Lactase

To systematically review evidence on the efficacy and safety of using a lactase supplementation for managing infant colic. The MEDLINE, EMBASE, and Cochrane Library databases were searched (up to September 2023) for randomized controlled trials (RCTs) comparing oral lactase supplementation with placebo or no intervention in infants younger than 6 months old with infant colic. The risk of bias was assessed using the revised version of the Cochrane risk-of-bias tool. Outcomes measured were selected according to a standardized core outcome set. Five RCTs involving a total of 391 infants were identified. Three RCTs reported reduced crying duration, but one showed effect only in a compliant group (40.4%, p = 0.0052). A meta-analysis of two RCTs found no difference in crying duration and fussing time during 1 week of lactase treatment compared with placebo (mean difference [MD] -17.66 min/day, 95% confidence interval [CI], -60.8 to 25.5; I2 = 68% and MD 2.75, 95% CI, -58.2 to 57.2; I2 = 80%, respectively). Other outcomes were assessed only in individual studies or not reported. The risk of bias was low in only one RCT, high in three, and raised some concerns in one. While individual trials have shown some promise, the overall evidence for the efficacy of lactase supplementation in treating infant colic remain inconclusive. Further well-designed RCTs are necessary to determine the effects of lactase on managing infant colic. © 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

BACKGROUND: Infantile colic is typically defined as full-force crying for at least three hours per day, on at least three days per week, for at least three weeks. This condition appears to be more frequent in the first six weeks of life (prevalence range of 17% to 25%), depending on the specific location reported and definitions used, and it usually resolves by three months of age. The aetiopathogenesis of infantile colic is unclear but most likely multifactorial. A number of psychological, behavioural and biological components (food hypersensitivity, allergy or both; gut microflora and dysmotility) are thought to contribute to its manifestation. The role of diet as a component in infantile colic remains controversial. OBJECTIVES: To assess the effects of dietary modifications for reducing colic in infants less than four months of age. SEARCH METHODS: In July 2018 we searched CENTRAL, MEDLINE, Embase , 17 other databases and 2 trials registers. We also searched Google, checked and handsearched references and contacted study authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of dietary modifications, alone or in combination, for colicky infants younger than four months of age versus another intervention or placebo. We used specific definitions for colic, age of onset and the methods for performing the intervention. We defined 'modified diet' as any diet altered to include or exclude certain components. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcome was duration of crying, and secondary outcomes were response to intervention, frequency of crying episodes, parental/family quality of life, infant sleep duration, parental satisfaction and adverse effects. MAIN RESULTS: We included 15 RCTs involving 1121 infants (balanced numbers of boys and girls) aged 2 to 16 weeks. All studies were small and at high risk of bias across multiple design factors (e.g. selection, attrition). The studies covered a wide range of dietary interventions, and there was limited scope for meta-analysis. Using the GRADE approach, we assessed the quality of the evidence as very

OBJECTIVES: To determine the strength of evidence for commonly used interventions for colic in breast-fed and mixed-fed infants younger than 6 months. METHODS: Searches of PubMed, CINAHL, Embase, AMED, and Web of Science databases were conducted from July 2014 to July 2015. Included studies were randomised controlled trials involving mothers and their colicky infants younger than 6 months; assessed colic against the Wessel or modified Wessel criteria; and included phytotherapies, prescription medicines, and maternal dietary interventions. Studies with <16 participants were excluded. Meta-analyses were conducted where data were sufficient to enable pooling. Quality was assessed against the Cochrane Risk Bias Assessment Tool. RESULTS: A total of 17 articles met the inclusion criteria for this review. The 6 studies included for subgroup meta-analysis on probiotic treatment, notably Lactobacillus reuteri, demonstrated that probiotics appear an effective treatment, with an overall mean difference in crying time at day 21 of -55.8 min/day (95% CI -64.4 to -47.3, P = 0.001). The 3 studies included for subgroup meta-analysis on preparations containing fennel suggest it to be effective, with an overall mean difference of -72.1 min/day (95% CI -126.4 to -17.7, P < 0.001). CONCLUSIONS: Probiotics, in particular L reuteri, and preparations containing fennel oil appear effective for reducing colic, although there are limitations to these findings. The evidence for maternal dietary manipulation, lactase, sucrose, glucose, and simethicone is weak. Further well-designed clinical trials are required to strengthen the evidence for all of these interventions.

4. J Pediatr Gastroenterol Nutr. 2016 May;62(5):668-86. doi: 10.1097/MPG.0000000000001075. Infant Colic-What works: A Systematic Review of Interventions for Breast-fed Infants. Harb T(1), Matsuyama M, David M, Hill RJ. Author information: (1)*Child Health Research Centre, Children's Nutrition R

Cognitive control, which is critical for goal-directed behavior, involves resolving conflicts between competing stimuli and is influenced by neurotransmitter interactions within cortico-subcortical areas. This study investigated the relationship between baseline amino acid transmitter levels and interference control, focusing on the effects of experimentally enhancing catecholaminergic signaling. Using a double-blind, placebo-controlled crossover design with two dosage groups, n = 71 healthy human adults underwent proton magnetic resonance spectroscopy once to assess baseline GABA+ and Glx levels in the anterior cingulate cortex (ACC), striatum, and supplementary motor area (SMA). Participants then performed a subliminally primed flanker task inducing different scales of conflict twice while EEG was recorded: once after receiving a placebo (lactase) and once more under either low (0.25 mg/kg) or medium (0.50 mg/kg) doses of methylphenidate (MPH), which modulates the catecholaminergic and amino acid transmitter systems driving cognitive and interference control. Medium MPH doses were more effective than low doses at reducing subliminal interference effects, highlighting dose-specific behavioral improvements. Higher striatal GABA+ levels led to better interference control at low doses, while lower ACC GABA+ and GABA+/Glx levels were associated with better interference control at medium doses, suggesting a dose-dependent shift from striatal to ACC dominance in conflict resolution. Neurophysiological (EEG data) analyses revealed increased theta-band (TBA) and alpha-band activity (ABA) overlapping in the mid-superior-frontal and inferior-frontal clusters under conditions of heightened cognitive control demands. The findings highlight that whether and how amino acid transmitter levels in cognitive control-relevant regions modulate interference conflicts depends on the degree of catecholaminergic signaling. © 2025 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.

Some studies have shown that only A2 β-casein-containing milk (A2 milk) causes fewer gut symptoms in milk-sensitive individuals compared with milk containing both A1 and A2 β-caseins (A1A2 milk). However, in most of the previous clinical studies, the role of lactose in symptom generation has been largely overlooked. Partial hydrolysis of β-caseins during milk processing has been noted to influence gastrointestinal symptoms of sensitive individuals, such as those with irritable bowel syndrome. Currently, there is no clear conclusion about the factors behind gut symptoms in milk-sensitive individuals, aside from lactose in those who are lactose intolerant, or milk protein allergy. Our study involved a 3-leg, 3-d randomized crossover trial examining the effects of heat-treated, homogenized A2 and hydrolyzed A1A2 milk on gastrointestinal symptoms, fecal calprotectin, and plasma inflammation markers in 36 self-reported milk-sensitive volunteers. During the result interpretation phase, the participants were categorized into groups according to their lactase enzyme genotype. There was no difference in the amount of perceived gut symptoms between A2 and A1A2 hydrolyzed milk in the lactose-tolerant group, while gut symptoms increased in the lactose-intolerant group along with the increasing lactose content. Calprotectin and high-sensitivity CRP did not increase during any of the intervention periods compared with the milk-free run-in period. Weak evidence of certain inflammatory cytokine changes was seen, but no significant results were obtained. In conclusion, protein-hydrolyzed lactose-free A1A2 milk was as tolerated as A2 milk in lactose-tolerant volunteers and better tolerated by lactose-intolerant volunteers. The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: Previous research indicates that gastrointestinal discomfort from milk consumption may be attributable to A1 β-casein, rather than lactose intolerance alone. A2 milk (free of A1 β-casein) consumption may result in fewer symptoms compared to conventional milk containing both A1/A2 β-casein. Objective: In this five-week, double-blind, double-crossover study, we assessed the physiological responses to doses escalating in volume of lactose-free conventional milk (Lactaid), A2 milk, and lactose-free A2 milk in fluid milk-avoiding participants. Methods: Each milk type was consumed over three separate weeks with three increasing doses across five days per week, >one week washout. Gastrointestinal symptoms, blood glucose, and breath gases were monitored for twenty-four, two-, and three-hours post-consumption, respectively. Sensory evaluation was completed for each sample. Results: Fifty-three participants consented and were randomized, with forty-eight participants completing the study. Overall, symptoms were minimal. On Days 1 and 3, lower ratings of bloating and flatulence were observed in A2 compared to lactose-free A2. Breath hydrogen responses reflected lactose content, but were higher in lactose-free A2 than Lactaid on Day 5. Thirty-three participants were deemed lactose-intolerant and had higher fasting and average breath hydrogen for all samples. The only symptom corresponding to the increase in breath hydrogen among these participants was flatulence after A2 consumption. Surprisingly, flatulence was apparently higher for lactose-tolerant individuals when consuming Lactaid compared to A2. Conclusions: These findings suggest that adults who avoid conventional fluid milk consumption may experience minimal GI discomfort from lactose-free and/or A1-free milks.

BACKGROUND: Infantile colic is a common problem during the first three months of life. This randomized, double-blind, placebo-controlled trial conducted in an urban hospital in Delhi, India evaluated the efficacy and safety of oral lactase in management of infantile colic. METHODS: One hundred sixty-two clinically healthy infants aged < 5 months age [mean (SD) = 63.5 (30.5) days] fulfilling the Rome-IV diagnostic criteria for infantile colic were enrolled. Eligible children were randomly allocated to receive 5 drops of lactase (600 FCC units/mL) (n = 80) or placebo (n = 82) mixed with breast milk or formula feed four times a day for a duration of 4 weeks. Primary outcomes were duration of crying or fussing (min/d), and number of days with colic lasting > 3 h/d; secondary outcomes were parental satisfaction and adverse events. RESULTS: At the end of four weeks, mean (SD) crying or fussing time (min/d) was significantly shorter in infants receiving lactase in comparison to placebo [89.9 (115.2) vs.178.5 (153.2); P = 0.001]. The mean (SD) number of days with colic was also significantly less in the lactase group as compared to placebo group at the end of the treatment [12.1 (7.8) vs 17.6 (8.4); P < 0.001]. By the end of 4th week, parental satisfaction in terms of infant's mood, activity, alertness, comfort and oral intake was better in intervention group. The adverse event profile was comparable between two groups. CONCLUSIONS: Oral lactase treatment in infantile colic results in symptomatic relief in terms of shortening of duration of crying or fussing, and better parental satisfaction. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2017/12/010930) registered on 20/12/2017. © 2022. The Author(s).

OBJECTIVE: To study the efficacy and safety of lactase additive in improving lactose intolerance in preterm infants. METHODS: A total of 60 preterm infants with lactose intolerance who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 were randomly divided into a lactase treatment group and a control group, with 30 infants in each group. The infants in the lactase treatment group were given 4 drops of lactase additive (180 mg) added into preterm formula or breast milk, and those in the control group were given placebo, oral administration of probiotics (live combined Bifidobacterium, Lactobacillus and Enterococcus powder) at half an hour after feeding (1 g each time, twice a day), and clockwise abdominal massage around the belly button at 1 hour after feeding for 15 minutes each time, 3 times a day. Fecal pH, fecal reducing sugar, growth indicators, symptoms of lactose intolerance, and laboratory markers were measured at the end of the first and second weeks after intervention. RESULTS: Finally 29 infants in the lactase treatment group and 26 infants in the control group completed the trial. At the end of the first week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and gastric retention amount (P < 0.05) and a significantly higher proportion of infants with fecal pH > 5.0 (P < 0.05). At the end of the second week after intervention, compared with the control group, the lactase treatment group had significantly lower frequency of daily milk vomiting and 24-hour abdominal circumference difference (P < 0.05) and a significantly higher proportion of infants with the absence of gastric retention, fecal pH > 5.0, or negative reducing sugar in feces (P < 0.05). No adverse reactions associated with the lactase additive or probiotics were observed during the trial. CONCLUSIONS: Lactase additive can safely and effectively improve the clinical symptoms caused by lactose intolerance in preterm infants. 目的: 探讨乳糖酶添加剂对改善早产儿乳糖不耐受的有效性和安全性。 方法: 选取上海交通大学医学院附属新华医院2018年1月至2019年12月收治的有乳糖不耐受症状的早产儿60例纳入研究，随机分为乳

OBJECTIVE: This study aimed to investigate the therapeutic effects of sodium propionate in combination with Sishen Pill in the treatment of diarrhea with kidney-yang deficiency syndrome in mice, with a focus on its influence on intestinal microbiota, enzyme activity, and associated therapeutic outcomes. METHODS: A model of diarrhea with kidney-yang deficiency syndrome was established via adenine combined with Folium sennae administration. The model group was randomly assigned to the following treatment groups: natural recovery group, 100% Sishen Pill group, 75% Sishen Pill + 60 mg/kg sodium propionate group, 50% Sishen Pill + 120 mg/kg sodium propionate group, 25% Sishen Pill + 240 mg/kg sodium propionate group, and 480 mg/kg sodium propionate group. A variety of parameters, including general symptoms, body weight, rectal temperature, intestinal microbiota composition, microbial activity, and enzyme activity, were assessed. RESULTS: Compared with natural recovery group, the 480 mg/kg sodium propionate group presented significant improvements in mental state, anal temperature, fecal water content, the thymus index, and Bifidobacterium counts (p < 0.01). Compared with those in normal group, the fecal water content and Escherichia coli counts in the 100% Sishen Pill group were significantly different (p < 0.01), but no significant differences were observed compared with those in natural recovery group (p > 0.05). The 75% Sishen Pill + 60 mg/kg sodium propionate group showed improvements in mental state, food and water intake, body weight, rectal temperature, fecal water content, spleen, and thymus index, Bifidobacterium counts, total bacterial count, E. coli count, microbial activity, and lactase activity, which were close to normal levels, and significant differences were observed when compared to the natural recovery group (p < 0.01). The 50% Sishen Pill + 120 mg/kg sodium propionate group and 25% Sishen Pill + 240 mg/kg sodium propionate group also exhibited significant differences in mental status, microbial activity, and Lactobacillus count relative to those of normal group (p < 0.01). Furthermore, the 50% Sishen Pill + 120 mg/kg sodium propionate group presen

Sucrose produces physical dependence and reinforcing effects in rats. We hypothesized that similar effects could be demonstrated in planarians, the earliest animal with a centralized nervous system. We used two assays, one that quantifies withdrawal responses during drug absence as a reduction in motility and another that quantifies reinforcing effects using a conditioned place preference (CPP) design. In withdrawal experiments, planarians exposed to sucrose (1%) for 60 min and then tested in water for 5 min displayed reduced motility compared to water controls. Acute or continuous sucrose (1%) exposure did not affect motility. CPP experiments used a biased design to capitalize upon planarians' natural preference for the dark (pretest, sucrose conditioning in the light, posttest). Planarians conditioned with sucrose (1%) displayed a greater preference shift than sucrose-naïve planarians. Glucose (0.1, 1%), but not the non-digestible disaccharide lactulose (0.1, 1%), also produced a greater preference shift than water-exposed planarians. Development of sucrose-induced CPP was inhibited when sucrose (1%) conditioning was conducted in combination with dopamine receptor antagonists SCH 23390 (1 μM) or sulpiride (1 μM). These results suggest that the rewarding and reinforcing effects of sugar are highly conserved across species and that planarians offer an invertebrate model to provide insight into the pharmacological effects of sucrose and related sweeteners.

Glucocorticoids (GC) are considered as key modulators of glycogen homeostasis in peripheral tissues, but their role in the central nervous system has only partially been characterized. Exposure of primary cultures of cortical astrocytes to dexamethasone (DEX), a synthetic glucocorticoid, results in the reduction of noradrenaline (NA)-induced glycogen synthesis in a concentration-dependent manner with a IC50 of 4.88 nm and a maximum inhibition of 51%. Such an effect is mediated via glucocorticoid receptors (GRs), since it is mimicked by the glucocorticoid analogue RU28362 (100 nm) and prevented by the GR antagonist RU38486 (1 micro m). DEX does not act through alteration of signal transduction mechanisms, as cAMP formation induced by noradrenergic stimulation was unchanged. Moreover, glycogen synthesis was inhibited to the same extent when DEX was applied either together or only after a brief NA application. Neither [3H]2-deoxyglucose uptake nor lactate release was altered by DEX in the presence of NA, demonstrating that inhibition of glycogen synthesis is not a consequence of reduced glucose utilization or availability. Interestingly, enhancement of glycogen synthase activity induced by NA was reduced in the presence of DEX (-27%). These results suggest that GC could have a significant influence on neuroenergetics as they could modulate activity-related changes in brain glycogen metabolism.

Differentiation of human colonic cancer cells at confluency has been correlated to their increased resistance to chemotherapeutic agents. The aim of this study was to determine whether blocking Caco-2 cell differentiation could sensitize the cells to 5-fluorouracil (5-FU) treatment. We show that in cells at confluency, geraniol (400 microM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The antiproliferative effect of geraniol (400 microM) together with 5-FU (5 microM) was twice that of 5-FU alone. The cytotoxicity induced by 5-FU was enhanced in the presence of geraniol, as shown by a 50% increase of lactate dehydrogenase release in the culture medium. These effects are related to enhanced intracellular accumulation of 5-FU in the presence of geraniol as shown by a 2-fold increase in intracellular 5-[6-(3)H]FU (1.5 microCi/ml). It is concluded that geraniol sensitizes colonic cancer cells to 5-FU treatment, by increasing the cytotoxicity of the drug, and that this results from the facilitated transport of 5-FU and the blockade of the morphological and functional differentiation of the cancer cells.

The effect of cyclosporine A (CyA) on the pharmacokinetics of acyclovir in neonatal and adult rats was studied. CyA at 25 and 50 mg/kg for 2-week-old and adult rats, respectively, given as a subcutaneous injection, reduced growth of the 2-week-old rats and inhibited growth of adult rats. The plasma concentration of acyclovir after intravenous administration (20 mg/kg) to neonatal CyA-treated rats increased and the total body clearance decreased compared with the neonatal controls. The bioavailabilities of acyclovir for neonatal control and CyA-treated rats after oral administration were significantly different at 15.6 and 22.0%, respectively, but those for the adult control and CyA-treated rats were the same at 15.6 and 14.0%, respectively. Experiments using the everted sac method showed that the amount of acyclovir transferred was higher in neonatal CyA-treated rats than the controls, but there was no difference in adult rats. A good relationship was observed between the bioavailabilities (in vivo) and cumulative transferred amounts (in vitro) in CyA-treated and control rats. Lactase activity in the brush border membrane of the intestine in the neonatal CyA-treated rats was significantly higher than in the controls. These results suggest that the gastrointestinal maturation of CyA-treated neonates is suppressed, resulting in increased bioavailability of acyclovir, while the gastrointestinal absorption of acyclovir does not differ between adult CyA-treated and control rats.

Human colon adenocarcinoma cells, treated with deoxycholate for 24 h prior to exposure to 1 mM butyrate, exhibited dose-dependent increases in the activities of three markers of colonic differentiation (alkaline phosphatase, lactase and CEA). Treatment with deoxycholate alone, for 24 h or longer, did not increase the secretion of CEA or the activities of either of the brush border-associated enzyme activities. Increases in differentiation markers were found to be bile acid-specific. Pretreatment with either dehydrocholic acid or cholic acid, even at cytotoxic concentrations, led to no significant butyrate-induced increases in brush-border associated hydrolase activities. The addition of a bacterial superoxide dismutase decreased the short-term cytotoxicity of deoxycholate and increased the maturation-potentiating effects of the bile acid in HCT-116 DO cells. The results of these studies demonstrate that bile acids, which are commonly thought to have tumor promoting activities in vivo, may also have physiological effects which serve to limit carcinogenic processes in the human colon by potentiating tumor cell differentiation.

The synergistic effects of dexamethasone (DEX) and thyroxine (T4) on the postnatal maturation of the 13-d-old rodent small intestine has been studied. Previous studies have shown that hydrocortisone and T4 produced a synergistic response in enzyme maturation. However, T4 elevates corticosteroid-binding globulin, which reduces the clearance of hydrocortisone. Thus, the apparent synergy between T4 and hydrocortisone may have been due to increased glucocorticoid availability. DEX, which does not bind to corticosteroid-binding globulin, was given (d8-12) at 25 pmol (i.e. 0.01 micrograms)/g body wt/d as established by a dose-response study in which this dose of DEX induced one third the maximum response in sucrase activity. In this way, synergy with T4 (130 pmol/g body wt/d, i.e. 0.1 micrograms/g body wt/d, d 5-12) could still be observed. Glucoamylase, lactase, acid beta-galactosidase, alkaline phosphatase, and sucrase activities were determined in two regions of the small intestine. Overall, the results for the two hormones administered alone showed intestinal maturation to be not significantly affected in the T4 group and partially stimulated in the DEX group. When combined, DEX + T4 synergistically increased jejunal sucrase, ileal glucoamylase, and duodenal alkaline phosphatase, and lowered ileal acid beta-galactosidase. The striking exceptions to the general pattern were two brush border enzymes that normally decline during intestinal maturation, namely ileal alkaline phosphatase and jejunal and ileal lactase. For these enzymes, DEX alone did not elicit precocious maturation, and there was no evidence for a synergistic interaction of these two hormones. Serum corticosterone concentrations also were measured. When corticosterone concentrations were compared with enzyme activity, no correlation was found.(ABSTRACT TRUNCATED AT 250 WORDS)

During the third week of postnatal life, dramatic ontogenic changes occur in the morphology and enzymology of the small intestine of the infant rat, enabling the animal to make the transition from milk to solid food. To investigate the roles of T4 and GH in regulation of these changes, infant rats were hypophysectomized on day 6 of life by the transauricular technique. Hypophysectomy resulted in diminution of somatic and intestinal growth as well as abnormal maturation of the disaccharidases lactase, sucrase, and maltase when measured on day 25. Administration of either T4 or GH to hypophysectomized animals resulted in moderately increased intestinal growth, while complete restoration of small intestinal growth resulted from administration of the combination of both hormones. Although T4, GH, or the combination of hormones reduced lactase activities, T4 alone produced normal maturation of sucrase and maltase. Neither hypophysectomy nor hormone replacement affected aminooligopeptidase. The molecular structure of lactase, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was not altered to a major degree in hypophysectomized animals or animals that received hormone replacement, but minor alterations were evident in sucrase structure in hypophysectomy. These studies indicate that 1) T4 and GH actively participate in postnatal regulation of small intestinal ontogeny; 2) thyroid hormones act directly on developing intestinal tissues to independently produce the normal maturation of the disaccharidases by mechanisms that are not likely to involve alterations in processing of the enzyme-protein; and 3) maturation of aminooligopeptidase is not regulated by pituitary hormones, in distinct contrast to the disaccharidases.

The effects of thyroid hormone on lactase activities were studied in vitro organ culture of fetal rat intestine. Triiodothyronine inhibited lactase activities regardless the presence of dexamethasone. Also triiodothyronine decreased lactase activities when added after dexamethasone increased lactase activities. Our results suggest that thyroid hormone may have a role in the maturational changes of lactase activities during weaning.

The regulatory effect of epidermal growth factor (EGF) on the developmental pattern of brush border hydrolases was studied in the proximal jejunum and colon of the newborn rat. In the proximal colon, daily administration of EGF for 1, 3, or 5 days postpartum inhibited the postnatal increase in lactase, maltase, and aminopeptidase specific activities. In contrast, in the jejunum EGF did not influence lactase activity, inconsistently increased maltase activity, and partly prevented the early postnatal decrease in aminopeptidase activity. In the proximal colon, EGF showed additive effects with T4 and hydrocortisone on the inhibition of lactase activity. In the jejunum, EGF potentiated the effect of hydrocortisone and T4 on the expression of sucrase activity and had only a slight effect when injected alone. The incorporation rate of [3H]thymidine in the proximal colon and jejunum was not different in control and treated rats, indicating the absence of an effect of EGF on DNA synthesis. These results show that EGF may play an important physiological role in the enzymatic differentiation of the developing intestine during early postnatal development. Alone or acting with T4 or glucocorticoids, EGF may induce the decline of digestive hydrolases in the proximal colon. In the small intestine EGF may play a major role in the triggering of sucrase expression.

BACKGROUND: Approximately 70%-100% of the Asian adult population is lactase nonpersistent (LNP). The literature shows that many individuals with the LNP-genotype can consume ≤12 g of lactose without experiencing gastrointestinal discomfort. Repetitive consumption of lactose may reduce intolerance symptoms via adaptation of the gut microbiota. OBJECTIVE: This study aimed to assess the effects of daily consumption of incremental lactose doses on microbiota composition and function, and intolerance symptoms. METHODS: Twenty-five healthy adults of Asian origin, carrying the LNP-genotype were included in this 12-wk before and after intervention trial. Participants consumed gradually increasing lactose doses from 3 to 6 g to 12 g twice daily, each daily dose of 6 g, 12 g, or 24 g being provided for 4 consecutive weeks. Participants handed-in repeated stool samples and underwent a 25 g lactose challenge hydrogen breath test (HBT) before and after the 12-wk intervention. Daily gastrointestinal symptoms and total symptom scores (TSSs) during the lactose challenge were recorded. RESULTS: A significant increase from 5.5% ± 7.6% to 10.4% ± 9.6% was observed in Bifidobacterium relative abundance after the intervention (P = 0.009), accompanied by a 2-fold increase (570 ± 269 U/g; P < 0.001) in fecal β-galactosidase activity compared with baseline (272 ± 158 U/g). A 1.5-fold decrease (incremental area under the curve; P = 0.01) in expired hydrogen was observed during the second HBT (38 ± 35 ppm·min), compared with the baseline HBT (57 ± 38 ppm·min). There was a nonsignificant decrease in TSS (10.6 ± 8.3 before compared with 8.1 ± 7.2 after intervention; P = 0.09). Daily consumption of lactose was well tolerated, with mild to no gastrointestinal complaints reported during the intervention. CONCLUSIONS: Increased levels of Bifidobacterium indicate an adaptation of the gut microbiota upon repetitive consumption of incremental doses of lactose, which was well tolerated as demonstrated by reduced expired hydrogen concentrations during the second 25-g lactose HBT. Bifidobacteria metabolize lactose without gas production thereby potentially reducing intestinal gas formation in the gu

BACKGROUND: In adulthood the activity of the lactase enzyme is inherited as autosomal dominant form associated to Single nucleotide polymorphisms (SNPs). The present research was aimed to develop a novel genetic method to test lactase non persistence more powerfully. METHODS AND RESULTS: In our study, we selected eight different SNPs that are associated with lactase persistence from Caucasian, Arabian Bedouins, sub-Saharian Africans and Asian populations to set up an approach to detect all the eight different SNPs at the same time in the same sample. This technique is centred on the identification of SNPs with a single nucleotide primer extension method using Sanger sequencing and capillary electrophoresis. CONCLUSIONS: Our method allowed us to check the genotype asset of eight SNPs related to lactase persistence simultaneously and in a very efficient manner. It could be applied to a higher number of SNPs in a single reaction. © 2021. The Author(s).

BACKGROUND: A major protein component of cow's milk is β-casein. The most frequent variants in dairy herds are A1 and A2. Recent studies showed that milk containing A1 β-casein promoted intestinal inflammation and exacerbated gastrointestinal symptoms. However, the acute gastrointestinal effects of A1 β-casein have not been investigated. This study compared the gastrointestinal effects of milk containing A1 and A2 β-casein versus A2 β-casein alone in Chinese adults with self-reported lactose intolerance. METHODS: In this randomised, crossover, double-blind trial, with a 3-day dairy washout period at baseline, subjects were randomised to consume 300 mL of milk containing A1 and A2 β-casein (ratio 58:42; conventional milk) or A2 β-casein alone; subjects consumed the alternative product after a 7-day washout period. Urine galactose was measured at baseline after a 15 g lactose load. Subjects completed 9-point visual analogue scales for gastrointestinal symptoms (borborygmus, flatulence, bloating, abdominal pain, stool frequency, and stool consistency) at baseline and at 1, 3, and 12 h after milk consumption. RESULTS: A total of 600 subjects were included. All six symptom scores at 1 and 3 h were significantly lower after consuming A2 β-casein versus conventional milk (all P<0.0001). At 12 h, significant differences remained for bloating, abdominal pain, stool frequency, and stool consistency (all P<0.0001). Symptom scores were consistently lower with A2 β-casein in both lactose absorbers (urinary galactose ≥0.27 mmol/L) and lactose malabsorbers (urinary galactose <0.27 mmol/L). CONCLUSION: Milk containing A2 β-casein attenuated acute gastrointestinal symptoms of milk intolerance, while conventional milk containing A1 β-casein reduced lactase activity and increased gastrointestinal symptoms compared with milk containing A2 β-casein. Thus, milk-related gastrointestinal symptoms may result from the ingestion of A1 β-casein rather than lactose in some individuals. TRIAL REGISTRATION: NCT02878876 , registered August 16, 2016. Retrospectively registered.

OBJECTIVES: We systematically reviewed evidence to determine lactose intolerance (LI) prevalence, bone health after dairy-exclusion diets, tolerable dose of lactose in subjects with diagnosed LI, and management. DATA SOURCES: We searched multiple electronic databases for original studies published in English from 1967-November 2009. REVIEW METHODS: We extracted patient and study characteristics using author's definitions of LI and lactose malabsorption. We compared outcomes in relation to diagnostic tests, including lactose challenge, intestinal biopsies of lactase enzyme levels, genetic tests, and symptoms. Fractures, bone mineral content (BMC) and bone mineral density (BMD) were compared in categories of lactose intake. Reported symptoms, lactose dose and formulation, timing of lactose ingestion, and co-ingested food were analyzed in association with tolerability of lactose. Symptoms were compared after administration of probiotics, enzyme replacements, lactose-reduced milk and increasing lactose load. RESULTS: Prevalence was reported in 54 primarily nonpopulation based studies (15 from the United States). Studies did not directly assess LI and subjects were highly selected. LI magnitude was very low in children and remained low into adulthood among individuals of Northern European descent. For African American, Hispanic, Asian, and American Indian populations LI rates may be 50 percent higher in late childhood and adulthood. Small doses of lactose were well tolerated in most populations. Low level evidence from 55 observational studies of 223,336 subjects indicated that low milk consumers may have increased fracture risk. Strength and significance varied depended on exposure definitions. Low level evidence from randomized controlled trials (RCTs) of children (seven RCTs) and adult women (two RCTs) with low lactose intake indicated that dairy interventions may improve BMC in select populations. Most individuals with LI can tolerate up to 12 grams of lactose, though symptoms became more prominent at doses above 12 grams and appreciable after 24 grams of lactose; 50 grams induced symptoms in the vast majority. A daily divided dose of 24 grams was generally toler

BACKGROUND: Refeeding of artificially fed infants with lactose-containing formula after oral rehydration therapy in the treatment of acute diarrhea was concluded to be indifferent to non-lactose formula by a meta-analysis. In Thai as well as Asian infants and children with low lactase level from genetically determinant and with rotavirus infection, lactose malabsorption is most likely to occur and cause delayed recovery. The aim of this study was to compare the effect of a lactose-free and a lactose-containing formula in dietary management of acute childhood diarrhea. PATIENTS AND METHOD: A randomized, double-blind clinical trial of 80 male children, formula-fed, aged 3 to 24 months, admitted with acute watery diarrhea and mild or moderate dehydration, was carried out. All children received oral rehydration therapy for the first 4 hours. After appropriate rehydration, they were fed either a lactose-free formula (Dumex Lactose-Free Formula; treatment group, n = 40) or a lactose-containing formula (Dumex Infant Formula; control group, n = 40) in adjunction with oral rehydration solution. In addition, the infants were fed rice gruel as tolerated. Comparisons of duration of diarrhea, weight gain, vomiting, biochemical changes, stool frequency and weight and unscheduled intravenous fluid were made. RESULTS: Three children (2 treatment, and 1 control) dropped out from the study. The total number of unscheduled intravenous infusions were 6 of 80 children (7.5%), including 2 (5.0%) in the treatment group and 4 (10.0%) in the control group. Three children in the control group did not resolve from diarrhea within 7 days of treatment. Rotavirus was identified in approximately 50% of the children in each group. Using survival analysis, the median duration of diarrhea was significantly shortened by 20.5 hours in the treatment group compared to the control group (77.0 hours in the treatment group vs 97.5 hours in the control group; P = 0.002). Significantly decrease in stool frequency and increase in percent weight gain were seen in the treatment group at 24 hours. Moderate acidosis cleared up to near normal at 24 hours in the treatment group but acidosis persisted in the con

BACKGROUND: The prevalence of genetically determined lactase nonpersistence is based on the results of the lactose H2 breath test. This test, however, is an indirect test, which might lead to misinterpretation. DESIGN: We determined lactase activity in healthy Chinese and Dutch students using a novel 13C-lactose digestion test. The cut-off value of this test was established in a Chinese population with a homogenous genetic background of lactase nonpersistence and was compared with the results obtained in a Caucasian population. Twenty-five grams of a 13C-lactose solution was consumed by 12 known H2-positive and 5 H2-negative Chinese students and 48 Dutch students and, subsequently, 13C-glucose concentration in plasma and H2 excretion in breath were measured. RESULTS: A similar 13C-glucose response curve was found in all Chinese students. The mean response curve in the Dutch students was more pronounced (P < 0.01). The 1 h (peak) plasma 13C-glucose concentration was the best discriminator between lactose digesting and maldigesting subjects. The cut-off level of 2 mmol L-1 13C-glucose in plasma was defined in the H2-positive Chinese students group. Based on the 13C-glucose response the prevalence of lactose maldigestion in the Dutch subjects was 25%; based on the lactose H2 breath test 17%. CONCLUSIONS: Using the 13C-lactose digestion test the results demonstrate a higher prevalence of lactose maldigestion in a Caucasian population than indicated by the results of the H2 breath test. A moderate increase in the plasma 13C-glucose concentration after consumption of 13C-lactose in the young adult Chinese subjects indicates a residual lactase activity in that age group, even when a positive H2 breath test result is obtained. These results indicate that the 13C-glucose concentration in plasma more accurately reflects the small intestinal lactose digestion capacity than the lactose H2 breath test.

Impaired lactose digestion, primarily resulting from lactase non-persistence (LNP), is widely observed across African and non-African populations; however, its prevalence differs according to genetic background and dietary practices. Although numerous pastoralist cultures in Africa have independently developed lactase persistence (LP), a sizable portion of the population experiences primary or secondary lactose malabsorption, either as a natural genetic trait or as a secondary impairment resulting from intestinal damage. This review summarizes the genetic variants and environmental contributors associated with lactose digestion in Africa, highlighting ancestry-specific variants and the underrepresentation of African populations in prior studies. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-guided systematic review searched PubMed, African Journals Online, Wiley Online Library, and Google Scholar (1970 to June 2025) for studies on genetic and environmental contributors to lactose digestion in African groups. Inclusion focused on human studies reporting lactase persistence (LP)/LNP or secondary impaired lactose digestion. Data were extracted on variants, diagnostics, and outcomes. Twenty-eight studies were included, predominantly from East African pastoralists (53.3%), where LP alleles, including -13910T and -14010C in MCM6 intron 13, reached frequencies of 40%-43%.Southern or West/North African groups showed LNP rates >70%. Secondary impaired lactose digestion affected 65%-68% of malnourished/infected children, highlighting enteropathy and infections. Genotype-phenotype discrepancies were noted, with statistical associations due to linkage disequilibrium but not direct causation. Impaired lactose digestion in Africa reflects genetic adaptations in pastoralists and environmental stressors like malnutrition. Population-specific diagnostics and interventions are needed, integrating microbiome and dietary research for resource-limited settings.

Infantile colic is excessive crying for no apparent reason in an otherwise healthy infant. Although its physiopathology is not completely understood, therapies usually target gastrointestinal symptoms. This systematic review of randomized controlled trials (RCTs) analyzes the efficacy of lactase supplementation in infantile colic. PubMed, Embase, and Cochrane were searched for RCTs evaluating lactase supplementation in infants up to 6 months old with infantile colic. Out of six RCTs including 394 patients, three reported a significantly shorter crying time in the lactase group than in the placebo group, while the other three found no significant difference between groups. Of the two studies that performed the hydrogen breath test, only one reported a significant reduction in exhaled hydrogen levels. The pharmacological approach to infantile colic remains debatable, and new studies with standardized diagnostic criteria and outcomes are required to guide lactase supplementation in clinical practice. © 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Lactose intolerance (LI) is characterized by the presence of primarily gastrointestinal clinical signs resulting from colonic fermentation of lactose, the absorption of which is impaired due to a deficiency in the lactase enzyme. These clinical signs can be modified by several factors, including lactose dose, residual lactase expression, concurrent ingestion of other dietary components, gut-transit time, and enteric microbiome composition. In many of individuals with lactose malabsorption, clinical signs may be absent after consumption of normal amounts of milk or, in particular, dairy products (yogurt and cheese), which contain lactose partially digested by live bacteria. The intestinal microbiota can be modulated by biotic supplementation, which may alleviate the signs and symptoms of LI. This systematic review summarizes the available evidence on the influence of prebiotics and probiotics on lactase deficiency and LI. The literature search was conducted using the MEDLINE (via PUBMED) and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included randomized controlled trials. For each study selected, the risk of bias was assessed following the Cochrane Collaboration methodology. Our findings showed varying degrees of efficacy but an overall positive relationship between probiotics and LI in relation to specific strains and concentrations. Limitations regarding the wide heterogeneity between the studies included in this review should be taken into account. Only one study examined the benefits of prebiotic supplementation and LI. So further clinical trials are needed in order to gather more evidence.

Comment in Osteoporos Int. 2019 Feb;30(2):531. doi: 10.1007/s00198-018-4736-x. Osteoporos Int. 2019 Feb;30(2):527. doi: 10.1007/s00198-018-4799-8. Postmenopausal osteoporosis is a significant cause of morbidity and mortality. The role of primary lactase deficiency (PLD) in its development is not clear. This meta-analysis showed that PLD is a risk factor for osteoporosis in postmenopausal women. These women need special attention in terms of screening for osteoporosis and its prevention. INTRODUCTION: Postmenopausal osteoporosis is an important predictor of bone fractures. The purpose of the study was to conduct a systematic review and meta-analysis of association of PLD and bone mineral density (BMD) in postmenopausal women. METHODS: The electronic databases PubMed, Scopus, and Web of Science were searched over the course of July 2017 for any date of publication without language limitation. Studies were included in the meta-analysis if the diagnosis of PLD was made by genetic testing or H-2 breath tests and the diagnosis of osteoporosis was made by a modern reliable method for BMD measurement. Two investigators conducted a comprehensive, independent review of all the papers. Five of the studies initially identified met the inclusion criteria. We used MOOSE guidelines for abstracting data and assessing data quality and validity. Meta-analysis was performed using the random effects model. RESULTS: Five case-control studies with 2223 participants and 763 lactase-deficient cases fulfilled the inclusion criteria. Meta-analysis showed a significantly higher bone density Z-score in absorbers (mean difference 0.20, CI (0.14-0.27), P = 0.000), with no significant heterogeneity among the studies. Moreover, the Z-score in the vast majority of the measured sites (femoral head, femoral neck, lumbar spine, radius, and Ward's triangle) was significantly higher in absorbers. There was no significant overall difference in BMD in g/cm2 between absorbers and non-absorbers, but a significantly higher BMD using g/cm2 was observed in absorbers in the total hip site. CONCLUSIONS: Postmenopausal women with PLD had lower Z-scores at most anatomic sites compared to healthy controls.

Over 60 percent of the human population has a reduced ability to digest lactose due to low levels of lactase enzyme activity. Probiotics are live bacteria or yeast that supplements the gastrointestinal flora. Studies have shown that probiotics exhibit various health beneficial properties such as improvement of intestinal health, enhancement of the immune responses, and reduction of serum cholesterol. Accumulating evidence has shown that probiotic bacteria in fermented and unfermented milk products can be used to alleviate the clinical symptoms of lactose intolerance (LI). In this systematic review, the effectiveness of probiotics in the treatment of LI was evaluated using 15 randomized double-blind studies. Eight probiotic strains with the greatest number of proven benefits were studied. Results showed varying degrees of efficacy but an overall positive relationship between probiotics and lactose intolerance.