Pepsin is one of the most important digestive enzymes, which starts to break down proteins in your stomach. Read on to learn about the science behind its function and the benefits of supplementing!

What Is Pepsin?

Pepsin is an enzyme – a type of protein that helps carry out a chemical reaction. More specifically, pepsin is a protease (also sometimes called a peptidase): an enzyme that helps break proteins down into smaller pieces [1, 2].

Pepsin is one of the three major protein-digesting enzymes in the digestive system – the other two are chymotrypsin and trypsin. Pepsin is the first to start digesting proteins from the food you eat. The other two take over after pepsin has done the initial work [3+].

Snapshot

PROs

  • Aids protein digestion
  • Helps correct low stomach acid
  • Kills bacteria in the stomach
  • Relieves chronic stomach inflammation (gastritis)
  • May reduce symptoms of autism in combination with other enzymes
  • Can act as a marker of acid reflux

CONs

  • Not much evidence supporting the use of supplements
  • Often used in combination with other enzymes

What Does it Break Down?

Broadly speaking, pepsin breaks down proteins [1].

Proteins are made up of lengthy chains of amino acid building blocks. Pepsin is able to sever the connections between amino acids, thus breaking long protein chains into shorter chains called peptides [1, 3+].

Specifically, pepsin is an aspartic peptidase, which means that it has the amino acid aspartate in its active site. Aspartate enables pepsin to work and cut up proteins [3+, 4+, 5+].

Aspartic peptidases like pepsin are thought to play a role in diverse diseases, from stomach ulcers to breast cancer to Alzheimer’s disease [3+].

Pepsin is also a kind of endopeptidase, which means it can cut up a protein chain right in the middle – as opposed to exopeptidase that cut proteins up at the ends [3+, 4+].

After pepsin has done its job, the peptides it released pass to the intestine. Here other peptidases and proteases further break them down into amino acids you can absorb. Your body then uses these amino acids to build new proteins or burns them for energy [6, 7].

Where Is it Produced and Found?

Pepsin is produced by stomach cells. It is most commonly found in the acidic juices of the stomach in humans and many other animals. As such, it works best in acidic conditions [1, 8, 9+].

In acid reflux, stomach contents make their way up the esophagus or food pipe. In such cases, pepsin can also be found in the esophagus, saliva, and even in the lungs and airways. This can cause damage and inflammation [9+, 10].

Pepsinogen to Pepsin

The normal production of pepsin in the body is quite tightly regulated. Your body has to ensure that pepsin doesn’t digest important proteins in cells, which would cause serious damage.

For this reason, cells first make an inactive precursor to the enzyme, called pepsinogen. Pepsinogen is then released from cells, secreted into the stomach, and only then transformed to the active pepsin as needed [11].

Pepsin Uses & Benefits

1) Indigestion

In a study of 92 people with indigestion without a clear biological cause (called “functional dyspepsia), a pepsin-based treatment decreased symptoms like abdominal pain after 6 weeks of treatment [12, 13].

2) Low Stomach Acid

Pepsin supplementation can help correct low stomach acid – called hypochlorhydria or achlorhydria – especially when combined with an acid supplement like hydrochloric acid (pepsin HCl), as well as dietary changes [14+, 15, 16].

In addition to helping with digestion and abdominal pain, resolving low stomach acid can also help prevent bacterial infections and intestinal inflammation; it may even play a role in combating malnutrition [14+, 17, 15].

3) Diagnosing Stomach Cancer

Low levels of pepsinogen are linked with a higher likelihood of developing stomach cancer. Some have proposed using pepsinogen levels in the blood to help in early cancer diagnosis – though there is debate as to the usefulness of this strategy [18, 19, 20, 21, 22].

4) Autism

In trials including over 147 children and adults with autism spectrum disorder, pepsin-containing supplements had a range of beneficial effects. Supplementation helped improve behavior and emotional responses while decreasing vomiting [23, 24].

5) Relieving Chronic Gastritis

In one study, 82 people with chronic gastritis – long-term irritation of the stomach – were given pepsin tablets after meals. Pepsin treatment was effective for 75% of the people [25].

Additionally, low levels of pepsinogen are linked to the development of stomach inflammation and can be used to help diagnose gastritis [26, 27, 18, 22].

6) Killing Bacteria

Pepsin has been shown to kill bacteria in the lab. It is thus plausible that, in the stomach, pepsin might also help destroy bacterial invaders [28].

This, in turn, could have helped prevent food-borne illnesses and inflammatory bowel diseases [28, 29, 30+]

7) As a Reflux Marker

Reflux is when contents from the stomach come up the esophagus, causing issues like heartburn [9].

Pepsin from stomach juice can damage the cells in the esophagus – but residual pepsin can also be used to diagnose reflux events. Leftover pepsin in the esophagus can indicate that stomach contents “refluxed” [31, 32, 9, 33].

8) In Industry and Labs

Pepsin is used to help clean leather and to remove residue from photographic film [34, 35].

This enzyme also has applications in the food industry. For example, it is used to prepare gelatin and hot cereals. It’s also used to help remove the scales and shells from seafood [36+, 37, 38, 39].

Because pepsin cuts up protein chains at a specific sequence, laboratories use it to produce specialized proteins like F(ab’)2 fragments – portions of antibodies that are useful in some lab assays [40, 40].

Pepsin Food Sources & Natural Boosters

Pepsin is not found in food since it would basically digest your food before you got a chance to eat it. The human body can produce all the pepsin it needs. But certain foods can up your natural pepsin production [9+, 3+].

The body makes more pepsin when more protein needs to be digested. So, eating a high-protein meal is likely to increase your pepsin production [9+, 3+, 41].

A study in six healthy people indicated that pepsin is also produced at higher levels in response to ketogenic-like diet, which is higher in fat [41].

Pepsin Dosage & Supplements

Typically, a capsule contains around 20 mg of the enzyme.

Pepsin supplements, primarily pills, are available and are marketed to “aid digestion.” There do not appear to have been rigorous trials of such supplements in people.

HCl with Pepsin

Pepsin only works at low pH – that is, in highly acidic environments. Although the stomach is usually naturally acidic, some pepsin supplements include HCl (hydrochloric acid) to ensure acidity in which the enzyme can function optimally – particularly in people with low stomach acid [42+, 43+].

Betaine HCl with Pepsin

Betaine (trimethylglycine) HCl is a compound that was first isolated from sugar beets. It is sometimes included in pepsin supplements [44].

Betaine HCl raises stomach acidic levels, which would, in turn, also help pepsin work [44, 45].

However, you shouldn’t use Betaine HCl if you have normal gastric acid levels, as too much acid can damage the stomach lining and cause ulcers [43].

If you’re not sure whether your gastric levels are low, some practitioners recommend doing an “HCl challenge”: buy a supplement with betaine HCl (or betaine HCl with pepsin). Take 1 capsule before a large meal. If you feel burning or warmth in your stomach, indigestion, or an “acidic” sensation, you are probably producing enough gastric acid already. In that case, you shouldn’t take betaine HCl. If you don’t feel different, you may be deficient.

Practitioners recommend slowly increasing the dosage until you feel stomach warmth (but not to an unpleasant extent).

Okra Pepsin

In addition to pepsin, Okra Pepsin contains extracts from okra, which has various health benefits, as well as fiber and mucilage.

This combined supplement does not appear to have been scientifically studied specifically, but it is often used to help aid in gut health.

Supplement Reviews

Users of pepsin (alone or with betaine HCl) often report positive experiences, saying it helps relieve gut issues like heartburn. One user with poor digestion due to low stomach acid described betaine HCl with pepsin as the “best solution.”

However, other reviews are far less rosy. Users complained that supplementation didn’t improve their digestion at all.

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Takeaway

Pepsin is one of the most important protein-digesting enzymes. It starts working in your stomach and all the other enzymes that break down proteins in your intestines depend on it.

In combination with other digestive enzymes and/or Betaine HCl, supplemental pepsin can help with indigestion and low stomach acid, while it may also reduce symptoms of autism and kill harmful stomach bacteria. Ketogenic and high-protein diets might also boost your pepsin production.

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