Pancreatic Exocrine Insufficiency Is Surprisingly Common

June 15, 2026 jbenson@innovisionhm.com Journal Article 0

Lara Pizzorno, MS (Nutrition), MA, LMT; Joseph Pizzorno, ND, Editor in Chief

 

Abstract

Once again, an old-time concept once dismissed has now been shown as valid with modern research. Natural health clinicians have long recognized that digestive disturbances greatly contribute to chronic disease. To the roles in maldigestion of hypochlorhydria and dysbiosis we can now add pancreatic exocrine insufficiency (EPI). At least 20% of the population aged >50 to 75 years with no diagnosed disease has EPI, with higher percentages found in those with disease, especially diabetes. This editorial explores the prevalence of EPI and its diagnosis, causes, and interventions.

Keywords: Pancreatic exocrine deficiency, Pancreas function, Pancreatic enzyme replacement therapy.

 

Lara Pizzorno, MS (Nutrition), MA, LMT, co-author of Healthy Bones, Healthy You and a prolific writer on bone health. Joseph Pizzorno, ND, Editor in Chief, IMCJ; co-author, Textbook of Natural Medicine; Founding President, Bastyr University; Founding Member, Board of Directors, Institute for Functional Medicine.

 

Introduction

Pancreatic exocrine deficiency has been a concept in our medicine for about a century. Conventional medicine has in the past dismissed this concept. Research is once again catching up to clinician observations, and this condition is now labeled pancreatic exocrine insufficiency (EPI). This concept, which is clinically very useful, is now well documented. A quick review of PubMed found more than 20 000 citations on EPI in the past 20 years. As discussed below, in older, apparently healthy adults >50 to 75 years of age, 11.5% to 21.7% had moderate EPI, and as many as 5.1% had severe EPI, documenting this condition as far more common than generally realized.

In this editorial we briefly review pancreatic exocrine function, describe how it is damaged, and discuss EPI diagnosis and interventions.

The Pancreas

The pancreas is perhaps best known for its endocrine role in which it produces insulin. Interestingly, endocrine tissue makes up only about 2% of this small organ. The pancreas’ alpha and beta cells, located in the islets of Langerhans, produce and release the 2 hormones that are responsible for maintaining healthy blood sugar levels: insulin and glucagon.

When blood sugar rises after eating, the pancreas secretes insulin. Insulin activates cell surface receptors that lets blood sugar enter for energy production. Insulin also helps build muscle by increasing muscle tissues’ absorption of amino acids. When excess energy is available, insulin stimulates the liver to convert excess carbohydrates, proteins, and fats into triglycerides, which are then packaged into very low-density lipoprotein cholesterol and released into the blood.

When blood sugar drops between meals, the pancreas, specifically the alpha cells in the islets of Langerhans, secretes glucagon, which directs the liver to break down glycogen to release glucose into the bloodstream.

Figure 1 provides a graphic of the pancreas showing its islets of Langerhans. As can be seen, its alpha, beta, and delta cells are intertwined and surrounded by the exocrine acinar cells. The less well known delta cells secrete somatostatin that stays in the pancreas and inhibits its production of insulin or glucagon as needed, helping maintain stable blood sugar levels.

 

Figure 1. The Pancreas1

 

When the pancreas’ endocrine system stops functioning properly, blood sugar remains high, causing damaging glycosylation and inflammation throughout the body, including in the pancreas itself. Excessive glycosylation causes multiple physiological dysfunctions by binding sugar to proteins, enzymes, organelles, and so on, creating advanced glycation end products. The commonly measured hemoglobin A1c is an example of a glycosylated molecule.

The primary focus of this editorial is on the pancreas’ exocrine role in which it produces digestive enzymes. Although the insulin-producing beta cells get all the attention, 90% to 95% of the pancreas is actually exocrine tissue. The acinar cells make digestive enzymes. Once generated, these enzymes migrate through ducts in the pancreas that join up with the common bile duct, which is formed from the joining of ducts from the liver and gallbladder and empties into the duodenum. These enzymes play a critical role in digestion of carbohydrates, proteins, and fats.

The pancreas produces 3 types of digestive enzymes: amylase (which breaks down carbohydrates into simple sugars); proteases, including trypsin, chymotrypsin, and elastase (which break down proteins into amino acids); and lipases (which break down dietary fats into triglycerides).

When functioning properly, the pancreas secretes 1.5 to 2.5 L of pancreatic juice containing 6 to 20 grams of digestive enzymes into the duodenum per day, including an average of 720 000 units of lipase per meal.2

Obviously, without adequate pancreatic exocrine function, digestion is greatly impaired. Although most people think this impairment relates only to inadequate breakdown and absorption of proteins, fats, and carbohydrates, we now know that many other nutrients are affected as well. Without adequate digestion, the absorption of nutrients such as vitamins, minerals, carotenoids, polyphenols, and terpenes is greatly reduced.

 Diagnosis of Pancreatic Exocrine Insufficiency

Diagnosis of EPI is made both clinically and with laboratory tests. Table 1 provides a list of the typical symptoms found in EPI. Table 2 lists common diseases associated with EPI. Table 3 lists drugs that contribute to EPI. The astute clinician will recognize that causes and signs and symptoms of pancreatitis and EPI overlap substantially.

Table 1. Common Symptoms of Pancreatic Exocrine Insufficiency3

GI symptoms

Gas and bloating.

Abdominal discomfort or pain, sometimes crampy or midepigastric and radiating to the back.

Diarrhea, often chronic.

Steatorrhea: greasy, oily, pale or gray, bulky, frothy, very foulsmelling stools that float or stick to the toilet and are hard to flush.

Excess flatulence and burping, sometimes severe meteorism/bloating.

More frequent bowel movements and urgency after eating.

Nutritional and systemic signs

Unexplained weight loss, poor weight gain, or failure to thrive in children.

Loss of muscle mass, sarcopenia, and reduced muscle function.

Signs of fatsoluble vitamin (A, D, E, K) deficiency: night vision problems, bone pain or low bone mass/osteoporosis, easy bruising, poor wound healing, higher infection rates, neurological symptoms, muscle weakness, fatigue.

 

Table 2. Conditions Commonly Associated With Pancreatic Exocrine Insufficiency4,a

Celiac disease

Crohn disease

Cystic fibrosis

Diabetes

Gallstones

Hemochromatosis

Inflammatory bowel disease

MASLD43

Pancreatic cancer

Small intestinal bacterial overgrowth

Surgery on the digestive tract, including weight loss surgery

Ulcerative colitis

aSee additional references in the discussion below.

Clinical Presentation

See table 1 for common symptoms of Pancreatic Exocrine Insufficiency.3

Laboratory Assessment

Fecal Elastase-1. Fecal elastase-1 (FE-1) is the most common first-line test for EPI.5 It measures the level of elastase in stool. FE-1 is a protease enzyme secreted by the pancreas into the duodenum that survives intestinal transit and is eliminated in stool. It serves as a surrogate measure of total pancreatic enzyme output. Interestingly, FE-1 is not affected by pancreatic enzyme replacement, an advantage that makes it a popular test in EPI screening. Although excellent for detecting advanced EPI, FE-1 is far less accurate in cases of mild EPI or in watery diarrhea, so a normal level (>200 µg/g stool) does not rule out mild EPI. For accuracy, the test should be performed on semisolid or solid stool. For mild to moderate cases of EPI, if the FE-1 test is inconclusive, an empirical trial of enzymes can be useful.

  • Normal: >200 µg/g stool
  • Moderate EPI: 100-200 µg/g stool
  • Severe EPI: <100 µg/g stool

 

The 2026 standards suggest routine FE-1 screening for all patients with diabetes, as EPI prevalence is estimated at approximately 11% in people with type 2 diabetes and 30% to 60% in people with type 1 diabetes.6

For more precise diagnosis, particularly in challenging cases, the 72-hour fecal fat test, aka the coefficient of fat absorption test, explained below, may be used.

Secondary/Confirmatory Tests. If FE-1 results are borderline but clinical suspicion remains high, additional tests may be used. The 13C-mixed triglyceride breath test is a noninvasive alternative that measures fat digestion directly. It is highly accurate (90%-100% sensitivity) but often has limited availability in standard clinics. The coefficient of fat absorption test (aka 72-hour fecal fat test) measures the percentage of dietary fat absorbed by the body, with a normal, healthy range typically being 93% or higher in adults. Values below 85% indicate significant fat malabsorption. To run this test, a diet providing 100 g of fat each day must be followed and stools collected for
72 hours. Results of more than 7 g/day typically indicate fat malabsorption.

Imaging

Imaging, such as computed tomography, magnetic resonance imaging and magnetic resonance cholangio-pancreatography, and endoscopic ultrasonography, cannot diagnose EPI but identifies underlying causes such as chronic pancreatitis, tumors, or calcifications.

 Causes

There are many causes of EPI, and this editorial cannot fully discuss them. We focus on some of the most common and addressable causes.

Drugs

Table 3 lists drugs that can cause or contribute to EPI. Clearly, many of these drugs are regularly used by the general population.

 

Table 3. Drugs That Can Cause Pancreatic Exocrine Insufficiency7-9

Alcohol, greater than 1 fl oz of ethanol for women and 2 fl oz for men per day

Proton pump inhibitors

Diuretics: thiazides (hydrochlorothiazide), furosemide (Lasix)

Blood pressure medications: angiotensin-converting enzyme inhibitors (lisinopril, enalapril), methyldopa, losartan

Lipid-lowering drugs: statins (simvastatin), bezafibrate, gemfibrozil

Acetaminophen

Glucagon-like peptide-1 agonists

Immunosuppressants/chemotherapeutics: azathioprine, 6-mercaptopurine, L-asparaginase

Hormones: estrogens (in birth control), corticosteroids

Antibiotics: tetracycline, sulfa drugs, metronidazole

Neurological drugs: valproic acid (Depakote)

Others: didanosine, carbamazepine, interferons, metformin

Alcohol. Consuming more than the amount of alcohol deemed safe per day (for women, 1 fl oz of ethanol; for men, double that) contributes to EPI. Digestive enzymes, which are normally inactive in the pancreas until they reach the small intestine, can be activated prematurely inside the pancreas and “digest” the pancreas, causing cellular injury and inflammation (autodigestion).10 Alcohol alters the protein composition of pancreatic juice, increasing the production of proteins that can create thick plugs and block pancreatic ducts, trapping enzymes and causing pressure and damage. The pancreas also metabolizes ethanol into harmful substances such as acetaldehyde, which directly damage the pancreas’ cells and increase oxidative stress. Alcohol impairs cellular cleanup processes (autophagy) and activates inflammatory pathways, further promoting tissue damage. Repeated inflammation activates pancreatic stellate cells, which produce fibrous tissue, causing scarring. Even binge drinking (4 drinks in 2 hours for women, 5 drinks in 2 hours for men) can trigger pancreatitis.

Proton Pump Inhibitors. Proton pump inhibitors (PPIs) prevent secretion of cholecystokinin (CCK) and secretin, the hormones that signal the pancreas to release digestive enzymes. For these enzymes (zymogens) to become active, they must be exposed to an acidic pH in the duodenum. When stomach acid production is prevented by PPIs, activation of pancreatic enzymes is impaired.

The same proton pumps in the stomach that produce acid are also found in humans in the pancreatic ducts through which pancreatic enzymes and fluid secretions make their way into the duodenum. These proton pumps play an important role in pancreatic enzyme secretion, and PPIs inhibit these pumps. Proton pump inhibitors affect not only the stomach’s secretion of hydrochloric acid but also pancreatic enzyme secretion.11

Interestingly, PPIs are recommended for the treatment of EPI. The rationale is that enzyme supplements are typically enteric coated, which means they need an alkaline environment to dissolve.

Diuretics. Thiazides (hydrochlorothiazide) and furosemide (Lasix) decrease pancreatic blood flow, raise serum triglycerides, and may induce hypercalcemia (high blood calcium).12 Hypercalcemia can trigger premature activation of trypsinogen resulting in autodigestion of the pancreas.

High blood calcium levels also promote pancreatic duct obstruction via stone formation and damage cells by overloading the mitochondria with calcium, which disrupts the activity of the electron transport chain.13

Blood Pressure Medications. Angiotensin-converting enzyme (ACE) inhibitors (lisinopril, enalapril) and other blood pressure medications (methyldopa, losartan) increase bradykinin, a peptide that causes vasodilation—a good thing in the heart but a potential problem for the pancreas where bradykinin affects pancreatic microcirculation, increasing blood pressure within the pancreatic duct and causing direct damage to acinar cells.14 Recurrent ACE-induced inflammation leads to pancreatitis, fibrosis, and structural damage of the pancreas.7

Lipid-Lowering Drugs. In a very large study involving 467 072 patients (233 425 patients not taking statins and 233 647 patients taking statins), all of whom were between the ages of 40 and 75 years and had normal levels of low-density lipoprotein cholesterol (≤200 mg/dL) and triglycerides (≤150 mg/dL), patients on statin therapy were 33% more likely to develop pancreatitis compared with patients not on statin therapy.15 Suggested mechanisms include direct cellular toxicity, metabolic effects, an immune-mediated inflammatory response, and pancreatic duct constriction.

Diseases

Cystic Fibrosis. As would be expected in this serious pancreatic disease, EPI is found in about 85% of patients with cystic fibrosis.16 Pancreatic enzyme supplementation is part of the standard of care for this condition.

Disturbances in insulin secretion impair insulin’s “trophic” or anabolic effects. Insulin is a critical trophic factor for the exocrine pancreas, meaning it directly stimulates acinar cell growth and acinar cell synthesis of digestive enzymes, particularly amylase, which digests carbohydrates, the type of macronutrient most quickly converted to glucose.17 High local insulin concentrations from beta cells also promote the pancreas’ synthesis of the proteins its own cells need to function. In contrast, insulin deficiency leads to pancreatic atrophy. Insulin not only regulates pancreatic enzyme synthesis; it also enhances the secretion of CCK. This hormone is produced in the lining of the small intestine, triggers the gallbladder to contract and release bile, and stimulates the pancreas to produce all its digestive enzymes and release them via the common bile duct into the duodenum.

Hypoinsulinemia (low insulin) leads to pancreatic atrophy and the replacement of the pancreas’ exocrine tissue with fat. Both type 1 and type 2 diabetes are associated with hypoinsulinemia and reduced levels of FE-1, a marker of EPI. Levels of FE-1 inversely correlate with diabetes duration and glycated hemoglobin A1c levels. It is a bidirectional relationship in which insulin resistance impairs pancreatic exocrine function, resulting in a high prevalence of subclinical EPI.18

Hemochromatosis. Hemochromatosis and iron-loading anemias, such as thalassemias and sideroblastic anemia, can cause the accumulation of iron in the pancreas, increasing inflammation and promoting EPI. Hemochromatosis is a genetic disorder that causes the body to absorb and store too much iron, but symptoms (like fatigue, joint pain, loss of libido, arrythmias, and diabetes) typically do not appear until age 50 years in women, probably because menstruation helps eliminate excess iron.19 Thalassemias cause impaired red blood cell production (erythropoiesis), which results in increased iron absorption. Sideroblastic anemia involves defective utilization of iron, which accumulates in the mitochondria. An iron panel (serum ferritin, total iron binding capacity, serum iron, and transferrin saturation) is the first step in diagnosis.

Chron’s Disease. Chron’s disease promotes EPI via a variety of mechanisms.20 Production of pancreatic autoantibodies is seen in one-third of patients with Chron’s  disease but is rare in ulcerative colitis.21 Damage to the pancreatic duct, such as by scarring or inflammation, leads to reduced secretion of CCK. Drugs used to manage inflammatory bowel disease (IBD; eg, azathioprine, mesalamine, salazopyrin, metronidazole, and steroids) induce pancreatitis.22

Ulcerative Colitis. Pancreatic exocrine insufficiency has been reported in 22% in patients with ulcerative colitis, and the drugs used to manage ulcerative colitis (eg, mesalamine) increase the risk of pancreatitis.23 The pancreas’ secretions include several factors that protect the gut barrier (eg, secretory phospholipase A2, pancreatic lipase, trypsinogen, and glycoprotein 2), all of which provide antimicrobial effects that protect the epithelial layer, balance intestinal microbiota, prevent bacterial translocation, and activate germicidal proteins (eg, regenerating islet-derived protein 3-α and α‐defensin). These components of pancreatic fluids provide an important defense against an increase in pathobionts, which are normally beneficial bacteria that can cause damage if allowed to proliferate excessively.

Pathobionts such as Enterococcus gallinarum, Proteus mirabilis, and Escherichia coli can translocate across the intestinal epithelial barrier, provoking excessive immune responses that exacerbate intestinal inflammation, impair the mucosal barrier, and promote IBD and EPI.24

Decreased lipase has been reported in 80% of patients with ulcerative colitis.25 This lack of pancreatic enzymes then impairs digestion and promotes intestinal inflammation, leading to increased intestinal permeability (leaky gut).25 Many of these dysfunctions are circular and self-reinforcing.

Small Intestinal Bacterial Overgrowth. Small intestinal bacterial overgrowth (SIBO) has been described in 9% to 62% of patients with IBD (both ulcerative colitis and Crohn disease) and 36% of patients with pancreatitis.26 Small intestinal bacterial overgrowth is associated with elevated levels of calprotectin, a protein released by neutrophils (immune cells) that is excreted in feces. Calprotectin is also elevated in EPI.27 Hypochlorhydria, including acid suppression by PPIs, increases risk for SIBO.28

Gallstones. Gallstones can block the bile duct. They develop when the liver excretes more cholesterol than bile salts can dissolve, so crystals and stones form. Gallstone formation is due to the same issues that promote metabolic dysfunction–associated fatty liver disease (formerly known as nonalcoholic fatty liver disease). One example is a diet high in prepared or processed foods (ie, high in refined carbohydrates and fat and low in fiber), which promotes insulin resistance, metabolic syndrome, and type 2 diabetes. Other examples are obesity and rapid weight loss from weight loss surgery or glucagon-like peptide-1 medications.29 These conditions alter bile composition, primarily by slowing gallbladder emptying, which results in the formation of a more concentrated bile that forms crystals.

Other Causes

Arsenic. Once again, arsenic shows up as an underlying cause of physiological dysfunction affecting many systems. (See these previous editorials on arsenic.30,31) Arsenic induces inflammation, increases oxidative stress (reactive oxygen species), and causes ferroptosis in pancreatic cells.

Even low to moderate levels of arsenic in drinking water (below the [too high] United States Environmental Protection Agency standard of 10 µg/L) are associated with an increased risk of type 2 diabetes. Chronic, low-level arsenic exposure can induce pancreatic beta-cell dysfunction and apoptosis.32

High Triglycerides. The liver produces triglycerides from excess calories—whether the source is carbohydrates, fats, or protein. The liver either stores them, promoting fatty liver as they accumulate, or releases them directly into the bloodstream in the form of very low-density lipoproteins or into the lymph in large, lipid-carrying chylomicrons, which then enter the bloodstream.

Normally, when chylomicrons circulating in the bloodstream reach the pancreas, pancreatic lipases break down the triglycerides into free fatty acids within the pancreatic capillaries. High concentrations of these free fatty acids, however, are toxic to pancreatic acinar cells and to capillary endothelial cells. The large chylomicron particles increase blood viscosity in the pancreatic capillaries, slowing blood flow. This process leads to ischemia and acidosis in the pancreatic tissue, further damaging pancreatic cells.33

Cellular damage and acidosis can prematurely activate protease enzymes, which when inside the pancreas, are supposed to be in their inactive forms, called zymogens. Premature activation of zymogens (eg, if trypsinogen gets activated into trypsin) causes pancreatic autodigestion. The damaged cells release cytokines that amplify inflammation, leading to the characteristic symptoms of pancreatitis, which include disruption of both its endocrine and exocrine functions.34 Pancreatitis risk significantly increases with triglyceride levels greater than 500 mg/dL.

Aging

The volume of the pancreas reaches a plateau between 20 and 60 years of age and declines thereafter. With aging, the pancreas tends to atrophy. Pancreatic exocrine insufficiency affects 11.5% to 21.7% of older adults. For example, a study of people over 60 years of age without gastrointestinal disease or diabetes found that 21.7% had FE-1 less than 200 μg/g stool,35 an indication of EPI. In a large, population-based study of 914 asymptomatic adults aged 50 to 75 years (mean age, 61.9 years), the prevalence of EPI, assessed by pancreatic FE-1, was 11.5%. Of the participants, 105 had FE-1 less than 200 μg/g stool, and 47 (5.1%) had severe EPI indicated by FE-1 less than or equal to 100 μg/g stool.36

Leptin Receptor Single-Nucleotide Variations

Leptin receptors are expressed on pancreatic cells, where leptin plays a role in regulating both endocrine (insulin) and exocrine (enzyme) functions.37 The G allele of the leptin receptor negatively affects leptin’s binding to the leptin receptor, resulting in higher plasma leptin levels, which may lead to leptin resistance and higher daily energy intake (overweight/obesity) along with failure to suppress insulin secretion, resulting in chronic hyperinsulinemia and increasing risk of beta-cell burnout.

Leptin receptor G allele single-nucleotide variations are very common, often exceeding 40% in many populations. The most studied of these is rs1137101 (Gln223Arg). In a 1000 Genomes Project analysis, the minor G allele frequency was found to be approximately 46%. Other studies have shown frequencies of 40% to 55% in various groups.38,39

Treatment for EPI

The first step in treating EPI is to address as many causes as possible. Most of the causes discussed above are amenable to intervention. The very good news is that the acinar cells in the pancreas have been shown in animal studies to have substantial ability to regenerate.40 The human research is more limited, showing extensive regeneration after acute pancreatitis but little after chronic pancreatitis.41

 Pancreatic Enzyme Replacement

Pancreatic enzyme replacement therapy is the primary treatment of EPI by providing a combination of pancreatic enzymes (amylase, proteases, and lipases). This therapy restores normal physiologic digestive processes and prevents malabsorption. Pancreatic enzyme replacement therapy supplements are typically enterically coated. The pH of the normal stomach is acidic (1.5 to 3.0), low enough to denature or inactivate some or all of a pancreatic enzyme supplement if it is not enterically coated. The enteric coating protects the enzyme supplement from gastric acidity, allowing the supplement to reach the duodenum, where the pH is alkaline, before disintegrating. However, impairment of exocrine pancreatic function includes not only the release of digestive enzymes but also the pancreas’ secretion of a bicarbonate solution into the duodenum. For this reason, some protocols recommend gastric acid suppression or alkalinization to help the enteric coating to dissolve.

The typical starting dose of pancreatic enzyme replacement therapy is 500 units of lipase/kg/meal, with a half-dose administered with snacks. Dosages are determined based on the individual’s body weight and the amount of fat consumed per meal or snack. For example, for a woman weighing 110 pounds (50 kg), the dose would be approximately 50 × 500 = 25 000 lipase units.42

The vast majority of the research shows successful clinical outcomes with porcine-derived pancreatic enzymes. Determining the appropriate dosage of pancreatic enzymes depends on the individual’s weight, age, the severity of their condition, and the amount of fat in their diet. Start with the standard dosage and adjust according to patient response.

Conclusion

Pancreatic exocrine deficiency is surprisingly common. Even in supposedly healthy populations of older people, about 20% have moderate to severe deficiency. The percentage is much higher in older patients with the diseases already discussed or taking the drugs listed above, which contribute to pancreatic decline. The good news is that supplementation is easy and relatively inexpensive and patients quickly experience benefit.

 

References

  1. The Editors of Encyclopedia Britannica. Islets of Langerhans. Brittanica. Updated June 14, 2024. Accessed April 13, 2026. https://www.britannica.com/science/islets-of-Langerhans
  2. The pancreas and EPI. Identify EPI. Accessed April 13, 2026. https://www.identifyepi.com/hcp/digestive-pancreatic-enzymes
  3. Symptoms & causes for exocrine pancreatic insufficiency. National Institute of Diabetes and Digestive and Kidney Diseases. Reviewed January 2023. Accessed April 13, 2026. https://www.niddk.nih.gov/health-information/digestive-diseases/exocrine-pancreatic-insufficiency/symptoms-causes
  4. Exocrine pancreatic insufficiency (EPI). Cleveland Clinic. Updated June 10, 2021. Accessed April 13, 2026. https://my.clevelandclinic.org/health/diseases/21577-exocrine-pancreatic-insufficiency-epi
  5. Exocrine pancreatic insufficiency: noninvasive testing options to diagnose and monitor. Mayo Clinic Laboratories. Accessed April 13, 2026. https://news.mayocliniclabs.com/gastroenterology/malabsorption/exocrine-pancreatic-insufficiency
  6. 15 pieces of advice on exocrine pancreatic insufficiency. American Gastroenterological Association. October 30, 2023. Accessed April 13, 2026. https://gastro.org/news/15-pieces-advice-exocrine-pancreatic-insufficiency
  7. Kaufman MB. Drug-induced pancreatitis: a potentially serious and underreported problem. P&T. 2013;38(6):349-351.
  8. Tang C, Zhou J, Song Y, Liu S. Etiologies of exocrine pancreatic insufficiency. Gastroenterol Rep (Oxf). 2025;13:goaf019. doi:10.1093/gastro/goaf019
  9. Ksiądzyna D. Drug-induced acute pancreatitis related to medications commonly used in gastroenterology. Eur J Intern Med. 2011;22(1):20-25. doi:10.1016/j.ejim.2010.09.004
  10. Chowdhury P, Gupta P. Pathophysiology of alcoholic pancreatitis: an overview. World J Gastroenterol. 2006;12(46):7421-7427. doi:10.3748/wjg.v12.i46.7421
  11. Wang J, Barbuskaite D, Tozzi M, Giannuzzo A, Sørensen CE, Novak I. Proton pump inhibitors inhibit pancreatic secretion: role of gastric and non-gastric H+/K+-ATPases. PLoS One. 2015;10(5):e0126432. doi:10.1371/journal.pone.0126432
  12. Jones MR, Hall OM, Kaye AM, Kaye AD. Drug-induced acute pancreatitis: a review. Ochsner J. 2015;15(1):45-51.
  13. Phadwal K, Vrahnas C, Ganley IG, MacRae VE. Mitochondrial dysfunction: cause or consequence of vascular calcification? Front Cell Dev Biol. 2021;9:611922. doi:10.3389/fcell.2021.611922
  14. Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: an update. J Clin Gastroenterol. 2005;39(8):709-716. doi:10.1097/01.mcg.0000173929.60115.b4
  15. O’Connor CE, Dang BQ, Miles B, Mackey J. Statin therapy and pancreatitis: a multi-institutional retrospective analysis. Cureus. 2024;16(1):e51723. doi:10.7759/cureus.51723
  16. Singh VK, Schwarzenberg SJ. Pancreatic insufficiency in cystic fibrosis. J Cyst Fibros. 2017;16(suppl 2):S70-S78. doi:10.1016/j.jcf.2017.06.011
  17. Pap Á. Effects of insulin and glucose metabolism on pancreatic exocrine function. Int J Diabetes Metab. 2004;12(3):30-34. doi:10.1159/000497564
  18. Peddireddy N, Crossley J, Chen X, et al. The relationship between metabolic syndrome components and the incidence of pancreatic exocrine insufficiency in patients with chronic pancreatitis. Open J Intern Med. 2025;15(2):117-137. doi:10.4236/ojim.2025.152012
  19. American Liver Foundation. Updated March 20, 2023. Accessed April 13, 2026. https://liverfoundation.org/liver-diseases/rare-disease/hemochromatosis
  20. Hedström A, Steiner C, Valente R, Haas SL, Löhr JM, Vujasinovic M. Pancreatic exocrine insufficiency and Crohn’s disease. Minerva Gastroenterol Dietol. 2020;66(1):17-22. doi:10.23736/S1121-421X.19.02636-9
  21. Pavlidis P, Romanidou O, Roggenbuck D, et al. Ileal inflammation may trigger the development of GP2-specific pancreatic autoantibodies in patients with Crohn’s disease. Clin Dev Immunol. 2012;2012:640835. doi:10.1155/2012/640835
  22. Yi GC, Yoon KH, Hwang JB. Acute pancreatitis induced by azathioprine and 6-mercaptopurine proven by single and low dose challenge testing in a child with Crohn disease. Pediatr Gastroenterol Hepatol Nutr. 2012;15(4):272-275. doi:10.5223/pghn.2012.15.4.272
  23. Fousekis FS, Theopistos VI, Katsanos KH, Christodoulou DK. Pancreatic involvement in inflammatory bowel disease: a review. J Clin Med Res. 2018;10(10):743-751. doi:10.14740/jocmr3561w
  24. Zhang CX, Wang HY, Chen TX. Interactions between intestinal microflora/probiotics and the immune system. BioMed Res Int. 2019;2019:6764919. doi:10.1155/2019/6764919
  25. Antonini F, Pezzilli R, Angelelli L, Macarri G. Pancreatic disorders in inflammatory bowel disease. World J Gastrointest Pathophysiol. 2016;7(3):276-282. doi:10.4291/wjgp.v7.i3.276
  26. Feng X, Hu J, Zhang X. Prevalence and predictors of small intestinal bacterial overgrowth in inflammatory bowel disease: a meta-analysis. Front Med (Lausanne). 2025;11:1490506. doi:10.3389/fmed.2024.1490506
  27. Pezzilli R. Chronic pancreatitis: maldigestion, intestinal ecology and intestinal inflammation. World J Gastroenterol. 2009;15(14):1673-1676. doi:10.3748/wjg.15.1673
  28. Revaiah PC, Kochhar R, Rana SV, et al. Risk of small intestinal bacterial overgrowth in patients receiving proton pump inhibitors versusproton pump inhibitors plus prokinetics. JGH Open. 2018;2(2):47-53. doi:10.1002/jgh3.12045
  29. Ramírez-Mejía MM, Ponciano-Rodriguez G, Eslam M, Méndez-Sánchez N. GLP-1 receptor agonists and gallbladder disease risk: insights into molecular mechanisms and clinical implications. Ther Adv Endocrinol Metab. 2025;16:20420188251406456. doi:10.1177/20420188251406456
  30. Pizzorno J. Time to recognize and address the serious arsenic problem. Integr Med (Encinitas). 2024;23(1):6-9.
  31. Pizzorno J. Continuing the conversation about arsenic. Integr Med (Encinitas). 2024;23(3):6-10.
  32. Lu TH, Su CC, Chen YW, et al. Arsenic induces pancreatic β-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic reticulum stress-triggered signaling pathways. Toxicol Lett. 2011;201(1):15-26. doi:10.1016/j.toxlet.2010.11.019
  33. Feingold KR. Pancreatitis secondary to hypertriglyceridemia. In: Feingold KR, Adler RA, Ahmed SF, et al, eds. Endotext [Internet]. MDText.com, Inc; 2000-. Updated September 24, 2025. Accessed April 13, 2026. https://www.ncbi.nlm.nih.gov/books/NBK279082
  34. de Pretis N, Amodio A, Frulloni L. Hypertriglyceridemic pancreatitis: Epidemiology, pathophysiology and clinical management. United European Gastroenterol J. 2018;6(5):649-655. doi:10.1177/2050640618755002
  35. Herzig KH, Purhonen AK, Räsänen KM, et al. Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus. BMC Geriatr. 2011;11(1):4. doi:10.1186/1471-2318-11-4
  36. Rothenbacher D, Löw M, Hardt PD, Klör HU, Ziegler H, Brenner H. Prevalence and determinants of exocrine pancreatic insufficiency among older adults: results of a population-based study. Scand J Gastroenterol. 2005;40(6):697-704. doi:10.1080/00365520510023116
  37. Illangasekera YA, Kumarasiri PVR, Fernando DJ, Dalton CF. Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans. BMC Res Notes. 2020;13(1):34. doi:10.1186/s13104-020-4898-4
  38. Seufert J, Kieffer TJ, Leech CA, et al. Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. J Clin Endocrinol Metab. 1999;84(2):670-676. doi:10.1210/jc.84.2.670
  39. Veerabathiran R, P A, Bk I, D R, Rs AH. Genetic predisposition of LEPR (rs1137101) gene polymorphism related to type 2 diabetes mellitus – a meta-analysis. Ann Med. 2023;55(2):2302520. doi:10.1080/07853890.2024.2302520
  40. Zhou Q, Melton DA. Pancreas regeneration. Nature. 2018;557(7705):351-358. doi:10.1038/s41586-018-0088-0
  41. Socorro M, Esni F. Pancreatic regeneration: models, mechanisms, and inconsistencies. Version 2.0. Pancreapedia: Exocrine Pancreas Knowledge Base. November 23, 2020. Accessed April 13, 2026. doi:10.3998/panc.2020.10
  42. CREON dosing guide. CREON (pancrelipase). Accessed April 13, 2026. https://www.creonhcp.com/dosing-calculator
  43. Hammam, G.A., Abdelmalek, M.O., Mahmoud, A.A. et al. Evidence of Pancreatic Exocrine Insufficiency in patients with Metabolic Associated Fatty Liver Disease patients. Egypt Liver Journal 16, 8 (2026). https://doi.org/10.1186/s43066-025-00474-4

Be the first to comment

Leave a Reply

Your email address will not be published.


*