Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis

The traditional treatment for phenylketonuria (PKU) is a phenylalanine (Phe)-restricted diet, supplemented with a Phe-free/low-Phe protein substitute. Pharmaceutical treatment with synthetic tetrahydrobiopterin (BH4), an enzyme cofactor, allows a patient subgroup to relax their diet. However, dietary protocols guiding the adjustments of protein equivalent intake from protein substitute with BH4 treatment are lacking. We systematically reviewed protein substitute usage with long-term BH4 therapy. Electronic databases were searched for articles published between January 2000 and March 2020. Eighteen studies (306 PKU patients) were eligible. Meta-analyses demonstrated a significant increase in Phe and natural protein intakes and a significant decrease in protein equivalent intake from protein substitute with cofactor therapy. Protein substitute could be discontinued in 51% of responsive patients, but was still required in 49%, despite improvement in Phe tolerance. Normal growth was maintained, but micronutrient deficiency was observed with BH4 treatment. A systematic protocol to increase natural protein intake while reducing protein substitute dose should be followed to ensure protein and micronutrient requirements are met and sustained. We propose recommendations to guide healthcare professionals when adjusting dietary prescriptions of PKU patients on BH4. Studies investigating new therapeutic options in PKU should systematically collect data on protein substitute and natural protein intakes, as well as other nutritional factors

A review of the characteristics of dietary fibers relevant to appetite and energy intake outcomes in human intervention trials

Background: Many intervention studies have tested the effect of dietary fibers (DFs) on appetite-related outcomes, with inconsistent results. However, DFs comprise a wide range of compounds with diverse properties, and the specific contribution of these to appetite control is not well characterized. Objective: The influence of specific DF characteristics [i.e., viscosity, gel-forming capacity, fermentability, or molecular weight (MW)] on appetite-related outcomes was assessed in healthy humans. Design: Controlled human intervention trials that tested the effects of well-characterized DFs on appetite ratings or energy intake were identified from a systematic search of literature. Studies were included only if they reported 1) DF name and origin and 2) data on viscosity, gelling properties, fermentability, or MW of the DF materials or DF-containing matrixes. Results: A high proportion of the potentially relevant literature was excluded because of lack of adequate DF characterization. In total, 49 articles that met these criteria were identified, which reported 90 comparisons of various DFs in foods, beverages, or supplements in acute or sustained-exposure trials. In 51 of the 90 comparisons, the DF-containing material of interest was efficacious for ≥1 appetiterelated outcome. Reported differences in material viscosity, MW, or fermentability did not clearly correspond to differences in efficacy, whereas gel-forming DF sources were consistently efficacious (but with very few comparisons). Conclusions: The overall inconsistent relations of DF properties with respect to efficacy may reflect variation in measurement methodology, nature of the DF preparation and matrix, and study designs. Methods of DF characterization, incorporation, and study design are too inconsistent to allow generalized conclusions about the effects of DF properties on appetite and preclude the development of reliable, predictive, structure-function relations. Improved standards for characterization and reporting of DF sources and DF-containing materials are strongly recommended for future studies on the effects of DF on human physiology

Capturing health and eating status through a nutritional perception screening questionnaire (NPSQ9) in a randomised internet-based personalised nutrition intervention : the Food4Me study

BACKGROUND: National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. METHODS: Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. RESULTS: A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = -0.181, p < 0.001) and waist circumference (Β = -0.155, p < 0.001), and positively associated with total carotenoids (β = 0.198, p < 0.001), omega-3 fatty acid index (β = 0.155, p < 0.001), Healthy Eating Index (HEI) (β = 0.299, p < 0.001) and Mediterranean Diet Score (MDS) (β = 0. 279, p < 0.001). Findings from the longitudinal intervention study showed a greater reduction in BMI and improved dietary indices among participants with lower NPSQ9 scores. CONCLUSIONS: Healthy eating perceptions and dietary habits captured by the NPSQ9 score, based on nine questionnaire items, were associated with reduced body weight and improved diet quality. Likewise, participants with a lower score achieved greater health improvements than those with higher scores, in response to personalised advice, suggesting that NPSQ9 may be used for early evaluation of nutritional status and to tailor nutritional advice. TRIAL REGISTRATION: NCT01530139 .Peer reviewedFinal Published versio

Personalized Nutrition Advice Reduces Intake of Discretionary Foods and Beverages: Findings From the Food4Me Randomized Controlled Trial

© 2021 American Society for Nutrition. Published by Elsevier Inc. This is an open access article distributed under the Creative Commons Attribution License, https://creativecommons.org/licenses/by-nc-nd/4.0/Objectives This study aimed to examine changes in intake of discretionary foods and beverages following a personalized nutrition intervention using two national classifications for discretionary foods. Methods Participants were recruited into a 6-month RCT across seven European countries (Food4Me) and were randomized to receive generalized dietary advice (Control) or one of three levels of personalized nutrition advice (based on dietary, phenotypic and genotypic information). Dietary intake from a FFQ was used to determine change between baseline and month 6 in (i) % energy, % contribution to total fat, SFA, total sugars and salt and (ii) contribution (%) made by sweets and snacks to intake of total fat, SFA, sugars and salt from discretionary foods and beverages, defined by Food Standards Scotland (FSS) and the Australian Dietary Guidelines (ADG). Results A total of 1270 adults (40.9 (SD 13.0) years; 57% female) completed the intervention. At month 6, percentage sugars from FSS discretionary items was lower in personalized nutrition vs control (19.0 ± 0.37 vs 21.1 ± 0.65; P = 0.005). Percentage energy (31.2 ± 0.59 vs 32.7 ± 0.59; P = 0.031), % total fat (31.5 ± 0.37 vs 33.3 ± 0.65; P = 0.021), SFA (36.0 ± 0.43 vs 37.8 ± 0.75; P = 0.034) and sugars (31.7 ± 0.44 vs 34.7 ± 0.78; P < 0.001) from ADG discretionary items were lower in personalized nutrition vs control. The % contribution of sugars from sweets and snacks was lower in personalized nutrition vs control (19.1 ± 0.36 vs 21.5 ± 0.63; P < 0.001). At 3 months, effects were consistent for ADG discretionary items, while there was no significant differences in personalized nutrition vs control for FSS discretionary items. Conclusions Compared with generalized dietary advice, personalized nutrition advice achieved greater reductions in intake of discretionary foods and beverages when the classification included all foods high in fat, added sugars and salt. Future personalized nutrition strategies may be used to target intake of discretionary foods and beverages. Funding Sources European Commission Food, Agriculture, Fisheries and Biotechnology Theme of the Seventh Framework Programme for Research and Technological Development [265494]. KML is supported by a NHMRC Emerging Leadership Fellowship (APP1173803).Peer reviewe

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their revaluation

The threshold of toxicological concern (TTC) approach is a resource-effective de minimismethod for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritise substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenicmode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both the TTC for DNA-reactive mutagenicityand that applied by default to substances that may be carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class I-III compounds). Critical to the application of the TTC approach to substances that are likely to be DNA-reactive mutagens is the reliability of the software tools used to identify such compounds. Current methods for this task are reviewed and recommendations made for their application

Association between diet-quality scores, adiposity, total cholesterol and markers of nutritional status in European adults: findings from the Food4Me study

Diet-quality scores (DQS), which are developed across the globe, are used to define adherence to specific eating patterns and have been associated with risk of coronary heart disease and type-II diabetes. We explored the association between five diet-quality scores (Healthy Eating Index,HEI; Alternate Healthy Eating Index, AHEI; MedDietScore, MDS; PREDIMED Mediterranean DietScore, P-MDS; Dutch Healthy Diet-Index, DHDI) and markers of metabolic health (anthropometry,objective physical activity levels (PAL), and dried blood spot total cholesterol (TC), total carotenoids,and omega-3 index) in the Food4Me cohort, using regression analysis. Dietary intake was assessed using a validated Food Frequency Questionnaire. Participants (n= 1480) were adults recruited from seven European Union (EU) countries. Overall, women had higher HEI and AHEI than men (p< 0.05), and scores varied significantly between countries. For all DQS, higher scores were associated with lower body mass index, lower waist-to-height ratio and waist circumference, and higher total carotenoids and omega-3-index (p trends < 0.05). Higher HEI, AHEI, DHDI, and P-MDS scores were associated with increased daily PAL, moderate and vigorous activity, and reduced sedentary behaviour (p trend < 0.05). We observed no association between DQS and TC. To conclude,higher DQS, which reflect better dietary patterns, were associated with markers of better nutritional status and metabolic health

Mediterranean diet adherence and genetic background roles within a web-based nutritional intervention: the Food4Me study

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers

Phenotypic factors influencing the variation in response of circulating cholesterol level to personalised dietary advice in the Food4Me study

Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice on the basis of the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as responder and non-responder groups, respectively. There were no significant differences between demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18 : 0, P=0·034) and lower levels of palmitic acid (16 : 0, P=0·009). Total MUFA (P=0·016) and total PUFA (P=0·008) also differed between the groups. In a step-wise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intakes were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82 % and specificity of 83 %. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition

Higher vegetable protein consumption, assessed by an isoenergetic macronutrient exchange model, is associated with a lower presence of overweight and obesity in the web-based Food4me European study

The objective was to evaluate differences in macronutrient intake and to investigate the possible association between consumption of vegetable protein and the risk of overweight/obesity, within the Food4Me randomised, online intervention. Differences in macronutrient consumption among the participating countries grouped by EU Regions (Western Europe, British Isles, Eastern Europe and Southern Europe) were assessed. Relation of protein intake, within isoenergetic exchange patterns, from vegetable or animal sources with risk of overweight/obesity was assessed through the multivariate nutrient density model and a multivariate-adjusted logistic regression. A total of 2413 subjects who completed the Food4Me screening were included, with self-reported data on age, weight, height, physical activity and dietary intake. As success rates on reducing overweight/obesity are very low, form a public health perspective, the elaboration of policies for increasing intakes of vegetable protein and reducing animal protein and sugars, may be a method of combating overweight/obesity at a population level