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In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7-2 μg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ferrari, Patrizio, Mazzi, Ragusa, Botrini, Elia, Balestri, Barozzi, Rugani, Bracchitta, Stoppini, Frenzilli, Baldini, Virili, Benvenga, Fallahi and Antonelli.)

β-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems for carrying this enzyme in the active form up to the intestine, where the lactose digestion occurs. In this research, a new hydrogel was developed that could potentially be used for enzyme supplement therapy. In this regard, the chitosan-based β-Gal formulations described in the manuscript are an alternative long-acting preparation to the so far available preparations that allow for enzyme protection and mucosal targeting. These hydrogels were prepared from chitosan and polyethylene glycol and contained a covalently immobilized β-galactosidase from Aspergillus oryzae. The β-galactosidase in the hydrogel was protected from degradation in a gastric medium at a pH of 2.5 and retained 75 % of its original activity under subsequent intestinal conditions. In the case of a simulated gastric fluid with a pH of 1.5, a copolymer containing methacrylic acid functional groups was sufficient to protect the hybrid hydrogel from the extremely acidic pH. In addition, the surface of the hydrogel was chemically modified with thiol and amidine groups, which increased the binding to intestinal mucin by 20 % compared with the unmodified hydrogel. These results represent a promising approach for oral transport as a reservoir for β-galactosidase in the small intestine to reduce the symptoms of hypolactasia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niuris Acosta and Julia Revuelta reports financial support was provided by Community of Madrid., (Copyright © 2023. Published by Elsevier B.V.)

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.

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.

Background and Aims: Lactose intolerance (LI) is a global problem affecting more than half of the world's population. An ultra-purified, high-concentration galacto-oligosaccharide, RP-G28, is being developed as a treatment for patients with LI. The efficacy and safety of RP-G28 in reducing symptoms of lactose intolerance were assessed in a blinded, randomized, placebo-controlled trial. Methods: In this multiclinical site, double-blinded, placebo-controlled trial, 377 patients with LI were randomized to one of two doses of orally administered RP-G28 or placebo for 30 days. A LI test and symptom assessment were performed at baseline and on day 31. The primary endpoint was a ≥4-point reduction or a score of zero on LI composite score on day 31. Voluntary milk and dairy intake and global outcome measures assessed patients' overall treatment satisfaction and quality of life before therapy and 30 days after therapy. This study received Institutional Review Board (IRB) approval. Results: For the primary endpoint, 40% in the RP-G28 groups reported a ≥4-point reduction or no symptoms on LI symptom composite score compared to 26% with placebo (P = 0.016). Treatment with RP-G28 also led to significantly higher levels of milk and dairy intake and significant improvements in global assessments compared to placebo. RP-G28 but not placebo led to significant increases in five Bifidobacterium taxa. Conclusions: RP-G28 for 30 days significantly reduced symptoms and altered the fecal microbiome in patients with LI. Treatment with RP-G28 also improved milk/dairy consumption and quality of life and was safe and well tolerated.

Lactose intolerance is a common condition caused by lactase deficiency and may result in symptoms of lactose malabsorption (bloating, flatulence, abdominal discomfort, and change in bowel habits). As current data is limited, the aim of our study was to assess the efficacy of probiotics with a β-galactosidase activity on symptoms of lactose malabsorption and on the lactose hydrogen breath test (LHBT). The study group comprised eight symptomatic female patients with a positive LHBT. Patients were treated for 6 months with a probiotic formula with β-galactosidase activity (Bio-25, Ambrosia-SupHerb, Israel). All patients completed a demographic questionnaire as well as a diary for the assessment of symptom severity and frequency at entry, every 8 weeks, and at the end of the treatment period. Measurements of hydrogen (H 2 ) levels (parts per million, ppm) at each of these time points were also performed. End points were a decrease of 50% in symptom severity or frequency, and the normalization (decrease below cutoff point of 20 ppm) of the breath test. Mean age and mean body mass index (BMI) were 36.4 ± 18.6 years and 23.2 kg/m 2 , respectively. Compared to baseline scores, the frequency of most symptoms, and the severity of bloating and flatulence, improved after treatment. Normalization of LHBT was obtained in only two patients (25%). In this pilot study, Bio-25, a unique formulation of probiotics with β-galactosidase activity, demonstrated symptom resolution in most patients with lactose malabsorption. A larger randomized trial is warranted to confirm these preliminary findings.

Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Objective: Introduction: Excess lactose in the diet of modern man causes the development of not only lactase deficiency, but it can be a factor that contributes to obesity. The aim: To study associations between obesity and genotype C/C 13910 of lactase gene (LCT) in children, to investigate the effectiveness of treatment using drug exogenous lactase and a low-lactose diet., Patients and Methods: Materials and methods: genotyping of lactase gene by real-time polymerase chain reaction, determining the level of lactose maldigestion by hydrogen breath test (HBT), estimating the insulin resistance with the HOMA-IR index in 70 obese children and 40 healthy children 6 - 18 years. Obese children with genotype C/C 13910 and lactose maldigestion (n=40) were randomized in two groups: children from group I (n=20) received an exogenous lactase preparation, and children from group II (n=20) - low-lactose diet., Results: Results: in obese children, the genotype C/C 13910 is 2 times more often than in healthy children. Obese children with genotype C/C 13910 have a significantly higher value of HBT (32.8-39.8 ppm) compared to healthy children (p<0.05), and an increased value of the HOMA-IR index. After treatment, there was a significant decrease in HBT and the HOMA-IR index in the two comparison groups., Conclusion: Conclusions: signs of insulin resistance are observed in children with obesity, genotype C/C 13910 and lactose maldigestion. The use of exogenous lactase in the therapy or the administration of a low-lactose diet cause approximately the same decrease in the HOMA-IR index.

Objective: To determine the efficacy of lactase enzyme supplement in infant colic., Methods: The double-blind randomised clinical trial was conducted from November 2014 to June 2017 at Kharadar General Hospital, Karachi, and comprised infants aged 0-6 months with infant colic, excessive crying lasting at least 3 hours a day on at least 3 days a week for at least 3 weeks. The subjects were randomised into intervention group A which received lactase enzyme Colibid, and placebo group B. Five drops of intervention preparation were received by all the infants before each feed for two weeks. Confidentiality of active agent and placebo was maintained through drug codes. The duration of crying was recorded at baseline then after first and second weeks of intervention. The two groups were compared with level of significance set at p<0.05., Results: There were 104 subjects with 52(50%) in each of the two groups Overall, 50(48.1%) were boys. At baseline, all (100%) the subjects had infant colic or excessive crying. After two-week intervention, significant improvement was seen in the duration of crying in group A 45(86.5%) compared to group B 31(59.6%) (p<0.05)., Conclusions: Significant improvement was seen in the duration of crying in infants who received lactase enzyme supplement..

Strategies to avoid lactose malabsorption, which affects 70% of the world's population, are focused on the restriction of milk and dairy products or the use of non-human β-galactosidases or probiotics endowed with β-galactosidase activity added at mealtime. Our evaluation of a commercial blend of probiotics and enzymes (protease, lactase, lipase and amylase) and its potential application in lactase non-persistence management is described in this work. Recommended amounts (460-1000 mg) of the commercial probiotics-enzyme blend were shown to be adequate for performing in vitro lactose hydrolysis in standard solutions (0.25-5%) and commercial dairy products, namely milks (5% lactose) and yogurts (3% lactose), reaching hydrolysis values between 44 and 96%. According to these percentages, the use of the enzymatic preparation would guarantee the intake of less than 12 g, the recommendation of the EFSA for lactose intolerance. Furthermore, formation of prebiotic galactooligosaccharides was also detected, increasing the potential benefits of the enzymatic preparation in the gastrointestinal system.

Lactase (LCT) deficiency affects approximately 75% of the world's adult population and may lead to lactose malabsorption and intolerance. Currently, the regulation of LCT gene expression remains poorly known. Peroxisome proliferator activator receptorγ (PPARγ) is a key player in carbohydrate metabolism. While the intestine is essential for carbohydrate digestion and absorption, the role of PPARγ in enterocyte metabolic functions has been poorly investigated. This study aims at characterizing PPARγ target genes involved in intestinal metabolic functions. In microarray analysis, the LCT gene was the most upregulated by PPARγ agonists in Caco-2 cells. We confirmed that PPARγ agonists were able to increase the expression and activity of LCT both in vitro and in vivo in the proximal small bowel of rodents. The functional response element activated by PPARγ was identified in the promoter of the human LCT gene. PPARγ modulation was able to improve symptoms induced by lactose-enriched diet in weaned rats. Our results demonstrate that PPARγ regulates LCT expression, and suggest that modulating intestinal PPARγ activity might constitute a new therapeutic strategy for lactose malabsorption., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance., Objective: Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance., Methods: Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days., Results: Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment., Conclusion: The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

Maldigestion occurs when digestive enzymes are lacking to help break complex food components into absorbable nutrients within the gastrointestinal tract. Education is needed to help patients manage the intricacies of digestive enzyme replacement therapies and ensure their effectiveness in reducing symptoms of maldigestion.

The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

Thus, we have discovered that the children of the first half-year of life have different degrees of severity of transient lactase insufficiency basing on the results of hydrogen respiratory test. It was set that the starting dose of enzyme lactase must depend on the degree of severity of displays of transient lactase insufficiency, taking into account the indexes of hydrogen respiratory test.

"Lactose intolerance" is a medical problem for almost 70% of the world population. Milk and dairy products contain 5-10% w/v lactose. Hydrolysis of lactose by immobilized lactase is an industrial solution. In this work, we succeeded to increase the lactase loading capacity to more than 3-fold to 36.3 U/g gel using epoxy activated hydrogels compared to 11 U/g gel using aldehyde activated carrageenan. The hydrogel's mode of interaction was proven by FTIR, DSC, and TGA. The high activity of the epoxy group was regarded to its ability to attach to the enzyme's -SH, -NH, and -OH groups, whereas the aldehyde group could only bind to the enzyme's -NH2 group. The optimum conditions for immobilization such as epoxy chain length and enzyme concentration have been studied. Furthermore, the optimum enzyme conditions were also deliberated and showed better stability for the immobilized enzyme and the Michaelis constants, K m and V max, were doubled. Results revealed also that both free and immobilized enzymes reached their maximum rate of lactose conversion after 2 h, albeit, the aldehyde activated hydrogel could only reach 63% of the free enzyme. In brief, the epoxy activated hydrogels are more efficient in immobilizing more enzymes than the aldehyde activated hydrogel.

Objective: To establish whether supplementation with a standard oral dose of Beta-Galactosidase affects hydrogen breath excretion in patients presenting with lactose malabsorption., Methods: Ninety-six consecutive patients positive to H2 Lactose Breath Test were enrolled. Mean peak H2 levels, the time to reach the peak H2, the time to reach the cut-off value of 20 ppm, the cumulative breath H2 excretion, the areas under the curve, and a Visual Analogical 10-point Scale for symptoms were calculated. Genotyping of the C/T-13910 variant was carried out., Results: Following the oral administration of Beta-Galactosidase, in 21.88% of the cases, H2 Lactose Breath Test became negative (Group A), while mean peak H2 levels (74.95 ppm versus 7.85), P < 0.0000, in 17.71% (Group B) were still positive, with the H2 level 20 ppm above the baseline, but the peak H2 levels were significantly lower than those observed at the baseline test (186.7 ppm versus 66.64), P < 0.0000, while in 60.41% (Group C) they were still positive with the peak H2 levels similar to those observed at the baseline test (94.43 versus 81.60 ppm). All 96 individuals tested presented the C/C-13910 genotype nonpersistence., Conclusions: The response to oral administration of Beta-Galactosidase in patients with symptoms of lactose malabsorption presents a significant variability.

Aim: To estimate the incidence of secondary lactase deficiency (SLD) in patients with postinfectious irritable bowel syndrome (PIBS) and the value of the small bowel microflora in its development and to elaborate treatment options for SLD., Subjects and Methods: One hundred and thirty-eight patients with PIBS, including 112 (81.2%) women and 26 (18.8%) men, were examined. The patients' mean age was 33.9 +/- 9.1 years. The duration of the disease was 2.6 +/- 1.4 years. Lactase deficiency (LD) was diagnosed using the color scale to test biopsy specimens from the duodenal retrobulbar region. The bacterial overgrowth syndrome (BOS) was identified by a 2-hour lactulose (20 ml) hydrogen breath test. Sixty patients with moderate SLD were randomized to 2 groups: 1) 41 patients received basic therapy (mesim forte as one tablet t.i.d., no-spa, 40 mg, t.i.d.) and combined probiotic bifiform (Ferrosan) containing Bifidobacterium longum 107, Enterococcus faecium 107 as one capsule t.i.d. for 14 days. Group 2 patients (n = 19) had basic therapy in combination with placebo., Results: SLD was detected in 59.4% of the patients with PIBS, including 43.5 and 15.9% with moderate and severe forms, respectively. In all cases, SLD was accompanied by BOS in the small bowel lumen, as confirmed by the results of a hydrogen breath test [101 +/- 37 ppm (a normal value of < 20 ppm)]. After a 14-day course of therapy with the combined probiotic bifiform, restoration of eubiosis in the small bowel lumen was achieved in 70.8% of the patients, as shown by the lesser degree of BOS (86.9 +/- 40.9 and 17.4 +/- 6.6 ppm before and after treatment, respectively; p < 0.01) and by normalization of the lactase test (p < 0.01). In the comparative placebo group, 68.4% showed no clear positive changes, SLD and BOS remained., Conclusion: The changes in the small bowel intraluminal microflora, which developed after prior intestinal infection, played a great role in the development of SLD. Bifiform belongs to the currently available probiotics and may be recommended to correct SLD in patients with PIBS resulting from the impaired microbiota of the small bowel and to prevent BOS.

Background: The efficacy of some probiotic strains for the management of lactose intolerance remains to be established., Aim: To evaluate the effects of a 4-week consumption of a probiotic product containing Lactobacillus casei Shirota and Bifidobacterium breve Yakult (10(7)-10(9) CFU of each strain) on symptoms and breath hydrogen exhalation after a lactose load in lactose-intolerant patients and whether the beneficial results persisted after probiotic discontinuation., Methods: Twenty-seven patients with lactose maldigestion and intolerance participated in this study, which comprised 4 hydrogen breath tests: baseline condition (20 g lactose), after lactase ingestion (9000 FCC units), at the end of 4-week probiotic supplementation, and a follow-up test performed 3 months after probiotic discontinuation. For each test, the area under the breath hydrogen concentration vs time curve (AUC(180 min)) was calculated, and symptom scores were recorded., Results: The probiotic combination significantly reduced symptom scores (P < .01) and breath hydrogen AUC (P = .04) compared with the baseline condition. The comparison with the lactase test showed that symptom scores were similar (P > .05), despite the significantly higher (P = .01) AUC values after probiotic use. In the follow-up test, symptom scores and breath hydrogen AUC values remained similar to those found at the end of probiotic intervention., Conclusion: Four-week consumption of a probiotic combination of L casei Shirota and B breve Yakult seems to improve symptoms and decrease hydrogen production intake in lactose-intolerant patients. These effects may persist for at least 3 months after suspension of probiotic consumption.

The preferred treatment for hypothyroidism is oral levothyroxine (LT4) ingestion, in doses that ensure a sustained state of hormonal balance. Many different factors may significantly influence the absorption of LT4, including: interval between the ingestion of the drug and the last meal, eating habits, and different functional and organic pathologies of the gastro-intestinal tract. The main purpose of this paper is to review and systematise the available literature on the subject of the influence of different malabsorption syndromes on the effectiveness of LT4 preparations. The need to use high LT4 doses in the substitutional treatment of hypothyroidism is often the very first sign of one of the pathologies that are connected with malabsorption syndrome, which might have been asymptomatic and undiagnosed previously. Patients who require more than 2 μg/kg body weight of LT4 per day, with constantly increased thyrotropin level, should be diagnosed with the suspicion of pseudomalabsorption or real absorption disorder. An LT4 absorption test, using high doses of LT4, may be useful in the diagnosis of pseudomalabsorption. After excluding non-compliance, the differential diagnosis should include such disorders as lactose intolerance, coeliac disease, atrophic gastritis, Helicobacter pylori infection, bowel resection, inflammatory bowel disease, and parasite infection. Where there is a diagnosis of lactose intolerance, both a low lactose diet and a lactose-free LT4 preparation should be administered to restore euthyroidism or make it possible to decrease the dose of the LT4 preparation. In coeliac disease, a gluten-free diet usually allows a normalisation of the need for LT4, as do eradication of the H. pylori infection or parasite colonisation. In cases of atrophic gastritis or inflammatory bowel disease, treating the underlying diseases and regaining the state of remission may improve the absorption of LT4. In patients after gastro-intestinal tract surgery, a dose of LT4 higher than that typically used is needed to restore euthyroidism.

Background: Peroral β-galactosidase preparations for the management of lactose intolerance need to be administered in large doses (1500 to 6000 U) immediately before or together with a lactose-containing meal., Aim: Therefore, this work aimed at developing an innovative long-acting formulation. For this purpose, biodegradable polymeric microcarriers were functionalized with β-galactosidase and targeted with wheat germ agglutinin (WGA) for bioadhesion and thus prolonged residence time in the small intestine., Methods: Spray-dried poly(D,L-lactide-co-glycolide) (PLGA) particles with 2.78±1.05µm in diameter were functionalized with β-galactosidase from Kluyveromyces lactis and WGA using different types of spacers (polyethyleneimine, hexamethylene diamine, 6-aminocaproic acid) and coupling methods (carbodiimide and glutaraldehyde). The particle-bound enzyme activity was determined, and the bioadhesive characteristics were assessed by interaction with mucin coatings and Caco-2 cell monolayers., Results: Up to 1470 U β-galactosidase per gram PLGA were immobilized. The best results were obtained with hexamethylene diamine as a spacer applying the carbodiimide method. Thereby, a nearly 6-fold increase in enzyme activity was obtained as compared to particles without spacer. Upon targeting with WGA, binding to artificial human intestinal epithelium was increased considerably., Conclusions: For the delivery of β-galactosidase WGA-targeted PLGA microparticles were prepared, which represent promising candidates for a convenient biomimetic treatment regimen of lactose intolerance., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Extracellular beta-galactosidase produced by a strain of Aspergillus niger van Tiegh was purified to homogeneity using a combination of gel filtration, ion-exchange, chromatofocusing, and hydrophobic interaction chromatographies. The enzyme displayed a temperature optimum of 65 degrees C and a low pH optimum of between 2.0 and 4.0. The monomeric glycosylated enzyme displayed a molecular mass of 129 kDa and an isoelectric point of 4.7. Protein database similarity searching using mass spectrometry-derived sequence data indicate that the enzyme shares homology with a previously sequenced A. niger beta-galactosidase. Unlike currently commercialised products, the enzyme displayed a high level of stability when exposed to simulated gastric conditions in vitro, retaining 68+/-2% of original activity levels. This acid-stable, acid-active beta-galactosidase was formulated, along with a neutral beta-galactosidase from Kluyveromyces marxianus DSM5418, in a novel two-segment capsule system designed to ensure delivery of enzymes of appropriate physicochemical properties to both stomach and small intestine. When subjected to simulated full digestive tract conditions, the twin lactase-containing capsule hydrolyzed, per unit activity, some 3.5-fold more lactose than did the commercial supplemental enzyme. The acid-stable, acid-active enzyme, along with the novel two-segment delivery system, may prove beneficial in the more effective treatment of lactose intolerance.

Due to the increased immune activation in the intestinal tract of people with celiac disease, the digestive and absorptive processes of those affected may be compromised. Individuals with celiac disease are more susceptible to pancreatic insufficiencies, dysbiosis, lactase insufficiencies, and folic acid, vitamin B12, iron, and vitamin D deficiencies, as well as accelerated bone loss due to an increase in inflammatory signaling molecules. Beyond strict maintenance of a gluten-free diet, research has shown benefit with additional nutritional supplementation to assist in regulation of several of these complications.

Adverse food reactions are common in the general population. Nevertheless, our knowledge of the structure of food allergens and of the mechanisms involved is poor. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification based on the causative pathogenic mechanism. According to this classification, non-toxic reactions can be divided into food allergies when they recognize immunological mechanisms and food intolerance when there are no immunological implications. The treatment of food intolerance is avoidance of the particular food. There are specific treatments for some food intolerance (beta-galactosidases for the management of lactose intolerance).

This article reviews various forms of enzyme supplementation used clinically in digestive and absorption disorders. Enzyme supplementation plays an integral role in the management of various digestive disorders, particularly with regard to exocrine pancreatic insufficiency. However, application of enzymes may also be beneficial for other conditions associated with poor digestion including lactose intolerance. Historically, porcine and bovine pancreatic enzymes have been the preferred form of supplementation for exocrine pancreatic insufficiency. Use of microbe-derived lipase has shown promise with studies indicating benefit similar to pancreatic enzymes, but at a lower dosage concentration and with a broader pH range. Safety and efficacy of enzymes derived from microbial species in the treatment of conditions such as malabsorption and lactose intolerance is promising. Plant-based enzymes, such as bromelain from pineapple, serve as effective digestive aids in the breakdown of proteins. Synergistic effects have been observed using a combination of animal-based enzymes and microbe-derived enzymes or bromelain.

Background: A lactose-free diet is commonly prescribed to subjects with hypolactasia. We tested the effectiveness of a single ingestion of tilactase (a beta-D-galactosidase from Aspergillus oryzae) in adults with hypolactasia, previously assessed by lactose H(2)-breath test., Materials and Methods: After measurement of orocecal transit time (OCTT, by lactulose H(2)-breath test) and lactose H(2)-breath testing plus placebo, a total of 134 subjects were positive to hypolactasia and underwent lactose H(2)-breath testing plus either low (6750 U) or standard (11,250 U) doses of tilactase. The appearance of gastrointestinal symptoms during the tests was monitored., Results: OCTT was longer in malabsorbers (subjects without bloating, abdominal pain and/or diarrhoea, n = 25) than in intolerants (bloating, abdominal pain and/or diarrhoea, n = 109, P < 0.02). Malabsorbers had longer time to H(2) peak (P < 0.03), lower H(2) peak levels (P < 0.002) and smaller integrated H(2) excretion levels (P < 0.005) than intolerants. After tilactase ingestion, integrated H(2) levels were decreased by 75% (low dose) and 87% (standard dose) in malabsorbers, and by 74% (low dose) and 88% (standard dose) in intolerants. In the latter group, total symptom score were decreased by 76% (low dose) and by 88% (standard dose) (P < 0.0001)., Conclusion: A single oral administration of tilactase is highly effective in decreasing symptoms and hydrogen excretion of hypolactasia assessed by lactose H(2)-breath test. If confirmed by long-term observations, ingestion of tilactase might be a better option than exclusion diets in intolerant subjects with hypolactasia.

Functional screening studies revealed that Aspergillus carbonarius ATCC6276 produced extracellular beta-galactosidase activity potentially suited for use as a lactase digestive supplement in the treatment of lactose intolerance. The crude preparation contained two beta-galactosidase activities, beta-gal 1 and beta-gal 2, which were separated by ion-exchange chromatography. Both enzymes were purified to homogeneity by a combination of gel filtration, ion-exchange, chromatofocusing and hydrophobic interaction chromatographies. beta-gal 1 and beta-gal 2 displayed differences in molecular mass (110 kDa versus 120 kDa as judged by SDS PAGE) and in a range of additional physicochemical properties. Km values of 83 and 309 mM, respectively, were recorded using lactose as substrate while temperature optima of 55 degrees C versus 65 degrees C were obtained. Unlike current commercialized supplemental lactases, both of the purified enzymes displayed significant stability when exposed to simulated gastric conditions, with beta-gal 1 in particular retaining 70% residual activity after exposure to pH 2.0 in the presence of pepsin for 2 h. Overall the results indicate that the beta-galactosidases of Aspergillus carbonarius ATCC6276, either individually or in combination, may be suitable for use as a digestive supplement for the alleviation of lactose intolerance.

Selected microbial lactases are used to treat lactose intolerance. A series of experiments were carried out in vitro in order to determine the likely relative suitability of four major commercial lactase products used in this regard. The lactases displayed between 55 and 61% of maximum activity at 37 degrees C and significant activity between pH 3.0 and 6.5. They retained between 0 and 65% of original activities after exposure to full simulated digestive tract conditions for 6 h. All four enzymes proved to be particularly acid sensitive and only two products were enteric coated. The products demonstrated varying ability to hydrolyze lactose under simulated digestive tract conditions. The most effective product hydrolyzed 2.7 g lactose per capsule, suggesting that consumption of several capsules, as opposed to the usually recommended one or two, would be required to hydrolyze the entire 12 g lactose load characteristic of a dairy-based meal. All enzymes were substantially pure and displayed similar kinetic properties and molecular weights. None appeared ideally suited for use in the alleviation of lactose intolerance. The findings may in part explain the variability and often disappointing results previously reported for lactase-based clinical trials and will provide comparative baseline data against which candidate second-generation lactases may be assessed.

Lactose malabsorption (LM) may be secondary to several small bowel diseases, and small intestinal overgrowth (SIBO) may be one of them. We looked for a correlation between symptomatic diverticular disease of the colon and LM and assessed whether this correlation may be related to SIBO. Ninety consecutive patients (pts; 39 males, 51 females; mean age, 67.2 years; range, 32-91 years) affected by symptomatic uncomplicated diverticular disease of the colon were evaluated to assess orocecal transit time (OCTT), SIBO, and LM by lactulose and lactose H2 breath test (H2-BT) at entry and after 8 weeks of treatment. OCTT was delayed in 67 of 90 pts (74.44%). Fifty-three of 90 pts (58.88%) showed SIBO, and OCTT was normal in 23 of 90 pts (25.56%). LM was diagnosed in 59 of 90 pts (65.55%): 49 of 59 (71.74%) were simultaneously affected by SIBO and delayed OCTT (and thus 49 of 53 pts [92.45%] with delayed OCTT and SIBO were affected by LM); 3 of 59 pts (5.09%) showed only delayed OCTT; 7 of 59 pts (11.86%) did not show either SIBO or delayed OCTT. The association of LM and SIBO was statistically significant (P < 0.001). Seventy-nine of 86 pts (91.86%) showed normal OCTT, while OCTT remained prolonged but shorter in the remaining 7 pts (8.14%). SIBO was eradicated in all pts completing the study, while a new lactulose H2-BT showed persistence of SIBO in one pt with recurrence of symptomatic diverticular disease. Forty-seven of 59 pts (79.66%) had a normal lactose H2-BT (P < 0.002), while 12 of 59 pts (20.34%) showed persistence of LM. LM disappeared in 46 of 49 pts (93.88%) concurrently with normalization of OCTT and eradication of SIBO (P < 0.002); it also disappeared in 1 of 3 pts (33.33%) previously affected by delayed OCTT (without SIBO) and LM concurrently with normalization of OCTT. On the contrary, it persisted in all pts with normal OCTT and absence of SIBO. Moreover, it persisted also in the pt with recurrence of symptomatic diverticular disease and persistence of SIBO. In conclusion, most pts affected by symptomatic uncomplicated diverticular disease of the colon showed LM, and in more than 70% of cases it disappeared after successful treatment of the colonic disease.

Purpose: To assess the efficacy of oral probiotics in adults with lactose intolerance through a systematic review of its effects on symptoms and breath hydrogen tests, and whether adding probiotics to nonfermented dairy products decreases lactose intolerance at that meal., Methods: We searched randomized controlled trials published between 1966 and December 2002. Databases in the search strategy included Medline and AMED. We reviewed references of clinical trials and contacted authors of major articles and manufacturers of probiotic commercial products. Quality assessment was based on the McMaster guides and was performed by 5 independent reviewers. Data extraction was performed by 2 reviewers., Results: A master list of 90 articles was compiled. Ten articles met inclusion and exclusion criteria and were consistent with our clinical question. Of the 9 studies that measured breath hydrogen, 3 were positive, 3 were negative, and 3 had both positive and negative results. Of the 7 studies that measured symptoms, 1 yielded positive results, 5 were negative, and 1 had both positive and negative outcomes., Conclusions: Probiotic supplementation in general did not alleviate the symptoms and signs of lactose intolerance in adults in this review. Some evidence suggests that specific strains, concentrations, and preparations are effective. Further clinical trials of specific strains and concentrations are necessary to delineate this potential therapeutic relationship.

Background: Abdominal symptoms linked to lactose malabsorption may be caused by metabolic activity of colonic bacteria. Rifaximin, a non-absorbable rifampycin derivative, is active against colonic bacteria, it may be useful in the treatment of lactose intolerance., Aim: The aim of this study has been to evaluate short-term rifaximin therapy in patients with lactose intolerance., Methods: Thirty-two patients with lactose intolerance diagnosed using the hydrogen lactose breath test were studied. Fourteen patients received rifaximin 800 mg/day for 10 days, 13 patients followed a diet without milk for 40 days and 5 patients received a placebo for 10 days. Total breath H(2) excretion expressed as area under the curve, and the symptom score were evaluated in all patients at the start, and subsequently after 10 and 40 days., Results: In the 14 patients who received rifaximin for 10 days, area under the curve at day 10 and day 40 was statistically significantly lower than the one computed at basal (P<0.01). Diet reduced area under the curve progressively reaching statistical significance at day 40, while the placebo did not change area under the curve throughout the study. The total symptom score significantly improved after rifaximin and diet., Conclusion: In patients with lactose intolerance, a 10-day therapy with rifaximin as well as 40-day diet without lactose reduces the area under the curve and the symptom score.

Objective: To evaluate the efficacy of the addition to milk, 5 min and 10 h before its consumption, of a lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance., Design: Double-blind, placebo-controlled, crossover study., Setting: University Hospital., Subjects: In total, 11 male and 19 female (aged from 18 to 65 y, mean age 43.3 y) lactose malabsorbers with intolerance participated., Interventions: Each patient underwent three H(2) breath tests, in a random order. We used 400 ml of cow's semiskimmed milk as substrate and a beta-galactosidase obtained from K. lactis. The test A was carried out adding to the milk the enzyme (3000 UI), 10 h before its consumption; the test B was performed adding the beta-galactosidase (6000 UI) 5 min before milk ingestion and the test C was made using placebo. We evaluated the maximum breath H(2) concentration, the cumulative H(2) excretion and a clinical score based on intolerance symptoms (bloating, abdominal pain, flatulence and diarrhoea)., Results: Our study showed a significant reduction of the mean maximum H(2) concentration after both test A (12.07 +/- 7.8 p.p.m.) and test B (13.97 +/- 7.99 p.p.m.) compared with test C (51.46 +/- 16.12 p.p.m.) (ANOVA F = 54.33, P < 0.001). Similarly, there was a significant reduction of the mean cumulative H(2) excretion after both test A (1428 +/- 1156 p.p.m.) and test B (1761 +/- 966 p.p.m.) compared with test C (5795 +/- 2707 p.p.m.) (ANOVA F = 31.46, P < 0.001). We also observed a significant reduction of the mean clinical score after both test A (0.36 +/- 0.55) and test B (0.96 +/- 0.85) compared with test C (3.7 +/- 0.79) (ANOVA F = 106.81, P < 0.001). Moreover, with regard to the mean clinical score, there was a significant reduction after test A with respect to test B (Bonferroni's P = 0.03)., Conclusions: Our study shows that in lactose malabsorbers with intolerance, the lactase obtained from K. lactis can represent a valid therapeutic strategy, with objective and subjective efficacy and without side effects.

There is unequivocal evidence that administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea. Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections. There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly. Efficacy of probiotics in the prevention of traveller's diarrhoea, sepsis associated with severe acute pancreatitis, and cancers, the management of ulcerative colitis, and lowering of blood cholesterol remains unproven. In addition to firm evidence of efficacy (for a range of conditions), major gaps exist in our knowledge regarding the mechanisms by which probiotics modulate various physiological functions and the optimum dose, frequency, and duration of treatment for different probiotic strains.

Infantile colic is a common problem, but it is still a cause of great stress and anxiety to the parents of a colicky baby. Dipak Kanabar believes that failure of lactose digestion has an important part to play in colic and in this bulletin he reviews the causes of infantile colic and the available management options.

We compared two lactase preparations derived from Aspergillus orizae (AOL) and Penicillinase multicolor (PML) for stability in the stomach and overall enzymatic activity in 10 asymptomatic subjects with lactase deficiency. The subjects were given 10,000 FCC units of either AOL or PML 30 min prior to or simultaneously with 300 ml of milk. Gastric juice was withdrawn through a nasogastric tube immediately after and every 15 min for 60 min, and breath was sampled before and every 15 min for 6 h after the milk ingestion. When lactase was given simultaneously with the milk, gastric juice lactase activity and galactose concentration were significantly higher than the control levels. When lactase preparations were given 30 min prior to the milk, neither lactase activity nor galactose was detected in the gastric juice. The pH of the gastric juice was about 6.0 after the milk ingestion. Breath hydrogen did not increase when milk was ingested simultaneously with enzymes, but did increase if enzymes were given 30 min prior to milk ingestion. There were no significant differences in lactase activity, galactose concentration in gastric juice, or breath hydrogen when AOL and PML were compared. In conclusion, with exogenous lactase, digestion of lactose begins in the stomach when pH is raised to 6.0 by the buffering action of milk. Lactase preparations are effective assessed by breath hydrogen analysis in asymptomatic individuals with lactase deficiency if the enzymes are given simultaneously with milk.

Allergies to milk proteins are frequently encountered in the new born population. In order to prevent this allergy by inducing oral tolerance, one of the major allergenic milk protein, B lactoglobulin (BLG) was entrapped into biodegradable Poly (lactide-co-glycolide) microspheres and was then orally given to mice. Microspheres are able to protect proteins against degradation by intestinal proteolytic enzymes and to target the Peyers patches which are one important priming site of the mucosal immune system. Microspheres were prepared by the multiple emulsion solvent evaporation method. The goal of the formulation study was to associate large amounts of proteins to the smallest amount of polymer so that a minimal quantity of microspheres would be administered. It was shown that introducing tween 20 in the formulation was able to increase the encapsulation efficiency and to better control protein release reducing the burst release effect. Moreover, Oral administration of microspheres containing BLG reduced significantly (by 10.000) the amount of protein necessary to decrease both specific anti BLG IgE and DTH response. In conclusion, microspheres appear to be optimal systems to induce oral tolerance.

Colic, or persistent unexplained crying in infants, is commonly encountered by health professionals. While not harmful to the child, it can place a great deal of stress on the parents and family. The cause of colic has not been definitively identified. Transient lactose intolerance, as a result of inadequate production of the enzyme lactase, is one possibility. Studies have shown a reduced crying time when formula or breast milk is incubated with lactase. Colief Infant Drops consist of lactase in a glycerol and water solution which, when added to formula or breast milk, converts lactose to simple sugars and makes the feed more easily digestible.

A 2-week-old Toggenburg kid was evaluated for persistent diarrhea and poor body condition. The herd had high morbidity and mortality associated with diarrhea in neonatal kids. Lactose intolerance was diagnosed on the basis of results of a lactose tolerance test and glucose absorption test. Clinically normal herdmates were used as control animals. The kid responded to lactase supplementation. Cryptosporidium organisms were detected in feces of several affected kids during episodes of acute diarrhea. Lactose intolerance was presumed to have developed secondary to intestinal cryptosporidiosis.

Objectives: To examine a potential practical therapeutic use of loperamide (Lo) to decrease the symptoms of lactose intolerance., Subjects and Methods: Nineteen (eight men, 11 women) healthy lactose maldigesters (18 of 19 with symptoms) underwent a 25 g lactose challenge on five separate days. Breath hydrogen was measured, areas under the curve (AUC) were calculated for 4 h, and 4 and 12 h symptom scores were recorded. After establishing baseline measurements, test doses of 4 mg, 8 mg and 12 mg Lo were randomly administered without placebo in a double-blind manner. As well, each subject received seven lactase tablets, in a random, unblinded manner., Results: The median AUC and mean oral cecal transit time followed dose response expectations; however, only lactase treatment achieved significance. Nevertheless, 8 mg Lo significantly improved symptom scores, which were statistically indistinguishable from those of lactase. Four subjects complained of delayed constipation and cramps with various doses of Lo., Conclusions: Lo monotherapy for lactose intolerance is not economical and may have some side effects. However, Lo may be studied further as an adjunctive treatment of lactose intolerance in an effort to reduce the need for complete lactose digestion. Such a manoeuvre may allow rapid colonic adaptation, which in turn may be beneficial for prophylaxis for a number of colonic diseases.

The objective of this study was to evaluate the effects of lactase on lactose malabsorption and its intolerance symptoms, as well as the available way to improve lactose absorption. Healthy adults with a history of lactose intolerance were screened by 25 g lactose tolerance test. The individuals with higher H2 expired and/or lactose intolerance symptoms were selected as the subjects. Subjects were challenged twice with "400 ml low fat milk" and "400 ml low fat milk + 9000Fcc lactase" separately in 3 days interval. The breath H2 concentration and intolerance symptoms were tested in 4 hours after the challenge. The results showed that exogenous lactase can significantly decrease the incidence of lactose malabsorption (the abnormal expiration of H2 decreased from 100% to 48.9%) and milk intolerance symptoms(from 51.1% to 13.3%). The results from this study demonstrate that lactose malabsorption and intolerance symptoms are resulted from the reduced enzyme activities of individuals, and the exogenous lactase can improve lactose absorption and intolerance symptoms. Lactose supplementation may be an available way to increase the dairy consumption and promote health of people.

Background: The aim of this study was to evaluate the impact of irritable bowel syndrome (IBS) and lactose maldigestion in children with recurrent abdominal pain., Methods: Children who had abdominal pain associated with defecation or change in bowel habit, disordered defecation, and distension were diagnosed with IBS, and lactose maldigestion was defined by lactose breath hydrogen testing. Children with IBS were managed with increased fiber intake, while those with lactose maldigestion restricted dietary lactose. A telephone survey was conducted to determine the response to treatment., Results: The mean age of the 59 boys and 87 girls was 9.5 +/- 3.0 years. Children with IBS and lactose maldigestion had more frequent abdominal pain than children without these conditions, but they required less medication for relief of symptoms. CONCLUSIONS. Lactose maldigestion may be a contributory factor in children with IBS, and lactose avoidance in these patients may reduce medication use to relieve symptoms.

Background: The relationship between symptoms, intestinal mucosal histology, and disaccharidase activities is not well defined. An analysis of disaccharidase activities was performed in children grouped by age, symptoms, and intestinal mucosal histology and normal values established., Methods: Disaccharidase activities and histology of 246 endoscopically obtained duodenal biopsies in 232 patients (121 girls; age range, 0.08-17 years; mean, 5.9 years) in a 3-year period were reviewed. Patients were divided into two groups based on absence (group 1; n = 142) or presence (group 2; n = 90) of diarrhea and were subdivided by age into, less than 24 months of age and 24 months of age or more. Histologic changes within groups were classified as (A) normal, (B) mild, or (C) moderate to severe based on villus height abnormalities. A questionnaire was sent to 34 patients with hypolactasia to assess the efficacy of lactose avoidance and/or lactase supplementation., Results: All group 1 patients had normal findings in analysis of mucosal specimens, and their disaccharidase activities showed normal values because they had no diarrhea. The geometric means (95% confidence interval) in children aged less than 24 months are (in micromoles of substrate hydrolyzed per minute at 37 degrees C per gram protein) (units [U]) lactase, 36.7 (13.4-100.4); maltase, 178.5 (88.9-356.3); palatinase, 12.7 (3.8-41.5); and sucrase 60.0 (24.0-148.1). In children 24 months of age or more, the values are 23.2 (3.9-108.1), 167.6 (78.8-355.9), 12.7 (4.9-32.9), and 51.0 (20.5-126.0), respectively. Only lactase activity decreased with age (p < 0.05). No differences in disaccharidase activities were noted in patients with and without diarrhea if the mucosal histology was normal (group 1A vs. 2A). In patients with diarrhea, values were commensurate with the degree of mucosal injury, especially in the older group. Twenty-two of 27 patients (81%) who responded to the questionnaire had benefited from lactase supplementation and/or lactose avoidance., Conclusions: We have established normal values for disaccharidase activities in the pediatric population. Although the disaccharidase activities correlate more with degree of intestinal mucosal injury than with symptoms, their activities are difficult to predict accurately based on these criteria. If required, disaccharidase activities should be measured biochemically.

Diagnoses of Clostridium difficile enterocolitis and lactose intolerance were made in a neonatal foal with persistent diarrhea. It was determined that the foal had lactose intolerance on the basis of the results of a lactose tolerance test, and a diagnosis of C difficile enterocolitis was subsequently made. The foal responded to oral administration of metronidazole and lactase. Lactose intolerance is a secondary problem most commonly associated with rotavirus infection, but it can be caused by any condition affecting the small intestine. Because C difficile can affect the small intestine in foals, it was presumably the cause of the lactose intolerance in this foal with persistent diarrhea. Oral administration of lactase was not initially successful in this foal, most likely because of ongoing C difficile enterocolitis. Presumably, metronidazole was an effective treatment for C difficile enterocolitis and administration of lactase allowed for normal digestion of milk until endogenous lactose production returned. Clostridium difficile enterocolitis and lactose intolerance should be considered as differential diagnoses in neonatal foals with diarrhea, especially when the foal is bright and alert.

Background: In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose., Aim: To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms., Methods: After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded., Results: The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0-12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopramide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found., Conclusions: In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.

Background: Lactose intolerance is the most common disorder of intestinal carbohydrate digestion. Lactobacillus acidophilus BG2FO4 is a strain of lactobacilli with properties of marked intestinal adherence and high beta-galactosidase activity., Objective: This study was designed to determine whether oral feeding of Lactobacillus acidophilus BG2FO4 leads to a lactose-tolerant state., Design: We studied 42 subjects with self-reported lactose intolerance and performed breath-hydrogen tests to determine whether they were lactose maldigesters. Subjects with established lactose maldigestion (n = 24) were invited to be randomly assigned to an omeprazole-treated (hypochlorhydric) group or a non-omeprazole-treated group, but 6 subjects chose not to participate. All randomly assigned subjects (n = 18) ingested Lactobacillus acidophilus BG2FO4 twice per day for 7 d and stool samples were collected. Breath-hydrogen tests were performed and symptom scores were recorded at baseline and after lactobacilli ingestion., Results: Lactose maldigestion was established in 24 of 42 subjects (57%) with self-reported lactose intolerance. In 18 lactose-maldigesting subjects, overall hydrogen production and symptom scores after ingestion of Lactobacillus acidophilus BG2FO4 were not significantly different from baseline values. Live Lactobacillus acidophilus BG2FO4 was recovered in stool samples from 7 subjects., Conclusions: Lactose intolerance is overreported in subjects with gastrointestinal symptoms after lactose ingestion. Treatment of lactose-maldigesting subjects with and without hypochlorhydria with Lactobacillus acidophilus BG2FO4 for 7 d failed to change breath-hydrogen excretion significantly after lactose ingestion.

The effectiveness of a new beta-D-galactosidase pellet formulation in the treatment of lactose intolerance was studied. The encapsuled beta-D-galactosidase (lactase) pellets were first tested in vitro for their enzymatic activity within an environment simulating gastric conditions and subsequently within an environment simulating duodenal conditions. Effectiveness was measured by the % of glucose formed by hydrolysis of lactose. The pellets were found to retain their enzymatic activity in gastric pH conditions (mean 69 +/- 1 mg/dl glucose) and were found to hydrolyse lactose in human duodenal fluid (106.35 +/- 1 mg/dl). Finally the effectiveness of the new lactase formulation on glucose absorption was studied in 8 lactose intolerant subjects in a randomized, double blind, crossover trial. After fasting, the subjects were given one capsule containing 100 u/ml beta-galactosidase (i.e. 10 pellets of 10 u/ml each) or one capsule containing placebo pellets, followed by 100 g lactose dissolved in water. The washout period between lactose challenges was one week. Plasma glucose concentrations were measured before and at intervals after the challenges and the subjects completed symptom questionnaires every eight hours for 24 hours. Results showed a statistically significant increase in plasma glucose levels 30, 60, 90 and 120 min after lactose ingestion (repeated measures analysis of variance, p<0.01). Subjective ratings of the severity of abdominal cramping, belching, flatulence, vomiting and diarrhoea were significantly decreased following ingestion of the lactase pellets and lactose (no incidence of diarrhoea) compared with after ingestion of placebo and lactose. The results of the study were considered to be very promising as the beta-D-galactosidase formulation (which was produced at very low cost and with great ease) resisted inactivation in the stomach, effectively transformed lactose to glucose in vivo and reduced symptoms of lactose intolerance.

Background: The influence of pharmacologically prolonged oral caecal transit time on lactose handling is examined in the wake of finding improved lactose handling during naturally occurring prolonged oral-caecal transit time., Methods: Sixteen normal male volunteers with lactose maldigestion were pretreated with 8 and 12 mg loperamide on different days and lactose handling was compared by measuring areas under the curve during lactose breath H2 testing (3 h). The oral-caecal transit time was similarly measured using lactulose and exhaled breath H2. Symptom scores were recorded and, in three subjects, blood sugar was simultaneously measured., Results: The mean +/-S.E.M. baseline oral-caecal transit time was 56.9 +/- 5.9 min. Loperamide significantly prolonged oral-caecal transit time (90.3 +/- 11.1 and 82.1 +/- 13.9 min for 12 and 8 mg loperamide, respectively; P < 0.05). The lactose breath H2 area under the curve with 12 mg loperamide was significantly less than at baseline (7685 +/- 985.6 vs. 10243.1 +/- 1607, respectively; P < 0.05). Significantly fewer symptoms were recorded with both doses of loperamide during the 3 h test but with 12 mg loperamide only on follow-up. There was no significant rise in blood sugar at any time in the three subjects studied., Conclusions: Loperamide-induced graded prolongation of oral-caecal transit time is associated with significantly improved lactose handling as measured by a reduction of the area under the curve. Symptoms of lactose intolerance may also be improved with loperamide. Prolongation of oral-caecal transit time with loperamide may be useful as adjunctive or primary therapy of carbohydrate intolerance in patients with rapid transit.