Ultra-processed foods in public health nutrition: the unanswered questions.

There is a growing interest in the study of the degree of food processing and both health and nutritional outcomes. To that end, several definitions of the degree of processing have been proposed. However, when each of these is used on a common database of nutritional, clinical and anthropometric variables, the observed effect of high intakes of highly processed food, varies considerably.. Moreover, assigning a given food by nutritional experts, to its appropriate level of processing, has been shown to be variable. Thus, the subjective definitions of the degree of food processing and the coding of foods according to these classifications is prone to error is prone to error. Another issue that need resolution is the relative importance of the degree of food processing and the formulation of a processed food. Although correlational studies linking processed food and obesity abound, there is a need for more investigative studies.

Ultra-processed foods in public health nutrition: the unanswered questions.

There is a growing interest in the study of the degree of food processing and both health and nutritional outcomes. To that end, several definitions of the degree of processing have been proposed. However, when each of these is used on a common database of nutritional, clinical and anthropometric variables, the observed effect of high intakes of highly processed food, varies considerably.. Moreover, assigning a given food  by nutritional experts, to its appropriate level of processing, has been shown to be variable. Thus, the subjective definitions of the degree of food processing and the coding of foods according to these classifications is prone to error  is  prone to error. Another issue that need resolution is the relative importance of the degree of food processing and the formulation of a processed food. Although correlational studies linking processed food and obesity abound, there is a need for more investigative studies.

Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18-102 years.

BACKGROUND: The generation of the active form of vitamin B-6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining vitamin B-6 status is unclear. OBJECTIVE: To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. METHODS: Data from 5612 adults aged 18-102 y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples). Plasma PLP and erythrocyte glutathione reductase activation coefficient (EGRac), as a functional indicator of riboflavin, were determined. RESULTS: Older (≥65 y) compared with younger (<65 y) adults had significantly lower PLP concentrations (P < 0.001). A stepwise decrease in plasma PLP was observed across riboflavin categories, from optimal (EGRac ≤1.26), to suboptimal (EGRac: 1.27-1.39), to deficient (EGRac ≥1.40) status, an effect most pronounced in older adults (mean ± SEM: 76.4 ± 0.9 vs 65.0 ± 1.1 vs 55.4 ± 1.2 nmol/L; P < 0.001). In individuals with the variant MTHFR 677TT genotype combined with riboflavin deficiency, compared with non-TT (CC/CT) genotype participants with sufficient riboflavin, we observed PLP concentrations of 52.1 ± 2.9 compared with 76.8 ±0.7 nmol/L (P < 0.001). In participants with available dietary data (i.e., NANS cohort, n = 936), PLP was associated with vitamin B-6 intake (nonstandardized regression coefficient ß: 2.49; 95% CI 1.75, 3.24; P < 0.001), supplement use (ß: 81.72; 95% CI: 66.01, 97.43; P < 0.001), fortified food (ß: 12.49; 95% CI: 2.08, 22.91; P = 0.019), and EGRac (ß: -65.81; 95% CI: -99.08, -32.54; P < 0.001), along with BMI (ß: -1.81; 95% CI: -3.31, -0.30; P = 0.019). CONCLUSIONS: These results are consistent with the known metabolic dependency of PLP on flavin mononucleotide (FMN) and suggest that riboflavin may be the limiting nutrient for maintaining vitamin B-6 status, particularly in individuals with the MTHFR 677TT genotype. Randomized trials are necessary to investigate the PLP response to riboflavin intervention within the dietary range. The TUDA study and the NANS are registered at www.ClinicalTrials.gov as NCT02664584 (27 January 2016) and NCT03374748 (15 December 2017), respectively.Clinical Trial Registry details: Trinity-Ulster-Department of Agriculture (TUDA) study, ClinicalTrials.gov no. NCT02664584 (January 27th 2016); National Adult Nutrition Survey (NANS), ClinicalTrials.gov no. NCT03374748 (December 15th 2017).

Nutrition research challenges for processed food and health.

Existing highly processed food (HPF) classification systems show large differences in the impact of these foods on biochemical risk factors for disease. If public health nutrition is to consider the degree of food processing as an important element of the link between food and health, certain gaps in research must be acknowledged. Quantifying the food additive exposure derived from HPFs is a task made challenging by the lack of data available on the occurrence and concentration of additives in food and the degree to which the natural occurrence of additives in unprocessed foods confounds exposure estimates. The proposed role of HPFs in health outcomes could also be associated with altered nutrient profiles. Differences exist within and between HPF classification systems in this regard and there are conflicting data on the impact of controlling for nutrient intake. Furthermore, research is needed on how the sensory aspects of HPFs contribute to energy intake. Current data suggest that high energy intake rate may be the mechanism linking HPFs and increased energy intake. A high priority now is to clarify the basis of definitions used to categorize foods as highly processed and, in a constructive sense, to distinguish between the contributions of nutrients, additives and sensory properties to health.

Genetic and Environmental Contributions to Variation in the Stable Urinary NMR Metabolome over Time: A Classic Twin Study.

Genes, sex, age, diet, lifestyle, gut microbiome, and multiple other factors affect human metabolomic profiles. Understanding metabolomic variation is critical in human nutrition research as metabolites that are sensitive to change versus those that are more stable might be more informative for a particular study design. This study aims to identify stable metabolomic regions and determine the genetic and environmental contributions to stability. Using a classic twin design, 1H nuclear magnetic resonance (NMR) urinary metabolomic profiles were measured in 128 twins at baseline, 1 month, and 2 months. Multivariate mixed models identified stable urinary metabolites with intraclass correlation coefficients ≥0.51. Longitudinal twin modeling measured the contribution of genetic and environmental influences to variation in the stable urinary NMR metabolome, comprising stable metabolites. The conservation of an individual's stable urinary NMR metabolome over time was assessed by calculating conservation indices. In this study, 20% of the urinary NMR metabolome is stable over 2 months (intraclass correlation (ICC) 0.51-0.65). Common genetic and shared environmental factors contributed to variance in the stable urinary NMR metabolome over time. Using the stable metabolome, 91% of individuals had good metabolomic conservation indices ≥0.70. To conclude, this research identifies 20% of the urinary NMR metabolome as stable, improves our knowledge of the sources of metabolomic variation over time, and demonstrates the conservation of an individual's urinary NMR metabolome.

Genetic and environmental influences on covariation in reproducible diet-metabolite associations.

BACKGROUND: Early applications of metabolomics in nutrition and health research identified associations between dietary patterns and metabolomic profiles. Twin studies show that diet-related phenotypes and diet-associated metabolites are influenced by genes. However, studies have not examined whether diet-metabolite associations are explained by genetic or environmental factors and whether these associations are reproducible over multiple time points. OBJECTIVE: This research aims to examine the genetic and environmental factors influencing covariation in diet-metabolite associations that are reproducible over time in healthy twins. METHODS: The UCD Twin Study is a semi-longitudinal classic twin study that collected repeated dietary, anthropometric, and urinary data over 2 months. Correlation analysis identified associations between diet quality measured using the Healthy Eating Index (HEI) and urinary metabolomic profiles at 3 time points. Diet-associated metabolites were examined using linear regression to identify those significantly influenced by familial factors between twins and those significantly influenced by unique factors. Cholesky decomposition modeling quantified the genetic and environmental path coefficients through associated dietary components onto the metabolites. RESULTS: The HEI was associated with 14 urinary metabolites across 3 metabolomic profiles (r: ±0.15-0.49). For 8 diet-metabolite associations, genetic or shared environmental factors influencing HEI component scores significantly influenced variation in metabolites (ß: 0.40-0.52). A significant relation was observed between dietary intakes of whole grain and acetoacetate (ß: -0.50, P < 0.001) and ß-hydroxybutyrate (ß: -0.46, P < 0.001), as well as intakes of saturated fat and acetoacetate (ß: 0.47, P < 0.001) and ß-hydroxybutyrate (ß: 0.52, P < 0.001). For these diet-metabolite associations a common shared environmental factor explained 66-69% of variance in the metabolites. CONCLUSIONS: This study shows that diet-metabolite associations are reproducible in 3 urinary metabolomic profiles. Components of the HEI covary with metabolites, and covariation is largely due to the shared environment.

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project.

BACKGROUND: Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. METHODS: Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods. RESULTS: The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). CONCLUSIONS: The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

Exploring Covariation between Traditional Markers of Metabolic Health and the Plasma Metabolomic Profile: A Classic Twin Design.

Novel metabolomic profiling techniques combined with traditional biomarkers provide knowledge of mechanisms underlying metabolic health. Twin studies describe the impact of genes and environment on variation in traits. This study aims to identify relationships between traditional markers of metabolic health and the plasma metabolomic profile using a twin modeling approach and determine whether covariation is caused by shared genetic and environmental factors. Using a classic twin design, this study examined covariation between anthropometric, clinical chemistry, and metabolomic profiles. Cholesky decomposition modeling was used to determine the genetic and environmental path coefficients through successive anthropometric and clinical chemistry traits onto metabolomic derived metabolites. This study shows that WC, TAG, and a metabolomic signature composed of 7 metabolites are inter-related, and that covariation can be attributed to common genetic, shared and unique environmental factors as well as unique environmental factors specific to the metabolite. This quantitative modeling connecting the traditional anthropometry and clinical chemistry traits with the more recent and potentially more sensitive metabolomic profile approach may provide further insight on the pleiotropic genes or modifiable environmental factors influencing variation in metabolic health.

Breakfast: Shaping Guidelines for Food and Nutrient Patterns.

Whilst there is extensive literature on the health benefits of a regular breakfast, there are few guidelines to help policy makers to issue specific targets on optimal nutrient intake at breakfast or the selection of foods to attain these targets. The food and nutritional advice on breakfast offered by most governments is confined to simple advice on food servings. The USA and Mexico typify the few countries that have attempted to issue specific nutrient targets for breakfast. However, these simply reflect general nutrient guidelines for adults, adjusted to suit lower energy needs of toddlers and school children. Little guidance is issued on micronutrient intake, and the advice on food choice does not appear to be linked to patterns of nutrient intake. The application of cluster and principal component analysis, which is used to determine the patterns of daily or breakfast food consumption and also link them to nutrient intake, greatly improved our understanding of optimal breakfast choices. Using 6 national nutrition surveys (Canada, Denmark, France, Spain, the UK, and the USA), the International Breakfast Research Initiative has opted to score each individual with a measure of overall daily nutritional quality (based on the nutrient-rich food index). It is hoped that options for the derivation in breakfast nutrient targets and associated food-based guidelines will arise from an analysis of tertiles of this score. Ultimately, meal-based advice will become the basic building block for digitally based personalized dietary analysis and guidelines.

Ultra-Processed Foods: Definitions and Policy Issues.

Four categories of foods are proposed in the NOVA food classification, which seeks to relate food processing as the primary driver of diet quality. Of these, the category "ultra-processed foods" has been widely studied in relation both to diet quality and to risk factors for noncommunicable disease. The present paper explores the definition of ultra-processed foods since its inception and clearly shows that the definition of such foods has varied considerably. Because of the difficulty of interpretation of the primary definition, the NOVA group and others have set out lists of examples of foods that fall under the category of ultra-processed foods. The present manuscript demonstrates that since the inception of the NOVA classification of foods, these examples of foods to which this category applies have varied considerably. Thus, there is little consistency either in the definition of ultra-processed foods or in examples of foods within this category. The public health nutrition advice of NOVA is that ultra-processed foods should be avoided to achieve improvements in nutrient intakes with an emphasis on fat, sugar, and salt. The present manuscript demonstrates that the published data for the United States, United Kingdom, France, Brazil, and Canada all show that across quintiles of intake of ultra-processed foods, nutritionally meaningful changes are seen for sugars and fiber but not for total fat, saturated fat, and sodium. Moreover, 2 national surveys in the United Kingdom and France fail to show any link between body mass index and consumption of ultra-processed foods. The paper concludes that constructive scholarly debate needs to be facilitated on many issues that would be affected by a policy to avoid ultra-processed foods.

Whole grain intakes in Irish adults: findings from the National Adults Nutrition Survey (NANS).

PURPOSE: Observational studies link high whole grain intakes to reduced risk of many chronic diseases. This study quantified whole grain intakes in the Irish adult population and examined the major contributing sources. It also investigated potential dietary strategies to improve whole grain intakes. METHODS: Whole grain intakes were calculated in a nationally representative sample of 1500 Irish adults using data from the most recent national food survey, the National Adult Nutrition Survey (NANS). Food consumption was assessed, at brand level where possible, using a 4-day semi-weighed food diary with whole grain content estimated from labels on a dry matter basis. RESULTS: Mean daily whole grain intakes were 27.8 ± 29.4 g/day, with only 19% of the population meeting the quantity-specific recommendation of 48 g per day. Wheat was the highest contributor to whole grain intake at 66%, followed by oats at 26%. High whole grain intakes were associated with higher dietary intakes of fibre, magnesium, potassium, phosphorus, and a higher alternative Mediterranean Diet Score. Whole grain foods were most frequently eaten at breakfast time. Regression analysis revealed that consumption of an additional 10 g of whole grain containing 'ready-to-eat breakfast cereals', 'rice or pastas', or 'breads' each day would increase intake of whole grains by an extra 5, 3.5, and 2.7 g, respectively. CONCLUSIONS: This study reveals low intakes of whole grains in Irish adults. Recommending cereals, breads, and grains with higher whole grain content as part of public health campaigns could improve whole grain intakes.

Analysis of the National Adult Nutrition Survey (Ireland) and the Food4Me Nutrition Survey Databases to Explore the Development of Food Labelling Portion Sizes for the European Union.

The present study set out to explore the option of developing food portion size for nutritional labelling purposes using two European Union (EU) dietary surveys. The surveys were selected as they differed in (a) methodologies (food diary versus food frequency questionnaire), (b) populations (Irish National Adult Nutrition Survey (NANS) versus a seven-country survey based on the pan EU study Food4Me), (c) food quantification (multiple options versus solely photographic album) and (d) duration (4 consecutive days versus recent month). Using data from these studies, portion size was determined for 15 test foods, where portion size was defined as the median intake of a target food when consumed. The median values of the portion sizes derived from both the NANS and Food4Me surveys were correlated (r = 0.823; p < 0.00) and the mean of the two survey data sets were compared to US values from the Recognized as Customarily Consumed (RACC) database. There was very strong agreement across all food categories between the averaged EU and the US portion size (r = 0.947; p < 0.00). It is concluded that notwithstanding the variety of approaches used for dietary survey data in the EU, the present data supports using a standardized approach to food portion size quantification for food labelling in the EU.

Towards an Evidence-Based Recommendation for a Balanced Breakfast-A Proposal from the International Breakfast Research Initiative.

The International Breakfast Research Initiative (IBRI) set out to derive nutritional recommendations for a balanced breakfast using a standardized analysis of national nutrition surveys from Canada, Denmark, France, Spain, UK and the US. In all countries, the frequency of breakfast consumption by age was high and U-shaped with children and older adults having a higher frequency of breakfast consumption. Breakfast contributed 16% to 21% of daily energy intake. In all countries, breakfast was a carbohydrate- and nutrient-rich meal, providing more carbohydrates (including sugars), thiamin, riboflavin, folate, calcium, potassium, and magnesium, and less vitamin A, fats and sodium relative to its contribution to daily energy intakes. Breakfast consumers were stratified by tertiles of the Nutrient Rich Foods (NRF) index, used as a measure of diet quality. Breakfast intakes associated with the top tertile of NRF, along with the Codex Alimentarius international food standards and World Health Organization (WHO) diet guidelines, were used to derive the proposed nutrient recommendations. The goal was to preserve the nutrient density of existing breakfasts, while addressing concerns regarding added sugars, saturated fats, dietary fiber, and vitamin D. This initiative is unique in seeking to derive nutrient recommendations for a specific meal using the observed nutritional profile of such meal.

A proteomic signature that reflects pancreatic beta-cell function.

AIM: Proteomics has the potential to enhance early identification of beta-cell dysfunction, in conjunction with monitoring the various stages of type 2 diabetes onset. The most routine method of assessing pancreatic beta-cell function is an oral glucose tolerance test, however this method is time consuming and carries a participant burden. The objectives of this research were to identify protein signatures and pathways related to pancreatic beta-cell function in fasting blood samples. METHODS: Beta-cell function measures were calculated for MECHE study participants who completed an oral glucose tolerance test and had proteomic data (n = 100). Information on 1,129 protein levels was obtained using the SOMAscan assay. Receiver operating characteristic curves were used to assess discriminatory ability of proteins of interest. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Replication of findings were achieved in a second human cohort where possible. RESULTS: Twenty-two proteins measured by aptamer technology were significantly associated with beta-cell function/HOMA-IR while 17 proteins were significantly associated with the disposition index (p ≤ 0.01). Receiver operator characteristic curves determined the protein panels to have excellent discrimination between low and high beta-cell function. Linear regression analysis determined that beta-endorphin and IL-17F have strong associations with beta-cell function/HOMA-IR, ß = 0.039 (p = 0.005) and ß = -0.027 (p = 0.013) respectively. Calcineurin and CRTAM were strongly associated with the disposition index (ß = 0.005 and ß = 0.005 respectively, p = 0.012). In vitro experiments confirmed that IL-17F modulated insulin secretion in the BRIN-BD11 cell line, with the lower concentration of 10 ng/mL significantly increasing glucose stimulated insulin secretion (p = 0.043). CONCLUSIONS: Early detection of compromised beta-cell function could allow for implementation of nutritional and lifestyle interventions before progression to type 2 diabetes.

Breakfast in Human Nutrition: The International Breakfast Research Initiative.

Breakfast is often referred to as the most important meal of the day and in recent years has been implicated in weight control, cardio-metabolic risk factors and cognitive performance although, at present, the literature remains inconclusive as to the precise health benefits of breakfast. There are extensive reports of breakfast’s contributions to daily food and nutrient intakes, as well as many studies that have compared daily food and nutrient intakes by breakfast consumers and skippers. However, significant variation exists in the definitions of breakfast and breakfast skippers, and in methods used to relate breakfast nutrient intakes to overall diet quality. The present review describes a novel and harmonised approach to the study of the nutritional impact of breakfast through The International Breakfast research Initiative involving national dietary survey data from Canada, Denmark, France, Spain, the UK and the USA. It is anticipated that the analysis of such data along harmonised lines, will allow the project to achieve its primary goal of exploring approaches to defining optimal breakfast food and nutrient intakes. Such data will be of value to public health nutrition policy-makers and food manufacturers and will also allow consistent messaging to help consumers to optimize food choices at breakfast.

A Life in Food: A Grain of Salt and Some Humble Pie.

From my senior school days, I had wanted to pursue a career in food. In quite what capacity I was not too sure. So my starting points were within the fields of animal nutrition before moving for the major part of my career to medical schools to study human nutrition and health. My career scientific achievements lie within the Kuhnian spectrum of normal science, but within that normality, I was always one to challenge conventional wisdom. An academic career is about more than just research. It is about teaching and not just the minutiae of nutrition, but about life and living, about challenges and failures. Reflecting on the experience of that career, my advice to early stage researchers is this: Be patient, determined, and resilient in the very early stages. Hold no fear of change and be courageous in challenging conventional wisdom. Always favor openness and collaboration and always seek to help others. Citation indices are important to your career, but these other avenues that I advise you to follow are what you will eventually be most proud of.

Adiposity Associated Plasma Linoleic Acid is Related to Demographic, Metabolic Health and Haplotypes of FADS1/2 Genes in Irish Adults.

SCOPE: This study examines to what extent plasma linoleic acid (LA) is modified by adiposity, and explores any association between plasma LA, demographics, dietary intakes, markers of metabolic health, and haplotypes of the fatty acid desaturase (FADS) 1/2 genes. METHODS AND RESULTS: A total of 820 participants with fasting blood samples from the Irish National Adult Nutrition Survey are studied. Plasma fatty acids are determined using GC-MS. Fifteen SNPs of FADS 1/2 genes are genotyped. Plasma LA decreases, while γ-linoleic acid and dihomo-γ-linoleic acid increases in overweight/obese participants (p ≤ 0.002). Participants in the highest quartile of plasma LA show decreased plasma markers of de novo lipogenesis, insulin resistance, and of inflammation (TNF-α, PAI-1) (p ≤ 0.005). Adiposity (waist circumference and body fat) is strongly inversely associated with plasma LA accounting for 11.8% of variance observed, which is followed by FADS1/2 haplotypes (3.9%), quantity and quality of carbohydrate intakes (3.8%), dietary PUFA intakes (3.7%), systolic blood pressure (3.6%), and age (3.2%). CONCLUSION: Plasma LA is inversely associated with adiposity, followed by haplotypes of FADS1/2 genes, carbohydrate intakes, and dietary PUFA intakes. The association observed between plasma LA and adiposity may be linked to decreased de novo lipogenesis, insulin resistance, and inflammation.