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Treatment of chronic portal-systemic encephalopathy with lactose in lactase-deficient patients.

A controlled cross-over clinical comparison of lactose (50 g twice a day) versus neomycin (3 g/day) plus milk of magnesia, was carried out in ten cirrhotic patients with chronic portal-systemic encephalopathy and documented lactase deficiency. Serial semiquantitative assessments were done including: mental state, asterixis, number connection test, electroencephalogram, and blood ammonia levels. No patient developed deep coma while ingesting either lactose or neomycin plus milk of magnesia. However, a significant improvement of mental state, asterixis, number connection tests, and electroencephalograms was evident during lactose therapy. apart from mild diarrhea and bloating, no severe side effects were noticeable during lactose treatment. Based on these results, we propose lactose as a valuable alternate treatment of portal-systemic encephalopathy in lactase-deficient populations.

Chronic Disease↗

Interval sampling of breath hydrogen (H2) as an index of lactose malabsorption in lactase-deficient subjects.

Interval sampling of breath hydrogen content was used in lactose malabsorbers: (1) to compare hydrogen responses following increasing oral doses of lactose in milk and aqueous solutions; (2) to determine the reproducibility of interval breath sampling, and (3) to compare carbohydrate malabsorption following ingestion of either regular milk or milk containing Lactobacillus acidophilus. Significant differences in breath hydrogen responses due to increasing amounts of lactose in milk and aqueous solutions were observed. The individual breath hydrogen responses were reproducible using the same lactose dose on different days. There was no significant difference in breath hydrogen responses or symptoms following administration of either regular milk or milk containing Lactobacillus acidophilus. Breath hydrogen sampling at intervals, as performed in these studies, provides a sensitive and reproducible index of lactose malabsorption.

Administration, Oral↗

Blood glucose and plasma insulin responses to fat free milk and low-lactose fat free milk in healthy human volunteers.

The blood glucose and plasma insulin responses to test milk samples were studied in healthy normal volunteers. After an overnight fast the subjects were given 500 ml of either regular fat free milk (approximately 25 g lactose) or 500 ml of a new low-lactose fat free milk (3.75 g lactose and 4.25 g fructose). Blood glucose levels were not significantly altered after either milk sample, but plasma insulin responses were significantly elevated after milk consumption. The response was slightly but not significantly higher after regular fat-free milk than after the low-lactose fat free milk. The results suggest that fat free milk does not exert a fast effect on blood glucose concentration and therefore fat free milk and especially low-lactose fat free milk may prove to be suitable for diabetic diets.

Animals↗

Lactose causes heart arrhythmia in the water flea Daphnia pulex.

The cladoceran Daphnia pulex is well established as a model for ecotoxicology. Here, we show that D. pulex is also useful for investigating the effects of toxins on the heart in situ and the toxic effects in lactose intolerance. The mean heart rate at 10 degrees C was 195.9+/-27.0 beats/min (n=276, range 89.2-249.2, >80% 170-230 beats/min). D. pulex heart responded to caffeine, isoproteronol, adrenaline, propranolol and carbachol in the bathing medium. Lactose (50-200 mM) inhibited the heart rate by 30-100% (K(1/2)=60 mM) and generated severe arrhythmia within 60 min. These effects were fully reversible by 3-4 h. Sucrose (100-200 mM) also inhibited the heart rate, but glucose (100-200 mM) and galactose (100-200 mM) had no effect, suggesting that the inhibition by lactose or sucrose was not simply an osmotic effect. The potent antibiotic ampicillin did not prevent the lactose inhibition, and two diols known to be generated by bacteria under anaerobic conditions were also without effect. The lack of effect of l-ribose (2 mM), a potent inhibitor of beta-galactosidase, supported the hypothesis that lactose and other disaccharides may affect directly ion channels in the heart. The results show that D. pulex is a novel model system for studying effects of agonists and toxins on cell signalling and ion channels in situ.

Ampicillin↗

Can the elimination of lactose from formula improve feeding tolerance in premature infants?

OBJECTIVE: To determine whether a low-lactose formula (LLF, <5% lactose) would ameliorate feeding intolerance in premature infants. STUDY DESIGN: Prospective, randomized, controlled trial involving 306 infants <36 weeks' gestation and weighing <1800 g who received either lactose-containing formula (LCF) 24 kcal/oz or a specially prepared LLF, which was comparable to the LCF except for the functional replacement of lactose with maltose. We examined outcome variables of feeding intolerance and cases of necrotizing enterocolitis (NEC) and suspected NEC. RESULTS: One hundred forty-nine infants were assigned to receive LCF, of which 99 infants received LCF only. One hundred fifty infants were assigned to receive LLF, of which 102 infants received LLF only. The remaining infants received LCF or LLF plus some quantity of human milk or human milk alone. Infants receiving LLF had improved enteral caloric intake and weight gain, reached full feeds faster, had less gastric residual, spent less time without oral intake, and had fewer feedings stopped than the LCF group. The number of cases of NEC and suspected NEC was similar in both groups. CONCLUSION: Low-lactose premature infant formula improved feeding tolerance. There was no evidence that LLF altered the incidence of NEC, but the incidence of NEC in this study was too low to draw conclusions.

Enterocolitis, Necrotizing↗

Coincidental malabsorption of lactose, fructose, and sorbitol ingested at low doses is not common in normal adults.

Normal subjects may incompletely absorb either lactose, fructose, or sorbitol and may therefore have abdominal symptoms. The frequency of coincidental malabsorption of these sugars is not known. This is clinically important, since we often ingest them during the same day and malabsorption may cause abdominal symptoms. To shed light on this issue we studied 32 normal subjects. Volunteers drank in random order the following solutions: 20 g lactulose, 50 g sucrose, 50 and 25 g lactose, 50 and 25 g fructose, 20 and 10 g sorbitol. Semiquantitative carbohydrate malabsorption was estimated with lactulose standards. Frequency of 50-g lactose (69%), 50-g fructose (81%), and 20-g sorbitol (84%) malabsorption was not significantly different (P = 0.3). The estimated median fraction of the ingested high dose malabsorbed was 42, 19, and 68% for lactose, fructose, and sorbitol, respectively. At low challenging doses, 63% of the volunteers absorbed two of three or all three sugars, and 88% were asymptomatic to two or all three sugars. In conclusion, the frequency of coincidental malabsorption of lactose, fructose, and sorbitol and intolerance to these sugars is not common, when normal adults ingest them at low doses.

Adult↗

Genetically defined adult-type hypolactasia and self-reported lactose intolerance as risk factors of osteoporosis in Finnish postmenopausal women.

OBJECTIVE: To study the relationships of molecularly defined lactose malabsorption (LM) and self-reported lactose intolerance (LI) to bone mineral density (BMD) and fractures among Finnish postmenopausal women. DESIGN: A cross-sectional study of two cohorts. SETTING: Helsinki University Central Hospital. SUBJECTS: One cohort was population-based and comprised 453 women, aged 62-78 (mean 69) y. Another comprised 52 women, aged 69-85 (mean 75) y, with osteoporotic fractures and 59 control women, aged 69-83 (mean 74) y, without osteoporosis. METHODS: A single nucleotide polymorphism of the lactase (LCT) gene at chromosome 2q21-22 was studied. It shows complete association with intestinal disaccharidase activity, with the genotype CC(-13 910) meaning adult-type hypolactasia (primary LM) and the genotypes CT(-13 910) and TT(-13 910) lactose absorption. BMD of the heel was measured by dual-energy X-ray absorptiometry (DXA). RESULTS: In the population-based cohort, 16.0% of women had self-reported LI but only 15.3% of them had the CC(-13 910) genotype. Calcium intake from dairy products (P = 0.10) and BMD, adjusted for age, weight, height, exercise, smoking, and estrogen use (P = 0.71) were similar for the genotypes. Women with self-reported LI had reduced calcium intake from dairy products (P < 0.0001) but they were more frequent users of calcium supplements than lactose-tolerants (P < 0.0001). Adjusted BMD was similar for lactose intolerant and tolerant women (P = 0.60). Of 104 women with previous fracture in the population-based cohort, 13.5% had the CC(-13 910) genotype, which did not differ from the prevalence of 19.3% among 347 women without fractures (P = 0.29). The frequency of the CC(-13 910) genotype (23.1%) for 52 women with established osteoporosis was similar as for 59 control women (15.3%) (P = 0.19). CONCLUSION: Molecularly defined LM and self-reported LI are not risk factors for osteoporosis, if calcium intake from diet and/or supplements remains sufficient. Our study confirms the poor correlation between self-reported LI and LM established by different techniques.

Aged↗

Metabolic adaptations during lactogenesis. Fatty acid and lactose synthesis in cow mammary tissue.

1. Mammary-tissue biopsies were obtained from multiparous cows at 30 and 7 days pre partum and 7 and 40 days post partum. Investigations of the effect of lactogenesis on fatty acid and lactose synthesis involved measurements of biosynthetic capacity (tissue-slice incubations in vitro) and activities of relevant enzymes. 2. Fatty acid synthesis from acetate increased over 20-fold from 30 days pre partum to 40 days post partum. Changes in the lipogenic capacity of mammary-tissue slices more closely paralleled increases in the activities of acetyl-CoA carboxylase (EC 6.4.1.2) and acetyl-CoA synthetase (EC 6.2.1.1) than of other enzymes involved in acetate incorporation into fatty acids or in NADPH generation. 3. Lactose biosynthesis by mammary-tissue slices, lactose synthetase activity (EC 2.4.1.22) and alpha-lactalbumin concentration were all negligible at 30 days pre partum but increased 2.5-4-fold between 7 days pre partum and 40 days post partum. Phosphoglucomutase (EC 2.7.5.1), UDP-glucose pyrophosphorylase (EC 2.7.7.9) and UDP-glucose 4-epimerase (EC 5.1.3.2) had substantial activities at 30 days pre partum and increased less dramatically during lactogenesis. 4. Results are consistent with acetyl-CoA carboxylase and perhaps acetyl-CoA synthetase representing the regulatory enzyme(s) in fatty acid synthesis, with lactose synthetase (alpha-lactalbumin) serving a similar function in lactose biosynthesis.

Acetates↗

Lowering the milk lactose content in vivo: potential interests, strategies and physiological consequences.

Lactose is the major sugar present in milk and an important osmotic regulator of lactation. It is digested by intestinal lactase, an enzyme expressed in new-borns. Its activity declines following weaning. As a result, adult mammals are normally lactose-intolerant and more than 75% of the human adult population suffers from lactase deficiency. A reduction in milk lactose content could be beneficial for nutritional but also agricultural and industrial purposes (less volume to transport, better milk coagulation, less effluent production). Several attempts to create transgenic mice producing milk with modified carbohydrate compositions have recently been described. Depending on whether these modifications resulted from an alteration of lactose synthesis or from lactose hydrolysis, striking physiological differences are observed.

Animals↗

Lactase insufficiency in Chinese children detected by oral milk and lactose challenge.

A study to determine the incidence of late-onset lactose intolerance was undertaken in 68 normal Chinese children in Singapore using measurements of breath hydrogen concentrations, following a lactose or milk challenge, as indicator of lactose malabsorption. Evidence of lactose malabsorption was detected in 26% of children given a lactose challenge, and in 21% of those given a milk challenge. It is concluded that late-onset lactase insufficiency is common in Chinese children in Singapore.

Animals↗

The effect of the digestion products of lactose (glucose and galactose) on its intraintestinal, in vivo hydrolysis by exogenous microbial beta-D-galactosidase.

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.

Adult↗

Lactose intolerance among Mexican Americans.

Thirty-three Mexican Americans between the ages of 9 and 60 were interviewed and tested for lactose intolerance. The participants of the study included 16 children and 17 persons not related by birth, including the parents of the children. Determination of lactose intolerance was based on a rise of less than 25mg/100 ml of blood glucose as measured by an Ames Dextrostix/Reflectance Meter following consumption of a lactose load. Forty-seven percent of the 17 nonrelated Mexican Americans were lactose intolerant. There was a marked relationship between low rise in blood glucose and symptoms of diarrhea, flatulence, and distention. Sixteen children from four families had an incidence of 50 per cent intolerance. The findings of intolerance in two successive generations of three families and in both sexes of the families adds support to the contention that lactose intolerance has a genetic basis, without sex predilection.

Adolescent↗

Lactose malabsorption among adult Indians of the Great Basin and American Southwest.

The prevalence of primary adult lactose malabsorption and the pattern of milk use were studied among 109 Indians from various tribes of the American Great Basin and Southwest. Included were 100 persons who reported being full-blooded Indians as well as three with Mexican admixture and 6 with some European ancestry. Lactose malabsorption was found in 92% of the full-blooded Indians but in only 50% Indians who acknowledged European admixture. These results agree with those of studies of native Americans done elsewhere which show very high prevalences of such lactose malabsorption among adults reported as fullblooded and lower prevalences among individuals with admitted European ancestors. The suggestion made is that in pre-Colombian times, before interbreeding with Europeans began on any scale, such lactose malabsorption may have been nearly universal among native American adults. Most of the Indians studied consumed abundant milk since childhood but were nevertheless predominantly malabsorbers as adults. This argues against the induction hypothesis advanced by some to explain the striking ethnic differences that occur around the world in primary adult lactose malabsorption.

Adult↗

Reduced rate of breath hydrogen excretion with lactose tolerance tests in young children using whole milk.

On 14 occasions, 1.75 g/kg of body weight of lactose was given in whole milk to preschool children who had significant malabsorption with aqueous lactose solution. The volume of hydrogen excreted in the breath was less after the milk meal. Moreover, the hydrogen response to the nonabsorbable disaccharide, lactulose, was greater with aqueous, solution than with a liquid meal but their difference disappeared when metoclopramide was given with the lactulose: meal. The slower hydrogen production is attributed to slower intestinal delivery of lactose in meals; this phenomenon may account for clinical lactose tolerance often seen in children with demonstrated lactose malabsorption.

Animals↗

Breath hydrogen test for lactose absorption capacity: importance of timing of hydrogen excretion and of high fasting hydrogen concentration.

The breath hydrogen (H2) test for lactose absorption capacity is a simple, noninvasive method for the determination of the adult lactase phenotypes, lactose absorber and malabsorber, in healthy subjects. Two breath H2 tests with a load of 50 g lactose monohydrate were performed on 25 healthy adult lactose malabsorbers in order to determine the validity of simplified versions of the test for field studies. A high variability of peak H2 excretion times, rapid changes in breath H2 concentrations and a significant correlation of intraindividual peak H2 excretion times were observed. High fasting excretion of H2 in breath was a frequent cause of misclassification of probands. It is recommended that at least three breath samples per proband should be collected in field studies of lactose absorption and that special diagnostic criteria be applied in classifying subjects with high initial H2 excretion.

Absorption↗

Yogurt and fermented-then-pasteurized milk: effects of short-term and long-term ingestion on lactose absorption and mucosal lactase activity in lactase-deficient subjects.

Lactase-deficient subjects absorb lactose in yogurt more effectively than lactose in other dairy products. However, as all previous studies were performed without a double-blind design and only after a single ingestion of the test product, the mechanism of this enhanced absorption remains unclear. The aims of this double-blind study were 1) to evaluate lactose absorption after prolonged ingestion of yogurt and fermented-then-pasteurized milk (FPM) and 2) to assess the modification of the lactase activity of the duodenal mucosa. In 16 lactase-deficient subjects we confirmed that yogurt enhances lactose digestion, this beneficial effect being destroyed by pasteurization. Moreover, the long-term (8 d) ingestion of either yogurt or FPM does not modify the results of hydrogen breath tests in comparison with a 24-h ingestion. The mucosal lactase (Dahlquist method) and beta-galactosidase (ONPG method) activities were not significantly modified by yogurt or FPM ingestion. These results suggest that in lactase-deficient subjects no adaptation occurs after eating yogurt or FPM and that the increased lactose absorption in yogurt must be mainly related to an intraluminal process.

Adolescent↗

Relative effectiveness of milks with reduced amounts of lactose in alleviating milk intolerance.

The relative effectiveness of five milk products with various levels of lactose reduction [0%, 50%, 80% (#1), 80% (#2), and 95%] was evaluated in six subjects with lactose malabsorption. Breath hydrogen was measured for 4 h after consumption of 300 mL of each product in a single-blind, randomized design. The mean +/- SEM maximum breath-hydrogen rise (ppm) after the 0%, 50%, 80% (#1), 80% (#2), and 95% lactose-reduced (LR) milks was 31 +/- 6, 7 +/- 3, 5 +/- 3, 5 +/- 2, and 8 +/- 3, respectively. The difference between whole milk and the LR milks was statistically significant (P less than 0.05) but there was no difference between any of the LR milks. Whole milk provoked symptoms in most subjects whereas 95% LR milk produced none. Only one of six subjects reacted to the 50% and 80% LR milks. The results suggest that a 50% level of lactose reduction in milk may be adequate to relieve the signs and symptoms of milk intolerance in the majority of healthy adults with lactose malabsorption.

Adult↗

Lactose digestion and tolerance in adult and elderly Asian-Americans.

Twenty adult (20-40-y old) and 20 elderly (> or = 65-y old) Asian-Americans subjects were evaluated for baseline lactose consumption, fecal beta-galactosidase activity, and lactose maldigestion to determine whether there were differences in lactose metabolism and tolerance between these groups. Fasted subjects consumed a challenge dose of 0.5 g lactose/kg body wt. Breath-hydrogen production and symptoms were monitored. There were no statistically significant differences in total hydrogen production (P < 0.6), flatulence (P < 0.6), or fecal beta-galactosidase activity between the two groups. Fecal beta-galactosidase activity did not correlate with prior lactose consumption. The shape of the breath-hydrogen curves suggests a slightly delayed transit in the elderly subjects, but apparently this delay was insufficient to alter tolerance. Thus, the findings suggest that these two groups do not differ in their metabolism and tolerance of lactose.

Adult↗