Starch, sucrose and lactose constitute the main carbohydrates in the human diet. All are inexpensive sources of food. Together they constitute the major source of calories when considered worldwide. People in the Western world consume about 400 g of carbohydrates daily: 60% as starch, 30% as sucrose and 10% as lactose (milk contains 48 g of lactose per liter).

Starch present in wheat, rice and corn is a polysaccharide whose molecular weight ranges from 100,000 to greater than 1,000,000. The straight chain of glucose molecules in starch is bridged by an oxygen molecule between the first carbon (C₁) of one glucose unit and the fourth carbon (C₄) of its neighbor (a1,4 glucose link). This type of starch is called amylose and makes up as much as 20% of the starch in the diet. The glucose-to-glucose bridge is of the alpha type - in contrast to the beta type, which connects glucose units in cellulose, an indigestible saccharide. The remaining 80% of the starch that humans ingest has a branch point every 25 molecules along the straight a1,4 glucose chain. This starch is called amylopectin. These branches occur via an oxygen bridge between C₆ of the glucose on the straight chain and C₁ in the branched chain (a1,6 branch points), which then continues as another a1,4 glucose-linked straight chain (Figure 9).

Salivary and pancreatic a-amylases act on interior a1,4 glucose-glucose links of starch but cannot attack a1,4 linkages close to a 1,6 branch point. The products of amylase digestion are therefore maltose and maltotriose. Since a-amylase cannot hydrolyze the 1,6 branching links and has relatively little specificity for 1,4 links adjacent to these branch points, large oligosaccharides containing five to nine glucose units and consisting of one or more 1,6 branching links are also produced by a-amylase action. These are called a-limit dextrins, and represent about 30% of amylopectin breakdown.

The responsibility for digesting the oligosaccharides, including a-limit dextrins, and the amylose and amylopectin rests with the hydrolytic enzymes on intestinal epithelial cells (Figure 10 and Figure 11). These hydrolytic enzymes are called disaccharidases, but most are in fact oligosaccharidases: they hydrolyze sugars containing three or more hexose units. They are present in highest concentration at the villous tips in the jejunum and persist throughout most of the ileum, but not in the colon. Lactase breaks down lactose into glucose and galactose. Glucoamylase (maltase) differs from pancreatic a-amylase since it sequentially removes a single glucose from the nonreducing end of a linear a1,4 glucose chain, breaking down maltose into glucose. Sucrase is a hybrid molecule consisting of two enzymes - one hydrolyzing sucrose and the other, the a1,6 branch points of the a-limit dextrins. This enzyme is commonly called sucrase-isomaltase, because the isomaltase moiety hydrolyzes isomaltose, the a1,6 glucosyl disaccharide. However, the only products containing a1,6 linkages after amylase action on starch are the a-limit dextrins. Thus no free isomaltose is presented to the intestinal surface and the term "isomaltase" is a misnomer. The sucrase moiety thus breaks down sucrose into glucose and fructose.

Humans normally are born with a full complement of brush-border-membrane disaccharidases. Intake of large amounts of sucrose results in an increase in sucrase activity, probably as the substrate stabilizes the enzyme and reduces its rate of breakdown. In contrast, there is no evidence that dietary manipulation can regulate the activities of human lactase or maltase.

Once the disaccharides are broken down, how are the monosaccharides absorbed? Sodium facilitates glucose uptake by binding to the brush-border membrane carrier (SGLT1) along with glucose. Since intracellular Na⁺ concentration is low, the Na⁺ ion moves down its concentration gradient into the cell, to be pumped out subsequently at the basolateral membrane by Na⁺/K⁺-ATPase, an active process that utilizes energy derived from the hydrolysis of ATP. The electrochemical gradient thus developed by Na⁺ provides the driving force for glucose entry. Glucose accompanies Na⁺ on the brush-border carrier and is released inside the cell, where its concentrations may exceed those in the intestinal lumen. Glucose then exits from the basolateral membrane of the cell into the portal system by a non-Na⁺-dependent carrier (GLUT2).

Fructose, released from the hydrolysis of sucrose, is transported by facilitated diffusion, a carrier-mediated process in the brush-border membrane (GLUT5) that is independent both of Na⁺ and of the glucose transport mechanism.

From these physiological considerations, carbohydrate malabsorption can occur in the following circumstances: (1) severe pancreatic insufficiency; (2) selective deficiencies of brush-border disaccharidases - e.g., lactase deficiency; (3) generalized impairment of brush-border and enterocyte function - e.g., celiac disease, tropical sprue, gastroenteritis; and (4) loss of mucosal surface area - e.g., the short bowel syndrome.

Although infants often have a deficiency of amylase, starch is not usually fed for the first few months of life. In the adult, there is a great excess of pancreatic amylase secreted into the intestinal lumen, so that even in patients with severe fat malabsorption due to pancreatic exocrine insufficiency, residual salivary and pancreatic amylase output appears to be sufficient to completely hydrolyze starch to the final oligosaccharides by the time a meal reaches the mid-jejunum. Hence, maldigestion of starch rarely, if ever, occurs in humans.

Secondary deficiency of disaccharidases results from anatomic injury of the small intestine, as in celiac disease, tropical sprue and gastroenteritis. When disaccharidase levels are sufficiently low, the particular oligosaccharide or disaccharide remains unhydrolyzed within the intestinal lumen and augments intraluminal fluid accumulation by virtue of its osmotic effect. Bacterial fermentation of disaccharides that reach the colon produces fatty acids (butyric, formic, acetic and propionic acids), alcohols and gases (H₂ and CO₂) (Figure 12). The benefits of this bacterial fermentation to the host are twofold. First, the bulk of the caloric value present in carbohydrates remains in the fermentative products. Reabsorption of fatty acids and alcohols in the colon "salvages" calories from malabsorbed carbohydrates. Second, this colonic "salvage" reduces the number of osmoles in the lumen and hence lessens the water lost in feces. During the fermentation of carbohydrates to organic acids, colonic bacteria liberate H₂ and CO₂ gas. In general, the passage of large quantities of rectal gas suggests that excessive carbohydrates are reaching the colon. (Remember your beer-drinking days!)

Primary (congenital) deficiencies of disaccharidases are unusual. Such entities can be differentiated from a secondary defect, since general tests of absorption and mucosal histology are normal; however, assay of an intestinal biopsy reveals the absence of hydrolytic activity for a single disaccharide. Lactase deficiency (even when secondary) is very common.