Longitudinal Dietary Intake Data in Patients with Phenylketonuria from Europe: The Impact of Age and Phenylketonuria Severity.

In phenylketonuria (PKU), natural protein intake is thought to increase with age, particularly during childhood and adolescence. Longitudinal dietary intake data are scarce and lifelong phenylalanine tolerance remains unknown. Nine centres managing PKU in Europe and Turkey participated in a retrospective study. Data were collected from dietetic records between 2012 and 2018 on phenylalanine (Phe), natural protein, and protein substitute intake. A total of 1323 patients (age range: 1-57 y; 51% male) participated. Dietary intake data were available on 1163 (88%) patients. Patient numbers ranged from 59 to 320 in each centre. A total of 625 (47%) had classical PKU (cPKU), n = 357 (27%) had mild PKU (mPKU), n = 325 (25%) had hyperphenylalaninemia (HPA), and n = 16 (1%) were unknown. The mean percentage of blood Phe levels within target ranged from 65 ± 54% to 88 ± 49%. When intake was expressed as g/day, the mean Phe/natural protein and protein equivalent from protein substitute gradually increased during childhood, reaching a peak in adolescence, and then remained consistent during adulthood. When intake was expressed per kg body weight (g/kg/day), there was a decline in Phe/natural protein, protein equivalent from protein substitute, and total protein with increasing age. Overall, the mean daily intake (kg/day) was as follows: Phe, 904 mg ± 761 (22 ± 23 mg/kg/day), natural protein 19 g ± 16 (0.5 g/kg/day ± 0.5), protein equivalent from protein substitute 39 g ± 22 (1.1 g/kg/day ± 0.6), and total protein 59 g ± 21 (1.7 g/kg/day ± 0.6). Natural protein tolerance was similar between males and females. Patients with mPKU tolerated around 50% less Phe/natural protein than HPA, but 50% more than cPKU. Higher intakes of natural protein were observed in Southern Europe, with a higher prevalence of HPA and mPKU compared with patients from Northern European centres. Natural protein intake doubled with sapropterin usage. In sapropterin-responsive patients, 31% no longer used protein substitutes. Close monitoring and optimisation of protein intake prescriptions are needed, along with future guidelines specifically for different age groups and severities.

Protein Intake and High Uric Acid Stone Risk.

Rationale & Objective: We evaluated the metabolic differences between pure and impure uric acid stone formers in this retrospective study of uric acid kidney stone formers diagnosed between 1996 and 2021. Study Design: Demographics and medical history were compared by χ2 tests. Twenty-four-hour urine chemistries were compared using logistic regressions while controlling for demographics and comorbid conditions. Setting & Participants: Patients from Yale Urology and Nephrology Clinics with a documented kidney stone analysis containing uric acid were included. In total, 4,294 kidney stone formers had a stone analysis, and 722 (16.8%) contained uric acid. Patients with all stone analyses  ≥ 50% uric acid were allocated to the pure group, while patients with ≥1 stone analysis <50% uric acid were allocated to the impure group. Results: Among kidney stone formers, the prevalence of uric acid nephrolithiasis was 16.8%. Pure uric acid stone formers were more likely to be older, heavier, and were 1.5 times more likely to have chronic kidney disease. When controlling for age, sex, race, ethnicity, and body mass index, pure uric acid stone formers had lower urinary pH and lower urine citrate normalized for creatinine. Additionally, they had a higher protein catabolic rate, urine urea nitrogen, and urine sulfur normalized for creatinine, all markers of dietary protein intake. These findings persisted after controlling for chronic kidney disease. Limitations: This is a retrospective study from a single center. Conclusions: Pure uric acid stone formation is more common with diminished kidney function; however, after controlling for kidney function, pure uric acid stone formation is associated with protein intake, suggesting that modifying protein intake may reduce risk.

The impact of protein delivery on short-term and long-term clinical outcomes in critically ill patients: Protocol for a multicenter, prospective, observational study (The ACTION study).

BACKGROUND AND AIMS: Nutrition therapy is a vital part of the management of critically ill patients. Efforts have been made to optimize nutrition therapy in the ICU setting, and it is argued that protein might be the most important substrate to deliver during critical illness. However, the impact of protein delivery on patient-centered outcomes, including short-term and long-term outcomes, is controversial. Moreover, previous studies showed that compliance with the guidelines is poor in practice, and the amounts of protein intake vary significantly among different hospitals. The objective of this study is to describe the current practice of protein delivery for critically ill patients and to investigate the association between different protein delivery amounts and approaches during ICU admission and multiple patient-centered outcomes (short-term and long-term). METHODS: This is a multicenter, prospective, observational study conducted in 70 hospitals, aiming to recruit more than 1800 newly admitted critically ill patients who are expected to stay in ICU for at least 48 h. Data, including the baseline characteristics, illness severity scores, requirements of organ support therapy, and daily nutritional therapy, will be recorded until day 28 after enrollment unless discharge from the ICU or death occurs first. The key long-term clinical outcomes, like readmission post the index discharge and health-related quality of life, will be collected via telephone contact on Day 90 and Day 180 after recruitment. Quality of life will be assessed by the EuroQol five dimensions five-level questionnaire (EQ5D5L) visual analogue scale score. Apart from descriptive data, multivariate analyses adjusted for potential confounders will be applied to assess the association between protein intake during ICU stay and short-term and long-term clinical outcomes. ETHICS AND TRIAL REGISTRATION: This study was reviewed and approved by the ethics committee of Jinling Hospital (2021NZKY-027-01) and the participating sites. The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200067016) before enrollment.

Food choice, activity level, and carbon footprint: exploring potential for sustainable food consumption practices in young adults.

This study aims to explore climate consciousness in relation to food consumption in young adults, examining its relationship with physical activity level and gender. A mixed-method approach is utilized, integrating seven-day food records and semi-structured interviews, employing social practice theory in our analytical framework. Our cohort of 47 participants (25 women, 22 men) displays varied diets, from omnivores to vegans. Moderately-active women show the lowest carbon footprint, favoring climate-conscious choices related to lower energy needs and plant-based preferences. Highly-active individuals consume more energy, resulting in a higher carbon footprint. Gender differences are evident, women were inclined to climate-conscious food practices motivated by animal ethics and health concerns. Conversely, men demonstrated a tendency for meat consumption. Participants share an understanding of carbon footprint, reflecting a solid awareness of food-related climate impact but differ in priorities; performance for highly-active, and economy for moderately-active. This highlights a mix of commonalities and distinctions, informing flexible, sustainable food practices. Higher activity levels are linked to greater energy needs and a higher carbon footprint. Moderately-active women show the most climate-conscious food choices, leading to the lowest carbon footprint. Our findings indicate that highly-active individuals and men have significant potential to improve climate-adapted food consumption.

Exploring the impact of protein intake on the association between oxidative balance score and lean mass in adults aged 20-59: NHANES 2011-2018.

BACKGROUND: Previous studies have established a correlation between the pathogenesis of oxidative stress and sarcopenia. The Oxidative Balance Score (OBS) is an integrated measure that reflects the overall balance of antioxidants and pro-oxidants in dietary components and lifestyle. However, there are limited reports on the association between OBS and lean mass and the impact of protein intake on the association between OBS and lean mass. METHODS: Using data from the National Health and Nutrition Examination Survey from 2011 to 2018, multivariate linear and logistic regression analyses were conducted to explore the associations between OBS and outcomes. The findings were then illustrated through fitted smoothing curves and threshold effect analyses. RESULTS: This study included 2,441 participants, demonstrating that higher OBS is significantly associated with an increased ratio of appendicular lean mass to body mass index. Key inflection points at OBS 31 mark pronounced changes in these associations, with age and protein intake notably affecting the association. The effect of OBS on lean mass varies among populations with high and low protein intake. CONCLUSIONS: Our findings suggest that OBS is significantly and positively associated with lean mass. A high protein intake of more than 84.5 g/day may enhance the role of OBS in influencing muscle health to improve muscle outcomes.

A vegan dietary pattern is associated with high prevalence of inadequate protein intake in older adults; a simulation study.

BACKGROUND: A more sustainable diet with fewer animal-based products has a lower ecological impact but might lead to a lower protein quantity and quality. The extent to which shifting to more plant-based diets impacts the adequacy of protein intake in older adults needs to be studied. OBJECTIVES: We simulated how a transition towards a more plant-based diet (flexitarian, pescetarian, vegetarian, or vegan) affects protein availability in the diets of older adults. SETTING: Community. PARTICIPANTS: Data from the Dutch National Food Consumption Survey 2019-2021 of community-dwelling older adults (n = 607) was used MEASUREMENTS: Food consumption data was collected via two 24 -h dietary recalls per participant. Protein availability was expressed as total protein, digestible protein, and utilizable protein (based on digestibility corrected amino acid score) intake. The percentage below estimated average requirements (EAR) for utilizable protein was assessed using an adjusted EAR. RESULTS: Compared to the original diet (∼62% animal-based), utilizable protein intake decreased by about 5% in the flexitarian, pescetarian and vegetarian scenarios. In the vegan scenario, both total protein intake and utilizable protein were lower, leading to nearly 50% less utilizable protein compared to the original diet. In the original diet, the protein intake of 7.5% of men and 11.1% of women did not meet the EAR. This slightly increased in the flexitarian, pescetarian, and vegetarian scenarios. In the vegan scenario, 83.3% (both genders) had a protein intake below EAR. CONCLUSIONS: Replacing animal-based protein sources with plant-based food products in older adults reduces both protein quantity and quality, albeit minimally in non-vegan plant-rich diets. In a vegan scenario, the risk of an inadequate protein intake is imminent.

Dietary protein intake and its association with physical fitness test among older adults with pre-sarcopenia and sarcopenia: A cross-sectional study.

BACKGROUND: Low protein intake and physical inactivity are factors that associated with muscle deterioration and poor physical performance among older adults. AIM: To assess the association between dietary protein intake and physical fitness tests among older adults with pre-sarcopenia and sarcopenia. METHODS: A total of 110 older adults were recruited through a convenience sampling method. Data including sociodemography, anthropometry, body composition, medical history, and dietary protein intake were obtained through the interview-administered method. RESULTS: Most of the subjects have low household income (

Protein Supplement Tolerability and Patient Satisfaction after Bariatric Surgery.

PURPOSE: Disproportional fat-free mass loss often occurs post-bariatric surgery, partly due to insufficient protein intake during the post-surgery recovery phase. We compared five protein-enhancing strategies (PES) on patient tolerability, satisfaction and protein intake. MATERIALS AND METHODS: Ninety-four participants, scheduled for bariatric surgery, were enrolled and allocated to either of the following: (1) whey powder, (2) hydrolysed collagen powder, (3) plant-based powder, (4) protein-rich products, (5) protein gel, or control. PES groups were instructed to add 30 g of powder or 2 gels or protein products to their diet. Patient satisfaction and tolerability were evaluated with questionnaires. Dietary intake was assessed prior to and during PES use. RESULTS: Seven patients dropped out (i.e. loss of contact, personal reasons or post-surgery complications) yielding an analytical cohort of 87 participants. The majority of patients (61%) did not experience dietary complaints from PES and could use PES ≥ 5 days of the week. PES non-usage was mainly related to taste dislike (58%). Hydrolysed collagen scored highest on tolerability and satisfaction: 86% of the participants could use HC ≥ 5 days and 71% were satisfied with the product. PES increased protein intake from 54.7 ± 21.5 g/day to 64.7 ± 23.4 g/day during the intervention (p = 0.002), which differed from the control group (+ 10.1 ± 24.5 g/day vs. - 6.3 ± 23.8 g/day for controls, p = 0.019). Whey showed the highest increase, namely + 18.3 ± 16.3 g/day (p = 0.009). CONCLUSION: PES were tolerated by the majority of participants, and an improved protein intake with PES use was seen. However, the taste of the products could be improved to further enhance satisfaction and tolerability.

Protein intake and episodic memory: the moderating role of the apolipoprotein E ε4 status.

BACKGROUND: This study investigated the correlation between protein intake and Alzheimer's disease (AD)-related cognitive decline, particularly in episodic memory, among older adults without dementia. Furthermore, we assessed the moderating effect of apolipoprotein ε4 (APOE4) on this association and analyzed its influence on other cognitive functions beyond memory. METHODS: The study involved 196 participants who underwent assessments for protein intake, cognitive performance, APOE4 genotyping, and nutritional biomarkers. Protein intake was categorized into low, medium, and high based on the consumption of dairy, legumes, eggs, meat, and fish. RESULTS: High protein intake was significantly associated with better episodic memory and overall cognition. Moreover, a significant interaction was found between high protein intake and APOE4, indicating that APOE4 moderates the association between high protein intake level and episodic memory. Sensitivity analysis confirmed these results among participants with stable food intake. CONCLUSIONS: Our study results demonstrated that high protein intake is associated with better episodic memory among older adults without dementia. Furthermore, the findings highlight the significant role of APOE4 status in moderating the relationship between protein consumption and episodic memory. These results suggest that dietary interventions focusing on protein intake could be beneficial for cognitive health, particularly in individuals with a genetic predisposition to AD.

Opposing GPCR signaling programs protein intake setpoint in Drosophila.

Animals defend a target level for their fundamental needs, including food, water, and sleep. Deviation from the target range, or "setpoint," triggers motivated behaviors to eliminate that difference. Whether and how the setpoint itself is encoded remains enigmatic for all motivated behaviors. Employing a high-throughput feeding assay in Drosophila, we demonstrate that the protein intake setpoint is set to different values in male, virgin female, and mated female flies to meet their varying protein demands. Leveraging this setpoint variability, we found, remarkably, that the information on the intake setpoint is stored within the protein hunger neurons as the resting membrane potential. Two RFamide G protein-coupled receptor (GPCR) pathways, by tuning the resting membrane potential in opposite directions, coordinately program and adjust the protein intake setpoint. Together, our studies map the protein intake setpoint to a single trackable physiological parameter and elucidate the cellular and molecular mechanisms underlying setpoint determination and modulation.

Association between objectively measured protein intake and muscle status, health-related quality of life, and mortality in hemodialysis patients.

BACKGROUND: Protein intake is known to be associated with muscle mass, health-related quality of life (HRQoL), and mortality in patients with stage 5 chronic kidney disease undergoing dialysis. However, most studies evaluated protein intake based on 24 h dietary recall or food frequency questionnaire, and these methods are prone to bias. Therefore, this study aimed to evaluate the association of objectively measured protein intake with muscle mass and strength, HRQoL, and mortality. METHODS: Dietary protein intake was calculated based on the combined (urinary and dialysate) urea excretion rate according to the Maroni formula and indexed to body weight. Muscle mass was calculated based on the combined dialysate and urinary creatinine excretion rate, and muscle strength was assessed by handgrip strength. HRQoL was based on the Short Form 36. Linear and Cox regression were used for the analyses. RESULTS: We included 59 hemodialysis patients (mean age 65 ± 15 years, 37% female, median hemodialysis vintage 15 [6-39] months). Mean protein intake was 0.82 ± 0.23 g/kg/day, and 76% had a low protein intake (<1.0 g/kg/day). Higher protein intake was independently associated with higher muscle mass (Standardized beta (St. ß) [95% confidence interval (95%CI) = 0.56 [0.34 to 0.78]) and higher scores on the physical functioning domain of HRQoL (St. ß [95%CI] = 0.49 [0.25 to 0.73]), but not with muscle strength (St. ß [95%CI] = 0.17 [-0.10 to 0.43]). During a median follow-up of 21.6 [8.6-36.6] months, 16 (27.1%) patients died. Higher protein intake was associated with lower mortality risk (hazard ratio [95%CI] = 0.34 [0.16-0.73]). This association remained significant after adjustment for potential confounders. CONCLUSIONS: Protein intake is independently associated with muscle mass, physical functioning domain of HRQOL, and mortality. Clinicians and dietitians should closely monitor the protein intake of hemodialysis patients.

Prospective study of protein intake and mortality among US adults with chronic obstructive pulmonary disease.

Background: Protein is crucial for the rehabilitation of patients with chronic obstructive pulmonary disease (COPD), and appropriate daily protein intake is essential for COPD patients. However, the specific role of protein intake in COPD and its impact on mortality remain uncertain. This study aims to ascertain the relationship between protein intake and mortality in COPD patients. Methods: This investigation included 522 adult COPD patients from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018, with a focus on evaluating protein intake. Multivariate Cox proportional hazard models were constructed to analyze the correlation between protein intake and the prognosis of COPD patients. Additionally, the restricted cubic spline (RCS) was employed to investigate the potential non-linear association between protein intake and mortality. Results: A total of 522 patients with COPD were categorized into 4 groups based on the quartiles of protein intake: Q1 (< 25th percentile, 11.7-48.5 gm), Q2 (25-50th percentile, 48.5-67.7 gm), Q3 (50-75th percentile, 67.7-94.3 gm), and Q4 (≥ 75th percentile, 94.3-266.6 gm). Cox regression analysis revealed a significant trend in the p value of the Q3 group compared to the Q1 group when adjusting for other variables. The RCS-fitted Cox regression model indicated no non-linear relationship between protein intake levels and COPD mortality. Conclusion: There is no evidence of a non-linear relationship between protein intake and all-cause mortality in COPD patients. Further investigation is warranted to comprehend the intricate relationship between protein intake and COPD outcomes.

Estimating Dietary Protein and Sodium Intake with Sodium Removal in Peritoneal Dialysis Patients.

An increase in dietary protein intake (DPI) carries a risk with respect to increased sodium intake, which further leads to the development of cardiovascular morbidity in peritoneal dialysis (PD) patients. Dialytic (DSR) and urinary sodium removal (USR) are potential indicators of sodium intake. In this single-center cross-sectional study with 60 prevalent PD patients, we analyze the correlation of DPI with sodium intake and the association between residual renal function (RRF) and comorbidity grade, expressed as the Davies score with sodium removal and protein metabolism indices such as normalized protein catabolic rate (nPCR) and lean body mass (LBM). The value of RRF < 2 mL/min/1.73 m2 is significantly associated with lower USR (p = 0.000) and lower %LBM (p < 0.001). The greatest USR is detected in patients with low Davies comorbidity grade (p = 0.018). Compared to patients with DPI < 0.8 g/kg/day, patients with DPI > 0.8 g/kg/day have a greater sodium intake (3.69 ± 0.71 vs. 2.94 ± 0.86; p < 0.018) and a greater nPCR (p < 0.001). Protein intake is significantly correlated with sodium intake (p = 0.041), but not with total sodium removal (TSR). A strong correlation is observed between sodium intake and TSR (p = 0.000), although single TSR values are not the same as the corresponding sodium intake values. An increasing protein intake implies the necessity to determine both sodium intake and sodium removal. Preservation of RRF has a beneficial role not just in sodium removal, but also in the increase of LBM.

Hydroelectrolytic and nutritional needs of infants with epidermolysis bullosa during the first month of life.

Dehydration and malnutrition are common in infants with severe epidermolysis bullosa (EB), but their nutritional needs have been poorly studied. The principal aim was to assess the nutritional status, fluid and electrolyte balance, and nutritional intake of newborns with EB during the first month of life and estimate their needs during this period. This was a retrospective study over an eight-year period. Inclusion criteria were neonates with confirmed EB admitted to our neonatal referral unit during the first month of life. Exclusion criteria were hospitalisations <7 days. Twenty-seven patients with EB (mean [min-max] gestational age = 39 weeks [33; 41]; birth weight = 2986 g [1982; 4150]), were included. Four patients (15%) had hyponatraemia < 135 mmol/L at admission (age at admission = 4.8 days +/- 2.6 [2; 7]). Sixteen patients (59%) had a sodium deficit -requiring fluid and sodium intake well above recommendations from the World Health Organisation (WHO). The risk of hyponatraemia was significantly higher in infants with the greatest body surface area affected but did not appear to be related to EB subtype. Caloric and protein intake were well above the WHO's recommendations, preventing acquired growth restriction. The rate of sodium deficit in neonates with EB is high and related to the significance of skin exudate. The administration of nutrient intake greater than that recommended helps to prevent acquired growth restriction. We propose recommendations for nutritional intake and monitoring in neonates with EB in the first month of life.

Protein Adequacy, Plant Protein Proportion, and Main Plant Protein Sources Consumed Across Vegan, Vegetarian, Pescovegetarian, and Semivegetarian Diets: A Systematic Review.

BACKGROUND: There are several types of plant-based diets, with unknown differences across diets on total/plant protein intake and variety of plant protein sources consumed. OBJECTIVES: This systematic review aimed to compare total protein intake, proportion of plant proteins, and main plant protein sources consumed across 4 primarily plant-based diets: vegan, vegetarian, pescovegetarian, and semivegetarian. METHODS: We included observational studies reporting on protein intake and/or protein sources in generally healthy adults that were published between 2002 and 2023. We determined the following: 1) % energy from total and plant protein; 2) the proportion of plant protein relative to total protein intake; and 3) main plant protein sources (median percentage contribution of each source to total plant protein intake; interquartile range) consumed across the 4 diets. The plant protein sources were broadly classified into the following United States Department of Agriculture food groups: grains; nuts and seeds; soy products; and beans, peas, and lentils. RESULTS: We included 13 studies reporting on protein intake/sources that were conducted in the United States, Europe, and South Korea. Of these, 7 reported on vegan, 11 on vegetarian, 7 on pescovegetarian, and 7 on semivegetarian diets with total protein intake ranging from 10% to 17.4%. Vegan diets had the highest plant protein proportion (range: 77%-98%) and semivegetarian diets the lowest (range: 37%-83%). Plant protein source contribution was the highest from grains (range: 60%-78%). Nuts and seeds were the most consumed in vegetarian diets (7.9%; 2.9%-10.3%) and least in semivegetarian diets (3.7%; 2%-14.8%). Soy products and beans, peas, and lentils were most consumed in vegan diets (17.3%; 16.3%-19.9, and 19.6%; 14.6%-21.3, respectively) and least in semivegetarian (3.7%; 1.3%-13.9%, and 8.5%; 5.2%-10.2%) diets. CONCLUSIONS: Vegan diets has the highest plant protein proportion and a variety of plant protein sources, while semivegetarian diets has the lowest plant protein proportion and mainly relied on grains as a plant protein source.

Diet and physical exercise in elderly people with obesity: The state of the art.

Obesity is a disease that is assuming pandemic proportions in recent decades. With the advancement of medicine and increased access to care, average survival has increased, resulting in a larger number of elderly people. As a result, the amount of elderly people living with obesity is increasing, and the morbidity and impact of obesity on ageing implies severe limitations for these people. The link between obesity and ageing is not only epidemiological, but also strictly pathophysiological. Obesity accelerates the ageing process and ageing is characterised by pathophysiological mechanisms shared by obesity itself. Some examples of alterations shared by ageing and obesity are metabolic changes, sarcopenia and reduced functional capacity related to both loss of muscle strength and reduced cardiorespiratory fitness, as well as a general reduction in the perception of quality of life. The specific ability to antagonize these mechanisms through non-pharmacological treatment based on nutrition and exercise has always been one of the focal points of the international literature. Therefore, this review provides the state of the art on scientific knowledge regarding the main effects of an adequate nutritional plan and an individualised exercise prescription on the general health of elderly with obesity. In particular, this paper addresses the effect of nutrition and physical exercise on pathophysiological changes peculiar of ageing and obesity, providing also the scientific rational for nutritional and exercise prescription in the population.

Assessment of Within- and Inter-Patient Variability of Uremic Toxin Concentrations in Children with CKD.

To promote improved trial design in upcoming randomized clinical trials in childhood chronic kidney disease (CKD), insight in the within- and inter-patient variability of uremic toxins with its nutritional, treatment- and patient-related confounding factors is of utmost importance. In this study, the within- and inter-patient variability of a selection of uremic toxins in a longitudinal cohort of children diagnosed with CKD was assessed, using the intraclass correlation coefficient (ICC) and the within-patient coefficient of variation (CV). Subsequently, the contribution of anthropometry, estimated glomerular filtration rate (eGFR), dietary fiber and protein, and use of (prophylactic) antibiotics to uremic toxin variability was evaluated. Based on 403 observations from 62 children (median seven visits per patient; 9.4 ± 5.3 years; 68% males; eGFR 38.5 [23.1; 64.0] mL/min/1.73 m2) collected over a maximum of 2 years, we found that the within-patient variability is high for especially protein-bound uremic toxins (PBUTs) (ICC < 0.7; within-patient CV 37-67%). Moreover, eGFR was identified as a predominant contributor to the within- and inter-patient variability for the majority of solutes, while the impact of the child's anthropometry, fiber and protein intake, and antibiotics on the variability of uremic toxin concentrations was limited. Based on these findings, we would recommend future intervention studies that attempt to decrease uremic toxin levels to select a (non-dialysis) CKD study population with a narrow eGFR range. As the expected effect of the selected intervention should exceed the inter-patient variability of the selected uremic toxins, a narrow eGFR range might aid in improving the trial design.

Unraveling the Molecular Mechanisms of the Neurodevelopmental Consequences of Fetal Protein Deficiency: Insights From Rodent Models and Public Health Implications.

Fetal brain development requires increased maternal protein intake to ensure that offspring reach their optimal cognitive potential in infancy and adulthood. While protein deficiency remains a prevalent issue in developing countries, it is also reemerging in Western societies due to the growing adoption of plant-based diets, some of which are monotonous and may fail to provide sufficient amino acids crucial for the brain's critical developmental phase. Confounding variables in human nutritional research have impeded our understanding of the precise impact of protein deficiency on fetal neurodevelopment, as well as its implications for childhood neurocognitive performance. Moreover, it remains unclear whether such deficiency could predispose to mental health problems in adulthood, mirroring observations in individuals exposed to prenatal famine. In this review, we sought to evaluate mechanistic data derived from rodent models, placing special emphasis on the involvement of neuroendocrine axes, the influence of sex and timing, epigenetic modifications, and cellular metabolism. Despite notable progress, critical knowledge gaps remain, including understanding the long-term reversibility of effects due to fetal protein restriction and the interplay between genetic predisposition and environmental factors. Enhancing our understanding of the precise mechanisms that connect prenatal nutrition to brain development in future research endeavors can be significantly advanced by integrating multiomics approaches and utilizing additional alternative models such as nonhuman primates. Furthermore, it is crucial to investigate potential interventions aimed at alleviating adverse outcomes. Ultimately, this research has profound implications for guiding public health strategies aimed at raising awareness about the crucial role of optimal maternal nutrition in supporting fetal neurodevelopment.

The Developmental Origins of Health and Disease theory posits that suboptimal conditions during early life exert a profound influence on adult health, potentially predisposing individuals to conditions such as neuropsychiatric disorders. By reviewing studies in rodents, we identified common mechanisms of how inadequate fetal protein uptake alters brain development and may contribute to anxiety, impaired memory function, and altered metabolism in adulthood. Adequate protein consumption during pregnancy is therefore critical to support healthy brain development.