75 Lactose Intolerance and Malabsorption

Lactose malabsorption describes a physiological sit­uation. It is the basis for lactose intolerance. The inability to digest lactose is a quantitative phenome­non related to the enzyme lactase and its amount and activity in the intestine.

More recently, interest of physicians and nutrition­ists in the digestion of lactose stimulated reports during the late 1950s. One by A. Holzel and col­leagues (1959) reported on a severe diarrhea associ­ated with the ingestion of lactose in two young sib­lings who, as a consequence, were “failing to thrive.” Another report, by P. Durand (1958), diagnosed two patients with lactose malabsorption and Iactosuria. Since then, innumerable articles and reviews have appeared in the world’s literature (Scrimshaw and Murray 1988). Evaluations of that literature may be obtained by consulting G. Semenza and S. Auricchio (1989), G. Flatz (1989), and N. Kretchmer (1971).

Lactose: Chemistry, Digestion, and Metabolism

Lactose is a galactoside composed of glucose and galactose. This compound is found in the milk of most mammals, although in marsupials and mono- tremes it appears in conjugated form.

Lactose is digested in the small intestine by the lactase (a galactosidase), which is located in the brush border of the epithelial cells of intestinal villi. This enzyme is anchored to the membrane by a hy­drophobic tail of amino acids. Detailed descriptions have recently been published of the intimate in­tracellular metabolism of lactase (Castillo et al. 1989; Quan et al. 1990).

In most mammals the activity of lactose-digesting lactase is high during the perinatal period; after weaning the activity declines to about 10 percent of its original value. But in certain human groups the enzyme activity remains elevated throughout the lifetime of most of their members (Kretchmer 1977). Examples of these groups include northern Europe­ans, people of Magyar-Finnish extraction, and two African tribes, the Fulani and the Tussi.

Clinical Manifestations

The clinical manifestations of lactose intolerance in­clude increasing abdominal discomfort, borboryg- mus, flatulence, and finally fermentative diarrhea. Although an inordinate amount of any carbohydrate in the diet will produce a similar symptomatology, intolerance to lactose is the most prominent of these clinical syndromes. The basis of this phenomenon is primarily the activity of the lactase relative to di­etary lactose. The lower the activity, the less the capacity for the hydrolysis of the lactose, although other factors - such as intestinal motility and the presence of other nutrients — also play a role in this phenomenon.

When the capacity of the lactase is exceeded, the nonhydrolyzed dietary lactose passes into the large bowel where it is fermented by the myriad of colonic bacteria. This action in turn yields propionic acid, hydrogen, methane, and alcohols, and results in a watery diarrhea, the pH of which is acidic.

In general, the activity of lactase in the intestine in almost all mammals by the time of weaning has decreased to about 10 percent of that encountered during the perinatal period. This does not mean, however, that weaning is directly related to the de­crease in activity of lactase. There has been no docu­mentation indicating that there is any inductive re­lationship between the activity of the enzyme and the ingestion of milk. In fact, all the careful studies indicate that there is no relationship between the two events (i.e., the ingestion of milk and the activ­ity of lactase).

Classification

Lactose malabsorption can be classified into three categories:

1. Congenital malabsorption of lactase, a rare phe­nomenon, which has been documented in only a few cases.

2. Primary malabsorption of lactose, a worldwide situation that is encountered in humans after the age of 5 to 7 years, and in other animals after weaning. (This is considered to be a normal phys­iological process, transmitted genetically; indeed it resembles a classical Mendelian recessive trait.)

3. An acquired malabsorption of lactose that can be encountered at any age in infants and children under 7 years, as well as in adults who had previ­ously been lactose absorbers. This form can also be associated with nonspecific and specific diar­rhea of infancy, drugs that affect the intestinal mucosa, and diseases such as cystic fibrosis and gluten-sensitive enteropathy.

An interesting phenomenon is that the colonic flora of the lactose-intolerant individual seems able to adapt to a nonfermentive type of bacteria. A study was launched in Nigeria in which six medical stu­dents, all proven lactose nondigesters, were fed graded doses of 5 grams of lactose to a final amount of 50 grams over a 6-month period.

History and Geography

The ability to digest lactose is a nutritional event that can be clearly associated with evolutionary pres­sures. During the Neolithic period, human adults began to drink milk, probably in association with the domestication of animals. These ancient pasto-

ralists who originated in the Euphrates River Valley were nomadic, constantly in search of new pastures for their animals. It is assumed that they migrated in two main directions: to the northwest, toward Europe; and to the southwest, across the then-fertile Sahara toward east and west Central Africa. The exact time of these migrations is unknown, but pre­sumably the nomadic pastoralists of Africa (e.g., the Fulani, the Tussi, the Masai, and others) have their origins in these migrations as do those of northern Europe.

In the Americas, by contrast, there were no indige­nous pastoral groups, and thus, in the Western Hemi­sphere, there was no ingestion of milk after weaning until the Europeans arrived. An absence of dietary milk after weaning was also the case in Australia, the islands of the Pacific, Japan, and the rest of Asia. In these regions the individual after weaning ob­tained calcium from small bones, limestone, dark­green vegetables, and fermented or pressed (and thus much reduced in lactose) dairy products.

Thus the present-day geographic distribution of peoples who can or cannot digest lactose fits with our historical knowledge of the distribution of ancient pastoral groups and the milking of their animals. Nonetheless, confusion arises over questions of levels of lactose intolerance among peoples with no history of pastoral activity.

Table VIII.75.2. Distribution of the adult lactase phenotypes in human populations

Table VIII.75.1. Lactose absorption and malabsorption correlated with degree of Indian blood (children ≥4 years, and adults)

^oMalabsorbers represent 21 adults (> 18 years), 38 chil­dren (4-18 years).

⁶Ages 4, 4½, and 6 years.

Source: Johnson et al. 1977. Lactose malabsorption among the Pima Indians of Arizona. Gastroenterology 73(6): 1229-1304, p. 1391, by permission of Gastroenterology.

Table VIII.75.2. (cont.)

Note: LDC = lactose digestion capacity.

Source: G. Flatz. 1989. The genetic polymorphism Ofintestinal lactase activity in adult humans. In The metabolic basis of inherited disease, 6th edition, ed. G. R. Scriver, A. Z. Beaudet, W. S. Sly, and D. Valle, ρ. 3003. New York. By permission OfMcGraw-Hill B∞k Company.

percent who can drink milk, however, represent the genetic penetrance of the pure genetic pool of native Americans with a gene that affords them the ability to digest lactose. Without that genetic penetrance, the percentage that could not digest lactose would have reached 100.

Flatz (1989) has compiled a list of figures that report the distribution of lactose phenotypes for many populations of the world (see Table VII.75.2). These data support the cultural hypothesis first pro­mulgated by Frederick Simoons (1970), which states that the ability to digest lactose is associated only with a population that has a history of pastoralism.

Summary

Lactase has been shown in a number of careful inves­tigations to be the same enzyme in the infant as in the adult who can digest lactose, and in the residual activity found in the nondigester. In general, the lactose digester has 10 times more enzymatic activ­ity than the lactose nondigester. Thus, the bio­chemical genetics of lactose digestion is related to the amount and activity of lactase.

Today, lactose malabsorbers who would like to be able to drink milk can purchase various “lactase” preparations now on the market that “digest” the lactose in milk before it is ingested. Others who do not drink milk can overcome the potential dietary calcium deficiency by consuming fermented milks, pressed cheeses, dark-green vegetables, and small bones as in sardines.

The worldwide distribution of an inability to digest lactose after weaning in most human adults and all other mammals argues for this condition to be the normal physiological state. The ability to digest lac­tose would seem then to be evidence of a genetic polymorphism. It is only the bias of the milk-oriented societies of northern Europe and North America that casts lactose malabsorption as an abnormality.

Norman Kretchmer

Bibliography

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Holzel, A., V. Schwartz, and K. W. Sutcliff. 1959. Defective lactose absorption causing malnutrition in infancy. Lancet 1: 1126—8.

Johnson, J., et al. Lactose malabsorption among the Pima Indians of Arizona. Gastroenterology 73(6): 1299­1304.

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