Advances in Nutrition: An International Review Journal current issue

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 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 as CRD42016033210.

Dietary (Poly)phenols, Brown Adipose Tissue Activation, and Energy Expenditure: A Narrative Review

The incidence of overweight and obesity has reached epidemic proportions, making the control of body weight and its complications a primary health problem. Diet has long played a first-line role in preventing and managing obesity. However, beyond the obvious strategy of restricting caloric intake, growing evidence supports the specific antiobesity effects of some food-derived components, particularly (poly)phenolic compounds. The relatively new rediscovery of active brown adipose tissue in adult humans has generated interest in this tissue as a novel and viable target for stimulating energy expenditure and controlling body weight by promoting energy dissipation. This review critically discusses the evidence supporting the concept that the antiobesity effects ascribed to (poly)phenols might be dependent on their capacity to promote energy dissipation by activating brown adipose tissue. Although discrepancies exist in the literature, most in vivo studies with rodents strongly support the role of some (poly)phenol classes, particularly flavan-3-ols and resveratrol, in promoting energy expenditure. Some human data currently are available and most are consistent with studies in rodents. Further investigation of effects in humans is warranted.

Effect of Soy and Soy Isoflavones on Obesity-Related Anthropometric Measures: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials

Soy may be a suitable food for anti-obesity efforts because of its high protein and isoflavone content. We conducted this meta-analysis to evaluate potential effects of soy and soy isoflavones on weight, waist circumference, and fat mass. PubMed, MEDLINE, Scopus, EMBASE, and Cochrane databases were searched. Twenty-four trials with soy and 17 trials with isoflavones passed the eligibility stage. According to the results, soy showed no overall statistically significant effect on weight, waist circumference, or fat mass, but a significant increasing effect on weight was observed in some circumstances: for instance, in obese subjects [mean difference (MD): 0.80 kg; 95% CI: 0.15, 1.45 kg; P = 0.02], with ingestions of ≥40 g soy protein/d (MD: 0.94 kg; 95% CI: 0.11, 1.77 kg; P = 0.03), with short-term applications (1–3 mo) (MD: 0.45 kg; 95% CI: 0.05, 0.86 kg; P = 0.03), and when soy was compared with meat (MD: 0.36 kg; 95% CI: 0.09, 0.64 kg; P = 0.03) and whey protein (MD: 1.53 kg; 95% CI: 0.10, 2.96 kg; P = 0.04). In contrast to the effects of soy on weight, soy significantly decreased waist circumference in older ages (MD: –0.36 cm; 95% CI: –0.71, –0.01 cm; P = 0.04), in women (MD: –0.32 cm; 95% CI: –0.57, –0.08 cm; P = 0.01), and at doses of <40 g soy protein/d (MD: –0.31 cm; 95% CI: –0.57, –0.05 cm; P = 0.02). Isoflavone studies, conducted only in women, showed that isoflavones may reduce body mass index (BMI; in kg/m2) (MD: –0.26; 95% CI: –0.55, 0.04; P = 0.085), especially in dosages <100 mg/d (MD: –0.48; 95% CI: –0.90, –0.06; P = 0.02) and in intervention periods of 2–6 mo (MD: –0.28; 95% CI: –0.56, 0.00; P = 0.053), but no effect was observed in higher doses or longer intervention periods. Also, a trend for reduced BMI after consumption of isoflavones was observed in Caucasians (MD: –0.35; 95% CI: –0.74, 0.04; P = 0.08). Overall, results showed that, although soy is the major source of isoflavones, soy and isoflavones may have different impacts on weight status.

Anthropometric Indicators as Body Fat Discriminators in Children and Adolescents: A Systematic Review and Meta-Analysis

We analyzed the discriminatory capacity of anthropometric indicators for body fat in children and adolescents. This systematic review and meta-analysis included cross-sectional and clinical studies comprising children and adolescents aged 2–19 y that tested the discriminatory value for body fat measured by anthropometric methods or indexes generated by anthropometric variables compared with precision methods in the diagnosis of body fat [dual-energy X-ray absorptiometry (DXA), computed tomography, air displacement plethysmography (ADP), or MRI]. Five studies met the eligibility criteria and presented high methodologic quality. The anthropometric indicators that had high discriminatory power to identify high body fat were body mass index (BMI) in males [area under the curve (AUC): 0.975] and females (AUC: 0.947), waist circumference (WC) in males (AUC: 0.975) and females (AUC: 0.959), and the waist-to-height ratio (WTHR) in males (AUC: 0.897) and females (AUC: 0.914). BMI, WC, and WTHR can be used by health professionals to assess body fat in children and adolescents.

Abdominal Obesity and Risk of Hip Fracture: A Systematic Review and Meta-Analysis of Prospective Studies

Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the association between abdominal obesity and the risk of hip fracture. The present systematic review and meta-analysis of prospective studies was undertaken to summarize the association between abdominal obesity and the risk of hip fracture. We searched online databases for relevant publications up to February 2017, using relevant keywords. In total, 14 studies were included in the systematic review and 9 studies, with a total sample size of 295,674 individuals (129,964 men and 165,703 women), were included in the meta-analysis. Participants were apparently healthy and aged ≥40 y. We found that abdominal obesity (defined by various waist-hip ratios) was positively associated with the risk of hip fracture (combined RR: 1.24, 95% CI: 1.05, 1.46, P = 0.01). Combining 8 effect sizes from 6 studies, we noted a marginally significant positive association between abdominal obesity (defined by various waist circumferences) and the risk of hip fracture (combined RR: 1.36; 95% CI: 0.97, 1.89, P = 0.07). This association became significant in a fixed-effects model (combined effect size: 1.40, 95% CI: 1.25, 1.58, P < 0.001). Based on 5 effect sizes, we found that a 0.1-U increase in the waist-hip ratio was associated with a 16% increase in the risk of hip fracture (combined RR: 1.16, 95% CI: 1.04, 1.29, P = 0.007), whereas a 10-cm increase in waist circumference was not significantly associated with a higher risk of hip fracture (combined RR: 1.13, 95% CI: 0.94, 1.36, P = 0.19). This association became significant, however, when we applied a fixed-effects model (combined effect size: 1.21, 95% CI: 1.15, 1.27, P < 0.001). We found that abdominal obesity was associated with a higher risk of hip fracture in 295,674 individuals. Further studies are needed to test whether there are associations between abdominal obesity and fractures at other bone sites.

Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 {beta}-Casein

This is the first systematic review, to our knowledge, of published studies investigating the gastrointestinal effects of A1-type bovine β-casein (A1) compared with A2-type bovine β-casein (A2). The review is relevant to nutrition practice given the increasing availability and promotion in a range of countries of dairy products free of A1 for both infant and adult nutrition. In vitro and in vivo studies (all species) were included. In vivo studies were limited to oral consumption. Inclusion criteria encompassed all English-language primary research studies, but not reviews, involving milk, fresh-milk products, β-casein, and β-casomorphins published through 12 April 2017. Studies involving cheese and fermented milk products were excluded. Only studies with a specific gastrointestinal focus were included. However, inclusion was not delimited by specific gastrointestinal outcome nor by a specific mechanism. Inclusion criteria were satisfied by 39 studies. In vivo consumption of A1 relative to A2 delays intestinal transit in rodents via an opioid-mediated mechanism. Rodent models also link consumption of A1 to the initiation of inflammatory response markers plus enhanced Toll-like receptor expression relative to both A2 and nonmilk controls. Although most rodent responses are confirmed as opioid-mediated, there is evidence that dipeptidyl peptidase 4 stimulation in the jejunum of rodents is via a nonopioid mechanism. In humans, there is evidence from a limited number of studies that A1 consumption is also associated with delayed intestinal transit (1 clinical study) and looser stool consistency (2 clinical studies). In addition, digestive discomfort is correlated with inflammatory markers in humans for A1 but not A2. Further research is required in humans to investigate the digestive function effects of A1 relative to A2 in different populations and dietary settings.

Effects of Probiotics on Necrotizing Enterocolitis, Sepsis, Intraventricular Hemorrhage, Mortality, Length of Hospital Stay, and Weight Gain in Very Preterm Infants: A Meta-Analysis

Probiotics are increasingly used as a supplement to prevent adverse health outcomes in preterm infants. We conducted a systematic review, meta-analysis, and subgroup analysis of findings from randomized controlled trials (RCTs) to assess the magnitude of the effect of the probiotics on health outcomes among very-low–birth-weight (VLBW) infants. Relevant articles from January 2003 to June 2017 were selected from a broad range of databases, including Medline, PubMed, Scopus, and Embase. Studies were included if they used an RCT design, involved a VLBW infant (birthweight <1500 g or gestational age <32 wk) population, included a probiotic intervention group, measured necrotizing enterocolitis (NEC) as a primary outcome, and measured sepsis, mortality, length of hospital stay, weight gain, and intraventricular hemorrhage (IVH) as additional outcomes. The initial database search yielded 132 potentially relevant articles and 32 (n = 8998 infants) RCTs were included in the final meta-analysis. Subgroup analysis was used to evaluate the effects of the moderators on the outcome variables. In the probiotics group, it was found that NEC was reduced by 37% (95% CI: 0.51%, 0.78%), sepsis by 37% (95% CI: 0.72%, 0.97%), mortality by 20% (95% CI: 0.67%, 0.95%), and length of hospital stay by 3.77 d (95% CI: –5.94, –1.60 d). These findings were all significant when compared with the control group. There was inconsistent use of strain types among some of the studies. The results indicate that probiotic consumption can significantly reduce the risk of developing medical complications associated with NEC and sepsis, reduce mortality and length of hospital stay, and promote weight gain in VLBW infants. Probiotics are more effective when taken in breast milk and formula form, consumed for <6 wk, administered with a dosage of <109 CFU/d, and include multiple strains. Probiotics are not effective in reducing the incidence of IVH in VLBW infants.

Withholding Feeds and Transfusion-Associated Necrotizing Enterocolitis in Preterm Infants: A Systematic Review

Limited evidence exists to support the withholding of feeds during packed red blood cell (PRBC) transfusion to reduce the incidence of transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants. The aim of the manuscript was to systematically review studies reporting the effect of implementing a policy of withholding feeds on the incidence of TANEC in preterm infants. The following databases were searched for relevant studies published between the databases’ inception and December 2016: PubMed, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index of Nursing and Allied Health Literature, and Pediatric Academic Societies Abstract Archive. Other relevant sources were also searched. There were no restrictions on study design. Studies reporting on the incidence of TANEC (stage ≥2 necrotizing enterocolitis within 48–72 h) after implementation of a policy of withholding feeds in the peritransfusion period in preterm infants were included. This meta-analysis used a random-effects model with assessment of quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. There were no randomized controlled trials (RCTs). Pooled results from 7 non-RCTs (n = 7492) showed that withholding feeds during PRBC transfusion significantly reduced the incidence of TANEC (RR: 0.47; 95% CI: 0.28, 0.80; P = 0.005; I2 = 11%). The overall quality of evidence was moderate on GRADE analysis. These findings suggest that withholding feeds during the peritransfusion period may reduce the risk of TANEC in preterm infants. Adequately powered RCTs are needed to confirm these findings.

Evaluation of Nutrition Interventions in Children in Conflict Zones: A Narrative Review

Food and nutrition insecurity becomes increasingly worse in areas affected by armed conflict. Children affected by conflict, or in war-torn settings, face a disproportionate burden of malnutrition and poor health outcomes. As noted by humanitarian response reviews, there is a need for a stronger evidence-based response to humanitarian crises. To achieve this, we systematically searched and evaluated existing nutrition interventions carried out in conflict settings that assessed their impact on children’s nutrition status. To evaluate the impact of nutrition interventions on children’s nutrition and growth status, we identified published literature through EMBASE, PubMed, and Global Health by using a combination of relevant text words and Medical Subject Heading terms. Studies for this review must have included children (aged ≤18 y), been conducted in conflict or postconflict settings, and assessed a nutrition intervention that measured ≥1 outcome for nutrition status (i.e., stunting, wasting, or underweight). Eleven studies met the inclusion and exclusion criteria for this review. Five different nutrition interventions were identified and showed modest results in decreasing the prevalence of stunting, wasting, underweight, reduction in severe or moderate acute malnutrition or both, mortality, anemia, and diarrhea. Overall, nutrition interventions in conflict settings were associated with improved children’s nutrition or growth status. Emergency nutrition programs should continue to follow recent recommendations to expand coverage and access (beyond refugee camps to rural areas) and ensure that aid and nutrition interventions are distributed equitably in all conflict-affected populations.

Nutritional Sustainability: Aligning Priorities in Nutrition and Public Health with Agricultural Production

Nutrition science–based dietary advice urges changes that may have a great impact on agricultural systems. For example, the 2016 Dietary Guidelines for Americans (DGA) recommends greatly increased fruit and vegetable consumption, but the present domestic production is insufficient to accommodate large-scale adoption of these guidelines. Increasing production to the extent needed to meet the DGA will necessitate changes in an already stressed agriculture and food system and will require nutrition and agriculture professionals to come together in open and collegial discourse. All involved need to understand the stress placed on the food system by increasing populations, changing diets, and changing environments, and recognize the major diet-based public health challenges. Furthermore, there is a need to understand the intricate interplay of the myriad parts of the food system and the vast amount of work necessary to make even small changes. New systems approaches are needed, especially at the research level, where nutrition, public health, agriculture, and the food industry work together to solve interconnected problems. Future well-being depends on a sustainable food system that continues to deliver optimal health with minimal impact on the environment.

Perspective: A Definition for Whole-Grain Food Products--Recommendations from the Healthgrain Forum

Whole grains are a key component of a healthy diet, and enabling consumers to easily choose foods with a high whole-grain content is an important step for better prevention of chronic disease. Several definitions exist for whole-grain foods, yet these do not account for the diversity of food products that contain cereals. With the goal of creating a relatively simple whole-grain food definition that aligns with whole-grain intake recommendations and can be applied across all product categories, the Healthgrain Forum, a not-for-profit consortium of academics and industry working with cereal foods, established a working group to gather input from academics and industry to develop guidance on labeling the whole-grain content of foods. The Healthgrain Forum recommends that a food may be labeled as "whole grain" if it contains ≥30% whole-grain ingredients in the overall product and contains more whole grain than refined grain ingredients, both on a dry-weight basis. For the purposes of calculation, added bran and germ are not considered refined-grain ingredients. Additional recommendations are also made on labeling whole-grain content in mixed-cereal foods, such as pizza and ready meals, and a need to meet healthy nutrition criteria. This definition allows easy comparison across product categories because it is based on dry weight and strongly encourages a move from generic whole-grain labels to reporting the actual percentage of whole grain in a product. Although this definition is for guidance only, we hope that it will encourage more countries to adopt regulation around the labeling of whole grains and stimulate greater awareness and consumption of whole grains in the general population.

Perspective: Improving Nutritional Guidelines for Sustainable Health Policies: Current Status and Perspectives

A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication professionals for sustainable health and nutritional policies. Currently, a strong rationale and available data support a personalized dietary approach according to personal variables, including sex and age, circulating metabolic biomarkers, food quality and intake frequency, lifestyle variables such as physical activity, and environmental variables including one’s microbiome profile. There is a strong and urgent need to develop a successful commitment among all the stakeholders to define novel and sustainable approaches toward the management of the health value of nutrition at individual and population levels. Moving forward requires adherence to well-established principles of evidence evaluation as well as identification of effective tools to obtain better quality evidence. Much remains to be done in the near future.

Perspective: Neuroregenerative Nutrition

Good health while aging depends upon optimal cellular and organ functioning that contribute to the regenerative ability of the body during the lifespan, especially when injuries and diseases occur. Although diet may help in the maintenance of cellular fitness during periods of stability or modest decline in the regenerative function of an organ, this approach is inadequate in an aged system, in which the ability to maintain homeostasis is further challenged by aging and the ensuing suboptimal functioning of the regenerative unit, tissue-specific stem cells. Focused nutritional approaches can be used as an intervention to reduce decline in the body’s regenerative capacity. This article brings together nutrition-associated therapeutic approaches with the fields of aging, immunology, neurodegenerative disease, and cancer to propose ways in which diet and nutrition can work with standard-of-care and integrated medicine to help improve the brain’s function as it ages. The field of regenerative medicine has exploded during the past 2 decades as a result of the discovery of stem cells in nearly every organ system of the body, including the brain, where neural stem cells persist in discrete areas throughout life. This fact, and the uncovering of the genetic basis of plasticity in somatic cells and cancer stem cells, open a door to a world where maintenance and regeneration of organ systems maintain health and extend life expectancy beyond its present limits. An area that has received little attention in regenerative medicine is the influence on regulatory mechanisms and therapeutic potential of nutrition. We propose that a strong relation exists between brain regenerative medicine and nutrition and that nutritional intervention at key times of life could be used to not only maintain optimal functioning of regenerative units as humans age but also play a primary role in therapeutic treatments to combat injury and diseases (in particular, those that occur in the latter one-third of the lifespan).

Interindividual Variability in Biomarkers of Cardiometabolic Health after Consumption of Major Plant-Food Bioactive Compounds and the Determinants Involved

Cardiometabolic disease, comprising cardiovascular diseases, type 2 diabetes, and their associated risk factors including metabolic syndrome and obesity, is the leading cause of death worldwide. Plant foods are rich sources of different groups of bioactive compounds, which might not be essential throughout life but promote health and well-being by reducing the risk of age-related chronic diseases. However, heterogeneity in the responsiveness to bioactive compounds can obscure associations between their intakes and health outcomes, resulting in the hiding of health benefits for specific population groups and thereby limiting our knowledge of the exact role of the different bioactive compounds for health. The heterogeneity in response suggests that some individuals may benefit more than others from the health effects of these bioactive compounds. However, to date, this interindividual variation after habitual intake of plant bioactive compounds has been little explored. The aim of this review is to provide an overview of the existing research that has revealed interindividual variability in the responsiveness to plant-food bioactive compound consumption regarding cardiometabolic outcomes, focusing on polyphenols, caffeine and plant sterols, and the identified potential determinants involved.

The Impact of the Mediterranean Diet on the Cognitive Functioning of Healthy Older Adults: A Systematic Review and Meta-Analysis

Evidence from epidemiologic studies suggests a relation between the Mediterranean diet (MeDi) and cognitive function, but results are inconsistent. Prior reviews have not provided pooled data from meta-analysis of longitudinal studies and randomized controlled trials (RCTs), or they included younger adult participants. This systematic review and meta-analysis examines the impact of the MeDi on the cognitive functioning of healthy older adults. Fifteen cohort studies with 41,492 participants and 2 RCTs with 309 and 162 participants in intervention and control groups, respectively, were included. The primary outcome of interest was cognitive function, divided into domains of memory and executive function. Meta-analysis of cohort studies revealed a significant association between MeDi and older adults’ episodic memory (n = 25,369, r = 0.01, P = 0.03) and global cognition (n = 41,492, r = 0.05, P ≤ 0.001), but not working memory (n = 1487, r = 0.007, P = 0.93) or semantic memory (n = 1487, r = 0.08, P = 0.28). Meta-analysis of RCTs revealed that compared with controls, the MeDi improved delayed recall (n = 429, P = 0.01), working memory (n = 566, P = 0.03), and global cognition (n = 429, P = 0.047), but not episodic memory (n = 566, P = 0.15), immediate recall (n = 566, P = 0.17), paired associates (n = 429, P = 0.20), attention (n = 566, P = 0.69), processing speed (n = 566, P = 0.35), or verbal fluency (n = 566, P = 0.12). The strongest evidence suggests a beneficial effect of the MeDi on older adults’ global cognition. This article discusses the influence of study design and components of the MeDi on cognitive function and considers possible mechanisms.