential Study Quality Descriptors for Data from Nutritional Epidemiologic Research

Pooled analysis of secondary data increases the power of research and enables scientific discovery in nutritional epidemiology. Information on study characteristics that determine data quality is needed to enable correct reuse and interpretation of data. This study aims to define essential quality characteristics for data from observational studies in nutrition. First, a literature review was performed to get an insight on existing instruments that assess the quality of cohort, case-control, and cross-sectional studies and dietary measurement. Second, 2 face-to-face workshops were organized to determine the study characteristics that affect data quality. Third, consensus on the data descriptors and controlled vocabulary was obtained. From 4884 papers retrieved, 26 relevant instruments, containing 164 characteristics for study design and 93 characteristics for measurements, were selected. The workshop and consensus process resulted in 10 descriptors allocated to "study design" and 22 to "measurement" domains. Data descriptors were organized as an ordinal scale of items to facilitate the identification, storage, and querying of nutrition data. Further integration of an Ontology for Nutrition Studies will facilitate interoperability of data repositories.

Perspective: An Extension of the STROBE Statement for Observational Studies in Nutritional Epidemiology (STROBE-nut): Explanation and Elaboration

Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called "the STROBE-nut." The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading.

Perspective: The Paradox in Dietary Advanced Glycation End Products Research--The Source of the Serum and Urinary Advanced Glycation End Products Is the Intestines, Not the Food

Inconsistent research results have impeded our understanding of the degree to which dietary advanced glycation end products (dAGEs) contribute to chronic disease. Early research suggested that Western-style fast foods, including grilled and broiled meats and French fries, contain high levels of proinflammatory advanced glycation end products (AGEs). However, recent studies with state-of-the-art ultraperformance LC-tandem mass spectrometry (UPLC-MS) found that there is no evidence that these foods have elevated levels of dAGEs relative to other foods. Paradoxically, observational research found that the intake of fruits (mainly apples), fruit juices (apple juice), vegetables, nuts, seeds, soy, and nonfat milk, which are foods synonymous with healthy eating, as well as the intake of cold breakfast cereals, whole grains (breads), and sweets, which are sources of high-fructose corn syrup (HFCS), were associated with elevated serum and urinary N--carboxymethyl-lysine (CML). Ironically, these are the same foods found to have lower CML levels, as measured by UPLC-MS. One possible explanation for this paradox is that the source of the elevated CML is the intestines, not the food. When considered collectively, dAGE research results are consistent with the "fructositis" hypothesis, which states that intake of foods and beverages with high fructose-to-glucose ratios (HFCS-sweetened foods and beverages, agave syrup, crystalline fructose, apple juice, and apple juice blends) promotes the intestinal in situ formation of readily absorbed, proinflammatory extracellular, newly identified, fructose-associated AGE, an overlooked source of immunogenic AGEs.

Effects of Anthocyanins on Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Numerous clinical trials have examined the role of anthocyanins on cardiometabolic health, but their effects have not been quantitatively synthesized and systematically evaluated. The aim of our study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of anthocyanins on glycemic regulation and lipid profiles in both healthy populations and those with cardiometabolic diseases. The MEDLINE, EMBASE, Cochrane database, OVID EBM Reviews, and clinicaltrials.gov databases were searched until February 2017. RCTs with a duration of ≥2 wk that evaluated the effects of anthocyanins on glycemic control, insulin sensitivity, and lipids as either primary or secondary outcomes were included. The Cochrane Risk of Bias tool was used to assess the study quality. Standardized mean differences (SMDs) were determined by random-effects models. Meta-regression, sensitivity, and subgroup analyses were performed to explore the influence of covariates on the overall effects. Thirty-two RCTs (1491 participants) were eligible for meta-analysis. Anthocyanins significantly reduced fasting glucose (SMD: –0.31; 95% CI: –0.59, –0.04; I2 = 80.7%), 2-h postprandial glucose (SMD: –0.82; 95% CI: –1.49, –0.15; I2 = 77.7), glycated hemoglobin (SMD: –0.65; 95% CI: –1.00, –0.29; I2 = 72.7%), total cholesterol (SMD: –0.33; 95% CI: –0.62, –0.03; I2 = 86.9%), and LDL (SMD: –0.35; 95% CI: –0.66, –0.05; I2 = 85.2%). Sensitivity analyses showed that the overall effects remained similar by excluding the trials with a high or unclear risk of bias. The significant improvements in glycemic control and lipids support the benefits of anthocyanins in the prevention and management of cardiometabolic disease. Further well-designed RCTs are needed to evaluate the long-term effects of anthocyanins on metabolic profiles and to explore the optimal formula and dosage. The protocol for this review was registered at https://www.crd.york.ac.uk/PROSPERO/#index.php as CRD42016033210.

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