Acids Of Formula Research Articles

Docosahexaenoic Acid in Formulas for Term Infants: The Way from Pioneer Idea to Mandatory Dietary Recommendation.

Docosahexaenoic acid (DHA) is a novel mandatory constituent of breast-milk-substitute infant formula in Europe. The aim of the present narrative review was to summarize available data in connection with the background of the novel European mandatory dietary recommendation to add at least 20 mg/100 kcal (4.8 mg/100 kJ) DHA to infant formula. The literature search with the expression "docosahexaenoic acid with (infant or human milk or formula)" revealed nearly 2000 papers, including more than 400 randomized controlled trials (RCTs). DHA is a persistent constituent of human milk (HM) with a worldwide mean level of 0.37% (standard deviation: 0.11%) of all fatty acids in HM. RCTs on supplementing DHA to lactating women showed some indications, though no direct evidence of the beneficial effect of enhanced HM DHA on the development of breastfed infants. The most-recent Cochrane review of RCTs investigating the effect of DHA supplementation to infant formula for full-term infants reported no evidence for recommending supplementation. The controversy between the Cochrane view and the actual recommendation may be related to the numerous hurdles in organizing high-quality studies in this field. On the basis of the official food composition recommendation, today in Europe, DHA should be considered as a fatty acid essential for infants.

Evaluation of sn-2 fatty acid composition in commercial infant formulas on the Chinese market: A comparative study based on fat source and stage

The sn-2 fatty acid composition of 180 commercial infant, follow-on and growing-up formulas with three fat sources (plant oil, cows’ milk and goats’ milk) was investigated and compared with mature human milk (MHM). Sn-2 fatty acids in formulas were mostly dependent on fat source and stage. Compared with MHM, all types of formulas contained lower levels of palmitic acid (PA), saturated fatty acid and long-chain polyunsaturated fatty acids (LC-PUFA), and higher levels of oleic acid (OA), linoleic acid (LA) and α-linolenic acid (LNA) at the sn-2 position. Even some formulas were supplemented with 1,3-dioleoyl-2-palmitoylglycerol, the proportions of relative PA at the sn-2 position in formulas were much lower than that in MHM. Moreover, formulas had higher proportions of relative OA, LA and LNA, and lower LC-PUFAs at the sn-2 position. This study indicated that there were significant differences in the positional distribution of fatty acids between formulas and MHM.

Evaluation of fatty acid composition in commercial infant formulas on the Chinese market: A comparative study based on fat source and stage

The fatty acid compositions of 180 commercial infant, follow-on and growing-up formulas with different fat sources (plant-oil, cows' milk, goats' milk) on the Chinese market were analysed and compared with mature human milk. Fatty acid composition in formulas was dependent on fat source. The plant-oil formulas were more similar to mature human milk, while the cows' milk and goats' milk formulas contained higher levels of saturated (C4:0–C10:0) and lower levels of oleic acid and long-chain polyunsaturated fatty acids than those of mature human milk. There was little difference among formulas for the three stages except for the goats' milk formulas. The major fatty acids of formulas were similar to those of mature human milk, while levels of some micro-fatty acids in formulas, such as nervonic acid and long-chain polyunsaturated fatty acids, were significantly lower than in mature human milk.

Synthesis, Characterization and Crystal Structure of a Novel Three-Dimensional Supramolecular Architecture Formed by Cobalt(II) and Pyridine-2,5-dicarboxylic Acid

A novel three-dimensional supramolecular compound formed by Co(II) and pyridine-2,5-dicarboxylic acid of formula [Co(Pydc)2(H2O)2] (1) (Pydc = pyridine-2,5-dicarboxylic acid) has been synthesized and characterized by elemental analyses, IR, UV-vis spectra, thermogravimetric analysis and X-ray diffraction techniques. The complex 1 crystallizes in the Monoclinic crystal system, space group C12/c1 with a = 8.529(3), b = 12.164(4), c = 15.436(6)Å, β = 101.590(6)° and Z = 4. X-ray structural analysis of reveals that the central Co(II) ion is coordinated by two water molecules and two chelated Pydc ligands, and the intermolecular hydrogen bonds play an important role on the additional stabilization to construct the supramolecular networks in the packing structure. The water molecules coordinate with Co(II) ions in a cis mode in the complex 1.

Application of a sensitive fluorometric HPLC assay to determine the sialic acid content of infant formulas

The developing human brain requires high amounts of sialic acids. While human milk is very rich in sialic acids, cow's milk based infant formulas provide lower amounts of sialic acids, and sialic acids are absent in soy milk based formulas. This has prompted interest in the supplementation of formulas with sialic acids, either free or bound to glycoconjugates. In order for fortification of infant formulas with sialic acids to be appropriate for the developmental needs of the infant, an accurate quantitation of sialic acid content of infant formulas through a reliable and easy-to-use method is, therefore, of great interest to industry. In the present method, we describe the application of one of the most widely used analytical techniques to the quantitation of sialic acids in infant formulas. Briefly, sialic acids are hydrolyzed from glycoconjugates, derivatized using 1,2-diamino-4,5-methylenedioxybenzene dihydrochloride (DMB), and separated using reversed-phase high-performance liquid chromatography. The method fulfilled the established criteria for validation, with an interassay standard deviation of less than 5%, accuracy greater than 97%, and surrogate recovery between 98 and 104%. An investigation of the ruggedness of the method identified two key criteria: both standards and samples must be subjected to the same temperature and pH conditions for an accurate quantitation; and prolonged storage (more than 2 days) of the DMB reagent and derivatives must be avoided. In conclusion, this method is specific, straightforward, and accurate and can be easily performed in a quality-assurance laboratory to track the level of sialic acid in formulas that contain both inherent and fortified amounts of sialic acids. Figure Infant formula and HPLC vials used for the sialic acid quantitation.

Synthesis, characterization and crystal structure of a novel three-dimensional supramolecular architecture formed by manganese(II) and pyridine-2,5-dicarboxylic acid

A novel three-dimensional supramolecular compound formed by Mn(II) and pyridine-2,5-dicarboxylic acid of formula [Mn(Pydc)2(H2O)2] (Pydc = pyridine-2,5-dicarboxylic acid) has been synthesized and characterized by elemental analyses, IR, electronic spectra, thermogravimetric analysis and X-ray diffraction techniques. The X-ray structure shows that the central Mn(II) ion is coordinated by two water molecules and two chelated Pydc ligands. Water molecules coordinate with Mn(II) ions in the cis mode. Intermolecular hydrogen bonds play an important role in stabilization of the lattice and construction of the supramolecular network.

Synthesis and structure of a novel three-dimensional compound formed by copper(II) and picolinic acid

A novel compound formed by copper(II) and picolinic acid of formula [Cu(PCA)2(H2O)2] (PCA = picolinate) has been synthesized. The complex crystallizes in the monoclinic space group P21/c with a = 5.4479(11), b = 10.910(2), c = 10.396(2) Å, β = 98.22(3)° and Z = 2. X-Ray analysis reveals that the Cu(II) ion lies in the usual distorted octahedral environment; two nitrogen atoms and two oxygen atoms from the PCA form the basal plane and two oxygen atoms from coordinated water molecules occupy the axial position. [Cu(PCA)2(H2O)2] units are connected in a three-dimensional structure by intermolecular hydrogen bonds.

Fatty acids in formulae for term infants: compliance of present recommendations with the actual human milk fatty acid composition of geographically different populations

Aim: Recommendations for formula fatty acids (FA) are largely based on the mature human milk FA composition. This study aimed to investigate whether current recommendations for formula FA for term infants comply with the actual breast‐milk FA composition of geographically distinct populations and to provide more realistic grounds for future recommendations. Methods: 455 mature breast‐milk samples were collected in different countries over 25 y. Recommendations of different organizations were projected on their FA data. FA interrelationships were calculated with Spearman's rank tests. FA compositions of 30 formulae were compared with those of breast milk. Results: Many samples from non‐Western communities did not meet the recommendations for formula 12:0, 14:0 and 18:2ω6, since these are mainly based on breast milk of mothers living in Western countries. Recommendations for 18:3ω3, 18:2ω6/18:3ω3, 20:4ω6 and 22:6ω3 were not met by many milk samples, which may point to the poorly developed recommendations for long‐chain polyunsaturated FA. Most of the investigated breast‐milk FA (12:0, 14:0, 16:0, 18:0, 18:3ω3, 22:6ω3, 18:2ω6, 20:4ω6, 18:lω9) were either positively or negatively interrelated. Many formulae had FA compositions that were not consistent with the physiological interrelationships of FA in breast milk. Conclusion: Future recommendations, if based on human milk, should derive from its FA balance, as indicated by the FA interrelationships. A “humanized” formula FA composition would in this sense be any composition that cannot be distinguished from that of breast milk by techniques such as principal component analysis.

Compliance of present recommendations of fatty acids in formulas for term infants with the actual human milk fatty acid composition in different populations

Fats are the only dietary agents possibly modulating the individual membrane composition, which otherwise is “genetically” determined. In infancy, human milk represents the first natural source of fats. Although the fat intake of breastfed infants is quantitatively and qualitatively unique, it is not known to what extent their varying requirements are met by the fat composition in the milk of their mothers. Conclusion: The fat composition of arbitrarily chosen human milk is not always the best standard for that in infant formula.

Fatty acids in formulae for term infants: compliance of present recommendations with the actual human milk fatty acid composition of geographically different populations

Recommendations for formula fatty acids (FA) are largely based on the mature human milk FA composition. This study aimed to investigate whether current recommendations for formula FA for term infants comply with the actual breast-milk FA composition of geographically distinct populations and to provide more realistic grounds for future recommendations. 455 mature breast-milk samples were collected in different countries over 25 y. Recommendations of different organizations were projected on their FA data. FA interrelationships were calculated with Spearman's rank tests. FA compositions of 30 formulae were compared with those of breast milk. Many samples from non-Western communities did not meet the recommendations for formula 12:0, 14:0 and 18:2omega6, since these are mainly based on breast milk of mothers living in Western countries. Recommendations for 18:3omega3, 18:2omega6/18:3omega3, 20:4omega6 and 22:6omega3 were not met by many milk samples, which may point to the poorly developed recommendations for long-chain polyunsaturated FA. Most of the investigated breast-milk FA (12:0, 14:0, 16:0, 18:0, 18:3omega3, 22:6omega3, 18:2omega6, 20:4omega6, 18:1omega9) were either positively or negatively interrelated. Many formulae had FA compositions that were not consistent with the physiological interrelationships of FA in breast milk. Future recommendations, if based on human milk, should derive from its FA balance, as indicated by the FA interrelationships. A "humanized" formula FA composition would in this sense be any composition that cannot be distinguished from that of breast milk by techniques such as principal component analysis.

Concentration and distribution of sialic acid in human milk and infant formulas

In animal studies, sialic acid supplementation is associated with increases of gangliosides in the brain and improved learning ability. Only limited data are available on the sialic acid content of human milk and infant formulas. We compared the concentrations of oligosaccharide-bound, protein-bound, and free sialic acid in milk from mothers of full-term and preterm infants and in a range of infant formulas. The milk from 20 and 14 mothers of full-term and preterm infants (mean gestational age: 31 +/- 3 wk), respectively, was collected at 4 stages of lactation (colostrum, transition, 1 mo, and 3 mo) and compared with 21 different infant formulas. Total sialic acid concentrations were highest in colostrum (x +/- SEM: 5.04 +/- 0.21 mmol/L in full term) and decreased by nearly 80% over the next 3 mo. Human milk from mothers of preterm infants contained 13-23% more sialic acid than did milk from mothers of full-term infants at 3 of the 4 lactation stages (P < 0.02). The sialic acid content of most formulas was <25% of that found in mature human milk (P < 0.01). Most of the sialic acid in the formulas ( approximately 70%) was bound to glycoproteins, whereas in human milk most sialic acid was bound to free oligosaccharides. Human milk, including milk from mothers of preterm infants, is a rich source of oligosaccharide-bound sialic acid, which contrasts with the relatively small amounts found in infant formulas. The nutritional significance of sialic acid is presently unknown, but it is plausible that it is a conditional nutrient that contributes to sialic acid accretion in the brain.

CRYSTAL STRUCTURE OF THE ISOMORPHOUS COMPLEXES TETRAAQUABIS(2,6-DIHYDROXY-BENZOATO-O)(2,6-DIHYDROXY-BENZOATO-O,O)TERBIUM(III) AND HOLMIUM(III) DIHYDRATE

The structures of isomorphic Tb(III) and Ho(III) complexes with 2,6-dihydroxybenzoic acid of formula [Tb(C7H5O4] 2H2O and [Ho(C7H5O4)3 4H2O] 2H2O has been determined by X-ray diffraction and refined to a residual R = 0.030 for 5376 observed reflections and R = 0.0284 for 5660 observed reflections, for Tb(III) and Ho(III) complexes, respectively. Crystals are triclinic, space group P1 with a= 10.748(2), b=11.309(2), c = 12.452(2)Å, α = 82.28(3), ᵬ = 73.05(5), γ = 68.27(3)° for Tb(III) and a= 10.731(2), b=11.269(2), c = 12.436(2)Å, α = 82.25(3), β = 72.92(3), γ = 68.46(3)° for Ho(III). In the structure of these monomelic complexes the metal ions are coordinated by oxygen atoms of one bidentate chelating and two monodentate carboxylate groups and four molecules of water. Tb-O distances are in the range 2.323(3)-2.506(3) Å and Ho-0 2.297(3)-2.486(3) Å. The crystal structure, consisting of discrete units of neutral complexes with two molecules of water of crystallization is stabilized by intra-and intermolecular hydrogen bonds.

Requirements for long-chain polyunsaturated fatty acids in the preterm infant.

Dietary long-chain polyunsaturated fatty acids have demonstrable beneficial effects on early development. The effects on neural development are of particular interest. Human milk is the best and only time-proven source of fat and essential fatty acids in the infant diet. Technologic procedures based on chemical and physical separation of the unsaturated fatty acids have permitted the isolation of concentrated sources of docosahexaenoic acid and arachidonic acid for clinical use. Virtually all infant formulas in developed countries have increased the levels of gamma-linolenic acid, and several manufacturers in Europe and in Japan have added docosahexaenoic acid, or docosahexaenoic acid plus arachidonic acid, or have also included gamma-linolenic acid in formulas for preterm and term infants. The efficacy of this practice for preterm infants seems fairly well established. The use of stable isotope methods to evaluate biosynthesis of long-chain polyunsaturated fatty acids from dietary precursors may help to better define optimal amounts and relationships of fatty acids in infant formula.

The crystal structures of two neodymium(iii) complexes with pyridine‐2, 6‐dicarboxylic acid

The structures of two complexes of neodymium(III) with pvndine-2.6-dicarboxvlic acid of formula (NH4), [Nd(C7H3NO4)3]-7H2O (1) and (NH4)[Nd3(C7H3NO4)5 8H2O]-5H2O (2) have been determined by X-ray diffraction. Crystals of 1 are monoclinic, P21/c, a = 17.925(4). b = 10.198(2), c = 18.707(4) Å, β = 112.22(3)°. Z = 4. Crystals of 2 are monoclinic C2/c, a = 22.205(4), b = 13.774(3), c = 17.783(4) Å, β = 112.55(3)°, Z = 4. Both structures were solved by the heavy-atom method and refined to R = 0.032 for 7568 reflections (1) and 0.030 for 3267 reflections (2). The water molecules and NH+ 4 groups in both crystals participate in a network of hydrogen bonds.

A dose response study of arachidonic acid in formulas containing docosahexaenoic acid in term infants: Gibson R, Makrides M, Neumann M, Hawkes J, Pramuk K, Lien E, Euler A; Paediatrics, Flinders Medical Centre, Adelaide, AU; Wyeth Nutritionals International, Radnor, PA, USA

A dose response study of arachidonic acid in formulas containing docosahexaenoic acid in term infants: Gibson R, Makrides M, Neumann M, Hawkes J, Pramuk K, Lien E, Euler A; Paediatrics, Flinders Medical Centre, Adelaide, AU; Wyeth Nutritionals International, Radnor, PA, USA

Diet-Induced Changes in Liver and Bile but Not Brain Fatty Acids Can Be Predicted from Differences in Plasma Phospholipid Fatty Acids in Formula- and Milk-Fed Piglets ,

The fatty acid composition of plasma phospholipids differs between infants fed formula and infants fed human milk, but the extent to which this is accompanied by differences in tissue phospholipid fatty acids is unclear. This paper describes analysis of plasma, liver and brain fatty acids from piglets fed one of seven formulas, varying in saturated, monounsaturated, (n-6) and (n-3) fatty acids or sow milk from birth for 18 d. Bile fatty acids were analyzed because they are secreted from liver and may be an important source of fatty acids for intestinal lipoprotein synthesis. The results were used to determine the relation between diet-related differences in plasma phospholipid fatty acids and those in brain, liver and bile. Where significant associations were found, prediction limits were constructed to assess the usefulness of analysis of plasma phospholipid fatty acids to predict diet-induced changes in tissue fatty acids. The proportions (g/100 g fatty acids) of 16:0, 18:0, 18:1, 18:2(n-6) and 20:4(n-6) in plasma phospholipids were significantly associated with the proportions of the same fatty acids in liver and bile, but not brain. The results show a reasonably precise, predictable association between plasma and liver, and plasma and bile fatty acids. Brain 20:4(n-6) and 22:6(n-3), in contrast, were not reliably associated with plasma phospholipid 20:4(n-6) and 22:6(n-3) for piglets fed milk or formula providing about 1.5% energy as 18:3(n-3).

Ratios of linoleic acid to α-linolenic acid in formulas for term infants

Commercial infant formulas with a ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) of 10:1 or higher are nutritionally inadequate; the tissue levels of docosahexaenoic acid (DHA) are lower and the visual function indices are reduced in infants who are fed these formulas. All the evidence points to using LA:ALA ratios of less than 8:1, but there has been only one study in infants that used formulas with reduced LA:ALA ratios, and only biochemical indices were monitored. There is a need for both short-term studies to establish the ratios of LA to ALA that will make possible the accumulation of DHA to levels close to those in breast-fed infants and long-term trials to determine the effects of such fat blends on growth and development.

Medium-chain triglycerides in formula for preterm neonates: Implications for hepatic and extrahepatic metabolism

Medium-chain fatty acids are an important energy source for preterm neonates. Based on assumptions from earlier investigations, 40% to 60% of fatty acids in formula designed for preterm neonates are C6:0 to C12:0. This review will reevaluate these assumptions about C6:0 to C12:0 fatty acids. More recent investigations have indicated that when C6:0 to C12:0 fatty acids are administered in high concentrations, they are metabolized in several tissues by carnitine-dependent mechanisms. Incomplete oxidation of C6:0 to C12:0 fatty acids may result in elevated dicarboxylic acid levels. Feeding formulas high in C6:0 to C12:0 fatty acids has not improved nitrogen retention or growth of preterm neonates. Current data indicate that the fatty acid profiles of formula for preterm neonates are not optimal. Optimization of the fatty acid profile in the diet awaits an improved understanding of the metabolism of fatty acids of all chain lengths in the preterm neonate.

Homopolymerization of Four New Hydroxyamic Acids and Polycondensation of Glycerol With Dibasic Amic Acids

Abstract During the past 15 years or so, research in our laboratory has been mainly directed toward the synthesis of cyclic imides and isoimides for different purposes [1–4]. Thus a large number of substituted amic acids and bis-amic acids were prepared as intermediates. These amic acids were readily purified, crystallized, and obtained in excellent yields. In the present paper two types of amic acids are prepared. The first type is hydroxyamic acids of formula A, while the second type consisted of dibasic amic acids such as B: