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Pepsin Enzyme Definition, Function & Supplement Benefits

Written by Marisa Wexler, MS (Pathology) | Last updated:
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Marisa Wexler, MS (Pathology) | Last updated:

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Pepsin

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?

Overview

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+].

That’s why pepsin is often described as one of the most important digestive enzymes.

Snapshot

Proponents

  • Aids protein digestion
  • Claimed to correct low stomach acid
  • May soothe chronic stomach inflammation (gastritis)
  • Being researched in autism in combination with other enzymes
  • Can act as a marker of acid reflux

Skeptics

  • Solid evidence is lacking to support the use of supplements
  • Long-term safety of supplementation is unknown
  • 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 passes 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 & Potential Benefits

Pepsin supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Insufficient Evidence:

The following purported benefits are only supported by limited, low-quality clinical studies.

There is insufficient evidence to support the use of pepsin supplements for any of the below-listed uses.

Pepsin or other digestive enzymes should never be used as a replacement for approved medical therapies.

1) Indigestion

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

2) Autism

In trials including over 147 children and adults with autism spectrum disorder, pepsin-containing supplements were purported to have a range of beneficial effects [14, 15].

The authors claim supplementation helped improve behavior and emotional responses while decreasing vomiting. However, it’s impossible to tease apart the effects of pepsin since these studies used multi-ingredient products [14, 15].

3) Chronic Gastritis

In one study, 82 people with chronic gastritis – long-term irritation of the stomach – were given pepsin tablets after meals. The authors suggested that pepsin treatment was effective for 75% of the people. Nonetheless, future studies have yet to replicate their results [16].

Additionally, low levels of pepsinogen have been linked to the development of stomach inflammation and may be used to help diagnose gastritis [17, 18, 19, 20].

Lacking Evidence:

No clinical evidence supports the use of pepsin supplements for any of the conditions listed in this section.

Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

4) Low Stomach Acid

Pepsin supplementation has been suggested to 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 [21+, 22, 23].

This approach is advocated by some functional practitioners. However, it remains unproven since it relies mostly on clinical experience while proper clinical trials are lacking to attest to its effectiveness and safety [21+, 22, 23].

Theoretically, resolving low stomach acid helps with digestion and abdominal pain. It may also help prevent bacterial infections and intestinal inflammation; limited research suggests it may even play a role in combating malnutrition, but far more research is needed [21+, 24, 22].

5) Bacterial Infections

Scientists are investigating whether pepsin can kill bacteria in the lab. It is thus plausible that, in the stomach, pepsin might also help destroy bacterial invaders [25].

This, in turn, is hypothesized to help prevent food-borne illnesses and inflammatory bowel disease (IBD) [25, 26, 27+].

However, far more animal and human research is needed before the impact of pepsin on bacterial infections is determined.

Other Proposed Uses

6) 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. Further studies are needed [19, 28, 29, 30, 20].

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].

Pepsin Food Sources, Supplements & Dosage

Food Sources

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 might up 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 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. This hasn’t been verified in large trials, though [41].

Dosage

Because pepsin supplements are not approved by the FDA for any condition, there is no official dose.

Users and supplement manufacturers have established unofficial doses based on trial and error. Discuss with your doctor if pepsin may be useful as a complementary approach in your case and which dose you should take.

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 is thought to function optimally (particularly in people with low stomach acid). This approach hasn’t been validated in clinical trials [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, though there’s no clinical research to support the use of this combination [44].

Betaine HCl raises stomach acidic levels, which should theoretically also help pepsin work [44, 45].

However, you shouldn’t use Betaine HCl if you have normal gastric acid levels, as studies highlight that 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.” The safety and effectiveness of this procedure haven’t been verified in human studies.

According to most practitioners, the HCl challenge goes like this: a person is told to buy a supplement with betaine HCl (or betaine HCl with pepsin) and take 1 capsule before a large meal. If they feel burning or warmth in the stomach, indigestion, or an “acidic” sensation, they are said to be producing enough gastric acid already. In that case, betaine HCl isn’t recommended. If they don’t feel different, deficiency is thought to be possible.

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

Talk to your healthcare provider before doing an HCl challenge.

Okra Pepsin

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

This combined supplement does not appear to have been scientifically studied specifically, but people often use it to improve gut health.

Supplement Reviews

The opinions expressed in this section are solely those of the users, who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.

Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

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.

Takeaway

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

Pepsin is being researched as a standalone supplement or in combination with other digestive enzymes and/or Betaine HCl. Scientists hypothesize it might help with indigestion and low stomach acid, but there’s still not enough evidence to support its use.

This enzyme is not found in foods. Ketogenic and high-protein diets might increase pepsin production in the body.

About the Author

Marisa Wexler

MS (Pathology)

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