Lactose Intolerance

Introduction to Lactose Intolerance

Lactose intolerance is a biochemical condition caused by the inability to digest fully the sugar in milk, i.e., lactose [1]. The condition of lactose intolerance is better described as “lactose sensitivity,” as everyone can tolerate some lactose, although this amount varies considerably between individuals [2]. It is essential to distinguish lactose intolerance from an allergy to milk proteins as there are major differences in the management of these two conditions and allergy occurs in 3–5 % of infants. Some four billion people around the world express low lactase levels (see below) and are thus potentially sensitive to lactose, suffering a range of gut and systemic symptoms (Fig. 1), unless diagnosed and then managed correctly. Lactose sensitivity is associated with two common gut conditions [3], irritable bowel syndrome (IBS, a disease characterized by abdominal pain, diarrhea, or constipation or both alternating) and inflammatory bowel disease (IBD, a group of inflammatory conditions affecting small intestine and colon, including Crohn's disease and ulcerative colitis) [4], and thus should be taken into account when diagnosing and treating these patients [5].

Lactose, galactose-1,4-β-glucose, is only found naturally in significant amounts in mammalian milk (cow's milk 49 g/l; human milk 70 g/l). Lactose is one sixth as sweet as sucrose and provides some 40 % of the energy requirements of a suckling infant. However, adults do not need lactose. Disaccharides (e.g., lactose, sucrose, and isomaltose) cannot be absorbed directly in the intestine, requiring an enzyme to cleave them into monosaccharides. Lactose is cleaved by lactase (lactase-phlorizin hydrolase), which occurs in the small intestinal microvilli. Galactose and glucose are subsequently absorbed into the enterocyte via the sodium-activated glucose transporter 1 (SGLUT1, also called SGLT1). Glucose and galactose are then taken up into the blood by the transporter GLUT2. Galactose is converted to glucose mainly by the Leloir pathway, where galactose is converted to UDP-glucose, particularly in the liver via galactose 1-phosphate (Gal-1-P) and UDP-galactose. Alternatively, humans can use the De Ley-Doudoroff pathway. Inherited mutations of enzymes in the Leloir pathway cause galactosemias, affecting 1 in 55,000 individuals. For example, galactosemia type 1 (galactose-1-phosphate uridylyltransferase deficiency) is seen in suckling infants causing severe illness, including not wanting to drink, vomiting, jaundice, hypoglycemia, enlarged liver (hepatomegaly), enlarged spleen (splenomegaly), proximal tubulus kidney damage, cataract, mental retardation, and failure to thrive.

Fig.1 Main metabolic changes in lactose intolerance. Under healthy conditions, lactose is digested by lactase and incorporated causing an increase in blood glucose and galactose levels (left side). In patients who cannot hydrolyze lactose fully in the small intestine (lactose intolerant/sensitive, right side), lactose is transferred to the large intestine and metabolized to metabolic toxins. The metabolic toxin groups are shown, with the respective gut and systemic symptoms. SGLT1 sodium-activated glucose transporter 1, GLUT2 glucose transporter 2, H2 hydrogen, CH4 methane

Galactose synthesis occurs mainly in the mammary gland, via the reversible conversion of UDP-glucose to UDP-galactose. UDP-galactose then reacts with glucose to form lactose, though 65 % of galactose for lactose comes from the blood. Galactose can also be synthesized de novo from glycerol. Galactose has an important role in cerebrosides.

SGLT1 is inhibited by triand tetrasaccharides (e.g., raffinose and stachyose) found in root vegetable, pulses, and soya. People who eat a lot of these can exhibit symptoms similar to hypolactasia (lack or reduced amounts of lactase).
A further problem is the increasing prevalence of sensitivity to fructose. There is an increased use of fructose as a sweetener in many foods and drinks, and sensitivity to fructose can lead to similar symptoms to those of lactose intolerance. Fructose is absorbed into the enterocyte by GLUT5. Like, glucose and galactose, fructose is transferred into the blood by GLUT2.

In diagnosis, hypolactasia is often overlooked and not tested for if the patient only complains of systemic symptoms, as opposed to gut symptoms. Yet, in many hypolactasia/lactose intolerant patients, systemic symptoms can be more significant than those in the gut.

Interestingly, the symptoms that affected Charles Darwin for 50 years match exactly those of lactose intolerance [6]. Yet, he was never diagnosed because his doctors did not understand the link between the gut and the peripheral tissues.

Lactose intolerance is often confused in babies with allergy to milk proteins, particularly αS1casein, as symptoms are similar [1]. Protein allergy usually disappears by 3 years, whereas lactose intolerance can get worse with age. The allergy severity ranges from mild to anaphylactic (see chapter “Allergies”). Depending on the allergen, changing the origin of the milk, e.g., to goat's milk, can be effective, though this is not always the case. Additionally, many patients suffering from lactose intolerance are also sensitive to other substances in foods, the most common being wheat.

 
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