Exocrine pancreatic insufficiency (EPI) occurs when the pancreas does not produce enough enzymes or produces defective enzymes. The deficiency causes issues with digestion, the absorption of key nutrients, and the metabolization of carbohydrates, fats, and protein.

EPI can cause serious quality of life issues and complications that can lead to death. However, treatment options are available. Treatment often consists of supplements and pancreatic enzyme replacement therapy (PERT).

This article covers causes and treatments associated with EPI in more detail.

Several conditions and factors can cause EPI. However, researchers say that the most common cause is chronic pancreatitis.

Other contributing factors include cystic fibrosis, genetics, surgery, and other health conditions.

Although doctors can often identify a cause, about 25% of EPI cases are idiopathic. This means that there is no known cause.

The following are some potential causes of EPI.

Chronic pancreatitis

The most common cause of EPI is chronic pancreatitis. Chronic pancreatitis refers to inflammation in the pancreas that gets progressively worse over time. The inflammation can eventually damage the pancreas, and this damage can cause EPI.

EPI affects about 60–90% of people who have been living with chronic pancreatitis for around 10–12 years. The condition is also the most common pancreas condition in the United States, affecting 42–73 per 100,000 people.

Cystic fibrosis

Cystic fibrosis is an inherited, progressive condition. It causes chronic lung infections that eventually make it difficult to breathe. The condition affects over 30,000 U.S. individuals and around 70,000 people worldwide.

For some people living with the condition, a sticky, thick mucus forms in the lungs and organs of the digestive tract, including the pancreas. This buildup of mucus can cause EPI to develop, which can lead to digestive issues.

According to a 2021 paper, nearly 90% of people with cystic fibrosis also present with EPI. Cystic fibrosis is the leading cause of EPI in children.

Other conditions

Several other factors and health conditions can cause EPI. According to a 2021 article, some other potential causes include:

  • autoimmune conditions such as Sjögren’s disease, primary biliary cirrhosis, and inflammatory bowel disease
  • chronic renal failure
  • hyperlipidemia
  • hypercalcemia
  • irregularities and blockages in the pancreas
  • alcohol and tobacco use

People with diabetes may be at higher risk. According to a 2019 paper, about 30–50% of people with type 1 diabetes and about 20–30% of people with type 2 diabetes also have EPI.

The paper also mentions some other conditions that have a notable amount of people living with EPI. These include:

  • celiac disease
  • HIV
  • benign pancreatic tumor
  • pancreatic cancer


According to a 2021 article, there may be specific genetic mutations that make a person more susceptible to developing EPI. Those genetic factors include:

  • CFTR mutations: The cystic fibrosis transmembrane conductance regulator (CFTR) mutation causes the CTFR protein to be made incorrectly or not at all.
  • SPINK1 mutations: Serine peptidase inhibitor Kazal type 1 (SPINK1) is responsible for coding a protein released in the fluids of the pancreas, and the mutation is associated with hereditary pancreatitis.

Side effect of surgery

Surgery to or around the pancreas can also be a cause of EPI. According to a 2019 paper, some surgical procedures that can cause EPI include:

  • pediatric intestinal transplantation
  • pancreatic surgery
  • gastrointestinal surgery

Although surgery can lead to EPI in some cases, it can help improve EPI in others. The same paper notes that benign tumors in the pancreas can cause EPI before surgery, meaning that the surgical removal of the tumors may improve the condition.

Once a person has a diagnosis of EPI, they can start treatment for it. The goal of treatment is to make sure that the person receives all necessary nutrients.

PERT is the main treatment for EPI. PERT takes the form of prescription pills. The pills provide the enzymes the pancreas is not making during a meal to aid digestion. So, people should take these pills with food.

Making dietary changes may also help treat EPI. For example, people with cystic fibrosis and EPI should eat a high calorie diet with additional fat. A doctor may also prescribe or recommend vitamin and mineral supplements to make up for the vitamins and minerals the body is not absorbing.

It is important to regularly check in with a doctor or nutritionist to make sure that treatment is working. People living with EPI should also work with a doctor to address and treat any underlying health conditions, which may also help EPI improve.

EPI occurs when the pancreas does not produce enough enzymes or produces defective enzymes needed for the digestion of key nutrients. The most common causes of EPI include chronic pancreatitis and cystic fibrosis. Other medical conditions may also lead to EPI.

Several other factors — including gene mutations, surgery side effects, and tobacco and alcohol use — can also cause EPI.

A person with EPI can treat their symptoms with PERT, dietary changes, and vitamin and mineral supplements. Addressing the underlying condition that is causing EPI may also improve symptoms.