Why Pepsin (Not Acid) Is Driving Your LPR Symptoms — With Dr. Inna Husain

You're taking your PPI. You've cut out coffee, citrus, and everything else on the trigger list. You're sleeping with your head elevated. And your throat still burns. That lump feeling is still there. The chronic clearing won't stop.

If that's where you are, I want you to hear this clearly: you're probably not doing anything wrong. Your treatment might just be targeting the wrong thing.

I sat down with Dr. Inna Husain — Harvard and Northwestern-trained laryngologist, author of over 50 peer-reviewed articles, and one of the leading LPR specialists in the country — for the latest episode of The Reflux Revolution Podcast. What came out of that conversation is the most comprehensive explanation I've ever heard for why LPR is so resistant to standard treatment.

The Problem With Only Treating Acid

Most people — and most doctors — think of reflux as an acid problem. And it is, in part. But the word "reflux" just means movement: content from your stomach moving up into your esophagus and throat. And your stomach isn't full of acid alone. It contains digestive enzymes, bile salts, and a protein-digesting enzyme called pepsin.

When you have a reflux event, pepsin comes up along with the acid. And pepsin behaves very differently from acid once it reaches your throat.

Here's what makes pepsin uniquely problematic for LPR patients: it can hide in the cells of your throat tissue. It sits there, dormant, waiting. Then, if you drink something acidic — a soda, orange juice, coffee, or even just food with a low pH — that pepsin becomes activated again, causing tissue inflammation that produces the exact same sensation as acid exposure. Your throat burns. That lump comes back. And your PPI had nothing to do with stopping it, because PPIs don't stop pepsin. They reduce stomach acid. That's it.

Dr. Husain put it plainly: "Pepsin can actually hide in the tissue. It can lay dormant waiting for exposure to acid from our diet to become activated. And once pepsin becomes activated, that can cause a lot of tissue inflammation."

The clinical research behind this comes largely from the work of Dr. Nikki Johnston — if you want to go deeper, her lab's publications on pepsin and laryngeal tissue are worth reading.

Why PPIs Often Fall Short for LPR

PPIs (proton pump inhibitors) reduce the acidity of your stomach contents. In theory, a less acidic environment means pepsin is less active. The problem: it takes a very, very low acid level to truly inactivate pepsin — levels that are difficult to maintain consistently. And PPIs don't stop reflux from happening. They just change what comes up.

So pepsin still refluxes. It still attaches to throat tissue. And it can stay there for two to three days. If another reflux event happens within that window, the clock resets. This is how LPR symptoms become chronic even in people who are "compliant" with their treatment plan.

The practical implication: treating LPR well means working on two things at once. First, reduce the reflux events themselves (mechanical triggers, sphincter function, hiatal hernia management). Second, reduce dietary acid exposure that can reactivate tissue-bound pepsin even when reflux isn't actively happening.

What's Coming: A Drug That Actually Targets Pepsin

Here's the part of this conversation I found most exciting. Dr. Husain shared that there's currently a drug called Fosamprenavir in clinical trials as the first direct pepsin inhibitor.

Fosamprenavir was originally developed as an anti-retroviral for HIV patients. Researchers noticed that those patients had unusually low rates of reflux symptoms — and the mechanism turned out to be the drug's ability to deactivate pepsin. Dr. Nikki Johnston's lab has been leading this research, and trials are now underway to evaluate it specifically for LPR and GERD.

If it works, it would be the first treatment that directly inhibits pepsin — not just reduces stomach acid to try to indirectly make pepsin less active. Dr. Husain called it a potential game-changer, and that's the right framing.

Gaseous Reflux: The Reflux You Can't Feel

One of the most clarifying moments in this conversation was when Dr. Husain explained gaseous reflux — also called vapor reflux.

Your stomach vents itself regularly through what are called transient lower esophageal relaxations. These happen more at night. When the stomach vents, gas rises — and gas is silent. There's no liquid sensation, no burning feeling in the chest, no heartburn. But if that gas carries pepsin or acid, it can travel all the way up through the throat to the back of the nose and cause significant irritation in those tissues.

This is likely part of why some patients still have LPR symptoms even after reflux surgery. Surgery can create a tighter seal, but it can't completely close the lower esophageal sphincter — you still have to swallow. Gaseous reflux can still occur.

Alginates — algae-based supplements that create a gel raft on the surface of stomach contents — can help here. Both Dr. Husain and I recommend Reflux Raft specifically. The alginate creates a physical barrier that gaseous reflux has to work against. It's not a complete solution, but it's a meaningful tool, especially taken before bed.

Laryngeal Hypersensitivity: When the Nerves Become the Problem

There's another layer to persistent LPR symptoms that doesn't get talked about enough: laryngeal hypersensitivity, also called irritable larynx syndrome. These terms are interchangeable and describe the same thing — sensory nerves in the throat that fire signals they don't need to.

The larynx (voice box) is one of the most highly innervated organs in the body. It has to be — it's there to protect your airway. Those sensory nerve endings are branches of the vagus nerve, and when the larynx has been chronically irritated (by reflux, infection, or other causes), those nerves can become hyperactivated. They start sending alarm signals for stimuli that shouldn't register.

This is why some patients feel symptoms constantly, around the clock, even when testing shows no active reflux. The tissue has settled, but the nervous system hasn't caught up.

Treatment for laryngeal hypersensitivity is multi-pronged. Speech language pathologists play a critical role — working with patients on cough suppressive therapy, redirecting the urge to throat clear toward less traumatic behaviors (like a hard swallow or humming), and increasing awareness of what can and can't be controlled. For cases that don't respond, Dr. Husain uses superior laryngeal nerve blocks — a local anesthetic and steroid injection near the nerve — or neuromodulators, which are medications that reduce nerve sensitivity.

A Note on Throat Clearing (and Why It Makes Things Worse)

One thing Dr. Husain mentioned that I think is underappreciated: the act of throat clearing itself causes the same kind of irritation as a reflux event. When symptoms have been going on for a long time, it becomes genuinely difficult to separate what's being driven by reflux and what's being perpetuated by the throat clearing response.

This is where SLP work becomes so valuable. Before you can know how bad the reflux actually is, you have to reduce the traumatic behaviors first. Then you can see what remains.

What to Do If You're Still Stuck

Dr. Husain's closing message was this: if you've been diagnosed with LPR and you're not improving, it's worth going back to the beginning. Not everyone with laryngopharyngeal symptoms has LPR. There can be other explanations — hypersensitivity, muscle tension dysphonia, allergies, or a combination of several things. A second opinion with a laryngologist (not just a general ENT, but someone who specializes in the larynx) can be the turning point.

The science in this space is moving fast. We have better tools for understanding LPR than we did five years ago, and we're close to having better treatments too. You don't have to keep accepting "just stay on your PPI" as the only answer.

Ready to heal your gut for good?

If you are tired of simply treating the symptoms of GERD or LPR apply for a personalized 1:1 program with a FLORA Nutrition GI Registered Dietitian. Our clients receive a custom roadmap to address the root causes of their symptoms, leading to lasting relief and restored digestive wellness. Take the next step toward feeling calm, comfortable, and confident in your body again. Apply to work with FLORA here.

👩‍⚕️ Author:

Molly Pelletier, MS, RD, is a Registered Dietitian specializing in Gastroesophageal Reflux Disease (GERD), Laryngopharyngeal Reflux (LPR), and integrative gut health nutrition. Through FLORA, she helps clients resolve complex GI symptoms using evidence-based, root-cause protocols.