Lactose Intolerance: from Diagnosis to Correct Management

Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2013; 17(Suppl 2): 18-25 Lactose intolerance: from diagnosis to correct management T. DI RIENZO, G. D’ANGELO, F. D’AVERSA, M.C. CAMPANALE, V. CESARIO, M. MONTALTO, A. GASBARRINI, V. OJETTI Department of Internal Medicine and Gastroenterology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy Abstract. Lactose and lactase This review discusses one of the most relevant problems in gastrointestinal clin - ical practice: lactose intolerance. Lactose digestion takes place in the small in - The role of lactase-persistence alleles the di - testine by the work of lactase-phlorizin hydro - agnosis of lactose malabsorption the develop - ment of lactose intolerance symptoms and its lase, a protein expressed on the brush border of management. intestinal villi (with the highest expression in the Most people are born with the ability to di - mid-jejunum), fingerlike protrusions, which in - gest lactose, the major carbohydrate in milk crease the total surface area and , therefore , the and the main source of nutrition until weaning. ability to absorb different substrates. The enzyme Approximately, 75% of the worldʼs population lactase is encoded by LCT gene that maps on loses this ability at some point, while others can digest lactose into adulthood. Symptoms chromosome 2 (2q21). Lactase has two active of lactose intolerance include abdominal pain, sites: the first hydrolyzes lactose in the two bloating, flatulence and diarrhea with a consid - monosaccharides glucose and galactose, making erable intraindividual and interindividual vari - them absorbable by the intestinal mucosa, the ability in the severity. second hydrolyzes phlorizin 1. Diagnosis is most commonly performed by Hydrolysis typically occurs in the first part of the non invasive lactose hydrogen breath test. the small intestine (jejunum ), which has low con - Management of lactose intolerance consists of two possible clinical choice not mutually ex - centrations of bacteria ; so just little portion of clusive: alimentary restriction and drug thera - lactose is fermented. py. Glucose and galactose are absorbed by intesti - nal enterocytes into the blood-stream; glucose is Keywords: ultimately utilized as a source of energy and Lactose breath test, Diagnosis, Therapy. galactose, into the liver, becomes a component of glycolipids and glycoproteins 2. If the lactase enzyme is absent (alactasia) or deficient (hypolactasia), unabsorbed lactose mol - Introduction ecules osmotically attract fluid into the bowel lu - men, leading to an increased volume and fluidity of the intestinal content. In addition, the unab - Lactose is a disaccharide sugar found in sorbed lactose passes into the colon, where it is mammalian milk; it makes up around 2 -8% of fermented by bacteria producing short-chain fat - milk (by weight), although the amount varies ty acids and gases (CO 2, CH4, H2) possibly lead - among species and individuals: 7.2 g/100 mL in ing to various gastrointestinal symptoms 3. mature human milk, 4.7 g/100 mL in cow’s milk but is negligible in the milk of some marine Human lactase mammals. Lactose is a large sugar molecule that is made up of two smaller sugar molecules, glu - cose and galactose. Lactose is first broke down Since 8 weeks of gestation, lactase activity can into D(+)glucose and D(+)galactose by lactase be detected on mucosal surface in the human gut. enzyme, then absorbed by intestinal enterocytes The activity increases up to 34 weeks from birth, into the bloodstream. were lactase expression reaches its peak of expres - 18 Corresponding Author: Veronica Ojetti, MD, Ph.D; e-mail: [email protected] Lactose intolerance: from diagnosis to correct management sion. However, since the first month of life, lactase Sicily) were could reach 70% of populations 11,12 . activity starts to decrease ( lactase non persistance ) The “normal ” condition is represented by the loss and its decline is highly variable from weaning to of lactase expression, defined as “non-persistent ”. undetectable levels as a consequence of the normal In fact, in human life, the power supply is based maturational down-regulation of lactase activity 4-6 . exclusively on breast milk for the first few In humans, about 30% of the population has con - months of life. It is , therefore , understandable tinuous activity of lactase after weaning and in how the adjustment expression of the lactase gene adulthood ( lactase non persistance )2,7 . may predict its progressive decline in later stages of life. However, the genotype that determines the Hypolactasia persistence of lactase, is found only in Northern Europe populations, in some African and Arab nomadic tribes. In Europe, the persistence or not Hypolactasia, or lactase deficiency, a condi - persistence of the expression of lactase is associ - tion that determines the malabsorption of lactose, ated with the so-called point polymorphism C/T occurs generally no earlier than 6-7 year age, but 13910. This consists in the substitution of a single is also sometimes much later 8, showing a steady nucleotide base in a sequence of DNA, that car - increase in prevalence even in the age groups ries regulatory on the lactase gene: genotype CC above 65 years 9. The kinetics of the reduction is associated with hypolactasia (lactase residual is and the amount of residual lactase have consider - approximately 10% compared to the levels of able variability between different ethnic groups birth), while the TT genotype with lactase persis - and even between individuals. However , the re - tence of activity. The presence of a CT genotype, duction of up to 50% of lactase is sufficient to instead, predisposes to the presence of levels of ensure effective digestion of lactose 10 . intermediate expression 13 . Hypolactasia, exists in three distinct forms: The secondary hypolactasia occurs, instead, congenital, primary and secondary. when a mucosal damage of bowel causes a tempo - The congenital is an autosomal recessive rary lactase deficiency. Typically, all diseases of (AR) condition characterized by severe diarrhea the small intestine, such as the Celiac or Crohn ’s with event of watery stools since the first intake disease, ulcerative colitis, irritable bowel syn - of milk by the infant; it persists for all the life drome, radiation, immunological deficiencies, are and requires the complete exclusion of the capable of causing a secondary deficiency of lac - sources of lactose. This extremely rare condition tase, but more commonly bacterial or viral infec - has been described in about 40 cases, in which tions, parasitic infections (such as a giardiasis) or the non-lactase activity was caused by a non- drug treatment 6 induce a transient loss of enzyme sense mRNA. The deficiency of nutrients causes in the mucosa affected by the process inflammato - a delay in growth, with the rapid onset of dehy - ry or infectious. It is obviously a reversible condi - dration and alkalosis. tion requiring a lactose-free diet until it is restored The primary lactase deficiency ( lactase non to a normal intestinal mucosa 14 . persistance ) is an autosomal recessive (AR) con - dition resulting from the physiological decline of Lactose malabsorption lactase activity of intestinal cells and features a in coeliac patients large proportion of individuals. It is a well- known cause of abdominal disorders such as di - arrhea, bloating and flatulence. A recent study by our group demonstrated The primary hypolactasia is a condition ex - that a large proportion of patients with lactose tremely widespread in the world population, but malabsorption is affected by an otherwise silent with substantial variations between different eth - coeliac disease, a gluten-sensitive enteropathy nic groups, the prevalence of disease is minimal caused by a permanent intolerance to gliadin and in Northern European populations (Finland, Swe - its related proteins in individuals genetically sus - den, Germany, Austria, Switzerland, France, ceptible. Celiac disease damaging the brush bor - Great Britain, Holland, Ireland) and groups de - der causes a partial deficiency of lactase. scended from them, and is particularly high in Moreover, other data indicate that a large pro - Asia, Africa and Australia. In Italy, the lactase portion of patients with coeliac disease experi - non persistence effects average 40-50% of the enced a regression of lactose malabsorption after population, particularly in south (Campania and being on a gluten-free diet 15,16 . In some patient ’s 19 T. Di Rienzo, G. D’Angelo, F. D’aversa, C. Campanale, V. Cesario, M. Montalto, A. Gasbarrini, V. Ojetti intraluminal deficit, which brings to the damage ated with a normalization of the majority of pre - of the brush border, could be associated with viously positive lactose, fructose and sorbitol many diseases, as chronic pancreatitis, chronic breath test. These findings suggest that, in pres - hepatitis, irritable bowel syndrome (IBS) and ence of SIBO, the large amount of intestinal small intestinal bacterial overgrowth (SIBO). bacteria may unspeciﬁcally ferment sugars, IBS is a common chronic disorder of un - causing an abnormal H2 production and conse - known origin, characterized by abdominal pain, quently , a misleading diagnosis of lactose, fruc - bloating and constipation alternating with diar - tose or sorbitol malabsorption. An alternative rhoea 17-19 . Abnormal visceral sensation, altered hypothesis could be that the bacterial over - motility and psychosocial factors

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