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Diagnosing Gastroparesis – Part 6

Sep 10, 2015

Diabetes Solution
Richard K. Bernstein, MD, FACE, FACN, FACCWS
Part 6 Chapter 22


Erythromycin ethylsuccinate is an antibiotic that has been used to treat infections for many years. It has a chemical composition that resembles the hormone motolin, which stimulates muscular activity in the stomach. Apparently, when stimulation of the stomach by the vagus nerve is depressed, as with autonomic neuropathy, motolin secretion is diminished. Three papers delivered to the 1989 annual meeting of the American Gastroenterological Association demonstrated that this drug can stimulate gastric emptying in patients with gastroparesis.  In people without gastroparesis, erythromycin can cause nausea, unless taken after drinking fluids. I ask my patients to drink two glasses of water or other fluid before each dose. I prescribe erythromycin ethylsuccinate oral suspension just before meals. We start with 1 teaspoon of the 400 mg/tsp concentration, and increase to several teaspoons if necessary. As each teaspoon of this suspension contains 3.5 grams of sucrose (table sugar), it will be necessary to increase slightly the doses of insulin covering meals to reduce blood sugar elevation while this medication is used. If the liquid is kept in a refrigerator, the taste begins to deteriorate after 35 days.At room temperature, taste deteriorates after 14 days. I have seen no side effects from this medication. I insist that patients who use it chronically take 1 probiotic capsule (such as Florastor [saccharomyces boulardii], Culturelle Lactobacillus GG, or Nature’s Way Primadophilus Reuteri) at least 2 hours before or after each dose. This is to restore to the intestine natural bacteria that can be destroyed by this antibiotic. It is also wise to consume one 150 mg fluconazole tablet per month to inhibit growth of fungus in the GI tract. I have not found erythromycin to be especially effective for treating gastroparesis, despite published studies.


Betaine hydrochloride with pepsin is a potent combination that can predigest food in the stomach by increasing acidity and adding a powerful digestive enzyme. It can be procured at most health food stores or at Rosedale Pharmacy. Because of its acidity it should not be used by those with gastritis, esophagitis, or stomach/duodenal ulcers.  Food that has been predigested will more likely pass through the narrowed pyloric valve of gastroparesis.We initially use 1 tablet or capsule midmeal. If no burning is perceived, we increase the dose to 2 and then eventually 3 tablets or capsules spaced evenly throughout subsequent meals. It should never be chewed or taken on an empty stomach.  Since betaine HCl with pepsin, unlike cisapride, does not attempt to stimulate the vagus nerve, it is frequently of value for even severe cases of gastroparesis.

Nitric Oxide Agonists
Although the aforementioned agents can be very effective when gastroparesis is mild, their effectiveness in minimizing blood sugar uncertainty after meals diminishes when this condition is more severe.

My frustration in trying to circumvent this problem has led to my investigation of a class of substances called nitric oxide agonists. Such agents are currently being used to relieve effects of angina in patients with cardiac disease. Since they work by relaxing the smooth muscle in the walls of coronary arteries, I assumed that they could also relax the smooth muscle of the pyloric valve.

My initial trial was with a medication called isosorbide dinitrate. I had it prepared as a suspension in almond oil (with flavoring) so that it could coat the pylorus and work directly upon it. I had it compounded in a concentrate of 5 mg/tsp (1 mg/ml). I was pleased to see that my assumption proved correct—it was very effective for nearly all ofmy patients who used it. Thus far, it appears to be more successful than any of the agents described above. Nevertheless, it is only partially effective for more severe cases of gastroparesis.

This formulation can be prepared by any compounding chemist (see footnote, page 202). The only adverse effect I’ve observed has been headache in about 10 percent of the users. Although the headache usually resolves after several days of use, I try to prevent it by starting with very small doses that can then be gradually increased.

I therefore recommend that initially . teaspoon be taken 30–60 minutes before dinner. After one week, we increase the dose to 1 teaspoon.
If this fails to level off blood sugars at bedtime and the following morning, we continue 1 teaspoon for a week and then increase it to 2 teaspoons. If this is not fully effective, we then increase to 3 teaspoons.  If this dose doesn’t do the trick, I discontinue the treatment, as further increases are unlikely to be effective. If 1–3 teaspoons work, we then use the same dose 30–60 minutes before each meal. It’s been unusual for this formula to be totally ineffective. The liquid must be vigorously shaken before use.

If you have a cardiac condition, isosorbide dinitrate should not be used for gastroparesis unless approved by your cardiologist.

Unfortunately, like tegaserod maleate, isosorbide dinitrate usually stops working after a period of weeks to months. I therefore attempt to increase effectiveness and lower blood sugar levels by applying a chemically similar product to the skin directly over the pylorus. What I prescribe is a nitroglycerine skin patch. These are available by prescription at any pharmacy in strengths of 0.1, 0.2, 0.4, and 0.8 mg. The patch is placed over the pylorus, which is located on the midline of the abdomen above the navel, about 1. inches (37 mm) below the middle of the lowest rib where it forms an inverted V. The patch is applied on arising in the morning and removed at bedtime. We start with the 0.1 mg patch and increase the size each week if there are no adverse effects.  As with isosorbide dinitrate, nitroglycerine should not be used for gastroparesis without your cardiologist’s approval if you have a cardiac condition.

Another alternative is the clonidine adhesive skin patch. This product is sold as Catapres in all pharmacies to lower blood pressure and requires a prescription. It is a powerful smooth muscle relaxant. It can, however, cause somnolence (sleepiness) in some people. We therefore start at the smallest size (1 mg) for the first week and increase it to 2 mg for the second week, then 3 mg for the third week and thereafter.  Although each patch will work for a week on most people, we remove it at bedtime and replace it the next morning. Since the patch’s adhesiveness will be reduced after it’s removed, you can use paper tape to keep it attached after the first day. If it causes tiredness, we lower the patch dosage or discontinue it.

Like the aforementioned nitric oxide agonists, it can stop working eventually. If it has been effective and stops working, we discontinue it and restart it after a couple of months. Some patients find that a patch will stop working after 3–4 days. For these people, we change to a new patch midweek.

The reason we remove the clonidine (or nitroglycerine) patch from the skin at bedtime is to slow down the development of tolerance to its action which eventually occurs. I also recommend alternating daytime skin patches—one week on clonidine and one week on nitroglycerine— alternating over and over.

We would like to thank the publisher Little Brown and Company and Dr. Richard K. Bernstein, for allowing us to provide excerpts from The Diabetes Diet.

Copyright © 2005 by Richard K. Bernstein, M.D. All rights reserved. No part of this book may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without permission in writing from the publisher, except by a reviewer who may quote brief passages in a review.

Author’s Note:
This book is not intended as a substitute for professional medical care. The reader should regularly consult a physician for all health-related problems and routine care.

For more information on Dr. Bernstein’s and to purchase his books, CD’s or get access to his free monthly webinars, visit his website at DiabetesBook.com.