Phytosterol and phytostanol-mediated epigenetic changes in cancer and other non-communicable diseases: a systematic review.

Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.

Practical Lifestyle Management of Nonalcoholic Fatty Liver Disease for Busy Clinicians.

Weight loss achieved through a combination of healthy eating patterns that encompass the principles of the Mediterranean diet and regular physical activity is the most evidence-based treatment for nonalcoholic fatty liver disease. Although other types of diets have demonstrated efficacy in liver fat reduction, the Mediterranean diet confers additional cardiometabolic benefits. Macronutrient composition, food choices, and timing of eating can be tailored to individual preferences, culture, and financial circumstances; however, recommended healthy eating patterns are characterized by minimally processed or unprocessed foods (vegetables, legumes, nuts and seeds, fruits, whole grains, and unprocessed meats and fish) that are low in sugar, refined carbohydrates, and saturated fat and high in fiber, polyphenols, vitamins, minerals, and healthy fats. Physical activity can independently improve steatosis, prevent fibrosis and cirrhosis, and reduce mortality.

The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety of cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters and receptors display micromolar binding constants; these are consistent with its typically micromolar tissue concentrations but far above its serum/plasma concentration (normally tens of nanomolar), suggesting large gaps in our knowledge of its transport and mechanisms of action, in that the main influx transporters characterized to date are equilibrative, not concentrative. In addition, it is a substrate of a known anion efflux pump (ABCC4), whose in vivo activity is largely unknown. Exogeneous addition of L-tryptophan or L-kynurenine leads to the production of KYNA but also to that of many other co-metabolites (including some such as 3-hydroxy-L-kynurenine and quinolinic acid that may be toxic). With the exception of chestnut honey, KYNA exists at relatively low levels in natural foodstuffs. However, its bioavailability is reasonable, and as the terminal element of an irreversible reaction of most tryptophan degradation pathways, it might be added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show that it has valuable bioactivity. Given the above, we review its potential utility as a nutraceutical, finding it significantly worthy of further study and development.

Ergothioneine: an underrecognised dietary micronutrient required for healthy ageing?

Ergothioneine is a naturally occurring amino acid and thiol antioxidant found in high amounts in mushrooms and fermented foods. Humans and animals acquire ergothioneine from the diet through the pH-dependent activity of a membrane transporter, the large solute carrier 22A member 4 (SLC22A4), expressed on the apical membrane of the small intestine. The SLC22A4 transporter also functions in the renal reabsorption of ergothioneine in the kidney, with avid absorption and retention of ergothioneine from the diet observed in both animals and humans. Ergothioneine is capable of scavenging a diverse range of reactive oxygen and nitrogen species, has metal chelation properties, and is predicted to directly regulate nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Although not lethal, the genetic knockout of the SLC22A4 gene in multiple organisms increases susceptibility to oxidative stress, damage and inflammation; in agreement with a large body of preclinical data suggesting the physiological function of ergothioneine is as a cellular antioxidant and cytoprotectant agent. In humans, blood levels of ergothioneine decline after the age of 60 years, and lower levels of ergothioneine are associated with more rapid cognitive decline. Conversely, high plasma ergothioneine levels have been associated with significantly reduced cardiovascular mortality and overall mortality risks. In this horizon's manuscript, we review evidence suggesting critical roles for dietary ergothioneine in healthy ageing and the prevention of cardiometabolic disease. We comment on some of the outstanding research questions in the field and consider the question of whether or not ergothioneine should be considered a conditionally essential micronutrient.

NAFLD and vitamin D: Evidence for intersection of microRNA-regulated pathways.

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease, worldwide. The molecular pathogenesis of NAFLD is complex, involving numerous signalling molecules, including microRNAs (miRNAs). Dysregulation of miRNA expression is associated with hepatic inflammation, fibrosis and hepatocellular carcinoma. Although miRNAs are also critical to the cellular response to vitamin D, mediating regulation of the vitamin D receptor and vitamin D's anti-cancer effects, the role of vitamin-D-regulated miRNAs in NAFLD pathogenesis has been relatively unexplored. Therefore, this review aims to critically assess the evidence for a potential subset of miRNAs that are both dysregulated in NAFLD and modulated by vitamin D. Comprehensive review of eighty-nine human studies identified twenty-five miRNAs found dysregulated in more than one NAFLD study. In contrast, only seventeen studies, including a protocol for a trial in NAFLD, had examined miRNAs in relation to vitamin D status, response to supplementation, or vitamin D in the context of the liver. This paper summarises these data and reviews the biological roles of six miRNAs (miR-21, miR-30, miR-34, miR-122, miR-146, miR-200) found dysregulated in multiple independent NAFLD studies. While modulation of miRNAs by vitamin D has been understudied, integration of the data suggests seven vitamin-D-modulated miRNAs (miR-27, miR-125, miR-155, miR-192, miR-223, miR-375, miR-378) potentially relevant to NAFLD pathogenesis. Our summary tables provide a significant resource to underpin future hypothesis-driven research, and we conclude that the measurement of serum and hepatic miRNAs in response to vitamin D supplementation in larger trials is warranted.

Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low- and High-Risk Women Living in the UK.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common global pregnancy complication; however, prevalence varies substantially between ethnicities, with South Asians (SAs) experiencing up to 3 times the risk of the disease compared with white Europeans (WEs). Factors driving this discrepancy are unclear, although the metabolome is of great interest as GDM is known to be characterized by metabolic dysregulation. OBJECTIVES: The primary aim was to characterize and compare the metabolic profiles of GDM in SA and WE women (at <28 wk of gestation) from the Born in Bradford (BIB) prospective birth cohort in the United Kingdom. METHODS: In total, 146 fasting serum metabolites, from 2,668 pregnant WE and 2,671 pregnant SA women (average BMI 26.2 kg/m2, average age 27.3 y) were analyzed using partial least squares discriminatory analyses to characterize GDM status. Linear associations between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2 h postglucose) were also examined. RESULTS: Seven metabolites associated with GDM status in both ethnicities (variable importance in projection ≥1), whereas 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy-weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the metabolite values analyzed in relation to dysglycemia, lactate, histidine, apolipoprotein A1, HDL cholesterol, and HDL2 cholesterol associated with decreased glucose concentration, whereas DHA and the diameter of very low-density lipoprotein particles (nm) associated with increased glucose concertation in WE women, and in SAs, albumin alone associated with decreased glucose concentration. CONCLUSIONS: This study shows that the metabolic risk profile for GDM differs between WE and SA women enrolled in BiB in the United Kingdom. This suggests that etiology of the disease differs between ethnic groups and that ethnic-appropriate prevention strategies may be beneficial.

In the context of the triple burden of malnutrition: A systematic review of gene-diet interactions and nutritional status.

Genetic background interacts with dietary components to modulate nutritional health status. This study aimed to review the evidence for gene-diet interactions in all forms of malnutrition. A comprehensive systematic literature search was conducted through April 2021 to identify observational and intervention studies reporting the effects of gene-diet interactions in over-nutrition, under-nutrition and micronutrient status. Risk of publication bias was assessed using the Quality Criteria Checklist and a tool specifically designed for gene-diet interaction research. 167 studies from 27 populations were included. The majority of studies investigated single nucleotide polymorphisms (SNPs) in overnutrition (n = 158). Diets rich in whole grains, vegetables, fruits and low in total and saturated fats, such as Mediterranean and DASH diets, showed promising effects for reducing obesity risk among individuals who had higher genetic risk scores for obesity, particularly the risk alleles carriers of FTO rs9939609, rs1121980 and rs1421085. Other SNPs in MC4R, PPARG and APOA5 genes were also commonly studied for interaction with diet on overnutrition though findings were inconclusive. Only limited data were found related to undernutrition (n = 1) and micronutrient status (n = 9). The findings on gene-diet interactions in this review highlight the importance of personalized nutrition, and more research on undernutrition and micronutrient status is warranted.

Putting nutrition education on the table: development of a curriculum to meet future doctors' needs.

COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training.With this imperative, the Association for Nutrition established an Interprofessional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service (NHS), royal colleges, medical schools and universities, government public health departments, learned societies, medical students, and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors.Through an iterative and transparent consultative process, thirteen key nutritional competencies, to be achieved through mastery of eleven graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skill acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students' achievement of the General Medical Council (GMC) Outcome for Graduates.As nutrition is an integrative science, the AfN IPG recommends that the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden for teaching staff.The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip frontline staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered associate nutritionist/registered nutritionist (ANutr/RNutr) or registered dietitian (RD) where this is likely to be beneficial.

Development and relative validation of a short food frequency questionnaire for assessing dietary intakes of non-alcoholic fatty liver disease patients.

PURPOSE: This work aimed to design and validate a novel short food frequency questionnaire (SFFQ) to assess habitual intakes of food items related to non-alcoholic fatty liver disease (NAFLD) in a cohort of European patients. METHODS: A 48-item SFFQ was created, with questions from existing FFQs and expert knowledge, emphasizing foods and nutrients implicated in NAFLD pathogenesis. Consenting, fibroscan-diagnosed, NAFLD patients completed the SFFQ during a short interview and were asked to complete a 4-day diet diary (4DDD) at home for return by mail. Nutritional intakes were assessed utilizing the myfood24™ food composition dataset and estimated energy requirements (EER) were calculated using sex-, age- and weight-specific equations. Agreement between the dietary instruments was assessed by Spearman correlations and Bland Altman analysis. RESULTS: Fifty-five patients completed both the SFFQ and the 4DDD within 30 weeks; 42 (76%) were diagnosed with simple steatosis, whereas 13 (24%) had biopsy-proven steatohepatitis; the majority were overweight or obese, with a median (25th; 75th percentile) BMI of 33.2 kg/m2 (29.3; 36.0). Reported energy intakes were well below EER with a median intake of 73% of requirements, suggesting widespread under-reporting. Significant correlations were observed between sugar (r = 0.408, P = 0.002), fat (r = 0.44, P = 0.001), fruits (r = 0.51, P = 0.0001) and vegetables (r = 0.40, P = 0.0024) measurements by the SFFQ and 4DDD. Bland Altman plots with regression analysis demonstrated broad comparability with the 4DDD for intakes of fat (bias - 13.8 g/day) and sugar (bias + 12.9 g/day). CONCLUSIONS: A novel SFFQ designed to be minimally burdensome to participants was effective at assessing dietary intakes in NAFLD patients.

Vitamin D and nonalcoholic fatty liver disease.

PURPOSE OF REVIEW: Vitamin D deficiency may impact disease progression of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to review recent studies examining either vitamin D status or the effects of supplementation in patients with NAFLD, along with investigating the roles of genetic polymorphisms and the gut microbiome. RECENT FINDINGS: Six heterogeneous observational studies of vitamin D status, and four randomized controlled intervention trials of vitamin D supplementation in NAFLD were conflicting. All studies were hampered by the challenges of diagnosing NAFLD, were underpowered, and lacked data on clinically important outcomes. The results of three cross-sectional studies, including a Mendelian randomization study, provide limited evidence for a role for genetic modifiers of vitamin D status in NAFLD. Genetic and experimental evidence suggests that vitamin D and the vitamin D receptor (VDR) may influence the gut microbiome in health and disease. SUMMARY: The evidence relating either lower vitamin D status to the prevalence and severity of NAFLD, or examining vitamin D supplementation in patients with NAFLD is inconclusive. Larger, higher quality trials with relevant endpoints are needed. Further mechanistic studies on the roles of vitamin D and VDR in influencing the gut-liver axis in NAFLD are warranted.

Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells.

Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but enhance metastatic colonization, indicating tumour suppressing and promoting roles. Phytosterols and phytostanols in plants, like cholesterol in mammals, are essential components of the plasma membrane and biochemical precursors, and in human cells can alter LXR transcriptional activity. Here, a panel of breast cancer cell lines were treated with four dietary plant sterols and a stanol, alone or in combination with oxysterols. LXR activation and repression were measured by gene expression and LXR-luciferase reporter assays. Oxysterols activated LXR in all cell lines, but surprisingly phytosterols failed to modulate LXR activity. However, phytosterols significantly inhibited the ability of oxysterols to drive LXR transcription. These data support a role for phytosterols in modulating cancer cell behaviour via LXR, and therefore suggest merit in accurate dietary recordings of these molecules in cancer patients during treatment and perhaps supplementation to benefit recovery.

Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE-/-) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted.

Correction to: Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease.

[This corrects the article DOI: 10.1186/s12953-018-0131-y.].

Systematic Review: Nutrition and Physical Activity in the Management of Paediatric Nonalcoholic Fatty Liver Disease.

OBJECTIVES: The aim of the study was to evaluate efficacy of nutrition and physical activity interventions in the clinical management of paediatric nonalcoholic fatty liver disease. The prevalence of paediatric nonalcoholic fatty liver disease continues to rise alongside childhood obesity. Weight loss through lifestyle modification is currently first-line treatment, although supplementation of specific dietary components may be beneficial. METHODS: Medline, CINAHL, EMBASE, Scopus, and Cochrane Libraries were systematically searched to identify randomized controlled trials assessing nutritional and physical activity interventions. Primary outcome measures were changes to liver biomarkers assessed by imaging, histology, or serum liver function tests. Study quality was evaluated using the American Dietetic Association Quality Criteria Checklist. RESULTS: Fifteen articles met eligibility criteria investigating nutritional supplementation (vitamin E [n = 6], probiotics [n = 2], omega-3 fatty acids [n = 5]), dietary modification (low glycaemic load [n = 1] and reducing fructose intake [n = 1]). No randomized controlled trials examining physical activity interventions were identified. Vitamin E was ineffective at improving alanine transaminase levels, whereas omega-3 fatty acids decreased hepatic fat content. Probiotics gave mixed results, whereas reduced fructose consumption did not improve primary outcome measures. A low glycaemic load diet and a low-fat diet appeared equally effective in decreasing hepatic fat content and transaminases. Most studies were deemed neutral as assessed by the American Dietetic Association Quality Criteria Checklist. CONCLUSIONS: The limited evidence base inhibits the prescription of specific dietary and/or lifestyle strategies for clinical practice. General healthy eating and physical activity guidelines, promoting weight loss, should remain first-line treatment until high-quality evidence emerges that support specific interventions that offer additional clinical benefit.

Sugar and metabolic health: is there still a debate?

PURPOSE OF REVIEW: There is considerable political and public awareness of new recommendations to reduce sugars and sugar-sweetened beverages in our diets. It is therefore timely to review the most recent changes in guidelines, with a focus on evidence for metabolic health, recent research in the area and gaps in our knowledge. RECENT FINDINGS: Sufficient evidence links a high intake of sugar to dental caries and obesity, and high intakes of sugar-sweetened beverages in particular to increased risk of type 2 diabetes. This has led to the updating of dietary recommendations related to added sugars in the diet. The effects of specific sugars at usual intakes as part of an isoenergetic diet are less clear. The glycaemic response to food is complex and mediated by many factors, but sugar intake is not necessarily the major component. SUMMARY: There are many challenges faced by healthcare professionals and government bodies in order to improve the health of individuals and nations through evidence-based diets. Sufficiently powered long-term mechanistic studies are still required to provide evidence for the effects of reducing dietary sugars on metabolic health. However, there are many challenges for research scientists in the implementation of these studies.

QSSPN: dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells.

MOTIVATION: Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype-phenotype relationships. Despite advances in quantitative biology, full parameterization of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-cell models through an iterative process of modelling and experimental validation. RESULTS: We formulate quasi-steady state Petri nets (QSSPN), a novel method integrating Petri nets and constraint-based analysis to predict the feasibility of qualitative dynamic behaviours in qualitative models of gene regulation, signalling and whole-cell metabolism. We present the first dynamic simulations including regulatory mechanisms and a genome-scale metabolic network in human cell, using bile acid homeostasis in human hepatocytes as a case study. QSSPN simulations reproduce experimentally determined qualitative dynamic behaviours and permit mechanistic analysis of genotype-phenotype relationships. AVAILABILITY AND IMPLEMENTATION: The model and simulation software implemented in C++ are available in supplementary material and at http://sysbio3.fhms.surrey.ac.uk/qsspn/.

Dietary assessment and prevention of hypertension in Nigeria: Protocol for a retrospective cross-sectional study for the development and validation of a food frequency questionnaire for clinical use.

Contrary to North America and Europe, the prevalence of hypertension is rising in West Africa. With a transition from whole foods to processed foods in Nigeria, diet plays a key driver of hypertension. To combat this, the national nutritional guidelines in Nigeria were implemented, but their translation into actionable tools for clinicians remains a challenge. Currently, there are no simple dietary assessment tools that are concise and suitable to be incorporated into clinical care without requiring extensive data analysis while still providing personalised dietary support to their patients. This study aims to deliver a clinically tested and validated short dietary assessment tool for clinicians, patients, and researchers across Nigeria to provide personalised dietary advice for patients with hypertension. The study will be conducted in two phases: Phase 1 (n = 75) will investigate the feasibility of the short FFQ and its agreement with 24-hour dietary recalls (3x) in a clinical setting in Nigeria. During the analysis of Phase 1 data, a scoring system will be developed based on the associations between individual food items in the FFQ and measures of hypertension. Phase 2 (n = 50) will assess the acceptability of the FFQ and validate the association between the FFQ score and hypertension. Expected outcomes: The development of a clinically tested and validated short food frequency questionnaire that will be ready to use by clinicians, patients, and researchers across Nigeria to support the prevention and management of hypertension. This study will contribute to knowledge on dietary assessment and hypertension prevention by developing a validated and acceptable FFQ, which will be valuable for clinicians and researchers for personalised dietary recommendations to combat hypertension in Nigeria.

Overnutrition is a risk factor for iron, but not for zinc or vitamin A deficiency in children and young people: a systematic review and meta-analysis.

INTRODUCTION: Traditionally associated with undernutrition, increasing evidence suggests micronutrient deficiencies can coexist with overnutrition. Therefore, this work aimed to systematically review the associations between iron, zinc and vitamin A (VA) status and weight status (both underweight and overweight) in children and young people. METHODS: Ovid Medline, Ovid Embase, Scopus and Cochrane databases were systematically searched for observational studies assessing micronutrient status (blood, serum or plasma levels of iron, zinc or VA biomarkers) and weight status (body mass index or other anthropometric measurement) in humans under 25 years of any ethnicity and gender. Risk of bias assessment was conducted using the American Dietetic Association Quality Criteria Checklist. Where possible, random effects restricted maximum likelihood meta-analyses were performed. RESULTS: After screening, 83 observational studies involving 190 443 participants from 44 countries were identified, with many studies having reported on more than one micronutrient and/or weight status indicator. Iron was the most investigated micronutrient, with 46, 28 and 27 studies reporting data for iron, zinc and VA status, respectively. Synthesising 16 records of OR from seven eligible studies, overnutrition (overweight and obesity) increased odds of iron deficiency (ID) (OR (95% CI): 1.51 (1.20 to 1.82), p<0.0001, I2=40.7%). Odds appeared to be higher for children living with obesity (1.88 (1.33 to 2.43), p<0.0001, I2=20.6%) in comparison to those with overweight (1.31 (0.98 to 1.64), p<0.0001, I2=40.5%), although between group differences were not significant (p=0.08). CONCLUSIONS: Overnutrition is associated with increased risk of ID, but not zinc or VA deficiencies, with an inverted U-shaped relationship observed between iron status and bodyweight. Our results highlight significant heterogeneity in the reporting of micronutrient biomarkers and how deficiencies were defined. Inflammation status was rarely adequately accounted for, and the burden of ID may well be under-recognised, particularly in children and young people living with overnutrition. PROSPERO REGISTRATION NUMBER: CRD42020221523.

The Nigerian Dietary Screening Tool: A Step toward Improved Patient-Clinician Communication in Nigerian Hospitals: A Pilot Implementation Study.

Implementing dietary screening tools into clinical practice has been challenging, including in Nigeria. This study evaluated the impact of the Nigerian dietary screening tool (NiDST) on patient-clinician communication and barriers to and facilitators of implementation. A mixed methods approach was used to collect data from patients (n = 151) and clinicians (n = 20) from outpatient clinics in Nigeria. Patients completed the validated 25-item NiDST prior to outpatient consultations. Both patients and clinicians completed the Measurement Instrument for Determinants of Innovations (MIDI) questionnaire to assess implementation determinants post-consultation. Semi-structured interviews were conducted for in-depth feedback. The fidelity of implementation was 92% for NiDST-reported dietary discussion, with a mean completion time of <6 min and an accepted marginal increase in consultation time (<10 min). For clinicians, 25% reported time constraints and their additional nutritional knowledge as barriers, while facilitators of NiDST implementation were the clarity and completeness of the NiDST, clinical relevance and improved patient-clinician communication, as reported by all the clinicians. Over 96% of patients reported the NiDST as quick to complete, with 90.7% reporting self-reflection on dietary intake. This study demonstrated the NiDST's potential to enhance patient-clinician communication and highlighted major facilitators of implementation in clinical practice to improve dietary discussion in Nigeria.