Breastfeeding for optimal mental development. The alpha and the omega in human milk.
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Biomedical subjects
Publications and source records attributed to R Uauy.
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A prospective study in healthy infants predefining both diet fatty acid and cholesterol, from birth to age 1 year, compared response of cholesterol fractions in three groups: random assignment to 1) monounsaturated-(Hi-Mono) (n = 20), or 2) polyunsaturated-(Hi-Poly) (n = 22) fatty acid-enriched diets, or 3) non-randomized selection to breast feeding (Human Milk) (n = 25). In each group, designated weaning foods and supplements maintained fatty acid and cholesterol intake similar to that of each group's defined formulas, with long-term compliance confirmed by plasma phospholipid fatty acid concentrations. By 12 months, total cholesterol was significantly lower in the Hi-Poly group compared to either of the other groups (P < 0.05). Low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations were significantly lower by 12 months in the Hi-Poly group, compared to the Hi-Mono groups. However, at the earlier 4-month interval, total cholesterol and LDL-cholesterol in both Hi-Mono and Hi-Poly groups were not different from each other, although each was significantly lower than the parallel Human Milk-group (P < 0.05). The Hi-Mono group increased gradually in total and LDL-cholesterol such that, after 12 months' feedings, all lipid fractions of this Hi-Mono group were no different from those of the Human Milk group. In independent group comparisons, there were no significant differences in HDL-cholesterol concentrations after 4 and 9 months on these diets. Independent of diet, HDL-cholesterol showed a falling trend as an overall time-effect across all groups (P < 0.001). These data suggest that prolonged feeding of a diet enriched in polyunsaturated acids in early infancy has a significant cholesterol-lowering effect compared to monounsaturates. These differences in total, LDL-, and HDL-cholesterol plasma concentrations between polyunsaturates and monounsaturates were not significantly evident until feedings had continued for a year.
The biological quality of an experimental milk substitute based on a raw wheat flour subjected to enzymatic hydrolysis in comparison to a control product based on extruded flours and milk protein was studied in 35 < > female school age children. The girls were fed their customary diet during 2 consecutive 14 and 12 day periods, and randomized to the experimental and control products in a double blind crossover fashion. Apparent absorption of protein, energy, calcium and phosphorus was evaluated. Mean nitrogen intake from the experimental product was significantly lower (223 vs 244 mg/Kg/d p<0.0001). Absorbed nitrogen was also lower (187 vs 203 mg&kg/d p<0.0001). Energy intake and excretion were similar with both products; 96 and 95% of intake was absorbed for experimental and control products respectively. The mean calcium intake was significantly lower than the experimental product (39.7 vs 60.2 mg/kg/d p<0.0001). Absorbed calcium from the experimental product was 50% of control (20.7 vs. 39.5 mg/Kg/d p<0.0001). Phosphorus intake was also lower with the experimental product relative to control (22.0 vs 27.8 mg/Kg/d p<0.0001) and absorbed P was 13.1 vs 16.5 mg/Kg/d respectively. Both products were well tolerated. We conclude that the experimental product based on wheat flour does not differ significantly in protein and energy digestibility but calcium and phosphorus absorption and digestibility are significantly lower limiting its use in school feeding programs.
Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency, we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk. This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth, clinical tolerance, coagulation test results, changes in erythrocyte membrane fluidity, and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age. "Healthy" preterm infants were maternally selected to receive human milk or selected at random to receive commercial ready-to-feed liquid formula, which provided limited omega 3 fatty acid, or experimental formulas supplemented with soy oil or soy and marine oils. Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth, clotting function, erythrocyte membrane fluidity, or vitamin A or E levels in healthy very low birth weight preterm infants. Additional studies to evaluate safety in a representative preterm population are required.
Studies have demonstrated that a fecal flora with a predominance of bifidobacteria develops in infants fed a nucleotide-supplemented commercial formula, closer to that in breast-fed infants. In contrast, enterobacteria predominate in the fecal flora of infants fed an unsupplemented formula. When given parenterally, nucleotides promote recovery from injuries caused by hepatotoxic agents. These results suggest that dietary nucleotides may potentially play a significant role in nutrition.
Dietary sources of nucleotides may be conditionally essential nutrients. Rapidly growing tissues such as the intestinal epithelium and lymphoid cells lack significant capacity for de novo synthesis of nucleotides and require exogenous sources of purine and pyrimidine bases. Dietary purines are not significantly incorporated into hepatic nucleic acids, but pyrimidines are. Both are taken up by intestinal cells with excess purines converted to uric acid. Nucleotides are important for normal development, maturation and repair of the gastrointestinal tract. Human milk is the best source of nucleotides for young infants because cow's milk is lacking in nucleotide content. It is likely that infant formulas should have sources of nucleotides added to more closely duplicate human milk and provide these substrates for maximal intestinal development and repair.
The consumption of dietary fluoride and its relationship with dental caries prevalence was determined in 780 preschool children and 802 school children from quique, Arica, Santiago and San Antonio, where drinking water has different fluoride concentration. Dietary fluoride was determined from dietary records and fluoride content of foods. The fluoride consumption from drinking water was calculated by Galagan and Vermillion formula. The total fluoride consumption was obtained. The dental caries prevalence was established by the evaluation of dental caries index in deciduous (dmft) and permanent (DMFT) dentition. Significantly lower DMFT values were founded in cities with lower fluoride levels in drinking water. The exception was San Antonio, where high dietary fluoride explained the lower DMFT values relative to Santiago. Our results suggest that not only fluoride in water but also the consumption of fluoride rich foods has a significant impact on the prevalence of caries.
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Fatty acid profiles were determined in red blood cell (RBC), plasma lipids and lipid fractions from 50 patients with autosomal dominant retinitis pigmentosa (ADRP) and 20 normal-sighted controls. In plasma of affected patients, significant increases in omega 6 long-chain derivatives compared to controls resulted in elevated fatty acid unsaturation whereas, in RBCs, significant decreases in the levels of omega 6 and omega 3 long-chain polyunsaturates and a reduced unsaturation index were demonstrated (P < 0.01). The disproportionate levels of long-chain fatty acids in plasma vs. RBCs were consistent with abnormal function of acyl group transfer from plasma lipids to target tissues such as RBCs or, possibly, retina. Metabolic lipid anomalies were evaluated in two sub-groups of patients with ADRP; ten with the highest and ten with the lowest RBC lipid levels of the omega 3 fatty acid, docosahexaenoic acid (DHA). Fatty acid product/precursor relationships in the sub-groups revealed reduced chain elongation and omega 3 fatty acid desaturation associated with reduced ratios of rod-to-cone electroretinographic amplitudes. Based on these results, we suggest that the heterogenic ADRP population includes a sub-group of patients characterized by abnormal fatty acid metabolism that may effect membrane structure and visual function.
Normal ovine pregnancy is associated with elevated levels of circulating vasodilator prostaglandins (PGs) and increases in PG production by uterine and systemic arteries. We hypothesized that the availability of fatty acid substrate may regulate PG production in vasculature from nonpregnant, pregnant and fetal sheep. In pregnant sheep, levels of arachidonic acid (20:4 omega 6), the immediate PG precursor, were significantly lower in phospholipids from uterine versus systemic (renal) arteries. Although linoleic acid (18:2 omega 6), the primary arachidonic acid precursor, was elevated (p < 0.001) in uterine arteries during pregnancy, levels in systemic arteries were decreased. Levels of omega 3 polyunsaturated fatty acids (PUFAs) also were increased (p < 0.001) in both uterine and systemic arteries during pregnancy. In fetal-placental arteries, the levels of arachidonic and linoleic acid were 50 and 90% less, respectively, than that in maternal arteries. We conclude that during ovine pregnancy vascular prostanoid production may be regulated, in part, by the availability of fatty acid precursors.
We undertook a preliminary study to determine if a clinical trial was feasible that would compare the effect of a low protein vs a control formula on GFR and growth in infants with congenital renal insufficiency (CIo < 55 ml/min/1.73 m2). In this report from the Infant Diet Protein Study, we describe validation of a method using the plasma clearance of iothalamate (CIo) as an estimate of glomerular filtration rate (GFR) and results of the preliminary study relating to renal function. The plasma CIo method was validated as an accurate estimate of GFR by showing it to be the same as the plasma clearance of inulin (CIn). In the preliminary study infants who qualified for the study were randomly assigned to a low protein or control formula and were followed from 8 to 18 months of age. CIo was measured at 8, 14 and 18 months of age in 21 of the infants and at 8 and 18 months of age in all twenty four infants that entered the study. Average absolute GFR in the 24 infants increased in the 10 month period from 5.3 +/- 2.7 to 7.6 +/- 4.5 ml/min. The percent increase in GFR was no different in infants whose GFR at 8 months of age was severely reduced from those whose GFR was only moderately reduced. When adjusted for age and body size, GFR did not change. Change in mean CIo or serum creatinine (SCr) from 8 to 18 months of age between the infants in each diet groups was not different. We conclude that a clinical trial enrolling more infants and extending the study period is necessary to evaluate dietary protein effect.
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Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat accretion during late pregnancy and must rely on formula to obtain fatty acids essential for normal development, particularly of the visual system. Preterm infants (30 wk postconception) receiving human milk were compared to infants given one of the following formulae: Formula A was a commercial preterm formula with predominantly 18:2 omega 6 (24.2%) and low (0.5%) 18:3 omega 3; Formula B was based on soy oil and contained similar 18:2 omega 6 levels (20%) and high 18:3 omega 3 (2.7%); Formula C was also a soy oil-based formula (20% 18:2, 1.4% 18:3) but was supplemented with marine oil to provide omega 3 long-chain polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%) equivalent to human milk. At entry (10 days of age), the fatty acid composition of plasma and red blood cell (RBC) membrane lipids of the formula groups were identical. By 36 wk postconception, the DHA content in lipids of group A was significantly reduced compared to that in the human milk and marine oil formula groups. Omega-3 LCP results were further amplified by 57 wk with compensatory increases in 22:5 omega 6 in both plasma and RBC lipids. Provision of 2.7% alpha-linolenic acid in formula group B was sufficient to maintain 22:6 omega 3 levels equivalent to those in human milk-fed infants at 36 wk but not at 57 wk. Effects on the production of thiobarbituric acid reactive substances and fragility of RBC attributable to the marine oil supplementation were negligible. The results support the essentiality of omega 3 fatty acids for preterm infants to obtain fatty acid profiles comparable to infants receiving human milk. Formula for preterm infants should be supplemented with omega 3 fatty acids including LCP.
Dietary n-6 or n-3 fatty acid deficiencies result in changes in brain and retinal phospholipid composition that can affect cell membrane and organ function. An n-3 fatty acid deficiency has been associated with altered electroretinograms and reduced visual acuity in animals. Other promising methods for assessing the effects of fatty acid deficiencies on brain and retinal maturation include visual-evoked potential acuity, sleep-wake cycle, auditory brain stem-evoked response, somatosensory-evoked potential measurements, and the Fagan and forced-choice preferential looking acuity tests. Preterm infants fed a formula low in alpha-linolenic acid (18:3n-3) had significant electroretinographic changes at discharge from the nursery, indicating a delay in rod photoreceptor maturation. However, infants fed human milk or supplementary n-3 fatty acids as marine oil had electroretinogram indexes like those of infants of comparable age tested soon after birth. Visual cortex function, measured by pattern reversal visual-evoked potential and forced-choice preferential looking visual acuity response, was also better in infants fed human milk or marine oil-supplemented formula than in infants fed formulas without docosahexaenoic acid (22:6n-3). Studies of term infants suggest that visual acuity is more mature in breast-fed than in formula-fed infants [corrected] at 4 months and 3 years of age.
We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p less than 0.0001) were as follows: total cholesterol, 76% to 79%; LDL-cholesterol, 78% to 81%; very low density lipoprotein cholesterol, 69% to 75%; high-density lipoprotein cholesterol, 27% to 40%; and triglycerides, 34% to 68%. There were statistically significant but clinically and biologically irrelevant changes in hematologic indexes, serum chemistry values, immunoglobulin levels, complement activity, and plasma concentrations of fat-soluble vitamins. Simple correlation analysis of the variables affecting total cholesterol removal showed significant correlation coefficients (r values) for preapheresis total cholesterol values (r = 0.70; p less than 0.01) and preapheresis LDL-cholesterol values (r = 0.61; p less than 0.01). A multiple regression model explained 82% of the variance based on the preapheresis cholesterol concentration, volume of whole blood processed, and the serum albumin concentration. Side effects of the LDL-apheresis treatments were rare and included abdominal cramping and urticaria. Two procedures were aborted because of intravenous access problems in the younger children. This study confirms that LDL apheresis using a dextran sulfate affinity column is efficacious in rapidly lowering total and LDL-cholesterol concentrations. Furthermore, the procedure is safe and well tolerated by children as young as 6 years of age. This treatment may prevent the progression of atherosclerosis in children with homozygous familial hypercholesterolemia and may therefore avert early death.
Short-term nitrogen-balance response to graded intakes of a vegetable mixed-protein diet and to a milk-egg protein diet was tested in eight healthy male children aged 12-14 y. They received 72, 104, 136, and 168 mg N.kg body wt-1.d-1 for 10 d while on the mixed diet, and 160 mg N.kg-1.d-1 on the milk-egg diet. The mean regression equation was nitrogen balance = 0.64 (nitrogen intake)-74, all values are in mg N.kg-1.d-1. Apparent digestibility was 86% and 85% for the mixed and milk-egg diets when the subjects received 168 and 160 mg N.kg-1.d-1, respectively. Mean nitrogen intake for satisfactory nitrogen retention for growth on the mixed diet was 147 mg N.kg-1.d-1; the recommended protein allowance to cover 97.5% of the population, which was derived by using a CV of 12.5%, is 1.15 g protein.kg-1.d-1. We conclude that FAO/WHO/UNU recommendations are adequate, at least for short-term nitrogen retention; long-term studies are needed to evaluate the chronic safety of this protein allowance.
The protein quality of Lupinus albus cv Multolupa was evaluated in young adult males using the nitrogen balance technique at graded levels of N intake, and compared with egg protein. Lupin protein was consumed at levels of 0.4, 0.6 and 0.8 g/(kg.d) and egg protein at 0.3, 0.45 and 0.6 g/(kg.d). Each period started with 1 d of consuming a protein-free diet; the next 6 d were used as adaptation and the last 4 d for balance. The levels of protein intake were randomly assigned by a modified Latin square. Energy intake was individually adjusted. Mean apparent N digestibility values of lupin protein were 78.8, 76.1 and 70.2% for the levels of 0.8, 0.6 and 0.4 g protein(kg.d), respectively, and 83.8, 78.3 and 67.1% for egg protein consumed at levels of 0.6, 0.45 and 0.3 g protein/(kg.d), respectively. The N balance results obtained when subjects consumed lupin were 16.4, 0.2 and -15.1 mg N/(kg.d) for protein intakes of 0.8, 0.6 and 0.4 g/(kg.d), respectively. Those obtained for egg consumption were 12.6, -3.6 and -17.1 mg N/(kg.d) for protein intakes of 0.6, 0.45 and 0.3 g/(kg.d), respectively. The linear regressions of intake and absorbed N to retained N for lupin were: N retained = -43.41 + 0.50 N intake and N retained = -36.30 + 0.53 N absorbed. The corresponding regressions for egg were: N retained = -45.0 + 0.65 N intake and N retained = -30.65 + 0.58 N absorbed. The net protein utilization of lupin was 77% that of egg protein.