The Science of Trial and Error

Almost two years ago I started to have a lot of stomach upset, a condition that is called Irritable Bowel Syndrome – IBS. Dealing with it has been a long learning path. Even if you don’t have any gastrointestinal issues, you may find it interesting to read this account. It demonstrates how
– Modern medicine still relies a lot on trial and error
– Why doing your own research is important
– How to collaborate with your doctor to find solutions to health problems

I never had a history of gastrointestinal (GI) problems. But with age and perhaps reactions to medicines, things change. I developed a typical gamut of gut (stomach) problems – cramps, gas, bloating, diarrhea. The pain and discomfort were not that severe but their erratic and sudden occurence created havoc with my daily life. I had accidents on occasions when I was out somewhere and was not able to get to a bathroom in time. I restricted some activities and most travel was out of the question.

I tended to have more stomach upset in the morning so I grew suspicious of some of my breakfast foods. I eliminated eggs and coffee from my diet. Eggs are very rich and coffee is well known to be a possible irritant of the GI tract. It wasn’t that hard for me to give up coffee. I had never gotten into the gourmet coffee grind and I never went to Starbucks. I also never liked coffee all that much, but it made milk and sugar taste good and went well with dessert. It was hard to tell if these changes in diet helped very much because my symptoms persisted and continued to be very erratic and unpredictable. 

Yhe next thing I tried was yogurt. I had long been a big believer and promoter of yogurt, ever since my student days when I had founded the Underground Yogurt Co-op (but that is another story). I was no longer eating yogurt regularly so I added it to my breakfast. Disappointingly this did not have the magic outcome that I had professed in my younger days. 

Next I upped my game to a probiotic. My wife had seen a gastroenterologist a number of years earlier about IBS symptoms and he had recommended Align, which had worked well for her.

Probiotics are live bacteria and yeasts that supplement the bacteria that inhabit your GI tract and play an important part in digestion. A number of foods such as yogurt contain probiotics but there are probiotic supplements that have more bacteria than you get from food. I took Align for several months but it did not seem to help me very much.

There are up to 1000 different types of bacteria in the GI tract. Which ones are the ones that are important for helping with IBS? I found this really comprehensive article about The Best Probiotics for IBS that had a guideline. Based on your symptoms, it recommended a particular type of probiotic.

Going through its checklist, I selected and found a probiotic containing Lactobacillus acidophilus. After what I thought had been such good research, I had high hopes for this probiotic. But it turned out to be an example of the gap between theory and practice. In practice this supplement exacerbated my cramps and diarrhea and I had to stop using it.

The next thing I tried was Metamucil. I had seen it recommended in a number of articles about IBS. Metamucil is a fiber supplement that is typically used daily to prevent constipation. It seems contradictory to take it when your digestive problems are the opposite, namely diarrhea. However it does seem that making sure you have enough fiber in your diet is good for general digestive and bowel health. I diligently took Metamucil for six weeks. While there might have been some slight improvement, it really was not effective enough. 

It occurred to me that perhaps a different sort of fiber might work better for me. Metamucil is psyllium husk but there are other fiber supplements. As I was browsing in the drugstore I found another fiber supplement that was made from guar gum and was advertised to be

Low FODMAP and CERTIFIED for IBS

I grabbed it off the shelf with great hope that this really sounded perfect for me. However it turned out to be a disaster. After 4 days my diarrhea had become worse than ever and I had to discontinue that supplement.

With this lack of success from common sense and my own devices, I turned to modern medicine. The first advice I got from my doctor was to try a stricter diet. He suggested lactose-free, gluten-free, and FODMAP. I tried them all. None led to any big improvement and I could not see any pattern between any particular food and the IBS symptoms.

My next step was a referral to a gastroenterologist. The first thing he wanted to do was a colonoscopy. I wasn’t quite due for another one according to the standard 5 year schedule but I succumbed to the annoying procedure in the hopes of reaching a diagnosis. Fortunately I had a very clean colon, but unfortunately there was no diagnosis. Some gastrointestinal conditions have physical symptoms which can be seen such as diseases like colorectal cancer, colitis, celiac disease or diverticulitis. If a gastroenterologist can’t see anything physical, your condition will generally just be lumped into the category IBS, a catch all to cover everything that modern medicine doesn’t understand yet. The GI guy didn’t suggest any medication or treatment.

So it was back to the drawing board. The Internet has a lot of information but sometimes it’s not easy to find the right information that’s going to help you. Eventually I came across IBS Tales, a website with a wealth of information. It was created by a woman who had IBS for over 20 years and had explored and documented many of its different aspects. One section of the website contained stories from people who have IBS. A lot of these were interesting but it wasn’t easy to draw conclusions from individual cases that would apply to me. The website had recommendations for a number of books. I bought this one, but in the end it did not help me very much.
The First Year: IBS: An Essential Guide for the Newly Diagnosed

The most interesting part of the website for me was the section on Treatment Reviews. In particular there was a subsection for IBS Medications. It had a long list of antispasmodic drugs. It is thought that one cause of IBS is abnormal “motility” in the digestive system. Normally the intestines rhythmically contract and then relax to move food through the intestines. Contractions that are stronger and last longer than usual can cause gas, bloating and diarrhea. Contractions that are weak can slow the passage of food and lead to constipation. Antispasmodic drugs slow the motility of the GI tract by relaxing the muscles in the stomach and intestines.

On a hunch, I decided to try and see if the FDA had approved any drugs for IBS. I soon hit paydirt. I was astounded to discover that there were not one, not two, not three, but four FDA approved drugs for IBS; two for IBS-C (constipation) and two for IBS-D (diarrhea). In my consultations with several doctors, this option had never been mentioned.

After some more digging I hit a gold mine. I found an article in the American Journal of Gastroenterology titled Clinical Guideline: Management of Irritable Bowel Syndrome. It was a review of studies of IBS treatments and provided a list of not only what was recommended but what not was not recommended.

Armed with my new medical knowledge, I made an appointment with the gastroenterologist for a follow up of my case.

In the meeting, I summarized the various things I had tried since my colonoscopy, all without real improvement. Then I asked him about using an antispasmodic drug. He said No he didn’t prescribe them, they were addictive. I had not come across this in anything I had read so I asked “There are quite a lot of antispasmodic drugs, are they all addictive?” 

He didn’t answer. Instead he said “Are you going to read things on the Internet and do your own research or did you come here for my medical advice?” 

I backed off and said No I would like to know what he recommended. He said I should use Metamucil. I replied that I had tried Metamucil and it really didn’t work for me. Then he asked if I used the flavored Metamucil. I said “Yes, I used the orange flavored one.” He said, “That’s your problem. The added sugar prevents Metamucil from working properly. I have a lot of patients using plain Metamucil and they’re all doing well.” 

So I said (dubiously) “Thank you. I will try that.”

At home I checked my Metamucil jar that was still on the shelf. Even though it was orange flavored, it was sugarless. So I don’t know what that sugar theory was. But if this doctor had so many IBS patients doing well with Metamucil, I decided I should give it another try. However to no avail. After six weeks I still saw no improvement.

He did give me one piece of useful advice. He suggested that before going on an outing, if my stomach was unsettled I could use Imodium as a preventative. I had relied on Imodium many times when diarrhea had become severe and it worked very well, but it was not recommended for use on a regular basis. However, using a lower dose of Imodium occasionally as a preventative measure slows the motility of the intestinal tract and it did prove to be helpful, but overuse could lead to constipation.

Then a curious thing happened. I got a cold that lodged in my chest. After seven weeks I got an antibiotic. Five days of levofloxacin cleared up my respiratory infection and it also cleared up my IBS cramps and diarrhea. It must be that the antibiotic had killed certain intestinal bacteria that had been interfering with my digestive system. 

This was a wonderful turn of events and I enjoyed it for about four months. But then my IBS symptoms gradually came back. 

I had pretty well tried all the non pharmacological treatments in the Journal of Gastroenterology IBS guidelines. I felt that the best way forward was to try one of the prescription drugs that was recommended for IBS. Going back to the gastroenterologist surely was a dead end, so I booked an appointment with my family doctor. I extracted the following summary of the pharmacological treatments from the Journal paper to bring in to review with him. He actually hadn’t seen the paper which had been published in 2021 or a very similar paper that had been published in 2019 by the Canadian Association of Gastroenterology.

___________________________________

1. We recommend against the use of antispasmodics currently available in the United States to treat IBS symptoms.
Conditional recommendation; low quality of evidence.

2. We recommend that TCAs (tricyclic antidepressants – amitriptyline, nortriptyline, imipramine, desipramine) be used to treat symptoms of IBS.
Strong recommendation; moderate quality of evidence.
57% improvement vs 36% placebo.

3. We recommend the use of rifaximin (FDA approved) to treat IBS-D symptoms. 
Strong recommendation; moderate level of evidence. 
Most favorable safety profile. 
41% improvement vs 32% placebo but relapses; 64% respond to retreatment.

4. We suggest that mixed opioid agonists/antagonists (eluxadoline FDA approved) be used to treat IBS-D symptoms.
Conditional recommendation; moderate quality of evidence.27% improvement vs 17% placebo.

___________________________________

He thought that treatment 2 would be the best. It had the highest response rate in trials; 57 % of patients had improved and he was familiar with the antidepressants drugs which he prescribed for a lot of patients with depression. 

I said I thought recommendation 3 might be a better option for me. It had a lower success rate in trials, only 41%, but I said that I was pretty sure that it would work for me, because this drug was actually an antibiotic and I had just had success with an antibiotic. In addition the treatment was only two weeks. I would not have to take it every day and it had the lowest risk of side effects of all the recommendations.

So that’s what we did. He wrote out a prescription for rifaximin. After the 14 day course of this antibiotic, my IBS symptoms improved immensely. After almost two years, I could lead a more normal life.

This is not a story that ends by saying “And he lived happily ever after.” People on rifaximin tend to relapse. At that point I will have to decide whether to use it again or try one of the other treatments. At this time IBS cannot be considered an illness that can be cured by a treatment. But there are a lot of options that can make it more manageable.

What is there to learn from this convoluted path of discovery?

First of all, no one treatment works for everybody. Even the FDA approved drugs didn’t work for most people; they worked for less than 50%. In the case of rifaximin, the clinical trial did not show a huge improvement over the placebo group, only 41% versus 32%. However this was enough to be statistically significant and receive FDA approval. 

What this means is that most things that you try will probably not work. You have to keep trying more options until hopefully you find a treatment that works for you. In spite of the many advances in modern medicine, a lot of medicine is really just trial and error, and it can be quite a lot of error.

The second thing to learn is how important it can be to do your own research. It was only after I found the Journal of Gastroenterology IBS guidelines which provided me with the direction to push for a treatment that ended up working for me.

And finally, it’s important to find a doctor that you can collaborate with so that you collectively arrive at good medical decisions.