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Overview of nutrient absorption and etiopathogenesis of malabsorption

Overview of nutrient absorption and etiopathogenesis of malabsorption
Author:
Joel B Mason, MD
Section Editor:
David Seres, MD
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF
Literature review current through: Dec 2022. | This topic last updated: Sep 01, 2021.

INTRODUCTION — There are many interdependent steps by which dietary fats, carbohydrates, proteins, vitamins, minerals, and trace elements are assimilated by the intestine into the systemic circulation, a collection of processes generally called intestinal absorption. This topic will review the mechanisms of intestinal absorption and conditions leading to malabsorption. The clinical features, diagnosis, and treatment of malabsorption are discussed separately. (See "Approach to the adult patient with suspected malabsorption" and "Overview of the treatment of malabsorption in adults".)

TERMINOLOGY

Definitions

Malabsorption refers to impaired absorption of nutrients [1].

Maldigestion refers to impaired digestion of nutrients within the intestinal lumen (eg, exocrine pancreatic insufficiency) or at the terminal digestive site of the brush border membrane of mucosal epithelial cells (eg, lactose maldigestion).

Although malabsorption and maldigestion are pathophysiologically different, the processes underlying digestion and absorption are interdependent, so that in clinical practice, the term malabsorption has come to denote derangements in either process. The term "malabsorption," as used in the remainder of this topic, refers to its more generic meaning (unless specifically designated otherwise).

Classification — Malabsorption may either be global or selective (isolated).

Global malabsorption – Global malabsorption results from diseases associated with either diffuse mucosal involvement or a reduced absorptive surface. An example is celiac sprue, in which diffuse mucosal disease can lead to impaired absorption of almost all nutrients.

Selective malabsorption – Selective or isolated malabsorption results from diseases that interfere with the absorption of specific nutrients. An example is pernicious anemia, a disease that leads to defective cobalamin (vitamin B12) absorption.

Primary, or congenital, malabsorption – Malabsorption results from congenital defects in the membrane transport systems of the intestinal epithelium.

Acquired malabsorption – Malabsorption results from acquired defects (eg, Crohn disease, celiac disease, or after extensive surgical resection or intestinal bypass operations) in the epithelial absorptive surface.

ETIOPATHOGENESIS OF MALABSORPTION — Three steps are required for normal nutrient absorption [2]:

Luminal processing

Absorption into the intestinal mucosa

Transport into the circulation

Malabsorption can result from defects in any of these three phases (table 1) [3]. Furthermore, one or more mechanisms may exist concurrently. Thus, while the clinical sequelae may be the same, the underlying pathophysiology and treatment may be different.

Fat

Mechanism of fat digestion and absorption — Most dietary lipids are absorbed in the proximal two-thirds of the jejunum. Absorption is influenced by several factors, including the types of dietary lipids consumed and the presence of other ingested nutrients. In normal children and adults, more than 94 percent of dietary fat is absorbed, although healthy neonates may absorb as little as 85 percent. As a result, on a diet containing 100 grams of fat per day in all but neonates, the presence of >6 grams of fecal fat in a 24-hour collection indicates fat malabsorption.

Central to the mechanism of fat absorption is the problem of solubilizing lipids in an aqueous environment. The process begins by the generation of a suspension of fat in water, known as an emulsion. Dietary lipids, consisting mostly of triglycerides, must be emulsified to expose a large surface area to lipolytic enzymes. Emulsification begins in the upper gastrointestinal tract through mastication and gastric mixing. Fat droplets released by these mechanical means are coated with phospholipids to form a stable emulsion. Ingested phospholipids (mostly phosphatidylcholine) exist in a ratio to triglycerides of approximately 1:30, which is adequate for coating. Additional phospholipid from bile is added once the emulsion reaches the duodenum.

Fat hydrolysis begins in the stomach by the actions of lingual lipase, which is secreted from von Ebner's glands near the circumvallate papillae, and gastric lipase. In adults, lingual lipase is much less important than in newborns, in whom it contributes to as much as 50 percent of lipid hydrolysis. The lipid emulsion enters the duodenum and is exposed to pancreatic lipase, which enzymatically degrades each triglyceride molecule into a 2-monoglyceride and two fatty acids. Optimizing the activity of pancreatic lipase depends upon the presence of another enzyme, colipase, which appears to anchor lipase to triglyceride droplets and prevent bile salts from deactivating lipase. Free fatty acids released by gastric lipolysis contribute to stimulating the secretion of pancreatic lipase and colipase. Pancreatic lipase and colipase are responsible for the majority of lipid hydrolysis. Two other factors optimize the effect of these pancreatic enzymes:

The entry of gastric hydrogen ions into the duodenum stimulates the release of secretin, which enhances pancreatic bicarbonate secretion. This raises the intraluminal pH to approximately 6.5, which is optimal for fat digestion. Diseases that substantially decrease duodenal pH, such as Zollinger-Ellison syndrome, can selectively inhibit fat absorption.

Bile salts further enhance fat solubilization, producing an emulsion of microscopic micelles consisting predominantly of fatty acids, 2-monoglycerides, cholesterol esters, and some diglycerides coated by phospholipid.

Dietary and biliary phospholipids and cholesterol are further hydrolyzed by the action of phospholipase A2 and pancreatic cholesterol esterase.

The resulting mixture is a complex soup of lipolytic products. These products, along with other lipids and fat soluble vitamins, are mixed with bile salts, forming small aggregates known as micelles or larger aggregates known as liposomes. In this form, 2-monoglycerides and fatty acids readily enter the unstirred water layer that lies adjacent to the enterocyte and are then absorbed across the apical membrane of the cell. The bile salts themselves remain in the intestinal lumen, eventually reaching the terminal ileum where they are actively resorbed, enter the portal circulation, and are then re-secreted into bile. This cycle is known as the enterohepatic circulation.

Although the absorption of fatty acids was once believed to occur entirely by passive diffusion, more recent evidence indicates that protein-mediated transport processes also contribute. Several proteins that have been implicated are fatty acid transport protein 4, CD36, SR-B1, and caveolin-1. The precise roles played by each of these proteins have yet to be fully understood [4,5].

Once within villus absorptive cells, fatty acids are transported intracellularly to the smooth endoplasmic reticulum where triglycerides are resynthesized by a series of acyltransferase enzymes. Triglycerides, cholesterol esters, phospholipid, and apoprotein B48 form an aggregate, which is then transferred to the Golgi for further processing into a fully mature chylomicron, which then binds to the basolateral membrane and is transported to the intestinal lymphatics to enter the general circulation [6]. Not all of the triglyceride re-synthesized in the endoplasmic reticulum is used to synthesize chylomicrons; some is trafficked into the cytoplasm and synthesized into cytoplasmic lipid droplets, which appear to serve both storage and metabolic functions [7].

Causes of fat malabsorption — Disturbances in any of the steps in fat assimilation can lead to fat malabsorption and steatorrhea (table 1). (See 'Mechanism of fat digestion and absorption' above.)

Small intestinal disease/resection – Small bowel disease, or resection, of greater than 100 cm of terminal ileum commonly results in severe impairment of the enterohepatic circulation of bile salts such that the liver's ability to upregulate de novo bile acid synthesis is inadequate to meet normal physiological needs for bile production, resulting in fat malabsorption.

Loss of shorter segments of the terminal ileum may still result in chronic diarrhea, even though it may not result in fat malabsorption, since the bile acids that are not absorbed in the small intestine may stimulate water and electrolyte secretion in the colon (which is called "cholerrheic diarrhea"). Bile acid diarrhea must be differentiated from fatty acid malabsorption as bile salt binders (eg, cholestyramine) can improve bile acid diarrhea but may worsen diarrhea due to increased fatty acid malabsorption.

Small intestinal bacterial overgrowth – Deconjugation of bile acids by florid small bowel bacterial overgrowth defunctionalizes the bile acids, and can also result in fat malabsorption. (See "Small intestinal bacterial overgrowth: Etiology and pathogenesis", section on 'Pathophysiology'.)

A much milder form of bacterial overgrowth often accompanies atrophic gastritis or the use of proton pump inhibitor (PPI) drugs, but this condition does not typically result in fat malabsorption. However, sustained administration of PPIs (and to a lesser degree, histamine H2 receptor antagonists) does interfere with the absorption of vitamin B12, sometimes to a degree sufficient to generate a clinically-significant deficiency syndrome [8]. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Vitamin B12 malabsorption'.)

Pancreatic exocrine insufficiency – Impaired production of pancreatic lipase, colipase, and bicarbonate of a degree significant enough to cause fat malabsorption may occur in patients with chronic pancreatitis and pancreatectomy. Other disorders associated with fat malabsorption in childhood include cystic fibrosis and Schwachman syndrome. Acidification of the duodenal contents due to Zollinger-Ellison syndrome can inactivate pancreatic lipase, creating a functional deficiency of the enzyme. (See "Cystic fibrosis: Clinical manifestations and diagnosis" and "Shwachman-Diamond syndrome", section on 'Pancreatic dysfunction'.)

Disorders of bile acid metabolism Inadequate synthesis (eg, cirrhosis) or secretion of bile salts (eg, cholestasis) can result in fat malabsorption due to inadequate micelle formation [9]. However, fat malabsorption is usually mild and weight loss is usually multifactorial. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)

Other causes – Inadequate synthesis or defective structure of apoproteins necessary for the packaging of chylomicrons (eg, abetalipoproteinemia) impairs their secretion into the lymphatics, or abnormalities in lymphatic flow (eg, intestinal lymphangiectasia) will impair their ability to reach the systemic circulation. (See "Protein-losing gastroenteropathy", section on 'Diseases with lymphatic obstruction/altered lymphatic flow' and "Low LDL-cholesterol: Etiologies and approach to evaluation", section on 'Abetalipoproteinemia'.)

Carbohydrate

Mechanism of carbohydrate digestion and absorption — Starch, sucrose, and lactose are the most abundant digestible carbohydrates in the human diet. Dietary starch and disaccharides must be broken down into their constituent monosaccharides prior to absorption (figure 1). Some plant polysaccharides, such as cellulose, cannot be digested in the small intestinal lumen, although they are fermented, to a degree, in the colon.

Dietary starch consists of the two principal polysaccharides: amylose and amylopectin. Both salivary and pancreatic amylase contribute to their digestion. The products of digestion by amylase are oligo- and disaccharides that are then further degraded at the level of the microvillus membrane. At this site, brush border enzymes (primarily disaccharidases) hydrolyze both digested and ingested oligo- and disaccharides into monosaccharides, which can be absorbed by either active or passive transport processes.

Carbohydrates that are not digested and absorbed in the small intestine undergo bacterial degradation in the colon [10-15]. The terminal phase of bacterial carbohydrate degradation is fermentation, which results in the formation of short-chain fatty acids (butyrate, propionate, acetate, lactate), as well as carbon dioxide, hydrogen, and methane. Excessive bacterial fermentation is the reason for acidic stools, abdominal distension, and flatulence in patients with the various forms of carbohydrate malabsorption.

Short-chain fatty acids are available as an additional energy source, as they are efficiently absorbed from the colon, and are a preferred energy source for colonic epithelial cells. This allows the body to recover a portion of the potential energy contained within indigestible food fiber and other undigested carbohydrates.

The production of hydrogen and methane, resulting from the fermentation of unabsorbed carbohydrates, and their subsequent excretion through the lungs constitutes the basis of a number of noninvasive breath tests designed to look for malabsorption of particular carbohydrates. The most common of these tests is the lactose breath test, which accurately defines those who are deficient in lactase [16]. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management", section on 'Malabsorption testing by hydrogen breath test'.)

Causes of carbohydrate malabsorption — Impaired absorption of carbohydrates may result from (table 1):

Deficiency in pancreatic amylase

Reduced disaccharidase activity in the small intestinal epithelium

Decreased absorptive intestinal surface area (eg, celiac disease)

Unabsorbable carbohydrates (eg, sorbitol)

In primary carbohydrate malabsorption, single functional elements of carbohydrate digestion or absorption are missing, such as in congenital lactase deficiency and sucrase-isomaltase deficiency. The latter is far less common than the former, although should not be overlooked since it may masquerade as irritable bowel syndrome [17].

Unabsorbed carbohydrate provides a substrate for bacterial fermentation (causing gas) and additional physiological consequences, which may include an increased osmotic load, alterations in gastrointestinal motility, and a change in the profile of the bacterial flora, conspiring to create the symptoms associated with carbohydrate malabsorption.

With the rising use of fructose as a sweetener in commercially prepared foods, often as high-fructose corn syrup, concern about fructose intolerance has emerged, although the clinical syndrome remains a matter of controversy. Some individuals seem to develop symptoms of carbohydrate malabsorption when sufficiently large quantities of fructose are consumed, particularly if the fructose is in a form other than as one of the monosaccharide components of sucrose. Primary fructose malabsorption results from defects in the fructose transporter (GLUT-5).

Up to one-half of the population cannot completely absorb a load of 25 g of fructose while daily intake varies from about 11 to 54 g per day [10,11,13-15,18]. In a study of healthy volunteers, 10 percent had positive breath test results after consuming 25 g of fructose while 80 percent had positive results with a 50 g load [15].

Dietary fructose is consumed in two forms (as a monosaccharide and as a disaccharide), since it is a component of the disaccharide, sucrose (glucose-fructose). For reasons that are incompletely understood, fructose absorption from sucrose is greater than the absorption of fructose as a monosaccharide [14].

The ability to absorb fructose (even in those with malabsorption) depends not only upon the amount of fructose consumed, but the presence of other sugars ingested with it. Concomitant ingestion of glucose, galactose, and some amino acids increases fructose absorption, while sorbitol decreases it [14,19]. These observations have implications for dietary recommendations in patients in whom fructose malabsorption is suspected, since foods that contain fructose may be well tolerated if they also contain glucose but may be less well tolerated if they also contain sorbitol (although sorbitol itself can cause diarrhea).

There are two commercially used forms of high fructose corn syrup (HFCS), one that contains approximately 42 percent and the other approximately 55 percent fructose (HFCS-55). The other main ingredient is glucose. For example, a 12-ounce soda containing HFCS-55 has about 22 g of fructose and 17 g of glucose providing an excess of only 5 g of fructose per can, an amount that can be absorbed completely in most healthy individuals. Thus, despite an abundance of fructose, HFCS may not be a major culprit in causing symptoms in individuals with fructose malabsorption (provided that its ingestion is modest) since it also contains similar amounts of glucose. (See "Overview of the treatment of malabsorption in adults".)

Protein

Mechanism of protein digestion and absorption — Protein digestion begins in the stomach by the action of gastric pepsins, which are released as proenzymes (pepsinogen 1 and 2), and undergo autoactivation at low pH. The amount of proteolysis achieved by gastric pepsins depends upon the composition of other dietary constituents, gastric motility, and pH. The observation that patients who are achlorhydric or who have rapid gastric transit can still digest proteins suggests that proteolysis within the stomach is not essential for protein digestion. However, amino acids released from gastric digestion play a role in releasing cholecystokinin (CCK) from duodenal and jejunal endocrine epithelial cells. CCK is critical for stimulating the release of pancreatic enzymes responsible for the digestion of all three macronutrients.

In the duodenum, several proteases act together to digest proteins into amino acids, or dipeptides and tripeptides. Like gastric pepsinogens, pancreatic enzymes are secreted as inactive proenzymes, which are activated by hydrolysis of a peptide bond. Central to this process is enterokinase, which is released from the microvillus membrane of duodenal absorptive cells by the action of bile salts. Enterokinase converts trypsinogen to trypsin, which then catalyzes the conversion of all other pancreatic proteases to their active forms, as well as auto-catalyzing the activation of additional trypsinogen.

Following pancreatic enzyme digestion, amino acids, dipeptides, and tripeptides can be absorbed through highly efficient sodium-dependent amino acid co-transporters at the brush border membrane; this step is passive but is called secondary active transport since the energy is indirectly provided by the sodium-potassium ATPase pump. By maintaining a low intracellular sodium concentration and a cell interior negative potential, the pump provides a strong inward gradient for sodium entry which can drive the absorption of amino acids.

Different classes of amino acid transporters exist on the brush border, as evidenced by selectivity expressed for neutral, basic, and acidic amino acids. Transporters for dipeptides and tripeptides are also distinct from those responsible for free amino acid transport. Additional peptidases are located within the brush border membrane and the cytoplasm of absorptive cells.

Causes of protein malabsorption — Impaired digestion and absorption of dietary protein occurs when pancreatic bicarbonate and protease secretion and/or activity is impaired, as in chronic pancreatitis or cystic fibrosis. Protein malabsorption can also occur in diseases associated with a generalized reduction of the intestinal absorptive surface.

Vitamins, minerals, and trace elements — Vitamins and minerals represent a wide array of compounds, possessing an equally wide array of biochemical properties [20]. It is therefore not surprising that the intestine has many types of transport mechanisms to facilitate assimilation of these nutrients across the intestinal barrier.

The proximal half of the small intestine is the predominant site for the absorption of most vitamins and minerals. Notable exceptions include vitamin B12, which is absorbed by a specific ileal receptor that recognizes the B12-intrinsic factor complex, and magnesium, which is primarily absorbed in the distal small intestine and colon.  

Calcium, iron and folate (vitamin B9) are predominantly absorbed in the upper small intestine, and deficiencies are a common consequence of expanded proximal small bowel resections. Malabsorption of calcium may be particularly severe because absorption is further hampered by the binding of calcium to malabsorbed fatty acids and by vitamin D deficiency. In contrast, the specific uptake mechanisms allowing absorption of vitamin B12 and of bile acids are limited to the terminal ileum so that deficiencies are to be expected in patients with distal small bowel resections; typically, a resection of >100 cms of distal ileum will result in clinically-significant vitamin B12 deficiency. The mechanism responsible for the intestinal absorption of magnesium remains ill-defined, but since it occurs most avidly in the distal intestine, including the colon, patients with distal small intestinal and colonic disease are particularly susceptible to hypomagnesemia. (See "Causes and pathophysiology of vitamin B12 and folate deficiencies", section on 'Small intestinal inflammation or surgery' and "Hypomagnesemia: Causes of hypomagnesemia".)

Some nutrients, such as the carotenoids, appear to be absorbed solely by passive diffusion, while others are absorbed by carrier-mediated, non-energy requiring processes, and some by active transport systems (ie, energy-requiring transporters that can work against a chemical gradient), such as folate and calcium. The type of transport varies in different portions of the small intestine for many micronutrients.

The avidity with which some nutrients are absorbed in the intestine is regulated by the nutritional status of the individual in regard to the specific nutrient. Examples include calcium, for which the upregulation of transport appears to be primarily a vitamin D-mediated process, and inorganic (ie, non-heme) iron absorption, for which systemic iron deficiency causes a remarkable increase in the efficiency of iron absorption.

A more detailed discussion of the transport mechanisms for each nutrient is beyond the scope of this discussion but a few general remarks can be made that have implications in regard to the clinical management of malabsorption:

Causes of malabsorption — The number of surgeries done to correct obesity continues to rise, underscoring the need to appreciate nutrient deficiencies that commonly accompany the resulting weight loss [21]. Roux-en-Y gastric bypass is presently the most common procedure of this type performed in the United States. In addition to discouraging the intake of food, this surgical procedure produces mild fat malabsorption of a multifactorial nature. Vitamin B12, iron, calcium, and vitamin D deficiencies are commonly observed. In the weeks to months immediately following such surgery, especially when recurrent nausea and vomiting have ensued, there have been many reports of thiamin deficiency, with classical symptoms of beriberi. Copper and selenium deficiencies have less commonly been described as a late complication. Routine multivitamin/mineral supplementation is indicated, although it is frequently insufficient to prevent micronutrient deficiencies, so ongoing monitoring is indicated, and targeted supplementation with specific micronutrients may be required. (See "Late complications of bariatric surgical operations".)

Fat-soluble vitamins – The fat-soluble vitamins (A, D, E, and K) require solubilization in a mixed micellar phase in order to be absorbed. As a result, factors that adversely impact fat absorption will usually affect absorption of these vitamins in a parallel manner. (See 'Causes of fat malabsorption' above.)

The excess fatty acids present in the intestinal lumen of patients with untreated fat malabsorption bind to divalent cations, such as calcium and magnesium, creating soaps and causing undue losses of these minerals. Calcium depletion in this setting is further magnified if vitamin D deficiency is also present.

Vitamin B12 – Extensive ileal disease or resection decreases B12 absorption and often leads to a deficiency state. As a general rule, ileal disease or resection exceeding 100 cm is associated with a high risk of B12 deficiency. As mentioned above, this degree of ileal impairment is also associated with fat malabsorption and may thereby interfere with assimilation of fat-soluble vitamins. (See "Causes and pathophysiology of vitamin B12 and folate deficiencies", section on 'Disorders affecting absorption in the small intestine'.)

SUMMARY AND RECOMMENDATIONS

Malabsorption can result from defects in any of the three phases of nutrient absorption (table 1) (see 'Introduction' above):

Luminal processing

Absorption into the intestinal mucosa

Transport into the circulation

Disturbances in the steps in fat assimilation can lead to fat malabsorption and steatorrhea. These include impaired production or activity of pancreatic lipase, colipase, and bicarbonate, a large increase in gastric acid secretion which inactivates pancreatic enzymes (eg, gastrinoma), disorders of bile acid metabolism or bile secretion, a decrease in the absorptive surface area, or abnormalities in lymphatic flow. (See 'Fat' above.)

Impaired absorption of carbohydrates may result from a deficiency in pancreatic amylase, reduced disaccharidase activity in the small intestinal epithelium, or decreased absorptive intestinal surface area. In primary carbohydrate malabsorption, single functional elements of carbohydrate digestion or absorption are missing, such as in congenital lactase deficiency and sucrase-isomaltase deficiency. Acquired carbohydrate malabsorption most often occurs from diseases leading to a reduced intestinal absorptive area, such as celiac disease, or a genetically programmed loss of lactase later in life. (See 'Carbohydrate' above.)

Impaired digestion and absorption of dietary protein occurs when pancreatic protease secretion and/or activity is impaired, as in chronic pancreatitis or cystic fibrosis. Protein malabsorption can also occur in diseases associated with a generalized reduction of the intestinal absorptive surface. (See 'Protein' above.)

The fat-soluble vitamins (A, D, E, and K) require solubilization in a mixed micellar phase in order to be absorbed. As a result, factors that adversely impact on fat absorption will usually affect absorption of these vitamins in a parallel manner. (See 'Vitamins, minerals, and trace elements' above.)

The proximal half of the small intestine is the predominant site for the absorption of most vitamins and minerals. Notable exceptions are magnesium and vitamin B12, the latter of which is absorbed by a specific ileal receptor that recognizes the B12-intrinsic factor complex. Thus, extensive ileal disease or resection decreases B12 absorption and often leads to a deficiency state. As a general rule, ileal disease or resection exceeding 100 cm is associated with a high risk of B12 deficiency. This degree of ileal impairment is also associated with fat malabsorption and may thereby interfere with assimilation of fat-soluble vitamins. (See 'Vitamins, minerals, and trace elements' above.)

Excess fatty acids present in the intestinal lumen of patients with untreated fat malabsorption bind divalent cations, such as calcium and magnesium, creating soaps and causing undue losses of these minerals. Clinically significant deficiencies of these minerals are common in untreated fat malabsorption and create a substantial risk for metabolic bone disease. The problem of calcium depletion in this setting will be further magnified if vitamin D deficiency is also present. (See 'Vitamins, minerals, and trace elements' above.)

  1. Hogenauer C, Hammer HF. Maldigestion and Malabsorption. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 10th ed, Feldman M, Friedman LS, Brandt LJ (Eds), Saunders, Philadelphia 2016. p.1788.
  2. Farrell JJ. Digestion and absorption of nutrients and vitamins. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 9th ed, Feldman M, Friedman L, Brandt L (Eds), Saunders, Philadelphia, PA 2010. p.1695.
  3. Shim J, Moulson CL, Newberry EP, et al. Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice. J Lipid Res 2009; 50:491.
  4. Cifarelli V, Abumrad NA. Intestinal CD36 and Other Key Proteins of Lipid Utilization: Role in Absorption and Gut Homeostasis. Compr Physiol 2018; 8:493.
  5. Siddiqi S, Sheth A, Patel F, et al. Intestinal caveolin-1 is important for dietary fatty acid absorption. Biochim Biophys Acta 2013; 1831:1311.
  6. Mansbach CM, Siddiqi SA. The biogenesis of chylomicrons. Annu Rev Physiol 2010; 72:315.
  7. D'Aquila T, Hung YH, Carreiro A, Buhman KK. Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes. Biochim Biophys Acta 2016; 1861:730.
  8. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013; 310:2435.
  9. Camilleri M, Vijayvargiya P. The Role of Bile Acids in Chronic Diarrhea. Am J Gastroenterol 2020; 115:1596.
  10. Gibson PR, Newnham E, Barrett JS, et al. Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 2007; 25:349.
  11. Choi YK, Johlin FC Jr, Summers RW, et al. Fructose intolerance: an under-recognized problem. Am J Gastroenterol 2003; 98:1348.
  12. Ravich WJ, Bayless TM, Thomas M. Fructose: incomplete intestinal absorption in humans. Gastroenterology 1983; 84:26.
  13. Nelis GF, Vermeeren MA, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology 1990; 99:1016.
  14. Skoog SM, Bharucha AE. Dietary fructose and gastrointestinal symptoms: a review. Am J Gastroenterol 2004; 99:2046.
  15. Rao SS, Attaluri A, Anderson L, Stumbo P. Ability of the normal human small intestine to absorb fructose: evaluation by breath testing. Clin Gastroenterol Hepatol 2007; 5:959.
  16. Abumrad N, Nassir F, Marcus A. Digestion and Absorption of Dietary Fat, Carbohydrate, and Protein. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 10th ed, Feldman M, Friedman LS, Brandt LJ (Eds), Saunders, Philadelphia 2016. p.1736.
  17. Kim SB, Calmet FH, Garrido J, et al. Sucrase-Isomaltase Deficiency as a Potential Masquerader in Irritable Bowel Syndrome. Dig Dis Sci 2020; 65:534.
  18. Rumessen JJ, Gudmand-Høyer E. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 1988; 95:694.
  19. Rumessen JJ, Gudmand-Høyer E. Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Gut 1986; 27:1161.
  20. Said H, Trebble T. Intestinal Digestion and Absorption of Micronutrients. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 10th ed, Feldman M, Friedman LS, Brandt LJ (Eds), Saunders, Philadelphia 2016. p.1765.
  21. Saltzman E, Karl JP. Nutrient deficiencies after gastric bypass surgery. Annu Rev Nutr 2013; 33:183.
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