Jean-Claude Maire

Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial

Probiotics and long-chain PUFA (LC-PUFA) may be beneficial supplements for infants who are not breast-fed. The aim of the present study is to evaluate the safety of an infant formula containing the LC-PUFA DHA and arachidonic acid (AA) and the probiotic Bifidobacterium lactis by comparing the growth rate of infants fed the supplemented and unsupplemented formulas. One hundred and forty-two healthy, term infants were enrolled in a single-centre, randomised, double-blind, controlled, parallel-group trial, and allocated to receive either standard or probiotic and LC-PUFA-containing experimental formulas. The infants were fed with their assigned formulas for 7 months. The primary outcome (weight gain) and the secondary outcomes (length, head circumference and formula tolerance) were measured throughout the study. LC-PUFA status was assessed at 4 months of age and immune response to childhood vaccines was measured at 7 months of age. There was no significant difference in growth between the two groups. The 90 % CI for the difference in mean weight gain was - 0.08, 3.1 g in the intention-to-treat population and 0.1-3.8 g in the per protocol population, which lay within the predefined boundaries of equivalence, - 3.9-3.9. There were no significant differences in mean length and head circumference. DHA and AA concentrations were higher in infants in the experimental formula group compared with the control formula group. No influence of the supplements on the response to vaccines was observed. Growth characteristics of term infants fed the starter formula containing a probiotic and LC-PUFA were similar to standard formula-fed infants.

Tolerance, safety, and effect on the faecal microbiota of an enteral formula supplemented with pre- and probiotics in critically ill children.

Objectives: The aim of this study was to demonstrate the tolerance and safety of an enteral formula containing prebiotics/probiotics, and its effect on the faecal microbiota in critically ill children. Subjects and Methods: Ninety-four patients between 1 and 3 years old under mechanical ventilation requiring enteral feeding were randomised to receive either a test formula containing a synbiotic blend (composed of 2 probiotic strains [Lactobacillus paracasei NCC 2461 and Bifidobacterium longum NCC 3001], fructooligosaccharides [FOS], inulin, and Acacia gum), or a control formula. Patients remained in the intensive care unit for 7 days and were examined at day 14. Tolerance was assessed by overall caloric intake and time to reach caloric goal. Safety was assessed by abdominal distention, vomiting, and stool frequency. Microbiota was analysed by culture- and molecular-based methods. Results: Overall caloric intake and time to reach caloric goal were similar between groups (noninferiority was shown). Abdominal distention, vomiting, and stool frequency were not affected by the supplementation with pre- and probiotics. Faecal bifidobacteria were higher in the test group at the end of the study. A similar trend was observed for total lactobacilli. L paracasei NCC 2461 and B longum NCC 3001 were detected in 80.4% and 17% of the test group patients, respectively. Enterobacteria levels remained unchanged during hospitalisation in the control group but diminished in the test group. Conclusions: The enteral formula supplemented with synbiotics was well tolerated by children in intensive care units; it was safe and produced an increase in faecal bacterial groups of previously reported beneficial effects.

Plasma glutamine response to enteral administration of glutamine in human volunteers (free glutamine versus protein-bound glutamine)

The goal of the present work was to compare the plasma glutamine response to exogenous glutamine administration in human volunteers; glutamine was provided as a free amino acid, bound to proteins, or in the form of peptides. Plasma glutamine concentrations were measured in eight human volunteers at 30, 60, 90, 120, and 240 min after receiving a drink containing 30 g of protein from one of the five different proteins tested (sodium caseinate, sodium caseinate + free glutamine, carob germ flour, carob protein concentrate, and carob protein hydrolysate). Peak plasma glutamine concentrations were 42% higher than postabsorptive basal values when exogenous glutamine was administered in the form of free glutamine added to caseinate (925.9 +/- 67.7 versus 651.3 +/- 44.0 micromol/L, respectively). In contrast, when glutamine was offered 100% bound to proteins (carob proteins), peak plasma glutamine concentration increased only between 18% and 23% from basal values, possibly because of the lower digestibility of carob proteins versus that of caseinate + free glutamine, to a different glutamine utilization at the gut level, or to a different response in endogenous glutamine kinetics to enteral administration of glutamine, depending on the molecular form of the glutamine source (free or protein bound).

Effects of diet-induced hyperthreoninemia. I). Amino acid levels in the central nervous system and peripheral tissues.

Rats were fed four levels of threonine (Thr, 0.4, 0.6, 0.8, and 5.8 g/100 g diet). After two weeks, Thr, serine (Ser), and glycine (Gly) levels were measured in plasma, liver, muscle, and central nervous system. The diet containing 5.8 g/100 g of Thr elevated Thr and Gly concentrations in plasma and nervous tissue in comparison with a standard diet. In muscle and liver, Thr concentrations were also raised but Gly levels did not change. The hepatic Thr dehydratase activity was enhanced. Diets containing moderate Thr quantities (0.6 and 0.8 g/100 g) induced slight elevations of Thr levels in all tissues. Gly concentrations were not modified. The activity of hepatic Thr dehydratase was diminished. Our results show that a high dietary content of Thr (15 times the normal levels) elevates Gly levels in various tissues, including the brain. On the contrary, diets containing 2 to 4 times the normal levels of Thr induce a weak hyperthreoninemia insufficient to modify brain Gly.

Neurotoxicology and amino acid intake during development: The case of threonine

The development of the central nervous system is highly dependent on an adequate supply of nutrients. In particular, protein and amino acid availability is of major concern during gestation and in early postnatal life. Numerous data have been published on some amino acids directly involved in brain functions as neurotransmitters or indirectly as precursors of neurotransmitters, but scant information is available on the possible consequences of hyperthreoninemia, a phenomenon repeatedly noted in clinical reports. The results of neurochemical and behavioral studies in the developing rat suggest that despite numerous possible effects of threonine on brain constituents, moderate hyperthreoninemia does not impair markedly the development of the central nervous system.

Effect of threonine on the behavioural development of the rat

Rats received different levels of threonine (Thr), one, 1.7 and four times the normal dietary intake, from conception to adulthood. The mothers were fed the experimental diets before and during pregnancy. Their offspring received a daily oral load of Thr or placebo until weaning. Thereafter, the juveniles were fed the same diet as their mothers. Morphologic development, ingestive behaviour, homing, and locomotion were observed before weaning. Exploration and spontaneous alternation were studied thereafter. Animals exposed during gestation to 1.7 times the normal Thr intake consumed more food during the test of independent ingestion. Grooming showed inconsistent variations between days 12 and 29 in pups fed 1.7 times the normal Thr intake. Rats performed equally well on the other behavioural tasks independently of the dietary treatment. We conclude that Thr intake as much as four times higher than the levels found in normal diets does not impair the behavioural ontogenesis of the rat.

Effects of diet-induced hyperthreoninemia. II) Tissue and extracellular amino acid levels in the brain

Growing rats were fed graded levels of threonine (Thr, 0.4, 0.8, and 3.3 g/100 g diet). Free amino acid content was measured in plasma and brain. Extracellular amino acid levels were measured by microdialysis in brain slices. Large quantities of dietary Thr (3.3 g/100 g) raised plasma and brain Thr and glycine (Gly) levels. Brain and spinal cord extracellular levels of Thr were also raised, whereas the other amino acid levels remained unchanged. A moderate level of dietary Thr (0.8 g/100 g) raised plasma Thr and Gly levels and brain Thr but not Gly level. The diet raised cortical Thr extracellular levels but did not modify the levels of the other amino acids, including glutamate (Glu) and aspartate (Asp). These data suggest that brain neurochemical processes involving Gly, Glu, and Asp are safeguarded in rats fed high Thr levels.