In vitro hydrolysis with a beta-galactosidase for treatment of intolerance to human milk in very low birthweight infants.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N W Solomons.
Explore the source record for details and available documents.
Loss of intestinal lactase activity among adults could theoretically limit milk consumption and hence dietary availability of calcium during pregnancy. The present study sought to define, using breath hydrogen (H2) production as an index of incomplete carbohydrate absorption, the prevalence during pregnancy of lactose maldigestion of 360 mL of milk (18 g of lactose), and to determine whether lactose digestion improved as pregnancy advanced. The prevalence of lactose maldigestion among 114 pregnant women tested before the 15th week of gestation was 54%. By term, 44% of those originally classified as maldigesters had become digesters. There was a significant reduction in the four-hour sum of the changes in breath H2 concentration from the period before 15 weeks (116.6 +/- 9.6 ppm) to the time after 36 weeks (54.4 +/- 7.3 ppm; P less than .01). This apparent adaptive improvement in intestinal handling of milk lactose during gestation has implications for calcium intake and absorption.
The experience of adverse gastrointestinal symptoms (gas, abdominal pain, and diarrhea) after the oral ingestion of 360 mL whole milk was investigated in 25 adults who claimed to be milk intolerant. The level of customary milk consumption by all subjects was low compared with that of 13 control subjects who denied a history of milk intolerance. After drinking the milk, which was accompanied by a hydrogen breath test, most of the subjects experienced some of their accustomed intestinal discomfort and the degree of intolerance was similar for the nine (36%) who proved to be true lactose-maldigester subjects and the 16 (64%) who had flat hydrogen breath responses, ie, who were classified as lactose-digester subjects. There is a subpopulation of lactose-intolerant milk-rejector individuals that absorbs lactose efficiently and responds to other milk-related factor(s) with the same subjective symptoms and dietary conduct as do true lactose-maldigester individuals.
We examined the efficiency of two beta-galactosidase preparations--one derived from the yeast, Kluyveromyces lactis (Lactaid), the other derived from the fungus, Aspergillus oryzae (Takamine)--to assist the in vivo digestion of lactose consumed by healthy Guatemalan preschool children. Milk prehydrolyzed by in vitro incubation with enzymes was used as the standard of reference, and the degree of incomplete digestion of lactose from 240 mL of milk was determined using the hydrogen breath test. In in vivo dose-response studies, both 3,250 neutral lactose units of Lactaid and 6,635 food and chemical codex lactose units of Takamine completely eliminated excess H2 excretion in a small sample of lactose-maldigesting subjects. When evaluated in a controlled, clinical trial setting, the same dose of Lactaid added directly to the milk at consumption produced an 82% relative reduction in H2 excretion, whereas Takamine was equally as effective as the prehydrolyzed milk. Thus, intraluminal conditions and gastrointestinal transit in the preschool child support the effective assisted digestion of milk lactose in an efficient manner and with the same enzyme to milk ratios as observed previously in adults.
Trace elements play a poorly understood role in human metabolism and nutrition. In the elderly, the normal effects of aging further complicate an understanding of trace element nutriture. The RDA standards established to date for the elderly have important limitations in that "healthy" persons 51 years of age and older constitute a single, regrettably imprecise category. Although any minor elemental constituent of the body is considered to be a trace element, only 16 are currently believed to be of biologic importance to humans. A recommended dietary allowance (RDA) has been established for only three of these--iron, zinc, and iodine.
Explore the source record for details and available documents.
Exogenous, microbial beta-D-galactosidases are capable of effecting hydrolysis of lactose in situ in the gastrointestinal tract of lactase-deficient subjects when given as replacement therapy at mealtime. As its digestion products-glucose and galactose-are known to inhibit lactose hydrolysis in vitro, the effect of adding excess monosaccharide to milk on the hydrolytic efficiency of a beta-galactosidase from Aspergillus niger in adult lactose-malabsorbers was tested. Subjects were studied with 360-ml volumes of milk containing 18 g of carbohydrate. This was administered as intact milk, as lactose-prehydrolyzed milk, and as milk to which 399 mg of Lactase N was added within 5 minutes of consumption. This latter Lactase N-treated milk was administered alone and with graded levels of glucose-9, 18, and 36 g-and with similar doses of galactose. The Lactase N enzyme alone at mealtime reduced breath H2 production by 68% as compared to intact milk. The addition of monosaccharides produced no change in the apparent hydrolytic efficiency of the Lactase N in situ. Thus, product inhibition is unlikely to be the basis for the limited efficiency of intraintestinal hydrolysis of milk lactose by the enzyme from A niger.
Explore the source record for details and available documents.
The degree to which inhibitors of zinc bioavailability actually influence the zinc status of humans who consume usual meals and diets is not known. The interaction of iron and zinc and competitive inhibition of zinc uptake by excess iron in ratios of 2:1 or greater, when the total amount of ionic species is greater than 25 mg, appear to have a measurable effect on human zinc nutriture. The physiological basis is the competition of these chemically similar ions for some portions of a common absorptive pathway shared between inorganic (nonheme) iron and zinc; this has been demonstrated in animal experiments and in zinc absorption studies in human volunteers. Thus, studies involving formula-fed infants, experimental zinc-depletion diets and pregnant women who took prenatal vitamin-mineral supplements containing high levels of iron have shown growth delay (infants) and a decreased circulating zinc pool (all age groups), suggesting a determinant impact of excessively high Fe/Zn ratios in the diet. Consideration of solutions to these problems, including conscious adjustment of the Fe/Zn ratios in human diets, foods and therapeutic nutrient supplements in order to reduce the zinc-inhibiting effects of iron, should become a priority in policy and marketing discussions within government regulatory agencies, industry and the scientific community of human and clinical nutritionists.
Absorption of selenium as the stable isotopic tracer [74Se]selenite was measured in four preschool children who were receiving liquid formula diets based on casein, isolated soy protein, and a 50:50 combination of the two protein sources. The children were in continuous ambulatory balance studies within the Clinical Research Center during three consecutive 11-day collection periods. The enrichment of the 74Se/76Se ratio in feces was measured by radiochemical neutron activation analysis, with fractional absorption estimated therefrom. Mean fractional absorption of selenium (+/- SD) from the formulas based on milk, isolated soy protein, and milk-soy were 64.2 +/- 14.6, 73.4 +/- 19.0, and 45.0 +/- 10.9%, respectively, with the combined formula having a significantly lower intestinal uptake for added selenite than the casein formula. Stable isotopes of selenium are safe and potentially useful tools for examining its bioavailability in the diets of young children.
Explore the source record for details and available documents.
The author speaks to the need to update our conceptual approach and our technical capacities for nutritional status assessment and to devise innovative ways to apply them to pediatric practice. The article discusses and evaluates conventional, static indices of nutriture and the importance of history and the physical examination. Focus is then placed on the concept of the functional assessment of nutritional status and its potential for clinical use.
Veterinary nutritional science has embraced the study of copper for decades, but copper has languished as an orphan among human nutritionists because of the obscurity of clinical copper-deficiency states in man. As medical investigators, we may have gone down a long road, missing the forest for the trees. Indeed, overt copper-deficiency syndromes in humans have been recognized since the 1960s, and the list of contributing factors is expanding. Unwise self-medication with megadoses of zinc, for instance, might produce a mini-epidemic of copper deficiency. Moreover, induced copper deficiency may someday prove to be a legitimate therapeutic intervention in some disease states. But, the influence of subtle differences in dietary intakes of copper on human health may be much more important than frank copper depletion. Moreover, the recognition of disordered copper metabolism simulating a deficiency state--as occurs in Menkes' KHS and in variant Elhers-Danlos syndrome--has important implications. The full description of the relationship that thionein and other intracellular proteins might have in the etiology of these alterations has yet to be written. The elegance of the interplay of biochemical defects, physiological dysfunction, and clinical manifestations in copper metabolism is virtually unmatched in nutritional biology; yet, our present abilities to determine human copper status are limited. Now that it is clear that intracellular redistribution as well as total-body depletion can effect the disruption of copper-dependent functions, a concerted effort to improve status assessment through the use of functional indices should become a high priority. Finally, the pursuit of the bases of copper's involvement in host defenses, antiotoxidant protection and carbohydrate metabolism--functions in which clear links to established mammalian cuproenzyme are at present elusive--should provide exciting substrate for investigators for years to come.
The effect of adding solid foods--cornflakes, banana and hard-boiled egg--to a meal with 360 ml of intact milk containing 18 g of lactose was investigated in 13 lactose-malabsorbers and 10 lactose-absorbers chosen from 36 Guatemalan adults screened for their capacity to digest and absorb completely the lactose in this volume of milk. A six-hour hydrogen breath test was used as the index of carbohydrate absorption. Minimal breath H2 was excreted by lactose-absorbers with either the intact milk alone, the intact milk with solid foods, or lactose-prehydrolyzed milk with solids. In lactose-malabsorbers, however, the 6-h excretion of H2 with intact milk plus solid food was intermediary between milk alone and prehydrolyzed milk with solids. A relative net reduction of 47% in lactose malabsorption was produced by adding food, and the peak-rise in breath H2 was delayed by 2 hours. A physiological consequence of taking solid foods along with milk is a slower rate of colonic fermentation, and this may be the basis for reducing gastro-intestinal symptoms in lactose-intolerant malabsorbers.
The feasibility and efficacy of adding microbial beta-galactosidase enzymes directly to milk at the time of consumption was explored in adult lactose-malabsorbers. The hydrogen breath test, and on one occasion, the rise in blood glucose, were used as indices of the completeness of intraintestinal hydrolysis and absorption of milk lactose. When added to 360 ml of cow milk containing 18 g of lactose, empirical dosages of three beta-galactosidases--one from Kluyveromyces (yeast) and two from Aspergillus (fungal)--had some effectiveness in reducing postprandial H2 excretion, although no in vivo treatment at the dosages chosen was as effective as pre-incubation of the milk in vitro. The yeast enzyme also reduced symptom frequency as compared to intact milk and enhanced postprandial rises in blood glucose. The replacement therapy with exogenous, food-grade beta-galactosidases may provide a useful intervention to reduce lactose malabsorption and milk intolerance in individuals with primary lactase deficiency.
The feasibility of enzyme replacement therapy with exogenous, food-grade, microbial enzymes at mealtime to effect intragastrointestinal hydrolysis of the lactose from 360 ml of cow's milk consumed with a solid food meal (breakfast cereals) was investigated in adult Guatemalan lactose-malabsorbers using a hydrogen breath-analysis procedure to quantify the completeness of postprandial carbohydrate absorption. Adding 2 g of a commercial preparation of beta-galactosidase from Kluyveromyces lactis at mealtime to milk taken with a refined cereal (cornflakes) and an unrefined cereal (bran) reduced the production of excess breath H2 attributable to lactose maldigestion to a level not significantly different from that achieved with lactose-prehydrolyzed milk. Sucrase, as expected, had no effect on H2 production. A beta-galactosidase from Aspergillus niger was less effective that the K. lactis enzyme for in vivo hydrolysis. Thus, exogenous betagalactosidases can eliminate lactose malabsorption in lactase-deficient individuals even in the presence of solid foods, allowing lactose intolerant persons to consume milk and dairy products without gastrointestinal discomfort.
Explore the source record for details and available documents.
We evaluated the role of initial iron stores on iron accumulation during recovery from severe edematous protein-energy malnutrition in children. Twenty-six preschool children were divided in two groups according to their initial iron reserves, as estimated from serum ferritin concentration, using a cutoff criterion of 30 ng/ml. The low ferritin (LF) group had a mean serum ferritin level of 12 +/- 8 ng/dl, and the high ferritin (HF) group, 86 +/- 32 ng/dl. Both groups had similar degrees of malnutrition and of anemia, as defined by hemoglobin concentration. All children received an adequate therapeutic diet and 60 mg iron daily as ferrous sulfate. The recovery of biochemical and anthropometric indicators of nutritional status, as well as of hemoglobin concentration, was similar in both groups. On the contrary, the LF group showed a marked increase in serum ferritin concentration from the onset of treatment, whereas the HF group had a net decline in this parameter by 30 days, and a stable level thereafter. The difference in serum ferritin concentration between groups was maintained until day 60, and both groups ended the study (90 days) with similar levels. Estimation of the utilization of exogenous iron from changes in total-body iron during the first 60 days of recovery showed the LF group to retain an average of 9.3% of iron intake, whereas the HF group retained only 1.4%.(ABSTRACT TRUNCATED AT 250 WORDS)