Function of Pepsin: What Does Pepsin Do?
Pepsin is a protease, a powerful enzyme that breaks down protein. It is so potent that scientists use “pepsinization” (usually with pig pepsin), as the first step in biochemistry to break down very large molecules into their component parts.
The idea that Acid Reflux is really Peptic Reflux is based on the science and cell biology, that is, how pepsin affects tissues and organs at a cellular level.1-18, 20, 21, 23, 24 Nikki Johnston and I have done much of the work, having reported how pepsin disrupts many cellular functions and causes inflammation, even neoplasia (cancer).1-4, 6-8, 10, 12, 16, 20, 24, 29, 40, 44
Shown under the microscope (photo below) is the histopathology of an ulcer of the vocal cord in a patient with Silent Reflux and hoarseness.40 This biopsy is stained for pepsin; the brown material is pepsin. You can see pepsin on the surface, in the tissue and even within inflammatory cells.
This is classic inflammation, most intense (dark area) over the ulcer. When combined with clinical data,41-43 this photo tells the story: Pepsin is the cause of reflux-related inflammation and tissue damage.1-21, 39, 40, 45, 49 Reflux laryngitis can also lead to vocal cord nodules, polyps and cancer; and similar effects can be seen in the nose, throat, voice box, sinuses and lungs. The causal link between pepsin and cancers of the aerodigestive tract (throat, esophagus, lung) has been established.17, 20, 22-24, 44, 45 In one study, we found pepsin in every laryngeal cancer biopsy.4 And after 40 years working in this field, I believe that one can get cancer without smoking, but not without reflux. And that’s all of them, laryngeal, pharyngeal (throat), esophageal and lung.
Pepsin is a protease, a powerful enzyme that breaks down protein. It is so potent that scientists use it, “pepsinization,” usually with pig pepsin, as the first step in biochemical analysis by breaking down large molecules into their component parts.
The idea that acid reflux is really peptic reflux is based on the science and cell biology, that is, how pepsin affects tissues and organs at a cellular level.1-18, 20, 21, 23, 24 Nikki Johnston and I have done much of the work; we have reported that pepsin disrupts many cellular functions and that it is the cause of inflammation, even neoplasia (cancer).1-4, 6-8, 10, 12, 16, 20, 24, 29, 40, 44
Shown (under the microscope) in the photo below is the histopathology of an ulcer of the vocal cord in a patient with silent reflux and hoarseness.40 This biopsy tissue is stained for pepsin, and the brown material is the pepsin. You can see pepsin on the surface, in the tissue, and even within inflammatory cell
When It Comes to Reflux Science, Pepsin Matters
Here is some science that you should know if you have reflux, because understanding how pepsin works, and how to get rid of it, are key to successful treatment.4-7, 10, 12, 40, 46 Remember that pepsin needs some acid to turn it on,5 and it is denatured (dies) at pH 9.5,46
Here is the pepsin activity curve.5 It shows that pepsin has 100% of activity at pH 2—the same pH as many soft drinks like Coca Cola—and 50% peptic activity at pH 5. Almost all soft drinks are pH <5, acidic enough to make soft drinks the number-one dietary risk factor for reflux.40 Yes, soda is very bad for refluxers! Don’t believe me? Purchase some pH paper to test the beverages that you drink for “pH-safety.” This is why I prohibit all bottled beverages as part of a Reflux Detox treatment program; see Dropping Acid: The Reflux Diet Cookbook & Cure. During this first phase, I recommend consuming nothing below pH 5.40,43
Meanwhile, there is still a small amount of peptic activity at pH 6. But pepsin is denatured, broken down, dies at pH 9.5,46 That’s why I recommend drinking alkaline water pH >9 and consumption of a low-acid diet during the initial phase of treatment.40, 43, 46
Pepsin Detection as a Diagnostic?
Pepsin is an excellent marker for reflux and it may be detected in tissue biopsies and in the saliva of people with LPR.47 I started work on developing a spit-in-a-cup pepsin assay in 1986. My epiphany and inspiration came when I learned that police forensics had a test for vomit based upon detecting a pepsin-like enzyme.
My work on developing a pepsin assay was patented in 1996.48 I never brought this test to market, because our internal data suggested that a one-time sampling was inaccurate, that is, people with reflux were often negative, and people without reflux were sometimes positive. I feel that spit-tests for pepsin (e.g., Peptest) do not have much value as diagnostic tests go. Far better would be an examination by an ENT physician who knows what s/he's looking at.
New Anti-Pepsin Anti-Reflux Treatment with Fosamprenavir
Clinical trials have failed to demonstrate a therapeutic benefit of PPIs for LPR.26-28, 32, 49, 50 N-Zyme Biomedical aims to provide a pepsin-inhibitor (Fosamprenavir) as the first safe, effective and efficient treatment for LPR (laryngopharyngeal reflux), addressing a significant unmet clinical need.38
- Fosamprenavir is an FDA approved retroviral therapy for HIV/AIDS.38 It is well-tolerated and targets a foreign virus not present in most people; so it is ideal to repurpose, potentially allowing safe assessment in planned phase 3 clinical trials.38
- Fosamprenavir binds to pepsin and inhibits its enzymatic activity. It has been shown to abrogate pepsin-mediated laryngeal inflammation and mucosal damage in an established in vivo mouse model of LPR.38
- Epidemiology data support its efficacy: 5/2062 (0.2%) patients taking an HIV-inhibitor have LPR, compared to 10-34.4% of the general population.38
At present, N-Zyme Biomedical anticipates using Fosamprenavir in an inhaler and in pill form. I will keep you, my readers, abreast of the progress of research as data become available. For potential investors contact N-Zyme Biomedical.
I normally would not normally include so many references in a blog; however in this case, I believe that the cited papers are important and much-overlooked, ignored. Perhaps, that’s because Dr. Nikki Johnston’s and my cell biology work was published in the otolaryngology (ENT) literature, and most ENT doctors don’t read basic science articles; and perhaps most scientists and physicians in other fields don’t read the otolaryngology literature.
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