Michael Radke

Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolyzed protein, a high β-palmitic acid level, and nondigestible oligosaccharides

Objectives The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics of a new infant formula containing partially hydrolyzed whey protein, modified vegetable oil with a high &bgr;-palmitic acid content, prebiotic oligosaccharides, and starch. Methods In a double-blind study, healthy formula-fed term infants aged younger than 2 weeks were randomized to receive either the new infant formula (NF) or a standard formula (SF) until the age of 12 weeks. Anthropometric measurements were taken at enrollment, 6 weeks, and 12 weeks. In a subsample of infants, blood samples were taken at 6 weeks and stool samples were taken at enrollment and 6 weeks. Blood samples were analyzed for biochemical measures of protein status and amino acids, and stools were analyzed for total bacteria and bifidobacteria. Mothers completed a feeding diary and questionnaire at 6 and 10 weeks. Results One hundred fifty-four infants were enrolled in the study; 102 completed the trial. The growth of infants in both formula groups was in line with published growth curves. During the first 6 weeks, NF girls gained more weight and head circumference than the SF girls. These velocity differences were not maintained throughout the 12-week study period. The NF stools had a higher proportion of bifidobacteria at 6 weeks compared with the SF stools, and they were softer. There were no clinically significant differences in the blood biochemical and amino acid values between groups. Both formulas were well tolerated by the infants. Conclusions When compared with a standard infant formula, the new formula supported satisfactory growth, led to higher counts of bifidobacteria in the feces, produced blood bio-chemical values typical of formula-fed infants, and was well tolerated.

Osteoporosis in pediatric patients suffering from chronic inflammatory bowel disease with and without steroid treatment.

Background: Children and adolescents suffering from inflammatory bowel disease (IBD) are at risk of developing osteoporosis as a result of treatment with corticosteroids as well as of nonsteroidal factors like inflammation and malnutrition. To study the impact of these factors on development of osteopathy, we compared the rate of osteoporosis in steroid-naive and steroid-treated pediatric IBD patients. Methods: In 90 patients (50 girls) with IBD (34 steroid-naive, 53 steroid-treated, 3 not known) aged 8.8 to 19.2 (14.4 ± 2.2) years and 52 controls (27 girls) aged 6.1 to 17.6 (12.9 ± 3.0) years, bone mineral density (BMD) of the lumbar spine was assessed with dual energy x-ray absorptiometry. Areal BMD values were transformed into volumetric densities called bone mineral apparent density (BMAD) and expressed as standard deviation scores (SDS) on the basis of the BMAD values of the controls. Results: The rate of osteoporotic patients (BMAD-SDS < −2) was 8% in girls and 20% in boys. There was a similar proportion of osteoporosis in steroid-naive (12%) and steroid-treated (11%) patients. SDS of body height showed a significant positive correlation with BMD-SDS but not with BMAD-SDS in almost all patient subgroups, indicating an interfering dependency of BMD from bone size. Conclusions: The prevalence of osteoporosis in pediatric patients with IBD is approximately the same as in adult patients. Osteoporosis is already present before steroid treatment. Data of dual energy x-ray absorptiometry measurements should be transformed into volumetric parameters to compensate for short stature. Otherwise, a lot of growth-stunted patients may be falsely diagnosed as osteopenic.

α-Lactalbumin-enriched low-protein infant formulas: a comparison to breast milk feeding

Tryptophan (TRP) is the limiting amino acid in low‐protein infant formulas. This is mainly due to lower α‐lactalbumin (αLA) content in cows milk whey as compared with human milk protein. To study the effect of αLA‐enrichment on the TRP supply, cross‐over studies were carried out in 20 healthy infants up to 3 months of age. In this study, two protein‐reduced (1.3%) infant formulas (moderate TRP content of 1.88% and higher TRP content of 2.10%) were alternately fed over a 2 week period in two groups of infants. Serum TRP levels of the formula‐fed infants with the higher TRP content did not differ significantly from an exclusively breastfed control group of 11 infants (10.5 ±4.8 versus 10.9±4.7mgl‐1, p= 0.841), whereas levels of the formula‐fed infants with the moderate TRP content were significantly lower (7.4 ± 3.9, p= 0.038). The supplementation of αLA resulting in a higher TRP supply to low‐protein diets is a further step towards the production of infant formulas more closely adapted to human breast milk.

Evaluation of oro-coecal transit time : a comparison of the lactose-[13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans

OBJECTIVE: The lactulose H2-breath test is the most widely used non-invasive approach for evaluation of oro-coecal transit time (OCTT). In the present study, doubly-labelled lactose-[13C, 15N]ureide (DLLU) was synthesized to investigate the OCTT in comparison to the conventional lactulose H2-breath test. Additionally, the bacterial breakdown rate (BBR) and rate of elimination and the metabolic pathways of the cleavage products of DLLU (13CO2, [15N]urea, and 15NH3) were investigated.DESIGN AND SUBJECTS: In a first study, DLLU was administered as a single oral-pulse-labelling (dosage: one gram) either without and after pretreatment of five grams of unlabelled lactoseureide (LU) on the day prior to the study to twelve healthy adult volunteers after breakfast. Breath and urine were collected in one and two hour-intervals, respectively, over a one-day period. 13C-enrichment in breath as well as 15N-enrichment in urine fractions were measured by continuous flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, lactulose was administered to the same subjects (dosage: ten grams). Breath was collected in quarter, half and one hour-intervals over a ten hour-period. Hydrogen concentration in breath was analysed using an electrochemical detector.RESULTS: The comparison of the lactose-[13C]ureide 13CO2-breath test and the lactulose H2-breath test showed that the mean increase of the 13C-enrichment in CO2 occurred 1.18 h later than the mean increase of H2 in breath. The resulting OCTTs derived from the two methods were 3.02±1.4 and 1.84±0.5 h (P<0.05) and the corresponding BBRs were 9.63±3.4 and 6.07±1.7 h (P<0.01), respectively. The 15N-enrichment of urinary urea and ammonia without and after pretreatment with LU started between two and three hours after DLLU-administration. The cumulative percentage urinary excretion of the 15N- and 13C-tracer was 29.9% and 13.6% respectively, and was slightly increased after LU-pretreatment to 32.1% and 14.6% of the dose administered. A total of 35.2% of the 13C was found to be exhaled and remained approximately constant after LU-pretreatment (36.2%).CONCLUSIONS: The use of the lactulose H2-breath test for evaluation of the OCTT showed a statistically significant shortening of 1.18 h in comparison to the lactose-[13C]ureide 13CO2-breath test in healthy adults. The most important limitations of the lactulose H2-breath test are its low specificity and sensitivity due to dose-dependent accelerations of OCTT, interfering H2-rise from malabsorbed dietary fibre and H2-non-producers. In contrast, our lactose-[13C]ureide 13CO2-breath test was confirmed to avoid these disadvantages and to yield reliable results. This test is recommended especially if higher sensitivity and specificity is required, if IRMS-technique is available and if lactulose H2-tests lead to insufficient results.SPONSORSHIP: Deutsche Forschungsgemeinschaft (DFG).

Triglyceride oxidation in cystic fibrosis: a comparison between different 13C-labeled tracer substances.

BACKGROUND For indirect evaluation of pancreatic lipase activity in cystic fibrosis, different 13C-labeled triglycerides may be used. METHODS Triglyceride oxidation in patients with cystic fibrosis was investigated after administration of different 13C-labeled triglycerides by comparing 13CO2 breath exhalation. In the comparative study, five patients with cystic fibrosis (age, 8-15 years; body weight, 22.5-39.8 kg) were treated with Pangrol (individual dosages: 1-3 capsules per morning meal; Berlin-Chemie, Berlin, Germany). [1,1,1-13C3]Glyceryl tripalmitate and [1,1,1-13C3]glyceryl trioleate were administered as a single oral pulse at 8:00 A.M. (dosage, 4 mg/kg each) with the standard diet Fresubin (dosage, 10 ml/kg; Fresenius, Bad Homburg, Germany). Alternately, the same subjects were given the synthetic mixed triglyceride 1,3-distearyl, 2[13C]octanoyl glycerol (dosage, 12.5 mg/kg) contained in the standard diet Nutri-Mix (dosage, 10 ml/kg; Nutricia, Zoetemeer, The Netherlands). Breath samples were taken in 15- and 30-minute intervals over 8 hours. The 13CO2 enrichment was measured by continuous-flow isotope ratio mass spectrometry. RESULTS After administration of the 13C-labeled tripalmitin-triolein mixture and the mixed triglyceride, mean maximum 13CO2 enrichments were 4.70 and 7.37 delta over baseline, occurring at 7.0 and 3.5 hours, respectively. The corresponding percentage cumulative 13CO2 exhalations were 12.25% and 29.19%, respectively, and differed significantly in the five paired subjects (p = 0.003). CONCLUSIONS After using different 13C-labeled triglycerides the resultant 13CO2 exhalation reflected the triglyceride hydrolysis and subsequent oxidation. It is concluded that the different cumulative 13CO2 exhalations were mainly caused by the rate-limiting step of triglyceride hydrolysis to free fatty acids and 2-monoglycerides and by fat deposition. Noninvasive 13C breath tests using different 13C-labeled triglycerides can be used for evaluation of pancreatic lipase activity before and during enzyme supplementation.

Symbiotic interactions between colonic microflora and protein metabolism in infants

ABSTRACT. The utilization of 15N nitrogen from 15N‐labelled bifidobacteria for whole body protein synthesis was studied in 4 infants by oral single‐pulse labellings and in 3 other infants, who had colostomies, by colonic pulse labellings. The bifidobacteria were harvested from a modified Petuely culture medium containing 15N ammonium chloride and 15N cystine as the only sources of nitrogen. The tracer dose chosen for the balance studies was 3 mg 15N/kg. 15N concentrations in urine and feces collected over 48 hours after the pulse labellings were determined by emission spectrometry. Oral administration of 15N‐labelled bifidobacteria resulted in absorption of approximately 90%, renal excretion of 15%, and fecal excretion of 12% of the tracer dose, respectively. Retention in the protein pool averaged 73%. After colonic single pulse labelling with 15N‐labelled bifidobacteria, the corresponding values were 85.5%, 2.2%, 14.5%, and 83.0%, respectively. Absorption and incorporation of the heavy nitrogen into body proteins were directly demonstrated by increased 15N atom percent excess values within the trichloroacetic acid (TCA) supernatants and the proteins of the plasma, 0.25 and 0.04 atom %, respectively, at 24 hours after oral pulse labellings. One half of the total 15N excreted in urine consisted of urea and approximately 8% was eliminated as ammonia.

Tracer kinetic studies on a methionine-supplemented soy-based infant formula using 1-13C- and 15N-methionine as tracers.

A tracer-kinetic study using 1-13C- and 15N-labeled L-methionine was conducted in order to measure the retention rate of free methionine added to commercially-produced soy-based infant formulas. Twelve male infants, fed on a soy formula, received a single-pulse labeling by oral administration of L-1-13C-methionine (5 mg/kg) and L-15N-methionine (10 mg/kg). The abundance of expired 13C-labeled CO2 was measured up to 7 h after administration at 15-, 30-, and 60-min intervals. Additionally, enrichment of total 15N and 15N in urinary ammonia were determined up to 48 h after administration. Retention rates of the labeled carboxyl group amounted to an average of 91.2% (SD 4.1) of the intake. A similar retention rate was measured for the 15N-label of methionine (90.0%, SD 4.3). The data point at the efficacy of methionine supplementation of soy-based infant formulas.

Response to sodium benzoate treatment in non-ketotic hyperglycinaemia.

Therapy with benzoic acid in a case of classic neonatal non‐ketotic hyperglycinaemia (NKH) was successful in stopping seizures but not in promoting mental development. Serum glycine levels were normalizable even by administering low doses of 53 mg sodium benzoate/kg body mass (BM) per day. Despite giving a higher dosage (240 mg/kg BM per day) normalization of glycine concentration in cerebrospinal fluid (CSF) was not achieved. However, seizures ceased. Restriction of protein intake (≤2 g/kg BM per day) seemed to be profitable. CSF glycine concentrations below 100 μmol/L may be sufficient to prevent seizures in older infants who have adapted to neuronal glycine exposure. No toxicity of sodium benzoate treatment was detected when administering doses of up to 470 mg/kg BM per day but side effects such as itching and hyperactivity were obvious.

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial

Objectives: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. Methods: In this controlled, multicenter, double-blind study, a sample of preterm infants ⩽32 weeks or ⩽1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = –1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. Results: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g · kg−1 · day−1 (cHMF) between study days 1 and 21 (D1–D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ⩽ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. Conclusions: nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.

Können Säuglingsnahrungen bifidogene Effekte erzeugen

ZusammenfassungHintergrund: Die durch Muttermilch bewirkte Entstehung einer Bifidobakterien-dominierten intestinalen Mikroflora ist ein in der Natur einmaliges Phänomen. Es gibt Hinweise dafür, daß gestillte Säuglinge in vieler Hinsicht von der Präsenz dieser Bakterien im mikrobiell besiedelten Dickdarm profitieren. Aus diesem Grund sind nach der Entdeckung der Bifidobakterien durch Tissier im Jahr 1900 zahlreiche Versuche unternommen worden, bifidogene Wirkungen in Säuglingsmilchnahrungen zu erzeugen. Im einzelnen wurden die niedrige Pufferkapazität, niedrige Eiweiß- und Eisenkonzentrationen, ein hoher Gehalt an Laktose, modifizierte Laktose und verschiedene andere Bifidusfaktoren für die bifidogene Wirkung verantwortlich gemacht. Bis heute gibt es jedoch kein überzeugendes Konzept für die Produktion einer solchen Formelnahrung. Die wesentlichen Schwachpunkte in der Bewertung der bisher durchgeführten Studien zur Erprobung bifidogener Säuglingsnahrungen beinhalten die fehlerhafte Interpretation der Bifiduskeimzahlen im Verhältnis zur Begleitflora, die Überbewertung einzelner Komponenten bzw. die Nichtbeachtung des Zusammenwirkens der Gesamtheit aller fördernden und hemmenden Komponenten. Diskussion: Es steht jedoch außer Zweifel, daß bifidogene Effekte erzielbar sind, wenn eine Annäherung an die Zusammensetzung der Muttermilch hinsichtlich der Quantität (und Qualität) des Eiweißes und der fermentierbaren Kohlenhydrate erfüllt ist. So haben unsere eigenen Untersuchungen mit modifizierten hydrolysierten Säuglingsmilchnahrungen ergeben, daß eine Bifidusdominanz in 30–40% der Fälle erzielt werden kann. Dies ist eine im Vergleich zur Muttermilch geringe Häufigkeit, die jedoch als vielversprechender Ausgangspunkt für weitere Forschungen auf diesem Gebiet dienen kann.SummaryBackground: The domination of the intestinal microflora of infants by bifidobacteria, induced by feeding with mother’s milk, is a unique natural phenomenon. There is evidence that breast-fed babies profit from the colonization of their large intestine by these bacteria in many respects. For this reason, following the discovery of bifidobacteria by Tissier in 1900 numerous attempts were made to reproduce the bifidogenic effects in infant feeding formulas. Low puffer capacity, low protein and iron concentration, high lactose content, modified lactose, and numerous other bifidogenic factors were claimed to be responsible for bifidogenic effects similar to those produced by mother’s milk. To date, there is no convincing concept for the production of such a formula. The main weaknesses in the evaluation previous studies lie in the incorrect interpretation of the number of bifidobacteria in the faeces in comparison to the remaining species, and in their focus on a single component, neglecting the interaction of all the components. Discussion: There is, however, no doubt that bifidogenic effects are obtainable if approximation to the overall composition of human milk with regard to the quantity (and quality) of protein and fermentable carbohydrate is achieved. Our studies with modified hydrolyzed infant formulas have shown a bifidobacteria-dominated microflora in 30–40% of cases. This is low compared to the results of feeding with mother’s milk, but can be considered a promising starting-point for further research in this field.