Lactose Intolerance in Adults: Biological Mechanism and Dietary Management.

Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance.

Food allergy in adolescence and adulthood.

In young children, food allergy is usually acquired via the gastrointestinal tract and directed toward egg and milk. Adolescent and adult patients, however, mainly acquire food allergy via primary sensitization to inhalant allergens on the basis of cross-reactivity between proteins in inhalant sources and in food. This type of food allergy is frequently mediated by sensitization to broadly represented allergens, or so-called panallergens. Food allergic reactions in adult patients - similar to those in children - range in severity from very mild and local symptoms, as in contact urticaria of the oral mucosa, to systemic symptoms involving distal organs, to a fatal outcome. Plant foods, such as fruits, nuts, and vegetables, are the most prevalent allergenic foods in this age group.

Lactose intolerance in irritable bowel syndrome patients with diarrhoea: the roles of anxiety, activation of the innate mucosal immune system and visceral sensitivity.

BACKGROUND: Irritable bowel syndrome patients with diarrhoea (IBS-D) often report intolerance to milk; however, the mechanism underlying these symptoms is unknown. AIM: To assess the role of psychological factors, immune activation and visceral sensitivity on the development of lactose intolerance (LI) in IBS-D patients. METHODS: Fifty-five IBS-D patients and 18 healthy controls (HCs) with lactase deficiency underwent a 20-g lactose hydrogen breath test (LHBT). Patients were categorised as lactose malabsorption (LM; malabsorption only) or LI [malabsorption plus increase in total symptom score (TSS). Measurements included (i) psychological status; (ii) enteric biopsies with quantification of mast cells (MCs), T-lymphocytes and enterochromaffin cells; (iii) serum cytokines; (iv) rectal sensitivity before and after lactose ingestion. RESULTS: LI was more prevalent in IBS-D patients than HCs [25/55 (46%) vs. 3/18 (17%), P = 0.029]. IBS-D patients with LI had (i) higher levels of anxiety than those with LM (P = 0.017) or HCs (P = 0.006); (ii) increased mucosal MCs compared with LM (P = 0.006) and HCs (P < 0.001); (iii) raised serum TNF-α compared with LM (P = 0.034) and HCs (P < 0.001) and (iv) increased rectal sensitivity after lactose ingestion compared with LM (P < 0.001) or HCs (P < 0.001). Severity of abdominal symptoms after lactose ingestion was associated with the increase in visceral sensitivity after lactose intake (r = 0.629, P < 0.001), MCs (r = 0.650, P < 0.001) and anxiety (r = 0.519, P < 0.001). CONCLUSIONS: IBS-D patients with lactose intolerence are characterised by anxiety, mucosal immune activation and increased visceral sensitivity after lactose ingestion. The presence of these biomarkers may indicate an IBS phenotype that responds to dietary therapy and/or mast cell stabilisers.

Is it just lactose intolerance?

Acquired delayed-onset hypolactasia is a common autosomal recessive condition. Cow's milk allergies, conversely, are less common conditions that may manifest with equivalent symptoms and are able to simulate and/or aggravate lactose intolerance. This study was designed to evaluate the contribution of IgE-mediated cow's milk sensitization to the symptomatology of adult patients with lactose-free diet refractory lactose intolerance. Forty-six adult patients with lactose intolerance and persistent symptoms despite a lactose-free diet underwent skin-prick test to investigate cow's milk, goat's milk, and soy protein-specific-IgE. SDS-PAGE immunoblotting was used to investigate the presence of cow's milk protein-specific IgE. The percentage of patients who had skin reactions to whole cow's milk, alpha-lactalbumin, beta-lactoglobulin, caseins, goat's milk, and soy was 69.5, 36.9, 56.5, 56.5%, 54.3, and 50%, respectively. The percentage of patients with immunoblot-detected IgE specific for alpha-lactalbumin, beta-lactoglobulin, caseins, and bovine serum albumin was 21.7, 63, 67.3, and 2.1%, respectively. IgE-mediated sensitization to cow's milk is a frequent comorbidity in subjects with lactose-free diet refractory lactose intolerance and is worth consideration in patients with this condition.

Lactosa, lactasa y el problema de la intolerancia. Primera parte: Importancia nutricional de la lactosa / Lactose, lactase and the problem of intolerance. Part One: Importance

La intolerancia a la lactosa es un trastorno no inmunológico de frecuente atención por alergistas. La lactosa es un disacárido constituido por glucosa y galactosa y sintetizado exclusivamente en la glándula mamaria con participación de la enzima lactosa sintetasa. Este disacárido no usual, que sirve como principal combustible para el lactante, tiene como ventajas su osmolaridad y la presencia de la unión (β1 4) entre glucosa y galactosa. Su absorción requiere de la actividad de una β-galactosidasa específica, la lactasa. La lactosa ingerida, que excede la capacidad de la lactasa para hidrolizarla,permanece en la luz intestinal provocando acumulación de agua y electrolitos. La lactosa no absorbida es fermentada por la microbiota colónica con producción de ácidos grasos de cadena corta y gases. La ingestión de este disacárido favorece el desarrollo de una flora acidófila capaz de sintetizar vitaminas e inhibir el desarrollo de gérmenes patógenos; además, estimula la absorción del calcio y otros cationes. La actividad de la lactasa intestinal es máxima en el período neonatal, disminuye al destete y llega a niveles bajos en el adulto. La caída en la actividad comienza entre los 2 y 3 años y se completa alrededor de los 5 ó 6 con diferencias étnicas. En los individuos sanos, en los que no disminuye, la lactasa permanece elevada durante toda la vida. Para explicar la distribución regional y étnica de la variabilidaden la actividad de la lactasa en los adultos de la especie humana, se sugirieron diferentes hipótesis de adaptación y genética.

Lactose intolerance is a non immunological disorder of frequent attention by allergologists. The lactose is a disaccharide of glucose and galactose synthesized exclusively in the mammary gland with participation of the enzyme lactose sinthetase. This non usual disaccharide, which serves like fuel for the suckling baby, has like advantages its osmolarity and its union (β1 4) between glucose and galactose. Its absorption requires of the specific activity of one β-galactosidase, lactase. The ingested lactose, that exceeds the capacity of lactase hydrolysis, remains in the intestinal light causing accumulation of water and electrolytes. The non absorbed lactose is fermented by colonic microbiota with production of short chain fatty acids and gases. The lactose is the main energy source during the first year of life. The lactose ingestion favors the development of acidophil flora able to synthesize vitamins and to inhibit the development of pathogenic germs; it stimulates the absorption of calcium and other cations. The activity of intestinal lactase is maximal in the neonatal period, diminishes to the weaning and arrives at low levels in the adult. The fall in the activity begins between the 2 and 3 years of life and it is completed around 5 or 6, with ethnic differences. In the healthy individuals, in who does not diminish, lactase remains high during along life. In order to explain the regional and ethnic distribution of the variability in the activity of lactase in adults of the human species, different hypotheses from adaptation and genetics were suggested.

Expression of the high-affinity IgG receptor FcRI (CD64) in patients with inflammatory bowel disease: a new biomarker for gastroenterologic diagnostics.

OBJECTIVES: We sought to determine the quantitative expression of the high-affinity Fc receptor (CD64) on polymorphonuclear neutrophils (PMNs) in inflammatory and functional conditions of the intestine and investigated its correlation with clinical and biological parameters of inflammation. METHODS: The quantitative expression of CD64 was determined by fluorescence-activated cell sorting analysis in patients with active or inactive inflammatory bowel disease (IBD, n=76), infectious enterocolitis, lactose and/or fructose intolerance, and healthy subjects. RESULTS: The quantitative expression of CD64 in patients with active IBD (3,398+/-3,589 molecules per PMN, n=27) was significantly higher than in healthy subjects (607+/-265, n=28, P<0.001) or in patients with lactose/fructose intolerance (531+/-150, n=32, P<0.001). The expression of CD64 correlated significantly with C-reactive protein (CRP, 0.65, P<0.0001), Crohn's disease activity index (CDAI, 0.53, P<0.0001), and colitis activity index (CAI, 0.63, P<0.0001) in patients with IBD. With a cutoff point of 800, CD64 had a sensitivity of 88% and a specificity of 93% in discriminating between lactose/fructose intolerance and active IBD. The quantitative expression of CD64 in patients with infectious enterocolitis (19,190+/-8,920, n=22) was significantly higher than in patients with active IBD (P<0.001). With a cutoff point of 10,000, CD64 showed a sensitivity of 96% and a specificity of 97% in discriminating between infectious enterocolitis and active IBD. CONCLUSIONS: CD64 could serve as a valuable tool to discriminate between IBD, infectious enterocolitis, and functional intestinal disorders.

[Studies of total antigenicyty of fermented dairy products].

Article displays the results of 63 dairy products ELISA studies. Total antigenicity of fermented dairy products varied in wide range. Molecular mass distribution of protein was additionally examined in 5 samples that differed significantly by their antigenicity. The relation was shown between antigenicity and beta-lactoglobulin content in product.

Should milk-specific IgE antibodies be measured in adults in primary care?

OBJECTIVE: To study the association of milk-IgE antibodies in serum to milk-related gastrointestinal symptoms in adults in primary care. DESIGN: Open clinical study. SETTING: Five outpatient clinics in primary care in Southern Finland. SUBJECTS: A total of 756 subjects who reported milk-related gastrointestinal symptoms in primary care and as controls 101 subjects with no such symptoms. METHODS: IgE values for specific food antigens were measured (Pharmacia CAP System) in a total of 857 subjects. All food screen-positive samples (>0.35 IU/l) were analysed further for IgE for untreated skimmed milk (milk-IgE) and for boiled milk. Those found positive for milk-IgE were invited for an open milk challenge test. RESULTS: Some 5.4% (46/857) of all subjects had a positive IgE antibody screen for food antigens. Of those with a positive food screen, 28% (13/46) had milk-IgE antibodies comprising 1.5% of the total group screened. The prevalence of milk-IgE was not statistically different between those with milk-related symptoms and those with no such symptoms. IgE antibodies for boiled milk were rare. All specific IgE antibody levels were low. Bloating was the only observed symptom in milk challenge tests. CONCLUSION: IgE antibodies to cow's milk were relatively rare in the adult population and were not indicative of milk protein allergy. The observed IgE levels were low and did not correlate with subjective milk-related symptoms. The measurement of milk-specific IgE in adults should be discouraged in outpatient clinics.

Cow's milk allergy: a complex disorder.

Cow's milk allergy (CMA) is a complex disorder. Numerous milk proteins have been implicated in allergic responses and most of these have been shown to contain multiple allergenic epitopes. There is considerable heterogeneity amongst allergic individuals for the particular proteins and epitopes to which they react, and to further complicate matters, allergic reactions to cow's milk are driven by more than one immunological mechanism. Finally, the incidence and dominant allergic mechanisms change with age, with IgE-mediated reactions common in infancy and non-IgE-mediated reactions dominating in adults. The complexity of CMA has lead to many public misconceptions about this disorder, including confusion with lactose intolerance and frequent self-misdiagnosis. Indeed, the prevalence of self-diagnosed CMA in the community is 10-fold higher than the clinically proven incidence, suggesting a sizable population is unnecessarily eschewing dairy products. Avoidance of dairy foods, whether for true or perceived CMA, carries with it nutritional consequences and the provision of appropriate nutritional advice is important. In this review, the epidemiology and natural course of CMA is discussed along with our current understanding of its triggers and immunological mechanisms. We examine current strategies for the primary and secondary prevention of allergic sensitization and the ongoing search for effective therapies to ultimately cure CMA.

Clinical tolerance to lactose in children with cow's milk allergy.

OBJECTIVE: Adverse reactions following the ingestion of lactose have been reported in children with cow's milk (CM) allergy. Whether this is attributable to the contamination of lactose with CM proteins is unknown. In this paper, we assessed clinical tolerance of lactose derived from CM whey in children hypersensitive to CM from 2 university hospital pediatric departments. DESIGN: Twenty-four children (5 girls and 19 boys, median 25 months old; range: 2-107 months) with immediate CM allergy confirmed at history or during double-blind, placebo-controlled food challenge (DBPCFC) were enrolled. DBPCFC with CM could be conducted in 11 of 24 patients. Children with a history of immediate/delayed reactions to soy formula (SF) were excluded. Clinical tolerance to CM, SF, and SF + lactose was assessed by: 1) skin prick test with casein, lactalbumin, soy commercial allergen preparations, fresh CM, SF, SF and lactose, lactose (Official Pharmacopoeia) in 4 concentrations (0.01%, 0.1%, 1%, 10%); 2) specific serum immunoglobulin E determination by CAP system technology; 3) DBPCFC in 8 incremental doses of SF + lactose and using SF as a placebo to make up a total of 240 mL of reconstituted formula. RESULTS: With a positive cutoff point of > or = 3 mm wheal diameter at SPT, all patients were sensitized to fresh CM, lactalbumin, and/or casein. Twenty-three of 24 patients (95.8%) were SPT-positive to CM formula, 16 of 24 to lactalbumin (66.6%), 14 of 24 to casein (58.3%), and none to SF, SF + lactose, or lactose alone at all dilutions. Complexed immunoglobulin E determinations were positive for CM in 23 of 24 cases and negative in all cases for soy. Challenge with SF + lactose was negative in all cases. CONCLUSIONS: Even children hypersensitive to CM are clinically tolerant to lactose and can safely consume foods and drugs with lactose from bovine sources as an ingredient. Lactose exclusion is unwarranted from soy preparations on grounds of potential allergic reactions to CM protein residue.

Milk hypersensitivity--key to poorly defined gastrointestinal symptoms in adults.

Lactose intolerance is a common adverse reaction to milk in adults, while milk hypersensitivity is a disorder of infancy. We hypothesized that milk hypersensitivity may cause many unspecific gastrointestinal disorders in adults. Twenty adults were subjected to double-blind, placebo-controlled milk challenge. Phagocyte activity, and Fc gamma and complement receptor expression of phagocytes were assayed, and serum total IgE, milk-specific IgE, and serum reactivity to milk protein were determined. The challenge increased phagocyte activity and complement receptor expression of phagocytes in subjects designated milk-hypersensitive, who had gastrointestinal symptoms from milk ingestion but normal lactose tolerance. The increase was not detected in lactose-intolerant or control subjects. The milk-hypersensitive group was also distinguished from the lactose-intolerant group by enhanced serum reactivity to milk protein. Only two out of nine milk-hypersensitive subjects had detectable milk-specific serum IgE. It is concluded that milk hypersensitivity in adults, occurring as gastrointestinal reactions, may be more common than previously thought.

Adverse reactions to food constituents: allergy, intolerance, and autoimmunity.

Food allergies and intolerance represent important health concerns to consumers who are predisposed to these illnesses. Unlike many current food safety issues, food sensitivities are complicated by both complex and multiple individual adverse reactions, which can vary from emotional to pathophysiological ailments. In some instances, the underlying mechanisms that result in the development of food allergies or intolerance have marked differences but produce common symptoms. The present-day diagnosis of these disorders can be impeded by intrinsic limitations in generating accurate information from patient history and biochemical, physicochemical, and immunochemical tests. Oral challenge tests represent effective methods for confirming and testing food allergens and food intolerance; however, these procedures are often restricted to clinical trials. It is important to be able to distinguish among food allergy, intolerance, and autoimmune disease in the management of these disorders. The role of food in the development of autoimmune disease may be exemplified by celiac disease, a food-induced enteropathy, requiring exposure to prolamins in wheat, rye, and barley. Various wheat and soy protein sources, including the soy protein isolates used to make infant formulas, have been related to juvenile or insulin-dependent diabetes mellitus (IDDM), a common chronic disease of childhood. Employing food process technologies to eliminate food constituents with potential for intolerance in some individuals is a potentially viable approach for reducing risk to food-related disorders. Finally, the development of food labelling regulations that require the identification of potential food allergens or agents for intolerance in the ingredient declaration on prepackaged food is a positive step toward the prevention of severe adverse reactions in hypersensitive individuals.

Primary prevention of insulin-dependent diabetes mellitus: simple approaches using thermal modification of milk.

Evidence is presented that new cases of primary insulin dependent diabetes mellitus (IDDM) will cease to occur when milk-processing temperatures are increased from current levels (72 degrees C) to at least 85 degrees C. This temperature is sufficient to denature bovine serum albumin (BSA), the environmental trigger molecule for IDDM. Morbidity and mortality from atherosclerotic vascular disease (ASVD) and a number of autoimmune diseases may also be reduced by such increases in milk-processing temperatures. BSA-free milk products commercially available now include those canned (> 100 degrees C), ultrapasteurized (138 degrees C), and ultrahigh-temperature (UHT) processed (149 degrees C). At less than 6400 feet elevation, BSA can be denatured by simply bringing milk to a boil (> 85 degrees C). Until such time as all milk is routinely heat-treated to denature BSA, the safest course to maintain good nutrition and prevent IDDM and other BSA-triggered diseases is selection of milk products processed at temperatures above 85 degrees C.

[Effects of dietary fat composition on food anaphylaxis and formaldehyde sensitization in guinea pigs]. / Vlianiie zhirovykh kompozitsii ratsiona na pishchevuiu anafilaksiiu i sensibilizatsiu formal'degidom u morskikh svinok.

Adult guinea pigs were fed for 10-14 days with synthetic diets, fat constituting 11% of its total energy. Dietary fat was composed of coconut, corn, dairy and soybean oils mixtures with ratio of polyunsaturated fatty acids (PUFA) omega-6 to PUFA omega-3 equal to 24.2 (K1) or 5.53 (K2). The animals were sensitized orally by pasteurized cow milk (PCM) or epicutaneously by formaldehyde (F) during these diets feeding. The degree of the sensitization was assessed in the reaction of active anaphylactic shock (AAS) in PCM-sensitized animals and in the reaction of leukocytes specific lysis (LSL) in F-sensitized guinea pigs. In the latter pigs the concentration of serum antibodies (Ab) against dietary soya protein was measured by ELISA. Animals fed by K1 and K2 were also tested for histamine mean lethal dose resistance. The lowest lethality in AAS, number of convulsions, of positive LSL cases and Ab level were found in animals fed by K1 compared to both K2 and to animals fed by common animal chew. Resistance to histamine was similar in K1 and K2 groups, but was significantly higher compared to control (chew) group. In convulsion, the changes in PUFA omega-6/PUFA omega-3 ratio have marked effect on different indices of allergic sensitivity.