The Importance of Pepsin in Digestive Health

Pepsin: Signs You Need More of This Digestive Enzyme & How to Get It in Your Diet

Pepsin is considered one of the main digestive enzymes that humans (and many other animals) produce. When is comes to digestive/gut health, what is pepsin needed for? It is essential for us to properly digest the proteins found in the foods we eat. In addition, it helps with functions like nutrient absorption and protection against allergies, yeast overgrowth and more.


Pepsin - Dr. Axe

Today pepsin supplements are available that can aid in digestion when low levels of this enzyme are produced. It can help curb indigestion and symptoms associated with pancreatitis, GERD, acid reflux and heartburn. Do you suspect that you might have low stomach acid? It can contribute to problems digesting protein. Symptoms like abdominal pain, bloating, diarrhea, and nutrient deficiencies in B12 and iron may all indicate that you lack adequate gastric juices and pepsin.

What Is Pepsin?

The definition of pepsin is a digestive enzyme in the stomach that breaks down proteins into smaller units called polypeptides (or peptides for short). This enzyme helps digest proteins — such as those found in meat, eggs, dairy products, nuts and seeds — by breaking bonds that link amino acids. Amino acids are described as “the building blocks of proteins.”

What organ is pepsin produced by, and where is pepsin found?

Pepsin is an enzyme made by the stomach. It also functions in the stomach. This enzyme is created when stomach acid changes a protein called pepsinogen into pepsin. (1) Pepsinogen is inactive, but it is converted to the active enzyme pepsin by the action of hydrochloric acid.

Pepsin can be found in gastric juices that are acidic and needed to properly metabolize the foods we eat. Glands in the mucous-membrane lining of the stomach, called peptic chief cells, are responsible for making pepsinogen. This happens after they are stimulated by the vagus nerve and hormonal secretions of gastrin and secretin. Pepsinogen mixes with hydrochloric acid and is then converted to the active enzyme pepsin.

How does pepsin work in the stomach?

Pepsin has maximal activity in acidic environments, ideally around a pH of about 1.5 to 2. This is considered the “normal acidity of gastric juices.” It stops working properly once the pH level reaches about 6.5 or higher. It then causes pepsin to be neutralized and denatured. This is important because inside the stomach is intended to be an acidic place.

Is pepsin an endopeptidase?

Yes, it is an endopeptidase that breaks down proteins into shorter polypeptide chains. Technically, it is an aspartic protease and one of three principal proteases in the human digestive system. Amino acids must be broken down before readily being absorbed by the small intestine. Once pepsin degrades proteins into smaller peptides, peptides are then absorbed from the intestine into the bloodstream or further broken down by pancreatic enzymes.

Some pepsin is capable of passing from the stomach into the bloodstream, where it continues to breaks down undigested fragments of protein. (2) Due to its specific structure, it is most efficient in cleaving/breaking peptide bonds between hydrophobic and aromatic amino. These include phenylalanine, tryptophan and tyrosine.

Proteolysis is another name for the “the breakdown of proteins or peptides into amino acids by the action of enzymes.” When pepsin is released, it initiates digestion through proteolysis. This is also believed to help keep the stomach free of most bacteria.

Benefits and Uses

How does pepsin work in the body? Its main function is to break down (or denature) proteins, but it also has other roles, including facilitating nutrient absorption and killing harmful microbes. The role of digestive enzymes is primarily to act as catalyst in chemical reactions in the body. Digestive enzymes turn larger molecules into more easily absorbed particles that the body can actually use to survive and thrive.

There are several main reasons why some people can benefit from taking pepsin enzymes. Pepsin benefits and uses include:

  • Assists the body in breaking down difficult-to-digest proteins.
  • Helps treat indigestion or leaky gut by taking stress off the gastrointestinal tract.
  • Manages pancreatitis, which interferes with the ability to properly produce enzymes needed to break down foods.
  • Helps prepare antibodies and digest IgG.
  • Stimulates bile secretion.
  • Aids liver detoxification.
  • Improves symptoms of acid reflux, heartburn and other issues like irritable bowel syndrome.
  • Enhances nutrition absorption and prevents nutritional deficiency, including vitamin B12, iron and calcium deficiency.
  • Counteracts enzyme inhibitors naturally in foods like peanuts, wheat germ, egg whites, nuts, seeds, beans and potatoes.
  • Used to help manage a wide variety of health problems, such as dyspepsia (recurrent pain or discomfort in the upper abdomen), vomiting caused by morning sickness during pregnancy, nausea and diarrhea, and indigestion associated with cancer treatments.

Although pepsin is an important digestive enzyme with many benefits, there are several digestive problems that are linked to dysfunction of pepsin. These include:

  • GERD (gastroesophageal reflux disease) and laryngopharyngeal reflux (or extraesophageal reflux). This happens when pepsin, acid and other substances from the stomach creep up into the esophagus. Pepsin can remain in the larynx following a gastric reflux event. When someone has laryngopharyngeal reflux, this means that pepsin and acid are traveling all the way up to the larynx.
  • GERD and laryngopharyngeal reflux can cause discomfort and even serious damage to the esophagus and laryngeal mucosa. These conditions commonly produce symptoms, including acid reflux, burning in the chest, hoarseness, chronic cough and involuntary contraction of the vocal cords.
  • Pepsin enzymes are capable of adhering to laryngeal cells, depleting their defenses and eroding membranes/tissue (called endocytosis). This may potentially increase the risk for esophageal and laryngeal cancer. (3)
  • Extraesophageal reflux is detected by testing acidification using a pH probe and by the identification of pepsin in saliva and in exhaled breath. Research suggests that proton pump inhibitors do not help the majority of people with extraesophageal reflux.
  • While pepsin is involved in conditions like GERD, GERD occurs when the lower esophageal sphincter valve is weak or relaxes inappropriately. This can happen due to inflammation, hernias or obesity. As a result, the stomach’s contents flow up into the esophagus. In many cases, GERD can be relieved through diet and lifestyle changes that help diminish inflammation. (4)

Pepsin - Dr. Axe

Top Sources

Foods in your diet do not actually contain pepsin, but they can affect your production of stomach acid and digestive enzymes.  As mentioned above, in the human body, this enzyme comes from “chief cells” found in the stomach. The volume you produce increases if you eat high volumes of protein. Examples of “high protein” meals include those with red meat, poultry, fish, eggs, dairy and protein powders.

Pepsin medications and supplements are also sources of pepsin. These are used to enhance digestion of food (especially proteins) when someone lacks proper pepsin secretion. They help manage conditions like pancreatitis as well. Pepsin supplements are usually produced from hog or swine (pig) stomachs.

The product called betaine hydrochloride (or betaine HCL with pepsin) is recommended by some practitioners a supplemental source of hydrochloric acid for people who have low stomach acid production (also called hypochlorhydria). This may help hydrochloric acid secreted by the stomach better convert pepsinogen and aid in digestion of protein. Plus, it may offer other benefits like reducing allergies and inhibiting the overgrowth of candida. (5)

Supplements and Dosage

Pepsin supplements include drugs that are available as over-the-counter pills that can be taken without a medical prescription. They are available in the form of tablets, compounding powders and capsules. The optimal pepsin dosage you should take depends on factors like your weight, height, age, diet, lifestyle and medical history. If you need a prescription-strength pepsin medicine, your doctor will decide how much you should take. Two examples of pepsin medicines are Nuzyme Tablets and Wegazyme Syrup.

If you take an over-the-counter digestive enzyme supplement, read directions carefully. Don’t take larger amounts than recommended. For the best results, look for a high-quality digestive enzyme blend that includes a variety of different enzymes.

Some products combine HCL and pepsin to boost effects. HCL with pepsin is a great thing you can start taking on a regular basis to help heal your GI tract, fight things like acid reflux and improve low stomach acid. It’s also a leaky gut supplement. HCL with pepsin is somewhat controversial, but it is typically taken while under the care of a physician. It’s important to start off with one capsule and increase your intake gradually. (6)

  • It should only be taken when you have protein during a meal. If you don’t consume protein in a meal, you don’t want to use it.
  • If you feel warmness in your stomach, that means you’re taking enough and may even need to decrease your dose.
  • Some people need only one capsule per day or one capsule per main meal. Other people may need to take up to nine capsules daily.
  • Look for a supplement that has about 530 milligrams of betaine HCL and around 20 milligrams of pure pepsin.
  • Always take this supplement with meals, not on an empty stomach.

Signs You Need More

In order to digest protein, your body requires enough stomach acid and enzymes. If you show signs of low stomach acid, there’s a good chance you also deal with low pepsin production. What happens if your stomach does not produce enough gastric juices?

If you have low stomach acid, you lack HCL. HCL is needed to create the active enzyme pepsin. Hydrochloric acid is naturally created in your stomach. It’s what makes your stomach a very acidic environment that can break down food.

If you’re deficient in hydrochloric acid/stomach acid and this interferes with pepsin production, you may experience symptoms like:

  • Indigestion
  • Bloating and gas
  • Stomach pains
  • Constipation or diarrhea
  • Nutrient deficiencies in vitamin B12, iron and calcium
  • And the related condition called leaky gut

Some reasons you may have a hard time producing pepsin and digesting protein include:

  • Nutrient deficiencies, such as due to calorie restriction or a very limited diet.
  • History of antacid use, especially long-term use.
  • History of frequent antibiotic use.
  • Overeating, rushing while eating, feeling stressed while eating.
  • Drinking too much water before or during meals.
  • Poor sleep, which interferes with appetite regulation and digestion.

To improve overall digestion, reduce inflammation that can contribute to GERD/reflux and balance your production of stomach acid, here are steps to take:

  • Eat foods that are naturally rich in enzymes, including pineapple, papaya, mango, banana, avocado, kiwi, kefir, yogurt, miso, soy sauce, tempeh, sauerkraut, kimchi, bee pollen, apple cider vinegar and raw honey.
  • Make sure to eat plenty of alkaline foods and a variety of protein sources. Variety is beneficial for obtaining different amino acids.
  • Eat small, balanced meals that are spread throughout the day. Try meals that combine protein, complex carbs and healthy fats.
  • Don’t eat within three to four hours before going to bed or lying down to sleep.
  • Slow down while eating. Eat in a relaxed environment, and take your time. Chew your foods about 30 times before you swallow.
  • Eat a variety of probiotic foods.
  • Use apple cider vinegar right before your meals. Take one tablespoon with a small amount of water one to three times daily.
  • Use Manuka honey, which has antimicrobial properties and can help manage small intestinal bacterial overgrowth  (SIBO) that’s associated with low stomach acid. Take a teaspoon once or twice a day.
  • If you have GERD or acid reflux, you may want to reduce the amount of acidic foods you consume. Be sure to eat more alkaline foods. Try keeping a food journal to pinpoint which types of foods aggravate your symptoms most.
  • Consider trying intermittent fasting. It has many benefits for gut health and low stomach acid.

Digestive Enzyme Recipes

  • Pineapple Smoothie with Cilantro Recipe or Anti-Inflammatory Juice Recipe with Pineapple
  • Strawberry Papaya Smoothie Recipe
  • Homemade Sauerkraut Recipe


Pepsin was first discovered by the German physiologist named Theodor Schwann in 1836. It was one of the first digestive enzymes to be identified. It is still considered one of the most important. It wasn’t until more than 90 years later, in 1929, that scientists working at the Rockefeller Institute for Medical Research were able to identify how exactly it worked. This enzyme gets its name from the Greek word pepsis, which means “digestion” (or from peptein, which means “to digest”).

Today, other than being used to make pepsin supplements, it is used for a variety of applications in food manufacturing, photography, leather making and other industries. For example, commercially prepared pepsin is used to modify soy protein and gelatin. It’s also used to manufacture nondairy snacks and precooked cereals, make protein hydrolysates for use in flavoring foods and beverages, and remove hair from tissues/hides in the leather industry. (7)

Risks and Side Effects

When taking pepsin medicine/supplements, it’s possible to experience side effects that are usually rare but sometimes serious. Some of the side effects include abdominal pain, strong indigestion, nausea, skin rash and diarrhea. (8) These adverse reactions are most likely to happen if you take too much at one time.

Always talk to your doctor if you observe any of the effects when using these supplements, especially if they continue to get worse with time. Also consult your doctor before taking any supplement if you take medications regularly; you have allergies or current diseases you are treating; or if you are pregnant, planning to get pregnant or breastfeeding.

Final Thoughts

  • Pepsin is a digestive enzyme in the stomach that breaks down proteins into smaller units called polypeptides (or peptides or short). What gland secretes pepsin? It is produced by cells in the lining of the stomach. This enzyme is made when the inactive enzyme called pepsinogen mixes with hydrochloric acid (stomach acid/gastric juices) and is converted to the active enzyme.
  • What substance in the stomach helps pepsin work? It works in an acidic pH, ideally in an environment that is a pH of 1.5–2. Gastric juices in the stomach that are highly acidic help this enzyme break down foods properly. That is why low stomach acid can be problematic.
  • Digestive enzymes called proteolytic enzymes are the type needed to digest protein. HCL with pepsin is an example of a supplement that is taken over-the-counter. However, it can have side effects so it’s best to consult with a doctor.
  • People who can benefit from taking digestive enzyme supplements include those with low stomach acid, pancreatitis, IBS, enzyme insufficiency, pancreatic insufficiency, vitamin B12 or iron deficiency, constipation, diarrhea, and bloating.
  • Foods that can help to provide you with natural digestive enzymes that support protein digestion include pineapple, papaya, kiwi, fermented dairy, mango, miso, sauerkraut, kimchi, avocado, bee pollen, apple cider vinegar and raw honey.

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