The Lack of Progress so Far

This is hard to write because I had hoped to fill this blog with good news. Here is a list of what I have tried and the results so far.

Nexium – no detectable effect

Xantac – no detectable effect

My Sodium Alginate, Sodium Bicarbonate, Potassium Bicarbonate mixture. This has a short term positive effect but I don’t like taking antacids long-term. It will settle my stomach but does not seem to directly influence my voice issues.

Betaine Hydrochloride with pepsin. This is counterintuitive, adding acid and enzymes to my diet. It didn’t do anything as far as I could tell. I neither got better nor worse.

I do have a list of things that make my condition worse. Eliminating these is a good idea but does not eliminate the problem.

Big meals

Rich meals

Sugar

Possibly wheat products

Drinking

Stress

Basically, I have run out of ideas. I can reduce the symptoms a bit but have so far been unable to slay the beast.

I will continue to seek out other treatments.

Update 9-23-2011

I haven’t posted in quite awhile – mostly because there hasn’t been anything significant to report. I am still trying to “cure” myself but the condition is stubborn.

Dr. Kessler, an acupuncturist,  has some interesting views on GERD in general at:

http://chriskresser.com/heartburn

He believes that GERD may be a result of low stomach acid which promotes bacterial growth. This is in line with my thinking that the main purpose of acid in the stomach is to act as an anti-microbial agent. He believes that certain bacteria actually block acid production as a survival technique. His recommendations include a paleo diet. This might in fact be effective but I have trouble staying on diet wagons. Also, he doesn’t specifically address LPR.

Overall, I like Dr. Kressler’s skeptical view of modern medicine. It seems to me that modern medicine is manipulated by big pharm and other immoral corporate forces. Most of us would be much healthier if we simply lived healthier, ate healthier and took fewer drugs.

As far as my progress goes, I have managed to quit coffee which I believe has helped. I have back slid and do have a cup of tea some mornings because it makes me feel content. I have tried the coffee substitute Cafix but have not found it very satisfying. I am good about avoiding spicy and rich foods but still eat meals that are too large at times – mere weakness on my part. I am healthy and strong – at 55 I can still cover 20 miles in an hour on my bike if the route is fairly flat and recently climbed a remote unclimbed, 3000’ rock face with one of my climbing buddies (I did lose 4 pounds in 4 days doing so which I haven’t gained back). My weaknesses are beer and high carb foods, both of which I am trying to control. I no longer take PPI’s of any sort and try to use the alginate/antacid concoction as little as possible.

The LPR is somewhat better but certainly not gone. I still wake up symptom free, probably because my digestive system has been asleep, but have trouble speaking through the middle of the day. I general have trouble from about 10 AM until around 3 PM. I often skip breakfast, a bad thing, since it seems to extend this symptom free period. I have quit talking to doctors since none of them have been able to provide help and they tend to give advice that is contrary to published research.

Experimentation with controlling LPR is difficult because there are too many variables and the scientific method is not very effective when that is the case.

Protease, Pepsin and LPR

I mentioned earlier that I do not believe acid is the active ingredient causing my LPR. I should stress the “my” because my experiences and condition may be very different from what others are living with. Reduction of acid production by taking PPIs does not seem to have any effect on what I have so, if reflux is the problem, it must be some other component of the reflux. The acid may play a role but either it is minor or the PPIs do not reduce the acidity enough.

First, we need to have an understanding of what happens in the stomach and how it happens. We chew up food, swallow and it drops into the stomach. The first thing the body needs to do is to protect itself from harmful microorganisms. Killing germs is the primary purpose of the acid. In fact, there are published papers that discuss the increase in harmful bacteria in the stomach and even pneumonia (6) due to reduced acidity from PPIs. Second, we need to break down proteins so that they can be absorbed. Proteins are broken down by enzymes in the stomach such as pepsin. The final chore that the stomach performs is churning the food into soup before it is expelled into the small intestine. (5)

Wikipedia tells us that “pH approximates but is not equal to p[H], the negative logarithm (base 10) of the molar concentration of dissolved hydronium ions (H3O+)” That probably doesn’t mean much to you since you have probably forgotten your high school chemistry. The only thing you need from the Wikipedia quote is that the scale is logarithmic. Logarithmic means that if the scale changes by a factor of 1, the concentration changes by a factor of 10. Distilled water is neutral and has a pH of 7. A lower pH is acidic and a higher pH is basic. Bleach is a strong base with a pH of 13. Gastric acid is a strong acid with a pH of 1. (2)

Pepsin is the main enzyme in the stomach that digests proteins. Pepsin works best in an acidic environment with a pH of 1.5 to 2.0. It is denatured, or loses functionality when the pH is above 5.0. Reducing stomach acid can block the action of pepsin and hinder the digestion of proteins. (3)

A pH of 5.0 isn’t very acidic. Coffee has a pH of about 5, tomato juice about 4 and orange juice is 3. It is unlikely that you can reduce the acid in your stomach enough to stop the action of pepsin. Some studies show that PPIs allow an acidic pH below 4.0 for one third to one half of the hours in a day(4)

Here is my hypothesis as to what is happening to my larynx. Even if I take PPIs, the reflux material is slightly acidic and the pepsin is still active. The active pepsin comes into contact with my larynx and does what it does which is to digest protein. My larynx is unhappy with being digested and becomes irritated, gets sore and I lose my voice. Since I need to pepsin to digest my food, what I need to do is keep it from getting out of my stomach.

1)      http://en.wikipedia.org/wiki/Protease

2)      http://en.wikipedia.org/wiki/PH

3)      http://en.wikipedia.org/wiki/Pepsin

4)      http://www.medscape.com/viewarticle/480912_3

5)      http://en.wikipedia.org/wiki/Stomach

6)      http://jama.ama-assn.org/content/292/16/1955.short

I mix my own remedy

After reviewing the papers referenced in my previous post, I set about making my own concoction. I also ordered some Gaviscon Advance to try and will post about it when I have done so. The 1979 paper indicated that they had good results with a mixture of Alginic acid with an antacid but the proportions were not given. The earlier references given in the paper need to be purchased or used Gaviscon so I couldn’t get proportions from them either. After I figured out the proportions on my own, I did find a 1977 US patent that does give proportions. Google search for patent 4140760 to see what they used.

I used Sodium Alginate which is the sodium salt of Alginic Acid. It is commercially available as a powder from cooking supply websites and cost me something like $30 with shipping for a pound. For an antacid I simply used baking soda (Sodium Bicarbonate) which I found for free in the kitchen. I also wanted a source of calcium ions to help set the gel and chose Calcium Citrate which I got from the local nutrition store in tablet form.

I chose Baking Soda for the antacid because it is readily available and produces bubbles when mixed with acid. The bubbles are needed to make the gel raft float at the top of the stomach. Since many people need to and perhaps all of us should reduce our sodium intake, I need to find a better antacid. Perhaps Potassium Bicarbonate will work and when I get around to trying it, I will post results.

Calcium Ions cause Alginate to gel. Most calcium supplements are in the form of Calcium Carbonate with is only soluble in an acid but since I was using an antacid, I wanted something more soluble and picked Calcium Citrate as a result. Calcium Chloride may work also and I have some but haven’t experimented with it very much yet. Calcium Chloride must be dissolved in water before taking it since it is exothermic and if taken dry, it will burn you.

Since I don’t want the Alginate to gel before I take it, I do not mix the calcium with the Alginate solution.

To make my concoction, I use a pint of either de-ionized or distilled water which I put in a blender. I used the de-ionized or distilled water because calcium from hard water can gel the alginate into a solid. Since acids also help gel the Alginate, I start the blender and add the Baking Soda first to buffer the solution, and then I add the Sodium Alginate. Sodium Alginate is water soluble but it doesn’t dissolve very easily or quickly, hence the blender. Let it blend for a long time.

Based on experiments so far, I use:

1 pint de-ionized water

1-1/2 teaspoon Sodium Alginate

1-1/2 teaspoon Baking Soda

The tablets contain 800 mg of calcium as Calcium Citrate

The stuff might spoil and make you sick so I make it in small batches and keep it refrigerated.

I use the stuff 30 minutes to 1 hour after eating or when I feel a need for it. I take a few tablespoons at a time. Before taking the solution, I chew up half a tablet of the Calcium Citrate to provide calcium ions in my stomach. Chew up the chalk, and then swallow some of the slime.

Calcium Citrate tastes just like chalk but it isn’t as bad as the reflux. The Aginate tastes like what it is, slightly fishy seaweed and very slimey. You could flavor and/or sweeten it but don’t add anything acidic or that contains calcium.

Warnings:

Talk to your doctor and your pharmacist before trying this.

The mix contains sodium which is bad for many people.

Too much calcium can kill you.

Taking antacids for an extended period can cause health problems.

Read about the risks of all ingredients.

Side effects are unknown

I learn something my doctors don’t know

After reading the papers mentioned in the previous post, I became convinced that the treatment prescribed by my doctors was not going to help and this conclusion was certainly supported by my experience. If anything, I was still getting worse.

I changed my search criteria from looking at the effectiveness of PPI treatment to alternative treatments. I came across a paper in the journal LARYNGOLOGY (1). This article states what I already knew:

“There is however growing evidence from randomized placebo-controlled trials that PPI treatment is not effective in improving symptoms for patients with LPR.”

The article discusses the treatment of LPR by means of reflux suppressants. A reflux suppressant isn’t a drug but a method of blocking the reflux of stomach contents by forming a physical barrier at the top of the stomach. The authors recognize that treatment with PPI’s only removes acid content but does not address other, more damaging, gastric reflux components such as pepsins and bile acids. The authors tested the effectiveness of a commercially available preparation called Gaviscon Advance. Gaviscon Advance is a sort of liquid antacid that not only neutralizes acid but forms a foamy gel which is believed to float at the top of the stomach preventing the stomach contents from moving up and out of the stomach. The authors found that treatment with Gaviscon Advance significantly reduced the symptoms of LPR.

Unfortunately, although Gaviscon products are available at local pharmacies, Gaviscon Advance is not. It can be found on the internet and ordered from the United Kingdom.

I went to the manufacturer’s website and found that Gaviscon Advance had two active ingredients; sodium alginate and potassium hydrogen carbonate. Sodium alginate is a product derived from seaweed and is used by cooks to make gels and for thickening. Potassium hydrogen carbonate, AKA potassium bicarbonate is used to help make bubbles in club soda. The two compounds basically make goo with bubbles in it. The idea is that the resulting mess floats in the stomach and blocks the reflux.

A bit more research finds a 1979 paper in THE JOURNAL OF NUCLEAR MEDICINE (2). It seems that these authors had this figured out 30 years ago. The authors investigate the treatment of reflux with a combination of alginic acid and a mixture of antacids (AAC). They found “that AAC reduces reflux by its floating, foaming, and viscous properties.”

Since acquiring Gaviscon Advance from the United Kingdom is not only slow but expensive I decided to see if I could find an alternative.

1)      The value of a liquid alginate suspension (Gaviscon Advance) in the management of laryngopharyngeal reflux; McGlashan, Johnstone, Sykes, Strugala and DettmarEuropean, Archives of Oto-Rhino-Laryngology, Volume 266, Number 2, 243-251

2)      The mode of action alginic acid compound in the reduction of gastroesophageal reflux J Nucl Med. 1979 Oct;20(10):1023-8. Malmud, Charkes, Littlefield, Reilley, Stern, Rosenberg, Fisher.

Educating Myself

Since the doctors didn’t seem to understand what is happening to me, I began to seriously research LPR and its treatment. I spend a lot of my time researching various topics both for my work and in pursuit of my interests. A long time ago, this research meant long hours in the basement of the library at my university going though indexes and searching for dusty volumes of bound journals. Very often the journals would have to be ordered from other libraries. Today, the internet has made this research a thousand times easier. Not only does Google Scholar make it easy to search for papers, almost all the papers are available to download. Although these papers often cost $25 or $35 to download, most libraries have contracts by which you can get them for free. My university library account allows me free access to a vast body of knowledge. If you are not associated with a university, check with your public library. My county library system also provides access to research journals.

If you haven’t read many research papers, there are a few things to keep in mind. Being published doesn’t mean it is accurate or correct, being published simply means that the paper is worth consideration. Not all papers are good; a good paper will be referenced by many others and will still be referenced long after it is written. When reading a paper, I will often look to see what papers it references first, I will generally read the conclusion second and only then read the paper if it still seems applicable to my question. Many papers are biased either by funding or the writer’s previous work.

I won’t reference all of the papers I reviewed but I think a few will document what I generally found. A 2005 paper in the Journal of the American Medical Association (1) States:

“Laryngeal pathology results from small amounts of refluxate—typically occurring while upright during the daytime—causing damage to laryngeal tissues and producing localized symptoms. Unlike classic gastroesophageal reflux, LPR is not usually associated with esophagitis, heartburn, or complaints of regurgitation.”

Hey, that’s me; I am fine at night and wake up without symptoms. This is contrary to the usual experience with acid reflux wherein suffering is worst during the sleeping hours. Farther along, the article states:

“Although some patients respond to conservative behavioral and medical management, as is the case with gastroesophageal reflux, most require more aggressive and prolonged treatment to achieve regression of symptoms and laryngeal tissue changes. Surgical intervention such as laparoscopic fundoplication is useful in selected recalcitrant cases with laxity of the gastroesophageal sphincter.”

Me again, I am not responding to conservative behavioral or medical treatment. The paper includes a treatment flow chart (see below). In the conclusion I find:

“Unlike with GERD, response to PPI therapy in patients with LPR has been described as highly variable. This is in part because LPR requires more aggressive and prolonged therapy than GERD.”

My path descends down the right hand path which rather disturbingly does not result in a cure or perhaps without even improvement. It seems that LPR is not usually improved or cured by PPI treatment and that it is difficult to treat.

“The few randomized, controlled trials have failed to demonstrate superiority of PPIs over placebo for treatment of suspected LPR.” (2)

“Pooled analysis of these two randomized-controlled trials failed to show any effect in favour of treatment with proton pump inhibitors.” (3)

One again, I am not a doctor and if this information seems applicable to you, share it with your doctor. Although doctors don’t know everything, they know a whole lot that you don’t know.

1)      http://jama.ama-assn.org/content/294/12/1534.full.pdf+html

2)      Empiric Treatment of Laryngopharyngeal Reflux with Proton Pump Inhibitors: A Systematic Review,    Karkos & Wilson, The Laryngoscope, Volume 116, Issue 1, pages 144–148, January 2006

3)      A systematic review of the role of proton pump inhibitors for symptoms of laryngopharyngeal reflux, Sen Georgalas & Bhattacharyya, Clinical Olaryngology, Volume 31, Issue 1, pages 20–24, February 2006

Part Two

At this point in my story I have been to three doctors, been diagnosed with LPR and have begun taking Nexium and sometimes Xantac (Ranitidine). Ranitidine is a histame blocker that inhibits acid production. The mechanism being different than Nexium implies that using both blocks more acid production than either one alone might. I am down to one cup of coffee a day, cutting back on rich foods and big meals, taking two medications, easing up on the hard exercise and am still not getting better.

Not being able to speak isn’t life threatening but it is certainly life disrupting. When I go rock climbing it is nice to be able to communicate with your partner who may be out of sight above or below you. Recently I was testifying as an expert in court and my voice was so bad that while I was trying to speak; the judge poured a paper cup of water and leaned over to hand it to me. Not being able to speak does not bode well for a guy who makes his living talking to people.

Anyway, I went back to my GP doctor and he sends me off to my second ear nose and throat specialist (ENT2). ENT2 pokes a fiber optic scope up my nose until he can see my vocal chords. He doesn’t see anything too bad so he has me come back for a stroboscopic inspection. Besides gagging me, this second look finds pretty much nothing. I realize that ENT2 is trying to identify the change in the mechanics of my vocal chords, not why they are changing so I go back to my GP  to plead for help.

My GP sends me to a gastroenterologist. The gut doctor is a nice guy and wants to scope my stomach to look for whatever might be there. This is apparently what gastroenterologists do. We do this fun little procedure and he finds nothing of interest. By taking a biopsy, he does verify that I do not have a certain bacterial infection that might be the cause of my condition. This is when he tells me that he has not had success in his efforts to treat this condition in other patients. He adds Sucralfate to my medication list. Sucralfate forms goop that coats the stomach and is usually used to fight ulcers.

Taking three medications and making lifestyle changes still has no effect. Redoubling my efforts, I completely quit coffee and all caffeinated drinks. I reduce food intake and never drink more alcohol than two beers. I never have red wine, citrus and very little in the way of tomato products. No chocolate and no bacon cheese burgers either. I start to work with timing and dosage of both food and medication, all with no significant result. This is getting depressing.

I notice that when I get up in the morning, my voice is usually okay. When I get hungry or eat, which I inevitably do, I become hoarse. This is atypical for acid reflux. People with acid reflux generally are at their worst at night in bed. I begin to suspect that what I have may be reflux but not acid reflux. Taking both Nexium and Xantc must reduce my stomach acid about as much as possible. I need to take matters into my own hands and see what I can do. The doctors all tell me they can’t fix it so I guess I will have to do it myself.