Low Protein Formula Research Articles

Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3–5: a randomized controlled trial

BackgroundAlthough combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3–5 CKD.MethodsIn this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records.ResultsThis study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups.ConclusionsCompared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3–5 helped relieve physical deterioration and increased micronutrient intake after three months.Trial registrationClinicalTrials.gov NCT05318014 (retrospectively registered on 08/04/2022).

Efficacy and Safety of a High-Energy, Low-Protein Formula Replacement Meal for Pre-Dialysis Chronic Kidney Disease Patients: A Randomized Controlled Trial

High-energy, low-protein formulas (HE-LPFs) are commonly used as oral nutritional supplements (ONSs) to help provide extra calories to patients who are adhering to a low-protein diet (LPD) after diagnosis with chronic kidney disease (CKD). This randomized controlled trial aimed to evaluate the efficacy and safety of an HE-LPF as either a partial or a total replacement for one meal in pre-dialysis CKD patients. Stage 4–5 CKD patients received either a once-daily HE-LPF (HE-LPF group) or normal food (control group) for a period of 4 weeks while following an LPD. Overall, 73 patients who completed the study were included in the intention-to-treat population. After analyzing the 3-day food records, the HE-LPF group experienced a significant decrease in the percentage of energy derived from protein (p &lt; 0.05) and an increase in the percentage of energy derived from fat (p &lt; 0.05) compared to the control group. The two groups had no significant differences in body weight, body composition, grip strength, renal function, electrolytes, or metabolic markers. The HE-LPF group had a high adherence (94.9% at week 4), and no adverse effects were observed. HE-LPFs are safe to employ as meal replacements for pre-dialysis CKD patients adhering to an LPD.

Protein and growth during the first year of life: a systematic review and meta-analysis.

Dietary protein intake in the first year of life might influence later growth. We conducted a systematic review to investigate the growth effects of interventions based on infant formula composition providing different amounts of protein within the first year of life of healthy term infants; in the absence of other comparable information over the investigated period, a meta-analysis further compared weight or length gain at 120 days from high- (>2.0 g/100 kcal) and low-protein (≤2.0 g/100 kcal) content formula groups. Twelve papers (n = 2275) were included and five of them (n = 677) contributed to the meta-analysis. Most studies compared a high-protein formula, a low-protein formula, and breastfeeding. Evidence from the systematic review was inconclusive due to heterogeneity in design and treatments. In the presence of modest heterogeneity but in the absence of publication bias, the weighted mean difference for weight gain at 120 days was -0.02 g/day (95% CI: -1.41, 1.45); with higher heterogeneity, the weighted MD estimate of length gain at 120 days was 0.004 cm/month (95% CI: -0.26, 0.27). Although limited and underpowered, evidence from the meta-analysis does not support the assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first months of life. Prospero registration number: CRD42017058535. IMPACT: The optimal amount of dietary protein that should be given to healthy full-term infants early in life is still debated. Despite heterogeneity in study design, treatments, and outcomes, this systematic review showed that there is no clear-cut effect on the growth of different amounts of protein intake from formulas or complementary feeding. Evidence from the meta-analysis based on the five articles enrolling infants <1 month of life does not support the previous assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first 4 months of life.

Low-Protein Formulas with Alpha-Lactalbumin-Enriched or Glycomacropeptide-Reduced Whey: Effects on Growth, Nutrient Intake and Protein Metabolism during Early Infancy: A Randomized, Double-Blinded Controlled Trial

Protein intake is higher in formula-fed than in breast-fed infants during infancy, which may lead to an increased risk of being overweight. Applying alpha-lactalbumin (α-lac)-enriched whey or casein glycomacropeptide (CGMP)-reduced whey to infant formula may enable further reduction of formula protein by improving the amino acid profile. Growth, nutrient intake, and protein metabolites were evaluated in a randomized, prospective, double-blinded intervention trial where term infants received standard formula (SF:2.2 g protein/100 kcal; n = 83) or low-protein formulas with α-lac-enriched whey (α-lac-EW;1.75 g protein/100 kcal; n = 82) or CGMP-reduced whey (CGMP-RW;1.76 g protein/100 kcal; n = 80) from 2 to 6 months. Breast-fed infants (BF; n = 83) served as reference. Except between 4 and 6 months, when weight gain did not differ between α-lac-EW and BF (p = 0.16), weight gain was higher in all formula groups compared to BF. Blood urea nitrogen did not differ between low-protein formula groups and BF during intervention, but was lower than in SF. Essential amino acids were similar or higher in α-lac-EW and CGMP-RW compared to BF. Conclusion: Low-protein formulas enriched with α-lac-enriched or CGMP-reduced whey supports adequate growth, with more similar weight gain in α-lac-enriched formula group and BF, and with metabolic profiles closer to that of BF infants.

Effect of Applying 6% Low-Protein Formula to Dietary Advice in Elderly CKD Patients: A Randomized Control Trial

Effect of Applying 6% Low-Protein Formula to Dietary Advice in Elderly CKD Patients: A Randomized Control Trial

Organ Growth and Intestinal Functions of Preterm Pigs Fed Low and High Protein Formulas With or Without Supplemental Leucine or Hydroxymethylbutyrate as Growth Promoters.

The goal of enteral nutritional support for infants born preterm or small for gestational age (SGA) is to achieve normal growth and development. Yet, this is difficult to achieve because of intestinal immaturity. Our objective was to determine if birth weight, protein intake, and the growth promoters leucine (10 g/L) or calcium-ß-hydroxy-ß-methylbutryate (HMB; 1.1 g/L) would affect trajectories of intestinal growth and functions and weights of other organs. Preterm pigs were delivered at gestational day 105 (91% of term) and fed for 6 or 7 days isocaloric formulas that differed in protein content (50 g or 100 g protein/L), with and without the growth promoters leucine or HMB. For comparative purposes organ weights were measured within 12 h after delivery for six term pigs of low and six of average birth weights. The responses of intestinal growth and total intestinal brush border membrane carbohydrases to protein level and supplemental leucine were of greater magnitude for preterm pigs of lower birth weight. Forskolin stimulated chloride secretion in the proximal small intestine was lower for pigs fed the low protein milk replacers. Capacities of the entire small intestine to transport glucose (mmol/kg-day) were not responsive to protein level, leucine, or HMB, and did not differ between small and large pigs. Relative organ weights of the small and average weight term pigs were similar, but some differed from those of the preterm pigs suggesting preterm birth and the standards of care used for this study altered the trajectories of development for the intestine and other organs. Although leucine is an effective generalized growth promoter that enhances gut development of small preterm pigs, it does not mitigate compromised neurodevelopment. Our findings using preterm pigs as a relevant preclinical model indicate nutrition support strategies can influence development of some gastrointestinal tract characteristics and the growth of other organs.

Hypercalcemia in an Infant With Pseudohypoaldosteronism Type 1

Background: Pseudohypoaldosteronism type 1 (PHA1) is an aldosterone resistance syndrome due to insensitivity of target tissues to aldosterone action, with supraphysiologic aldosterone and renin levels. PHA1 presents usually in infancy and is divided into autosomal dominant (AD) and autosomal recessive (AR) form. A secondary form of PHA1 associated with UTI and/or renal malformations was described. In AD PHA1, salt loss is due to renal mineralocorticoid resistance while hyponatremia in AR PHA1 is caused by multi-organ salt loss. PHA1 has variable signs/symptoms associated with hyponatremia and hyperkalemia; thus, this clinical picture can be attributed to more common conditions such as dehydration, poor feeding, congenital adrenal hyperplasia. Clinical Case: A 5-month old male was admitted for airway evaluation. He was a 23-week gestation preemie, with chronic lung disease, failure to thrive. Patient was found to have hyponatremia, hyperkalemia, high FeNa of 1.3% (intrinsic renal disease) and elevated BUN/Cr (92/1.15). Renal US found echogenic kidneys with poor cortical medullary differentiation suggesting renal disease. Further evaluation noted high aldosterone (1700 ng/dL) and renin (400 ng/mL/hr) levels. He was placed on low protein formula to help optimize BUN level. Baby was diagnosed with secondary PHA1 due to renal disease and started on NaCl supplementation. This led to normalization of BUN, creatinine and improvement in electrolytes. Patient also had high serum calcium ranging from 11.1 to 12.0 mg/dL. Hyponatremia, hyperkalemia, hypercalcemia could be attributed to possible CAH, however state screen and ACTH stimulation test were normal. Further workup showed high 25-OH-vitamin D > 99 ng/mL, PTH 46.9 pg/mL, phosphorous 5.4 mg/dL and 1,25-OH-vitamin D 63.1 pg/mL. Urine Ca/cr ratio was 0.522. Vitamin D supplementation was stopped and daily total fluids increased. Subsequently, there was improvement in serum Ca at 10.9 mg/dL and 25-OH Vitamin D of 74 pg/mL. Next Generation Sequencing (NGS) was carried out, with a focus on the etiology of persisting hypercalcemia, including familial forms of hypercalcemia and Williams Syndrome. NGS revealed a likely pathogenic variant, c.2365 + 2T>C (p.?), in NR3C2, consistent with a diagnosis of AD PHA 1. Conclusion: This is a case of AD PHA1, marked by renal mineralocorticoid receptor resistance associated with persisting hypercalcemia. Initial hypercalcemia could be explained by hypervitaminosis D. It is important to note that electrolyte abnormalities, including persistent hypercalcemia, could be also secondary to the kidney disease found on renal US. There are only few reports of hypercalcemia in patients with PHA1 in the literature. In children with electrolyte abnormalities and failure to thrive, monitoring of serum and urine electrolytes would facilitate early accurate diagnosis and timely treatment.

Early-Life Metabolic and Hormonal Markers in Blood and Growth until Age 2 Years: Results from a Randomized Controlled Trial in Healthy Infants Fed a Modified Low-Protein Infant Formula.

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age.

Neurodevelopment and growth until 6.5 years of infants who consumed a low-energy, low-protein formula supplemented with bovine milk fat globule membranes: a randomized controlled trial

We previously reported results from a randomized controlled trial in which we found that Swedish infants consuming an experimental low-energy, low-protein formula (EF) supplemented with bovine milk fat globule membranes (MFGMs) until 6 mo of age had several positive outcomes, including better performance in the cognitive domain of Bayley Scales of Infant and Toddler Development 3rd Edition at 12 mo of age, and higher plasma cholesterol concentrations during the intervention, than infants consuming standard formula (SF). We aimed to evaluate neurodevelopment, growth, and plasma cholesterol status at 6 and 6.5 y of age in the same study population. We assessed cognitive and executive functions using the Wechsler Intelligence Scale for Children 4th Edition (WISC-IV), Brown Attention-Deficit Disorder Scales for Children and Adolescents (Brown-ADD), and Quantified Behavior (Qb) tests, and behavior using the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF), at 6.5 y of age. Anthropometrics and plasma lipids were assessed at 6 y of age. There were no differences between the EF and SF groups in any of the subscales in WISC-IV or Brown-ADD at 6.5 y of age, in the proportion of children with scores outside the normal range in the Qb test, nor in clinical or borderline indications of problems in adaptive functioning from parental and teacher's scoring using the CBCL and TRF. There were no differences between the EF and SF groups in weight, length, or head or abdominal circumferences, nor in plasma concentrations of homocysteine, lipids, insulin, or glucose. Among children who as infants consumed a low-energy, low-protein formula supplemented with bovine MFGMs, there were no effects on neurodevelopment, growth, or plasma cholesterol status 6-6.5 y later.

Assessing the Lifetime Cost-Effectiveness of Low-Protein Infant Formula as Early Obesity Prevention Strategy: The CHOP Randomized Trial.

Background: Although there is a growing number of early childhood obesity prevention programs, only a few of them are effective in the long run. Even fewer reports exist on lifetime cost-effectiveness of early prevention strategies. This paper aimed to assess the lifetime cost-effectiveness of infant feeding modification aiming at reducing risk of later obesity. Methods: The simulation model consists of two parts: (a) Model I used data from the European Childhood Obesity Project (CHOP) trial (up to 6 years) and the German Interview and Examination Survey for Children (KiGGS) (6–17 years) to evaluate BMI trajectories of infants receiving either lower protein (LP) or higher protein (HP) content formula; and (b) Model II estimated lifetime cost-effectiveness based on Model I BMI trajectories. Compared to HP formula, LP formula feeding would incur lower costs that are attributable to childhood obesity across all decades of life. Results: Our analysis showed that LP formula would be cost-effective in terms of a positive net monetary benefit (discounted 3%) as an obesity prevention strategy. For the 19% of infants fed with formula in Germany, the LP strategy would result in cost savings of € 2.5 billion. Conclusions: Our study is one of the first efforts to provide much-needed cost-effectiveness evidence of infant feeding modification, thereby potentially motivating interventionists to reassess their resource allocation.

Early-Life Nutrition, Growth Trajectories, and Long-Term Outcome.

It is well established that nutrition during the first 1,000 days of life can have a long-term effect on growth, metabolic outcome, and long-term health. We review the long-term anthropometric follow-ups of children with risk of later morbidity: (a) very-low-birth-weight (VLBW) infants who have birth weights <10th percentile of weight and receive fortified breast milk, (b) infants from developing countries who are breastfed according to the present recommendations but have low birth weight and length, and (c) children from developed countries who were enrolled in randomized controlled trials (RCTs) to test if breastfeeding and low-protein formulas can prevent from rapid weight gain and childhood obesity. VLBW infants can be appropriate, small for gestational age (SGA), or intrauterine growth retarded (IUGR). SGA and IUGR (due to placenta insufficiency) infants are born with birth weights <10th percentile of weight for gestational age (GA). We provided fortified breast milk until 52 weeks of GA to 31 SGA and 127 IUGR infants and followed up growth until 24 months. IUGR infants showed lower weight gain between birth and 3 months and had lower weight between 3 and 24 months (p < 0.05; ANCOVA). No significant BMI differences between SGA and IUGR infants were observed. It seems that IUGR infants receiving fortified breast milk need special attention, because without further improvement in breast milk fortification weight gain after discharge from hospital might be too slow. In developing countries, length and weight of breastfed infants during the first 2 years are strongly influenced by the respective anthropometric parameters at birth. Studies in the Gambia and Zimbabwe indicate that only breastfed infants with birth length and weight above the respective WHO 0 z-scores continue with adequate growth and have length and weight above the WHO 0 z-scores at 18 and 24 months. Prevalence of stunting and wasting in the overall Gambia breastfed infant population rapidly increases during the first year, peaks at around 3 years, but decreases thereafter. Long-term growth trajectories indicate later start of puberty and slow pubertal growth, but adult weight and height are not reached before 20-24 years. In adulthood, prevalence of stunting and wasting is much lower than during any period of childhood. Maternal risk factors, such as childhood marriage and poor nutrition before and during pregnancy, need to come into focus to improve birth length and weight and lower high stunting rates. Term breastfed infants from overweight/obese mothers and breastfed infants with rapid weight gain during infancy have increased risk of childhood obesity. Infants who are exclusively breastfed 4-6 months or receive low protein follow-up formulas (high-quality protein) grow slower during the first 2-3 years than infants fed high-protein formulas. During follow-up examinations at 5-6 years, they have lower BMI and obesity prevalence. Body composition measurements (DEXA) at 5-8 years in children who were breastfed and received low- or high-protein formula during infancy indicate that breastfeeding and feeding low-protein formulas are associated with lower gain of fat mass. Longitudinal cohort studies show that high-protein intake during the first 2 years results in higher BMI at 9 years and during adulthood. The studies presented indicate that breastfeeding but also other pre- and postnatal nutritional, epigenetic, and environmental factors influence growth trajectories and long-term health.

Growth Responses of Preterm Pigs Fed Formulas with Different Protein Levels and Supplemented with Leucine or β-Hydroxyl β-Methylbutyrate

Growth after preterm birth is an important determinant of long-term outcomes. Yet, many preterm infants suffer ex utero growth retardation. We evaluated effects of leucine and the metabolite, β-hydroxy β-methylbutyrate (HMB) on growth of preterm pigs, a previously-validated translational model for preterm infants. After 48 h of parenteral nutrition preterm pigs were fed for 6 to 7 days isocaloric formulas with different levels of protein (50 or 100 g/L) with leucine (10 g/L, 76 mM) or HMB (at 1.1 g/L, 4 mM) added to stimulate protein synthesis or with alanine (6.8 g/L; 76 mM) as the control. Rates of growth of pigs fed the low protein formula with alanine (3.4 ± 0.2% gain per day) or leucine (3.7 ± 0.2) exceeded that of pigs fed the high protein formula (2.8 ± 0.2, p = 0.02 for comparison with both low protein formulas; p = 0.01 compared with low protein + leucine). Supplementing the high protein formula with leucine or HMB did not increase growth relative to alanine (2.72 ± 0.20, 2.74 ± 0.27, and 2.52 ± 0.20, respectively). Small pigs (<700 g birth weight) grew slower during parenteral nutrition and had a more pronounced response to leucine. Females fed the high protein formulas grew faster than males, and particularly for small pigs (p < 0.05). Blood urea nitrogen values were lower for pigs fed the low versus the high protein formulas (p < 0.05). Leucine and HMB improved growth of preterm pigs fed low, but not high protein formulas, even after controlling for birth weight and sex, which independently correlated with growth rates. They offer an option to improve growth without increasing the amino acid load, with its attendant metabolic disadvantages.

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.

A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

Clinical evaluation of two different protein content formulas fed to full-term healthy infants: a randomized controlled trial

BackgroundA high early protein intake is associated with rapid postnatal weight gain and altered body composition. We aimed to evaluate the safety of a low-protein formula in healthy full-term infants.MethodsA randomized controlled trial was conducted. A total of 118 infants were randomized to receive two different protein content formulas (formula A or formula B (protein content: 1.2 vs. 1.7 g/100 mL, respectively)) for the first 4 months of life. Anthropometry and body composition by air displacement plethysmography were assessed at enrolment and at two and 4 months. The reference group comprised 50 healthy, exclusively breastfed, full-term infants.ResultsWeight gain (g/day) throughout the study was similar between the formula groups (32.5 ± 6.1 vs. 32.8 ± 6.8) and in the reference group (30.4 ± 5.4). The formula groups showed similar body composition but a different fat-free mass content from breastfed infants at two and 4 months. However, the formula A group showed a fat-free mass increase more similar to that of the breastfed infants. The occurrence of gastrointestinal symptoms or adverse events was similar between the formula groups.ConclusionsFeeding a low-protein content formula appears to be safe and to promote adequate growth, although determination of the long-term effect on body composition requires further study.Trial registrationThe present study was retrospectively registered in ClinicalTrials.gov (trial number: NCT03035721 on January 18, 2017).

Low dietary protein and high carbohydrate infant formula affects the microbial ecology of the large intestine in neonatal rats.

The aim of this study was to investigate the effects of a low dietary protein and high carbohydrate infant formula on the large intestine of neonatal rats. A total of 24 neonatal Sprague-Dawley rats (14-days-old) were randomly assigned to the low protein, high carbohydrate infant formula-fed group (I group) and a human breast milk-fed group (H group). After 7 days, we selected 6 rats at random from each group to study. No significantly different microbial colonization patterns were observed in the 2 groups at the phylum level. At the family level, Enterobacteriaceae and Bacteroidaceae were the dominant bacteria in I and H rats. While Bacteroides was the most abundant bacteria at the genus level, no significant difference was observed between the 2 groups. Methanoic acid, acetate, and butyrate increased in concentration in the I group compared with the H group. Protease activities, ammonia, and indole in the large intestine were lower in I rats than H rats. A significant increase in the expression of GADPH and decrease in the expression of aquaporin 8, aminopeptidase A, cathepsin F precursor, and ubiquitin carboxyl-terminal hydrolase FAF-Y were observed in I rats compared with H rats. These results suggest that a low protein diet could modulate the microbial ecology in the large intestine of neonatal rats.

Effects of a novel nutritional formula specially developed for chronic kidney disease patients on protein-restricted diets: a randomized controlled trial

In chronic kidney disease (CKD), the patients on a low-protein diet are considered to be at high risk of protein-energy wasting. Furthermore, a low-protein diet conceivably results in reduced intake of various nutrients. The purpose of this study was to evaluate the effects of a novel high-calorie, low-protein liquid formula containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), lactulose, raffinose, and indigestible dextrin on CKD patients. A randomized controlled trial was conducted on the Department of Nephrology at the Tokyo Medical University Hospital, Tokyo, Japan. Forty-three CKD patients prescribed a protein-restricted diet were randomly assigned to a supplement (SUP) or control (CTR) group. All patients received dietary counselling. Only the SUP group was given one or two packs (125 or 250 mL) daily of high-calorie, low-protein liquid formula. The intervention period was 16 weeks. Outcome measures of the study were body weight; body mass index (BMI); dietary protein, energy, and salt intake; estimated glomerular filtration rate (eGFR); serum levels of albumin, triglyceride and LDL-cholesterol; plasma fatty acid composition; plasma indoxyl sulfate level; creatinine clearance (Ccr); and urine protein excretion. There were no differences in energy intake and protein intake between the two groups. Body weight, BMI, plasma eicosapentaenoic acid (EPA), and EPA/arachidonic acid (AA) ratio at 16 weeks were significantly higher in the SUP group than in the CTR group. At 16 weeks, the CTR group showed significant decline in eGFR and significant increase in plasma indoxyl sulfate, whereas the SUP group showed no significant changes from baseline. Supplementation of a novel liquid formula may be beneficial for the management in CKD patients on a protein-restricted diet.

Postnatal High Protein Intake Can Contribute to Accelerated Weight Gain of Infants and Increased Obesity Risk.

Worldwide, 38% of women are now overweight (BMI 25-30) or obese (BMI ≥30). There is increasing evidence that maternal obesity can result in unfavorable (epigenetic) pre- and postnatal programming of important genes of the offspring. Infants of overweight mothers show faster weight gain during infancy, which is associated with higher risk of obesity during childhood and adult life. This can have lifelong consequences such as increased risk of noncommunicable diseases. Many studies indicate that infants of obese and nonobese mothers who were fed traditional (high-protein) formulas gain more rapidly weight than breastfed infants. An updated meta-analysis (n = 1,150) indicates that infants from four continents who were fed a whey-based, low-protein (1.8 g/100 kcal) formula with an essential amino-acid profile closer to breast milk grow in accordance with the World Health Organization (WHO) growth standard (0-4 months). A new experimental low-protein (1.61-1.65 g protein/100 kcal) formula for infants between 3 and 12 months of age was recently tested in two randomized clinical trials. One trial in the general US population indicates lower weight between 4 and 12 months of age in infants fed the low-protein formula when compared to infants on the high-protein formula (p = 0.031). Weight gain was not inferior to the WHO growth standards. Longitudinal analysis of odds ratios from 4 to 12 months of age showed a lower incidence of infants with weight >85th percentile in the low-protein group compared with the high-protein group (p = 0.015). In the second trial, which was conducted in Chile and included infants of mothers with BMI >25, infants fed the low-protein formula gained less weight between 4 and 12 months (p = 0.022) and until 24 months (p = 0.031) than the high-protein group. Weight gain was similar to the breastfed reference group. In both trials, biomarkers of protein metabolism (insulin-like growth factor-1 and C-peptide) of the low-protein groups were closer to breastfed infants than the respective biomarkers of the high-protein groups. Health economic analyses indicate that feeding low-protein formulas to nonbreastfed infants would result in cost savings for both the individual and the society. Preventive measures against childhood and adult obesity should include promotion of breastfeeding for 6 months or longer, and use of low-protein formulas in nonbreastfed infants.

Metabolic Programming: Effects of Early Nutrition on Growth, Metabolism and Body Composition.

High protein requirements of premature infants during the first weeks of postnatal life are a well-established fact. Those infants gain fat-free mass and protein rapidly during the first weeks of postnatal growth and require a much higher protein/energy ratio than term infants. Recommended protein intakes are 3.5-4.0 g/kg per day. For term infants, on the other hand, FAO and WHO have recently lowered recommended protein intakes to better reflect our current knowledge about the protein concentration in breast milk during the first 12 months of lactation. Longitudinal randomized clinical trials now confirm that term infants who are fed infant and follow-up formulas with protein concentrations >2.25 g/100 kcal (high protein formulas) during the first year of life grow faster than indicated by the WHO growth standards. Rapid weight gain during infancy is a predictor of childhood and adult obesity. Infants fed high protein quality formulas with protein concentrations of 1.6-2.2 g/100 kcal from 3 to 4 months onwards experience weight gain that is very close to that of breastfed infants. Biomarkers (insulin or IGF-1) of infants receiving low protein formulas differ from those of infants receiving high protein formulas. Six-year-old children who received low protein formulas in the first year of life had a lower risk of childhood obesity (BMI >95th percentile of WHO standards) compared with children who received high protein formulas as infants. BMI at 5 years of age is similar in children who were breastfed or received low protein formulas as infants. It is most important that the new low protein formulas are safe and adequate for all healthy term infants. Based on new protein technologies, the levels of essential and branched-chain amino acids in low protein formulas are now close to those in breast milk. Safety has been confirmed by following anthropometric parameters to 5-6 years of age and comparing these parameters with the WHO growth standards. Body composition measurements indicate similar protein accretion between 3 and 6 months of age in infants fed high or low protein formulas. Longitudinal data on body composition indicate that children who received a low protein formula until age 12 months gain less fat between 6 and 60 months than children who received a high protein formula. Breastfeeding and the use of low/high protein quality formulas in term infants who cannot be breastfed can help support appropriate metabolic programming during this critical period and reduce the risk of later obesity.

Low Protein Formula: Consequences of Quantitative Effects of Pre-analytical Factors on Amino Acid Concentrations in Plasma of Healthy Infants.

Quantifying pre-analytical effects of postprandial sampling delay and daily protein intake on plasma amino acid concentrations in healthy infants fed formula with low protein content (1.8-1.9g/100kcal). Intake of formula with higher protein content bears a risk for later obesity (Kirchberg, J Clin Endocrinol Metab 100(1):149-158, 2015). Formulas containing less than 1.8g protein might be adequate but not safe (Fomon, J Pediatr Gastroenterol Nutr 28:495-501, 1999). With on-demand feeding reproducible controls of indispensible amino acid concentration cannot be made at trough level. Data of 102 healthy infants aged 1 month and 79 aged 4 months fed formula with low protein content were obtained from a previous study (Haschke-Becher, J Inherit Metab Dis 39(1):25-37, 2016). They were analysed by multiple regression. Independent variables were the postprandial sampling delay from 2.25 to 4.5h and the daily protein intake. Dependant variables were the amino acid concentrations. The combined effect was calculated with the natural logarithm of the amino acid concentration. Most amino acids fitted a significant exponential decrease due to the sampling delay, except of aspartate, citrulline, glutamine, glutamate, histidine, tryptophan and tyrosine at 1 month; and at 4 months except of citrulline, glutamine, glutamate, glycine and ornithine. Significant effects of protein intake were found for lysine and serine at 1 month and for glutamate at 4 months of age. Lowest limits of significant amino acid concentrations were calculated by extrapolation of sampling delay to 5h and using the 10th percentile after back-transformation to μmol/L. A procedure to avoid the pitfall of overestimating amino acid concentration is presented.

Reference values of amino acids and of common clinical chemistry in plasma of healthy infants aged 1 and 4 months.

To compare plasma levels of amino acids and clinical chemistry parameters in healthy infants at 1 and 4 months of age and to establish corresponding reference limits. Data of three multicenter studies assessing the safety of new infant formulas were used. During these studies infants of both age-groups were either breast-fed or received formulas of low or high protein content. All samples were analyzed centrally in the same accredited laboratory. Plasma was collected from 521 infants in total, 157 boys and 135 girls aged 1 month and 121 boys and 108 girls aged 4 months. At the age of 1 month, 62 infants had received exclusively breast milk, 198 exclusively formula, and 27 both; in the 4-months age group corresponding numbers were 49, 158 and 18, respectively; for 9 infants, diet was unknown. Concentrations of most amino acids and clinical chemistry parameters differed significantly between both ages. Regardless of age, most plasma amino acid levels were comparable or lower in breast-fed than in formula-fed infants whereas at 1 month of age most clinical chemistry parameters were higher. While in breast-fed infants the plasma urea concentration decreased over 4 months of age, it increased in formula-fed infants. There were significant differences between infants fed a low and high protein formula. At both ages, high protein formulas resulted in significantly higher threonine, 2-aminobutyrate, and urea concentrations. For clinical use, age- and diet specific reference limits in infants are warranted.