Lactose: structure, digestion, intolerance and symptoms

Lactose is the specific sugar of the milk and, with starch and sucrose, it is one of the three most common carbohydrates taken up with diet.
It consists of one unit of galactose plus one of glucose linked together by β-(1→4) glycosidic bond, then it is a disaccharide. It has the molecular formula C12H22O11 and molar mass 342.30 g/mol.
Structural Formula, drawn in Haworth projection, of lactoseIt is synthesized almost exclusively in mammary glands of mammals (whales and hippos make exceptions) during suckling period by the proteic complex called lactose synthetase, formed by α-lactalbumin (a milk protein) plus galactosil transferase; the last one catalyzes the link of galactose to glucose present on α-lactalbumin.
It accounts respectively for 7.5% and 4.5% of the composition of woman and cow’s milk and provides about 40% of energy that newborn obtain from mother milk; in adulthood it represents 5%-10% of dietary carbohydrates.
It is less soluble than other disaccharides and has a sweetness equal to 16% of sucrose’s.
Its fermentation to lactic acid by bacteria is responsible for the souring of milk.


Lactose intolerance

Many mammals do not consume milk after the species-specific weaning phase.
Lactase (EC, under normal physiological conditions, is presents at birth in all subjects, being crucial for the digestion of lactose in maternal milk. Opposite, it was estimated that the vast majority of world’s population (and this is truth for the other mammals as well) has low capacity of expressing lactase activity after the weaning phase.
For example, if we consider Mediterranean populations, that generally don’t consume much milk after the weaning phase, a drastic decrease of lactase activity can be already observed in childhood, up to values of 90% than that present at birth (lactase deficiency in adulthood is defined as hypolactasia); among White North American the deficiency involves 5%-20% of population, among Black North American it reaches to 70%-75%, among Asians, Filipino reaches 95% and Thai, the main ethnic group of Thailand, 99% as in Africa (Nigeria) the Yoruba.
On the contrary e.g. Danish, in which the deficiency involves only 3% of population, but also some nomadic, milk-consuming populations present in the arid zone of Arabia and North Africa.

Primary hypolactasia

So, the decline in lactase activity during childhood or, for someone, during the second decade of life as well, is a condition that should be considered phylogenetically normal. This condition is called primary hypolactasia and is due not to a damage in the gene coding for lactase but in one coding for a regulatory protein.

Secondary hypolactasia

Hypolactasia may also be secondary to conditions as:

  • cow’s milk protein intolerance;
  • non celiac gluten sensitivity (NCGS);
  • active celiac disease;
  • infectious diarrheas.

In these conditions, many brush border proteins are affected and, between membrane glycosidases, lactase is that which undergoes to the most severe reduction.
Treatment of the primary cause resolves the secondary hypolactasia; in these cases it is advisable to abstain from consuming milk and lactose-containing foods until the primary cause of deficiency is resolved.

Congenital lactase deficiency

There are also conditions in which a congenital lactase deficiency is present, a character inherited in autosomal recessive mode, in which the gene product is absent or defective. This primary deficiency is very rare and occurs within the first day or days of life with diarrhea. In this condition the only thing to do is to follow a lactose-free diet.

Lactose intolerance manifests itself with:

  • abdominal distension;
  • audible bowel activity;
  • flatulence;
  • abdominal pain;
  • nausea;
  • irritable bowel syndrome;
  • osmotic diarrhea.

All conditions are due to the presence of indigested lactose in colonic lumen, that causes an osmotic effect, and to its fermentation by colonic bacteria (they are coliform bacteria, a group of aerobic bacteria able to fermenting the disaccharide, between which the most important is Escherichia Coli) with production of short-chain fatty acids, that acidify the colonic content, plus gas, e.g. hydrogen.
It should be noted that lactose intolerance, though uncomfortable, does not seem to damage the gastrointestinal tract or to lead to long term pathologies.

Lactose and myelin

Of the two monosaccharides forming sugar of the milk, glucose is a very important energy source for lifelong, while galactose is used by newborns and in the early childhood for the “construction” of glycoproteins and galactolipids (cerebrosides), a class of lipids, present in many tissues but, above all, in the myelin sheaths of nerve fibers.
When myelination of nerve fibers and growth are ended, also galactose need reduces itself very much; perhaps this may explain, from the physiological point of view, the reduced or absent ability of many populations to digest the disaccharide already in young age.
Note: lactose intolerance is the main food intolerance in humans.

As previously mentioned, a small minority of population, largely from North-European extraction, is able to express great amounts of lactase throughout life. It is thought that at the basis of this ability there is a genetic modification favorable to survivor that induced the absorption of the disaccharide from milk produced by their animals during the severe winter in North Europe. So the mutation would have allowed individuals to survive, transmitting the character to offspring, while the others would die.

Lactose and lactulose

Lactose, in alkali environment or, in a certain extent, afterwards to milk heating, may undergo an isomerization to lactulose, in which the glucose unit of the disaccharide is isomerizated to fructose.
The new disaccharide is neither digested nor absorbed and seems to promote the growth of Bifidobacterium and Lactobacillus species in the colon. Colonization of the colon by these bacteria is effective in prevention of acute diarrhea.
Short chain fatty acid production from lactulose and polysaccharide fibers causes a reduction in pH of colon and limits the potential growth of pathogenic bacteria species.

Intestinal digestion

The reaction that cleaves the sugar of the milk into its monosaccharides, galactose and glucose (β-(1→4)-glycosidic reaction), is catalyzed by an enzyme called lactase localized on the brush border membranes of enterocytes.


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Bender D.A. “Benders’ Dictionary of Nutrition and Food Technology”. 8th Edition. Woodhead Publishing. Oxford, 2006

Stipanuk M.H., Caudill M.A. Biochemical, physiological, and molecular aspects of human nutrition. 3rd Edition. Elsevier health sciences, 2012

Wanes D., Husein D.M., and Naim H.Y. Congenital lactase deficiency: mutations, functional and biochemical implications, and future perspectives. Nutrients 2019;11(2):461. doi:10.3390/nu11020461

Biochemistry, metabolism and nutrition