Cow's milk allergy and lactose intolerance

Cow’s milk allergy is caused by an aberrant inflammatory immune response to milk proteins. It is distinct from cow’s milk intolerance which is caused by a deficiency in digestive lactase to break down lactose found in milk1 (Figure 1).

Figure 1. Differences between cow’s milk allergy and cow’s milk intolerance1

Cow’s Milk Allergy

Cow’s milk allergy (CMA) is a disorder characterised by an abnormal or exaggerated immunologic response to cow’s milk protein. Estimates of the prevalence of CMA vary from 2 to 7% in infants aged under 1 year2. It is further classified into disorders mediated by IgE antibodies or by non-IgE mediated mechanisms3. In general, IgE-mediated CMA occurs within minutes to a few hours (immediate-onset) and can result in a range of symptoms such as anaphylaxis, angioedema, urticaria, wheezing, vomiting and diarrhea. Non-IgE-associated CMA can take hours or days to become apparent (delayed-onset) and often result in enterocolitis/enteropathy syndromes with accompanying gastrointestinal symptoms3 (Figure 2).

Figure 2. In IgE-mediated allergy, the immune system is programmed to produce IgE antibodies. These antibodies attach to the surface of mast cells and basophils, arming them with an allergen-specific trigger. Subsequent exposure to milk proteins lead to “activation” when the cell-associated IgE binds the allergenic epitopes on the milk proteins and triggers the rapid release of powerful inflammatory mediators leading to allergy symptoms. The mechanism for non-IgE-mediated allergy is poorly understood and possibly mediated through Type-1 T helper cells1,3

 

In a local study of 3827 children aged 2 to 7 in Hong Kong, 8.1% had parent-reported adverse food reaction and 4.6% had doctor-diagnosed adverse food reaction. Cow’s milk was one of the top six leading causes of adverse food reaction and 5.7% of those with allergic reaction showed adverse reaction to milk4 (Figure 3).

Figure 3. In a group of Hong Kong children with adverse food reaction, the top leading causes of allergy were shellfish, egg, peanut, beef, cow’s milk and tree nuts. Other foods include: soybean, 1.7%; prune, chicken, wheat, cauliflower, pumpkin, zuhini, broad bean, potato, pear, apple, grape, honey, mango, papaya, kiwi, cucumber, coconut, curry, monosodium glutamate < 1.5% each4.

Lactose intolerance

Lactose is a disaccharide which is found in milk, including human milk, and is hydrolysed into galactose and glucose by the enzyme known as lactase5. This enzyme is produced by epithelial cells that reside in the brush border of the small intestine. In the absence of lactase, dietary lactose remains undigested in the intestine, raising the osmotic gradient and causing fluid to diffuse from the surrounding tissues to the lumen. A portion is metabolised by colonic bacteria to produce gas and organic acid.  The resulting symptoms include bloating, gas, abdominal pain, diarrhoea and in some cases, nausea and vomiting5.

There are four major types of lactose intolerance: congenital, primary, secondary and late onset. Congenital absence of intestinal lactase is extremely rare and is a lifelong disorder characterised by faltering growth and infantile diarrhoea from the first exposure to human milk5. Primary lactose (hypolactasia) intolerance occurs when normal levels of lactase have not yet developed in infants5. Secondary lactose intolerance refers to people that lose lactase enzyme expression in the brush boarder due to inflammation or structural damage such as enteropathy (i.e. viral gastroenteritis or coeliac disease)5. Late onset of lactose intolerance occurs when lactase expression declines during childhood and it has been shown that Chinese lose 80-90% of lactase activity within 3-4 years after weaning5.

There are several possible mechanisms for the common symptoms seen in lactose intolerance. The unabsorbed lactose passing through the colon increases the diffusion of water into the lumen thus, speeding time and softening stool. In addition, unabsorbed lactose is hydrolysed to galactose (Gal) and glucose (Glu) by bacterial ß-galactosidase present in lactic acid bacteria. These monosaccharides are fermented by bacteria to produce short chain fatty acid (SCFA) with hydrogen and carbon dioxide as by-products. The result is bloating in the small bowel and flatulence in the colon5.

Recovery from diarrhoea

Soy protein based formulas are lactose-free and a number of studies have shown that they improve recovery from infantile diarrhoea. In a meta-analysis of 13 studies that compared the outcome of children with acute diarrhoea treated with lactose-containing and lactose-free formulas, 22% of infants fed lactose-containing formulas experienced persistent diarrhoea compared to 12% of infants fed soy protein based formulas6. The duration of diarrhoea was also shown to be shorter for infants that received soy based formula (4.5 ± 3.6 days) than infants that received cow’s milk formula (6.6 ± 4.2 days) (Soy based formula vs cow’s milk formula, p = <0.01)7.

Figure 4. Role of soy protein based formulas in management of diarrhoea. Study group were infants (mean age 6.2 months) with acute diarrhoea treated with soy-based formula with oral rehydration solution. Control group were infants (mean age 6.3 months) with acute diarrhoea treated only with oral rehydration8.

Important notice:

Breast milk is best for babies. Infant formula is intended to replace breast milk when mothers do not breast-feed. Good maternal nutrition is important for preparation and maintenance of breast-feeding. Introducing partial bottle-feeding could negatively affect breast-feeding and reversing a decision not to breast-feed is difficult. Professional advice should be followed on infant feeding. Infant formula should be prepared and used as directed. Unnecessary or improper use of infant formula may present a health hazard. Social and financial implications should be considered when selecting a method of infant feeding.

Further information

American Academy of Pediatrics Policy: Use of Soy Protein-Based Formulas in Infant Feeding
Link to website

ESPGHAN
Soy Protein Infant Formulae and Follow-On Formulae: A Commentary by the ESPGHAN Committee on Nutrition
Link to website


Department of Health Hong Kong. Family Health Service: Feeding your babies (Newborns to 6 months old) – Bottle feeding
Link to website

References

1. Crittenden RG, Bennett LE. Cow's milk allergy: a complex disorder. J Am Coll Nutr. 2005 Dec;24(6 Suppl):582S-591S.
2. National Health Service (NHS). Food Allergy. http://www.nhs.uk/Conditions/food-allergy/Pages/Causes.aspx. Accessed on 08 August 2011.
3. Bahna SL. Control of milk allergy: a challenge for physicians, mothers and industry. Ann Allergy. 1978 Jul;41(1):1-12.
4. Leung TF, Yung E, Wong YS, Lam CW, Wong GW. Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: epidemiology, clinical spectrum and risk factors. Pediatr Allergy Immunol. 2009 Jun;20(4):339-346.
5. Lomer MC, Parkes GC, Sanderson JD. Review article: lactose intolerance in clinical practice--myths and realities. Aliment Pharmacol Ther. 2008 Jan 15;27(2):93-103.
6. Brown KH. Dietary management of acute diarrheal disease: contemporary scientific issues. J Nutr. 1994 Aug;124(8 Suppl):1455S-1460S.
7. Allen UD, McLeod K, Wang EE. Cow's milk versus soy-based formula in mild and moderate diarrhea: a randomized, controlled trial. Acta Paediatr. 1994 Feb;83(2):183-187.
8. Santosham M, Goepp J, Burns B, Reid R, O'Donovan C, Pathak R, Sack RB. Role of a soy-based lactose-free formula in the outpatient management of diarrhea. Pediatrics. 1991 May;87(5):619-622.

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