Treatment depends on the reason for the hypolac- tasia. Failure to treat correctly may leave patients with long-term damage to the intestine or other tissues and also other conditions, such as IBD or celiac disease.
As congenital loss and loss after weaning can- not be “reactivated,” avoidance of lactose in the diet is, in general, inevitable (Fig. 2 ) [ 2 ]. This is diffi cult, however, because lactose is “hidden” in many foods and drinks, not normally associated with milk (e.g., chocolate, bread, biscuits, pro- cessed meat) [ 3 ]. It is used in processed foods because it improves shelf life, browning, mouth feel, and fl avor. As fi ller, lactose bulks up expen- sive ingredients and often replaces fat removed from products in low-fat alternatives.
Dietary treatment
Removal of lactose (including hidden lactose)
Drug treatment Non-drug treatment
Laxatives Anti-motility Anti-spasmodic Anti-depressant IBS
Surgery for IBD
Avoidance of tri- and tetra-saccharides
Probiotics Monitoring of calcium
and vitamin D status
Exclusion of other food sensitivities
(e.g. wheat)
Steroids Azothiaphrine Infliximab IBD
NSAIDs
Migraine treatment Headache
Pain relief Anti-inflammatories Muscle and joint pain Anti-histamines
Asthma inhalers Anti-depressants Topical steroids β-blockers
Vitamins and minerals Triptans
Other systemic symptoms (fatigue, allergy, palpitations, cyclic vomiting)
Exclusion of protein allergy in babies and
children
Complimentary therapies Cognitive behavioral
therapy
Fig. 2 Infl uence of disease treatments on disease. Three general types of treatment are available for the various symptoms in lactose-sensitive patients: (1) dietary manip- ulation, particularly lactose exclusion; (2) drugs, which are often not very effective, if at all; and (3) nondrug ther- apy. The most effective and common treatment is removal of lactose from the diet. Other dietary restrictions might
be helpful, as well. Comorbidities and symptoms are often targeted using specifi c drugs. Cognitive behavioral therapy involves discussions with a psychologist, using standard psychological methods. Complimentary thera- pies involve acupuncture, refl exology, and exercise. IBS irritable bowel syndrome, IBD infl ammatory bowel dis- ease, NSAIDs nonsteroidal anti-infl ammatory drugs
A.K. Campbell and S.B. Matthews
147
Labeling of added lactose is poor as it is commonly part of “fl avorings” or “added sugar,”
being described as “natural.” It is possible to take the equivalent of a liter of milk in “hidden”
lactose, for example, after starting a weight loss regime using meal substitute drinks high in lac- tose. Symptoms of lactose intolerance are often aggravated by tri- and tetrasaccharides inhibit- ing SGLUT1 (see above) and leading to unab- sorbed sugars reaching the bacteria in the large intestine.
Natural yogurt is often tolerated, since the lac- tose content is much reduced. Substitutes, such as lactose-free cow’s milk or soya milk, are gen- erally useful, if soya intolerance is excluded.
Symptoms caused only by lactose can disap- pear within a few days after removing lactose from the diet.
Alternatively, the enzyme marketed as “lac- tase,” actually β-galactosidase, taken before eat- ing lactose, may alleviate symptoms, as it is supposed to digest lactose similar to the endoge- nous enzyme. β-galactosidase also hydrolyses lactose to galactose and glucose and is expressed in many bacteria and several molds. Yet, it has no sequence similarity to mammalian lactase, con- tains only one active center for lactose, and can- not hydrolyze cerebrosides (also known as monoglycosylceramides) as lactase does. The use of β-galactosidase is not routinely recom- mended, as most of the enzyme is degraded in the stomach. Timing and dose are critical to be effective.
Despite the best therapeutic approach of a lac- tose-free diet being drug free, many drugs are pre- scribed, or bought over the counter by people with lactose sensitivity, in an attempt to alleviate gut and systemic symptoms, the most common being IBS.
Treatment of IBS includes antispasmodics (e.g., mebeverine); bulk laxatives; antimotility drugs (e.g., loperamide); antidepressants (e.g., the tricyclic amitriptyline or a serotonin reup- take inhibitor), which reduce pain and cramps;
and analgesics. Probiotics can also reduce symptoms [ 12 ]. Patients often also take antac- ids and proton pump inhibitors to reduce stom- ach acidity and refl ux. However, these have
little or no consistent effect on the gut and sys- temic symptoms caused by lactose. Nondrug treatments of IBS include cognitive behavioral therapy; stress management; complementary therapies, including acupuncture and refl exol- ogy; and exercise.
Lactose sensitivity is commonly seen in IBD [ 4 ]. IBD treatment involves aminosalicylates, corticosteroids, and immunosuppressants. These are used to reduce the effect of infl ammation in the intestine, but do not alleviate the symptoms caused by lactose.
Infl uence of Treatment
on Metabolism and Consequences for Patients
Removal of lactose from the diet or uptake of digesting enzymes does not have adverse effects on the patient’s metabolism. It is vital to ensure calcium and vitamin D levels when milk, their major dietary source, is avoided.
Advice on the possible use of probiotics is also required. However, dietary removal of lactose may not solve all the problems, if the patient is intolerant to other foods. These need to be identifi ed and treated, most commonly by dietary means.
The systemic symptoms of lactose intolerance lead to unnecessary drug usage. Headaches are treated by regular analgesics and the risk of over- use is high. Migraine and cyclical vomiting syn- drome can be controlled by regular β-blockers and triptans (see chapter “ Migraine and cluster headache ”). Other commonly used drugs are antihistamines, anti-infl ammatories, steroids, and asthma inhalers, taken to alleviate allergic symp- toms (see chapter “ Asthma ”). Yet, unknown to most asthmatics, many inhalers also contain sig- nifi cant amounts of lactose.
Drug interaction from polypharmacy is a seri- ous potential risk, especially as many of the drugs are self-prescribed. There is also a danger of drug overuse. Furthermore, there can be an iatrogenic problem of taking too much lactose in drugs, as it is often included in pills, which then contributes to morbidity [ 13 ].
Lactose Intolerance
148
Perspectives
In diagnosis, the gold standard [ 5 ] for a patient presenting with unexplained gut and systemic symptoms should fi rst be to test for the polymor- phism C/T 13910. All CC should immediately change to a lactose-free diet, whereas CT or TT patients should undergo a hydrogen and methane breath test after lactose ingestion, together with a record of symptoms. A signifi cant number of patients show no positive hydrogen or methane breath test, but will exhibit symptoms after lac- tose ingestion. Hypolactasia caused by infec- tions, e.g., Giardia or rotavirus, which damage the lactase-containing intestinal villi (see chapter
“ Overview ” under the part “Gastrointestinal tract”), or hormonal imbalance, which can reduce lactase levels, should be investigated, if there is no evidence of family history. If the breath hydro- gen or methane is increased, together with induc- tion of symptoms by lactose, the patient should change to a lactose-free diet. All patients with a signifi cant increase in symptoms after the lactose load should undergo a supervised trial to deter- mine their lactose threshold. Every patient should be followed up in 12 weeks for a defi nitive diag- nosis, based on clinical improvement, following lactose removal from the diet.
Lactose sensitivity, and the production of met- abolic toxins by gut bacteria and archaeans, pro- vides a new mechanism linking the gut to other illnesses, such as type 2 diabetes (see chapter
“ Diabetes mellitus ”), Parkinson’s disease (see chapter “ Parkinson’s disease ”), Alzheimer’s dis- ease (see chapter “ Alzheimer’s disease ”), some cancers (see chapter “ Overview ” under the part
“Cancer”), and periodontal disease. The molecu- lar mechanisms responsible for the production of bacterial metabolic toxins are a good target for drug discovery in developing a new treatment for these conditions.
References
1. Campbell A, Jenkins-Waud J, Matthews S (2005) The molecular basis of lactose intolerance. Sci Prog 92:
241–287
2. Campbell AK, Matthews SB (2005) Tony’s lactose free cookbook: the science of lactose intolerance and how to live without lactose. The Welston Press, Pembrokeshire, p 204
3. Matthews SB, Waud JP, Roberts AG, Campbell AK (2005) Systemic lactose intolerance: a new perspec- tive on an old problem. Postgrad Med J 81:167–173 4. Eadala P, Matthews SB, Waud JP, Green JT, Campbell
AK (2011) Association of lactose sensitivity with infl ammatory bowel disease – demonstrated by analy- sis of genetic polymorphism, breath gases and symp- toms. Aliment Pharmacol Ther 34:735–746 5. Waud JP, Matthews SB, Campbell AK (2008)
Measurement of breath hydrogen and methane, together with lactase genotype, defi nes the current best practice for investigation of lactose sensitivity.
Ann Clin Biochem 45:50–58
6. Flatz G (1987) Genetics of lactose digestion in humans. Adv Hum Genet 16:1–77
7. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I (2002) Identifi cation of a variant associated with adult-type hypolactasia. Nature Genet 30(2):233–237
8. Campbell AK, Matthews SB, Vassell N, Cox C, Naseem R, Chaichi MJ, Holland IB, Wann KT (2010) Bacterial metabolic ‘toxins’: a new mechanism for lactose and food intolerance, and irritable bowel syn- drome. Toxicology 278(3):268–276
9. Matthews SB, Campbell AK (2000) When sugar is not so sweet. Lancet 355(9212):1330
10. Grimbacher B, Peters T, Peter HH (1997) Lactose intolerance may induce severe chronic eczema. Int Arch Allergy Immunol 113(4):516–518
11. Zuccotti G (2008) Probiotics in clinical practice: an overview. J Int Med Res 36(1):1–53
12. Eadala P, Waud JP, Matthews SB, Green JT, Campbell AK (2009) Quantifying the ‘hidden’ lactose in drugs used for the treatment of gastrointestinal conditions.
Aliment Pharmacol Ther 29(6):677–687
13. Campbell AK, Matthews SB (2005) Darwin’s illness revealed. Postgrad Med J 81(954):
248–251
A.K. Campbell and S.B. Matthews
E. Lammert, M. Zeeb (eds.), Metabolism of Human Diseases, 149 DOI 10.1007/978-3-7091-0715-7_24, © Springer-Verlag Wien 2014