intolerance in adulthood is very common. Many question the term because it
implies that significant lactase activity as an adult is normal. In fact,
some scientists believe that human adult lactase polymorphism evolved in
the Neolithic period, after animal milk became available for nutrition of
older children and adults. Expression of the lactase enzyme starts to
decrease in most humans at the age of 2 years; however, symptoms of
lactose intolerance rarely develop in people younger than 6 years.
After a normal amount of milk is ingested, lactase enzyme activity
usually persists at a low level. Milk intolerance in a term infant is
rarely due to primary lactase deficiency and is more likely due to allergy
to milk protein. While transient lactose intolerance may occur after acute
gastroenteritis, it is rarely clinically significant and, when present,
can easily be treated with a short course of a lactose-free diet.
Diagnosing lactose intolerance based on symptoms is fairly inaccurate;
however, self-reported symptoms of lactose intolerance correlate with low
calcium intake. Calcium supplementation should accompany any restriction
of milk products.
Pathophysiology: Lactose, a disaccharide unique to
mammalian milk, is hydrolyzed into the monosaccharide glucose and
galactose at the brush border of enterocytes on the villous tip by the
enzyme lactase (beta-D-galactosidase). Lactose appears to enhance the
absorption of several minerals, including calcium, magnesium, and zinc. It
also promotes the growth of Bifidobacterium and is a major source
of galactose, which is an essential nutrient for the formation of cerebral
galactolipids. The gene for lactase is located on chromosome 2. While no
differences exist in the DNA from individuals with low and high levels of
lactase activity, differences do exist in messenger RNA (mRNA), suggesting
the primary regulation of this enzyme occurs during translation.
Human and animal studies suggest that a number of modulators exist for
the variable expression of lactase at different ages. Thyroxine may
promote the decline in lactase enzyme expression that appears in childhood
whereas hydrocortisone appears to increase lactase levels. While premature
infants have partial lactose deficiency because of intestinal immaturity,
enzyme expression can be induced by lactose ingestion. Improvement of
lactose digestion in a previously intolerant child or adult is caused by
growth of lactose-digesting bacteria rather than an induction in activity
of the lactase enzyme.
Congenital lactase deficiency is an extremely rare autosomal recessive
disorder and is associated with a complete absence of lactase expression.
Childhood- and adult-onset lactase deficiency are extremely common and
inherited in an autosomal recessive manner, and persistent lactase
activity into adulthood is inherited in an autosomal dominant manner.
Transient lactase deficiency is due to damage of the intestinal mucosa by
an infectious, allergic, or inflammatory process and resolves once the
disease process is corrected and the intestinal mucosal healing restores
the brush border enzymes, such as lactase.
- In the US: Up to 22% of adult white Americans
experience lactase deficiency. The prevalence in other racial groups
parallels the country of racial origin. The frequency of lactase
deficiency in childhood is not well studied. Measurement of lactase
activity shows that the frequency of lactase deficiency in childhood is
about 60% of the adult frequency; however, symptomatic individuals
represent only about 50% of lactase-deficient individuals.
- Internationally: Adult-onset lactase deficiency
varies widely among countries. Northern Europeans have the lowest
prevalence at approximately 5%. Central Europeans have a slightly higher
prevalence at approximately 30%, and Southern Europeans have a much
higher prevalence at approximately 70%. The Hispanic and Jewish
populations also have a high prevalence at approximately 70%, while
Northern Indians have a much lower prevalence than the Southern Indians,
at approximately 25% and 65%, respectively. Almost all (90%) Asians and
Africans are affected.
Mortality/Morbidity: Usually, very little morbidity is
associated with lactase deficiency. Transient lactase deficiency affects a
significant number of infants with severe gastroenteritis and diarrhea.
Improper early feeding with lactose-based products without the recognition
of lactose malabsorption can lead to chronic diarrhea and malnutrition.
Race: See International Frequency.
- Lactase activity in the fetal intestine progressively increases
through the third trimester and approaches maximum expression at term.
Preterm infants have diminished levels of lactase. Few infants born at
28 weeks? gestation have significant intestinal lactase activity,
whereas approximately 40% of infants born at 34 weeks? gestation
demonstrate significant intestinal lactase activity. The premature
neonatal period is the only time in which lactase enzyme production and
expression can be induced. Because congenital lactase deficiency is very
rare, diagnoses such as milk-protein allergy should be considered in an
infant with symptoms of milk or milk-based formula intolerance. Neonatal
lactose intolerance is an exceedingly rare disorder; patients present
with severe systemic symptoms upon ingesting lactose-containing formula
or breast milk, and it resolves after the age of 6 months.
- Lactase activity is genetically programmed to decline at the age of
2 years. Signs and symptoms usually do not become apparent until after
the age of 6 years and may not be apparent until adulthood, depending on
dietary lactase intake and rate of decline of intestinal lactase
activity. Lactase enzyme activity is highly correlated with age,
regardless of symptoms.
- Secondary lactase deficiency due to intestinal mucosal injury can
appear at any age; however, children younger than 2 years are very
susceptible because of many factors, including a high sensitivity of the
gut to infectious agents, low reserve because of the small intestinal
surface area, and high reliance on milk-based products for nutrition.
- Gastrointestinal symptoms
- Bloating, abdominal pain, meteorism, and flatulence that occur
from 1 to several hours after ingestion of milk or dairy products may
signify lactose intolerance; however, other disorders such as
milk-protein sensitivity, allergic-type reactions to other substances
in the meal, or other saccharide intolerance may cause similar
- Approximately 240 cc of milk per day (12 g lactose) is rarely
enough to cause symptoms.
- Recurrent abdominal pain of childhood and irritable bowel syndrome
can mimic the symptoms of lactose intolerance and vice
- The rate of gastric emptying is important in the development of
symptoms, which may develop if lactose moves quickly to an intestine
low in lactase. Fats decrease the rate of gastric emptying, whereas
carbohydrates increase the rate of gastric emptying. Thus, if daily
products containing lactose are ingested with carbohydrates,
especially simple carbohydrates, symptoms are more likely.
- Allergies to other foods, particularly grains and proteins, can
mimic lactose intolerance.
- Milk protein allergy may also produce similar symptoms.
- Inflammation of the intestinal mucosa as a result of allergic or
protein-sensitive enteritis causes secondary lactose intolerance,
which can make diagnosis difficult in some cases.
- Stool characteristics: Loose watery stool often with excessive
flatus and associated with urgency that occurs several hours after the
ingestion of lactose-containing substances is typical.
- Gastroenteritis: Infectious diarrhea, particularly viral
gastroenteritis in younger children, damages the intestinal mucosa
enough to reduce the quantity of the lactase enzyme. Continued feeding
with lactose-containing products worsens and prolongs the course of the
diarrhea. Instituting a lactose-free diet during moderate-to-severe
gastroenteritis until the diarrhea has resolved is appropriate.
Breastfeeding can usually be continued after a bout of
- Food avoidance: Many people with lactose intolerance avoid products
that contain lactose.
- Failure to thrive and malnutrition (rarely observed)
- Abdominal pain: Nonspecific nonfocal abdominal pain and cramping are
common and sometimes associated with bloating and flatus. This pain may
mildly increase with palpation. Focal abdominal pain significantly
worsened by palpation, the presence of rebound tenderness, or guarding
should alert the clinician to a more serious and possibly surgical
- Borborygmi: A significant increase in peristaltic activity in the
small bowel can cause an audible or palpable increase in bowel
- Lactose intolerance: This is caused by a low or absent activity of
the enzyme lactase.
- Adult-onset lactose intolerance
- This deficiency results from an unusual mechanism involving a
developmentally regulated change of the lactase gene product,
resulting in a reduced synthesis of the precursor protein.
- Differences in the rate of gene transcription accounts for much of
the differences in lactose intolerance observed among racial
- Low lactase activity in the small intestine: This allows undigested
lactose to pass into the colon. In the colon, bacteria ferment the sugar
to hydrogen gas and organic acids. The gas produces distention of the
bowel, creating the sensation of bloating, cramping, and abdominal pain.
Organic acids can be absorbed, but the quantity produced is rarely large
enough to cause systemic symptoms or metabolic acidosis.
- Reducing substances in the stool indicate that carbohydrates are
not being absorbed. One common mistake, especially with
super-absorbent diapers, is to test the solid portion of the stool
instead of the liquid portion.
- Acidic stool is defined by a pH less than 5.5. This is an
indication of likely carbohydrate malabsorption, even in the absence
of reducing substances.
- Dietary elimination: Resolution of diarrhea and symptoms when a
suspected substance is removed from the diet, as well as resumption of
the diarrhea and symptoms when the substance is reintroduced are very
suggestive signs of intolerance. Lack of diarrhea resolution when a
substance is removed from the diet does not necessarily indicate
tolerance. Malabsorption of one dietary component can result in diarrhea
and subsequent malabsorption of other dietary components; thus, the
sensitivity of this procedure can be low. Conversely, resolution of
symptoms upon withdrawal of lactose-containing foods from the diet may
not confirm lactose intolerance. For instance, in the case of milk
products, a patient can be sensitive to the milk proteins, and symptoms
of such allergy resolve once the milk or milk product is withdrawn from
- Lactose tolerance test: Challenge the patient with 2 g/kg up to 50 g
of lactose after a fast. If blood glucose does not increase more than 20
mg/dL and symptoms develop, a diagnosis of lactose intolerance is
likely. However, this test uses a supraphysiologic dose of lactose,
which makes its generalization to normal milk or dairy ingestion
- Carbohydrate malabsorption results in bacterial fermentation of
the unabsorbed sugar. This biochemical process releases hydrogen gas
that is absorbed into the blood and excreted by the lungs. In the
absence of hydrolysis of lactose into its component monosaccharide
sugars, galactose and glucose, lactose cannot be absorbed and passes
into the large intestine. Thus, carbohydrate malabsorption can be
determined by measuring the exhaled hydrogen concentration after a
carbohydrate load is administered. Under normal conditions, the
fermenting bacteria reside only in the large intestine. When bacterial
overgrowth in the small intestine occurs, upper small bowel
fermentation of ingested but nonhydrolyzed lactose occurs and causes
an early rise in the exhaled hydrogen concentration. Under such
conditions, an additional later rise in exhaled hydrogen occurs during
large bowel fermentation.
- Antibiotic administration may cause falsely negative results of
this test. For diagnosis of lactose intolerance, 0.5-1.0 g/kg to 12-25
g of lactose is administered and an increase greater than 20 ppm of
H2 is diagnostic.
- When diagnosis is difficult to determine by the above tests, a
small intestinal mucosal biopsy can be easily obtained by endoscopy
for direct assay of lactase activity as well as that of other brush
- The presence of small intestinal mucosal injury can also be
assessed as a possible cause of secondary lactase
- Lactase: This can only be induced by lactose during the newborn
period. Studies demonstrate the utility of inducing lactase activity by
tube feedings with milk containing lactose in premature infants. Early
initiation of half-strength lactose-containing formula or breast milk
results in rapid induction of lactase activity in the brush border and
less feeding intolerance. A recent study suggests that full-strength
lactose formula resulted in more feeding intolerance than low-lactose
formula in premature infants; thus, the precise lactose concentration of
lactose for inducing lactase activity is still undetermined.
- Lactose intolerance: This can be improved by dietary manipulation.
If the quantity of lactose is increased slowly over time, lactobacilli
are stimulated to grow in the colon. A greater number of lactobacilli
allow the lactose to break down into monosaccharides. Although this
allows much of the sugar to be absorbed, some of the resulting
monosaccharides are still fermented by colonic bacteria; however, the
relative amount of colonic fermentation is decreased. Increasing lactose
intake to 1 L/d over 6-14 months has demonstrated some success. Because
some sugar is still fermented in the colon, this adapted system of
digestion is tenuous. Not overwhelming the gut with a high lactose load
is still important.
- Lactase derived from yeast can be added to milk products as drops
or ingested as chewable tablets prior to ingestion of
lactose-containing substances. Studies demonstrate varying success.
Digestive supplementations apparently are limited in their ability to
digest large quantities of lactose.
- Yogurt with live cultures is generally well tolerated by
lactose-intolerant individuals. Dairy products with reduced or no
lactose are widely available.
Consultations: Consultation with a gastroenterologist
is suggested if the patient has symptoms that do not resolve after dietary
elimination of lactose or if the patient has severe symptoms.
Diet: Lactose is believed to enhance the absorption of
several minerals, including calcium, magnesium, and zinc. In addition,
milk products that contain a large amount of lactose also contain a high
amount of calcium. Because calcium is extremely important in bone growth,
children can quickly become deficient if adequate calcium intake is not
maintained; thus, calcium supplementation is required in anyone restricted
from dairy products.
- Failure to recognize transient lactose intolerance in a young child
can lead to chronic diarrhea and bloating, which interferes further with
adequate nutritional intake, leading to weight loss. Severe cases may
lead to malnutrition and failure to thrive.
- Milk is the primary source of calcium for children.
Lactose-intolerant children who do not ingest proper quantities of dairy
products quickly become depleted of calcium, placing them at risk for
rickets and osteomalacia. Calcium supplementation, through dietary or
pharmacological supplements, is suggested for any child who does not
receive adequate calcium.
- Lower calcium levels are found in lactose-intolerant individuals;
thus, emphasizing the importance of calcium supplementation is
- Educate the patient about the following foods that contain hidden
- Some over-the-counter drugs can reduce symptoms (eg, simethicone for
relief of flatulence, exogenous lactase drops or tablets derived from