Lactose Intolerance versus Cow's Milk Allergy in Infants: A Clinical Dilemma.

Due to its very early introduction, cow's milk is one of the first foods that can cause adverse reactions in human beings. Lactose intolerance (LI) and cow's milk allergy (CMA) are the most common adverse reactions to cow's milk. While LI is due to insufficient small intestinal lactase activity and/or a large quantity of ingested lactose, CMA is an aberrant immune reaction to cow's milk proteins, particularly casein or ß-lactoglobulin. However, the clinical manifestations of LI and CMA, particularly their gastrointestinal signs and symptoms, are very similar, which might lead to misdiagnosis or delayed diagnosis as well as nutritional risks due to inappropriate dietary interventions or unnecessary dietary restriction. Formula-fed infants with LI should be treated with formula with reduced or no lactose, while those with CMA should be treated with formula containing extensive hydrolyzed cow's milk protein or amino acids. This review is therefore written to assist clinicians to better understand the pathophysiologies of LI and CMA as well as to recognize the similarities and differences between clinical manifestations of LI and CMA.

Myths and Facts about Food Intolerance: A Narrative Review.

Most adverse reactions to food are patient self-reported and not based on validated tests but nevertheless lead to dietary restrictions, with patients believing that these restrictions will improve their symptoms and quality of life. We aimed to clarify the myths and reality of common food intolerances, giving clinicians a guide on diagnosing and treating these cases. We performed a narrative review of the latest evidence on the widespread food intolerances reported by our patients, giving indications on the clinical presentations, possible tests, and dietary suggestions, and underlining the myths and reality. While lactose intolerance and hereditary fructose intolerance are based on well-defined mechanisms and have validated diagnostic tests, non-coeliac gluten sensitivity and fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) intolerance are mainly based on patients' reports. Others, like non-hereditary fructose, sorbitol, and histamine intolerance, still need more evidence and often cause unnecessary dietary restrictions. Finally, the main outcome of the present review is that the medical community should work to reduce the spread of unvalidated tests, the leading cause of the problematic management of our patients.

New Perspectives on Lactose Malabsorption, Celiac Disease and Related Disorders.

Lactose malabsorption (LM) is caused by the incomplete hydrolysis of lactose due to lactase deficiency [...].

Gastric Emptying of New-World Milk Containing A1 and A2 Β-Casein Is More Rapid as Compared to Milk Containing Only A2 Β-Casein in Lactose Maldigesters: A Randomized, Cross-Over Trial Using Magnetic Resonance Imaging.

Lactose maldigesters report an increase in abdominal pain due to the consumption of milk containing a mixture of A1 and A2 ß-casein as compared to milk containing only A2 ß-casein. Gastric transit affects gastrointestinal symptoms and rapid transit has been associated with an increase in abdominal pain. We conducted a double-blinded, randomized, crossover trial in 10 lactose maldigesters. Subjects consumed each of the two types of milk: conventional milk containing 75% A1 ß-casein and 25% A2 ß-casein and A2 milk containing 100% A2 ß-casein. Magnetic resonance images were acquired, and abdominal pain was rated and recorded at 0, 10, 30, 60 and 120 min after milk consumption. The volume of milk in the stomach was calculated using FSL software. The volume of milk in the stomach after consuming milk with 75% A1 ß-casein and 25% A2 ß-casein was significantly lower at 30 (p = 0.01), 60 (p = 0.002) and 120 (p < 0.001) minutes as compared to milk with 100% A2 ß-casein in the 10 lactose maldigesters. The transit of New-World milk containing A1 and A2 ß-casein was more rapid as compared to Old-World milk containing only A2 ß-casein. This difference in transit may mediate symptoms of lactose intolerance.

Does fecal calprotectin increase may be linked to lactose intolerance in patients with irritable bowel syndrome?

BACKGROUND: Irritable bowel syndrome (IBS) is a multifactorial condition without any specific investigation. Fecal calprotectin (FC) may be elevated in IBS without any explanation. In addition, some patients with IBS have symptoms related to lactose intolerance. Our main aim was to investigate whether an increase in FC could be related to lactose intolerance in patients with IBS. METHODS: In this retrospective single-center study, all patients with IBS who have underwent a FC test and a lactose respiratory test within a period of less than 6 months were eligible. A FC greater than or equal to 50 µg/g was considered abnormal. RESULTS: Severnty-six patients (48 females), mean age 38±15 years were included. Symptoms were respectively: bloating in 57%, diarrhea in 76% and abdominal pain in 46% of cases. Among the 76 patients: 22 (29%) had FC≥50 µg/g and 9/22 (41%) had a positive lactose test. No significant relationship could be identified between the increase in FC and the lactose test positivity. The value of the FC was also not related to the subtype of IBS or the positivity of the glucose test. CONCLUSIONS: In our study, the increase in FC was not significantly related to the presence of lactose intolerance. Nevertheless, our work, despite its originality, is limited by its retrospective nature and small number of patients. Future studies including larger numbers of patients may identify the causes of elevated FC in patients with IBS to individualize different subgroups of patients to best adapt therapeutic management.

Food intolerances in children and adolescents in Switzerland.

Adverse food reactions have become an important health concern in pediatrics. There are discrepancies between diagnosed and self-reported food allergies and intolerances, leading to food avoidance with possible psychological and nutritional implications in the latter. There is no data available so far on the number of children and adolescents, who reduce or completely avoid certain foods in their diet. The aim of this study was to determine the prevalence of children and adolescents in the Northwest of Switzerland, who omit foods from their diet because of a self-reported intolerance, as well as the prevalence of children and adolescents who eliminate well-tolerated foods for presumed health reasons. This is a cross-sectional study conducted in the Children's hospitals of Aarau and Basel (Switzerland) and in 4 pediatric private practices. A total of 2036 children and adolescents (54% male and 46% female) between 1 month and 18 years (mean age: 7.4 years) were included, of which 316 (16%) participants reported to avoid foods due to intolerance. Lactose intolerance is the most frequent one. In 55% of all cases, no medical tests had been performed to confirm such an intolerance. Avoiding tolerated foods for presumed health reasons was stated by 251 (12%) participants.  Conclusions: Clinicians should be aware of the high frequency of food avoidance in the pediatric population due to true intolerance, functional diseases, or due to lifestyle reasons. Milk is the most avoided food and half of the affected patients avoid foods without guidance by professional dieticians, therefore risking possible negative impacts on their physical and mental health. Pediatricians should perform further investigations or advise nutritional guidance if an avoidance of foods or specific diets occurs. What is Known: • The prevalence of food intolerances in children and adolescents is unknown. • Eating behavior in children is influenced by the consumption of social media. What is New: • Based on this large cross-sectional study, it was shown that 16% of children and adolescents avoid foods, half of them without any medical advice. • Food avoidance is common among this Swiss cohort of children because of different reasons: lifestyle habits, functional diseases, true intolerances with possible consequences such as micronutrient deficiencies if not properly monitored.

Bifidobacterium animalis subsp. lactis Bi-07 supports lactose digestion in vitro and in randomized, placebo- and lactase-controlled clinical trials.

BACKGROUND: Probiotics may alleviate lactose maldigestion. OBJECTIVES: The objective was to select a probiotic with high lactase activity and compare it with lactase and placebo in clinical trials. METHODS: Bacterial cultures were screened for lactase activity in a model of the upper gastrointestinal (GI) tract. Bifidobacterium animalis subsp. lactis Bi-07 (Bi-07) counts were adjusted in subsequent experiments to correspond to 4500 Food Chemicals Codex (FCC) units of lactase, the amount in the European Food Safety Authority (EFSA)-approved health claim. Two crossover clinical trials, Booster Alpha and Booster Omega, were performed in participants with lactose intolerance, where 2 × 1012 CFUs Bi-07, 4662 FCC lactase, or placebo was consumed simultaneously with a lactose challenge, with 1-wk washouts between challenges. The trial designs were identical except for the source of lactose. Breath hydrogen concentration (BHC) was measured to assess the effect of the investigational products on lactose digestion, for which incremental area under the curve (iAUC) was the primary outcome. Peak BHC, cumulative BHC, and GI symptoms were secondary outcomes. RESULTS: Bi-07 was superior to placebo in reducing BHC [iAUC, parts per million (ppm) ∙ h] in both trials (Booster Alpha: geometric least square mean ratio: 0.462; 95% CI: 0.249, 0.859; P = 0.016; Booster Omega: 0.227; 95% CI: 0.095, 0.543; P = 0.001). Lactase was superior to placebo in Booster Alpha (0.190; 95% CI: 0.102, 0.365; P < 0.001) but not Booster Omega (0.493; 95% CI: 0.210, 1.156; P = 0.102). Noninferiority of Bi-07 compared with lactase was observed in Booster Omega (0.460; 95% CI: 0.193, 1.096; P = 0.079; CI upper limit < 1.25 noninferiority margin). Odds of abdominal pain (compared with placebo: 0.32, P = 0.036) and flatulence (compared with placebo: 0.25, P = 0.007) were lower with lactase in Booster Alpha. Increased odds of nausea were seen with Bi-07 (compared with placebo: 4.0, P = 0.005) in Booster Omega. CONCLUSIONS: Bi-07 has high lactase activity, and in 2 clinical trials, it supported lactose digestion in individuals with lactose intolerance.These trials were registered at clinicaltrials.gov as NCT03659747 (Booster Alpha) and NCT03814668 (Booster Omega).

Gastrointestinal Conditions: Malabsorption Syndromes.

Malabsorption syndromes are a heterogenous group of conditions that can cause distressing gastrointestinal symptoms. Celiac disease is most common and is triggered by exposure to gluten. Tissue transglutaminase immunoglobulin A is the diagnostic test of choice; management is gluten avoidance. Lactose intolerance is caused by absence or declining levels of the enzyme lactase. Diagnosis typically is clinical, but breath tests can be helpful if diagnosis is uncertain. Management is lactose avoidance. Bile acid malabsorption results in unabsorbed bile acids in the colon, leading to diarrhea. The 75selenium homotaurocholic acid test is most accurate but is not widely available. Therefore, a trial of bile acid sequestrants (typically cholestyramine) is a reasonable alternative when the diagnosis is suspected. Exocrine pancreatic insufficiency is caused by decreased production of pancreatic enzymes, typically occurring in patients with preexisting pancreatic damage from alcohol, surgery, radiation, diabetes, or cystic fibrosis. Diagnosis involves fecal fat or fecal elastase-1 tests. Management is pancreatic enzyme replacement. Small intestinal bacterial overgrowth is caused by pathologic overgrowth of the small bowel microbiome. Diagnosis is by jejunal biopsy or, more commonly, breath tests. Antibiotics (typically rifaximin) are the initial management. Other options include dietary changes, probiotics, and prokinetic drugs.

Can Lactose Intolerance Be a Cause of Constipation? A Narrative Review.

Lactose intolerance and constipation are common in children and impact everyday life, not only for patients but also their families. Both conditions can be comorbid with other diseases or form a part of their clinical presentation, but constipation is not usually associated with lactose intolerance. The typical symptoms of lactose intolerance include abdominal pain, bloating, flatus, diarrhoea, borborygmi, and less frequently nausea and vomiting. In approximately 30% of cases, constipation can be a symptom of lactose intolerance. Constipation is characterized by infrequent bowel movements, hard and/or large stools, painful defecation, and faecal incontinence, and is often accompanied by abdominal pain. This paper provides a narrative review on lactose intolerance, its epidemiology, pathogenesis, the correlation between lactose intolerance and constipation in children, and potential mechanisms of such association.

Lactose Malabsorption and Presumed Related Disorders: A Review of Current Evidence.

BACKGROUND: Lactose malabsorption (LM) is a frequent clinical problem associated with several digestive and extra-digestive diseases. The aim of this manuscript was to clarify the real clinical impact of LM on these disorders. METHODS: A literature search for digestive and extra-digestive disorders related to LM was carried out using PubMed, Medline and Cochrane. RESULTS: A transient lactase deficiency is present in celiac disease (CD) on a normal diet. The persistence of symptoms in CD on a gluten-free diet may be instead, in part, attributed to a primary LM. Similar circumstances are present in inflammatory bowel diseases (IBD), in which LM can be responsible for a part of persistent symptoms in IBD on clinical remission. LM and irritable bowel syndrome (IBS) are instead independent conditions. On the other hand, a lactose-restricted diet may be useful for some IBS patients. A reduced lactose intake can lead to low bone mass and limited risk of fragility fractures. Finally, the absorption of levothyroxine could be conditioned by LM. CONCLUSIONS: LM can be responsible for persistent symptoms in CD and IBD. The association with IBS seems to be casual. Bone mass and levothyroxine absorption can be affected by LM.

Significance of validated symptom assessment versus breath testing for malabsorption after lactose load in children.

BACKGROUND AND OBJECTIVES: Lactose malabsorption and lactose-induced symptoms are poorly correlated, as shown by breath tests and various symptom assessment methods. Validated assessment is the key to overcome the limitations of biased symptom measurements. We characterized lactose-induced symptoms with the population-specific, validated paediatric carbohydrate perception questionnaire (pCPQ) and their correlation with the history of symptoms (HoS). METHODS: A total of 130 patients with functional gastrointestinal symptoms underwent a lactose hydrogen breath and tolerance test (LBTT) allowing for a diagnosis of malabsorption (M+) and lactose sensitivity (S+). HoS indicative of lactose-induced symptoms (abdominal pain, nausea, bloating, flatulence, diarrhoea) in the 4 weeks preceding the test was determined using a validated questionnaire. The pCPQ was used to score lactose-induced symptoms. MAIN RESULTS: The LBTT revealed 41 children (31.5%) with lactose malabsorption (M+), 56 (43.1%) with lactose sensitivity (S+) and 24 (18.5%) were M+/S+. Sensitivity correlated with HoS (P < 0.001), regardless of whether malabsorption was detectable. Malabsorption status did not correlate with HoS (NS). The odds of lactose sensitivity significantly increased when abdominal pain [odds ratio (OR) 3.5, confidence interval (CI) 1.6-7.8], nausea (OR 2.3, CI, 1.1-4.9) and flatulence (OR 3.1, CI 1.4-6.8) were reported in the 4 weeks preceding the LBTT. Symptoms after the lactose load were similar for M+/S+ and M-/S+, except for flatulence, which was more frequent in malabsorbers (P < 0.01). CONCLUSION: Our findings fit well with the emerging view of the important role of a validated symptom assessment after a lactose load. The determination of symptoms may be more relevant than malabsorption for the clinical outcomes of paediatric patients with lactose-related gastrointestinal symptoms.

Hypocalcemia and Vitamin D Deficiency in Children with Inflammatory Bowel Diseases and Lactose Intolerance.

BACKGROUND: A diet restricted in dairy products can cause calcium and vitamin D deficiency and, secondarily, lead to malnutrition and low bone mass. The aim of the study was to determine the incidence hypocalcemia and vitamin D deficiency in children with inflammatory bowel diseases and lactose intolerance (LI). MATERIAL AND METHODS: A total of 107 patients were enrolled to the study (mean age 14.07 ± 3.58 years; 46.7% boys): 43 with Crohn's disease (CD), 31 with ulcerative colitis (UC), and 33 with functional abdominal pain (AP-FGID). Hydrogen breath test with lactose and laboratory tests to assess the calcium-phosphate metabolism were performed in all patients. The results of densitometry were interpreted in 37 IBD patients. RESULTS: LI was diagnosed in 23.2% patients with CD, 22.6% with UC, and 21.2% children with AP-FGID, (p = 0.9). Moreover, 9.5% patients with CD, in 21.4% with UC, and in 51.5% with AP-FGID had optimal concentration of 25(OH)D (p = 0.0002). Hypocalcemia was diagnosed in 21% of patients with CD, 16.1% with UC patients, AP-FGID patients had normal calcium levels (p = 0.02). There was no difference in concentrations of total calcium, phosphorus, and 25(OH)D between patients on low-lactose diet and normal diet (p > 0.05). BMD Z-score ≤ -1 SD was obtained by 12 CD patients (48%), and 6 with UC (50%). CONCLUSION: The use of a low-lactose diet in the course of lactose intolerance in children with inflammatory bowel diseases has no effect on the incidence of calcium-phosphate disorders and reduced bone mineral density.

Lactose Intolerance Assessed by Analysis of Genetic Polymorphism, Breath Test and Symptoms in Patients with Inflammatory Bowel Disease.

Many patients with inflammatory bowel disease (IBD) restrict dairy products to control their symptoms. The aim of the study was to investigate the prevalence of lactose intolerance assessed with hydrogen breath test (H-BT) in IBD patients in clinical remission compared to a sex, age and BMI matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910 CC (wildtype) and the intermediate phenotype LCT-22018 CT and LCT-13910 AG; finally, we assess the correlation between genotype and H-BT. A total of 54 IBD patients and 69 control who underwent clinical evaluation, H-BT and genetic test were enrolled. H-BT was positive in 64.8% IBD patients and 62.3% control (p = 0.3). The wild-type genotype was found in 85.2% IBD patients while CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 9.3%, 1.8% and 3.7%. In the control group, the wild-type genotype, CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. Therefore, the wild-type and polymorphisms' prevalence did not differ between IBD population and control group (85.2% vs. 87%, p = 0.1) (14.8% vs. 13%, p = 0.7). The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73-16.29, p = 0.003) and in the IBD (OR 7.61, 95%CI 1.36-42.7, p = 0.02). The prevalence of lactose intolerance in IBD patients did not differ from that of control. Despite suggestive symptoms, about 1/3 of IBD patients are not lactose intolerant, thus not needing "a priori" elimination diet. This may encourage a rationale and balanced dietary management in IBD.

Low-fat, lactose-free and leucine-enriched chocolate cow milk prototype: A preliminary study on sensorial acceptability and gastrointestinal complaints following exhaustive exercise.

BACKGROUND: Chocolate milk has gained recent scientific support as a recovery drink. However, it is known that high exercise-demand triggers gastrointestinal discomfort which continues post-exercise, thereby hindering this nutritional strategy. In addition, those who are lactose intolerant cannot benefit from a milk-based beverage. Thus, the aim of this preliminary study was to develop a low-fat, lactose-free, and leucine-enriched chocolate cow milk prototype (CML) representing nutrition-related recommendations for football players, as well as assess athletes' individual subjective outcomes for gastrointestinal complaints and sensorial acceptability in a field-based setting following strenuous team-sport physical demands. METHODS: This study followed a single group and repeated-measured design with 10 football players (23 ± 2 yrs., 74 ± 14 kg, 174 ± 5 cm) who consumed CML following a 90-min football match simulation protocol (FMP). The total CML intake to achieve 0.150 g leucine·kg [BW]·h- 1 occurred in aliquots of 50, 30 and 20% at 0-, 45- and 75-min post-FMP, respectively. Athletes were evaluated by the prevalence, the type and severity (bloating, nausea, flatulence, and gastric reflux) of gastrointestinal complaints and sensorial acceptability (overall perception, appearance, consistency, and flavour) after drinking each aliquot in a 4-h recovery period. RESULTS: The CML showed higher scores for "Product Acceptability Index" (88%) and sensorial acceptability (~ 8 in 9-point hedonic scale). Kendall's W with bootstrapped resample (95%CI) revealed agreement among respondents as "moderate" (overall perception, flavour) to "strong" (appearance, consistency) and with no significant agreement differences between rater response in the timeline analysis (0.57 up to 0.87; p > 0.05). Agresti-Caffo add-4 analysis (95% confidence interval, [95%CI]) revealed no differences in each time-point analysis versus baseline for athletes classified as having severe gastrointestinal symptoms, but confirmed concern with bloating (three athletes showed a transient response at 2-h and only one continued until 3-h; p = 0.051). CONCLUSIONS: These preliminary findings suggest that CML presents good taste and high acceptability by the sampled athletes. Thus, CML may be an alternative sport drink for immediate post-workout supplementation to overcome the energy deficit, offer co-ingested leucine, maintain palatability and adherence including lactose intolerance following a team sport-specific fatigue. TRIAL REGISTRATION: RBR-2vmpz9 , 10/12/2019, retrospectively registered.

Lactose intolerance in patients with inflammatory bowel diseases and dietary management in prevention of osteoporosis.

Lactose intolerance affects 33% to 75% of the world population and may be associated with various genetic factors. Lactose in the diet can be found in milk and dairy products, which simultaneously constitute the primary sources of calcium. Gut microbiota also influences lactose tolerance. Patients with lactose intolerance often stop consuming milk and dairy products, which may lead to calcium and vitamin deficiency and osteoporosis. Insufficient production of lactase also occurs in patients with diseases of the gastrointestinal tract, such as inflammatory bowel diseases. Moreover, Crohn's disease and ulcerative colitis are risk factors for osteoporosis, and the intake of the proper amount of calcium is an essential element in preventing the decrease of bone mineral density. Diet may prevent the development of osteoporosis, thus, educating patients regarding proper diet should constitute a part of the treatment and prevention process. Patients should consume low-lactose, or lactose-free milk and bacterially fermented dairy products. Additionally, plant milk supplemented by calcium and vitamin D, mineral water with calcium, and certain vegetables also may be good sources of calcium.

Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal-Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p < 0.004 and p < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal-Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.

Association between Inflammatory Bowel Disease and Lactose Intolerance: Fact or Fiction.

Background/Aims: Inflammatory bowel disease (IBD) is a complex condition precipitated by genetic susceptibility and possibly a disturbed microbiome. The role of dairy foods in IBD is controversial. This study examined the association between lactose intolerance (LI) and IBD. Methods: Data on hospital admissions of all IBD adult patients were extracted from the National Inpatient Sample database between 2004 and 2014. The comorbidities and outcomes of interest were defined by querying all the diagnostic and procedural fields for the corresponding International Classification of Diseases 9th version (ICD-9) codes. Patients with IBD were defined as the "study group," and the patients who did not have IBD were defined as the "control group". LI was identified in both groups using the ICD-9 codes. Multivariate logistic regression was performed to examine the association between IBD and LI. Results: The total population was 71,342,237 patients, of which 598,129 (0.83%) had IBD. The IBD patients were younger (52 years vs. 57 years) and with fewer females (57.5% vs. 60.1%) (p<0.001 for all). After adjusting for the potential confounding factors, the IBD group had a significantly higher rate of LI (OR 2.71, 95% CI 2.55-2.88, p<0.001) compared to the non-IBD group. The findings were similar on the further stratification of IBD into Crohn's disease compared to the control group (OR 2.70, 95% CI 2.50-2.92, p<0.001) and ulcerative colitis compared to the control group (OR 2.71, 95% CI 2.46-2.98, p<0.001). Conclusions: IBD patients have a 2.7 times higher risk of LI. Screening for LI in this population is warranted to avoid confusing or overlapping symptomatology.

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers.

BACKGROUND: The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. METHODS: Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T-13910 polymorphism genotyping and fructose H2/CH4 breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. RESULTS: The median TMAO and zonulin serum concentrations were 2.66 (1.93-4.14) µmol/L and 40.83 (34.73-47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P = 0.011, ρ = 0.160). The strongest correlations were observed in 87 females (P = 0.010, ρ = 0.274) and 49 males (P = 0.027, ρ = 0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P = 0.062, ρ = -0.269). CONCLUSION: This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

Comparison of the impact of bovine milk ß-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial.

BACKGROUND: Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine ß-casein A1 has been proposed. OBJECTIVES: We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine ß-casein types. METHODS: Women (n = 40; age: 25.2 ± 0.5 y) with self-reported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI; n = 10, self-reported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI; n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT; n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON; containing A1 and A2 ß-casein and lactose), a2 Milk (A2M; exclusively containing A2 ß-casein with lactose), or lactose-free conventional milk (LF-CON; containing A1 and A2 ß-casein without lactose). Subjective digestive symptoms and breath hydrogen (measuring LM) were recorded regularly over 3 h, and further ad hoc digestive symptoms over 12 h. RESULTS: LI subjects experienced prolonged digestive discomfort with CON milk. A2M reduced (P < 0.05) some symptoms (nausea: A2M 8 ± 3 mm compared with CON 15 ± 3mm; fecal urgency: A2M 4 ± 1 compared with CON 10 ± 3 mm), and attenuated the rise in breath hydrogen over 3 h, relative to CON milk (A2M 59 ± 23 compared with CON 98 ± 25 ppm at 150 min; P < 0.01). In contrast, NLDI subjects experienced rapid-onset, transient symptoms (abdominal distension, bloating, and flatulence) without increased breath hydrogen, irrespective of milk type. CONCLUSIONS: In LI individuals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 ß-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or ß-casein type. This trial was registered at www.anzctr.org.au as ACTRN12616001694404.