Managing GI Issues in Amyloidosis – FAQ

Dr. John Clarke from Stanford University presented in a recent ARC Talks webinar on Gastro Intestinal Disturbances and Symptom Relief for Amyloidosis. This report covers the most frequently asked questions and recommendations.

A recording of our GI webinar from September 23rd is available below. Watch now to hear Dr. Clarke provide an explanation of what causes GI issues in amyloidosis and how to help control the symptoms:

GI issues caused by amyloidosis and in some cases treatment,  significantly impact many patients quality of life. Dr. Clarke provided very helpful information, and answered many questions on how to alleviate and manage these symptoms.

Q: Is there anything that can be done to prevent vomiting in the morning, besides not eating after 5pm?
A: Vomiting in the morning can have two causes: 1 – things aren’t emptying from the stomach well enough or 2 – reflux, and it’s hard to know which one is the cause. For dietary modifications, you could lengthen the time between dinner and when you’re lying down for bed, or try having a larger lunch and a smaller dinner. You could also try to have a liquid dinner, like soup, as liquid empties from the stomach in about 40 minutes whereas solid food takes about 6 hours. From a medication standpoint, we often recommend two approaches: one for reducing the acid in the stomach in case the cause of the vomiting is reflux, and also something to try to speed stomach emptying. So potentially erythromycin or a prokinetic might help in that scenario.

Q: Can any drugs that are rough on stomach/intestines be given subcutaneously to avoid the GI tract?
A: Generally, we recommend patients to try to stay away from NSAIDS, like Advil, which can cause pain and affect absorption as well. My gut feeling is that subcutaneous versus intravenous drugs probably wouldn’t make a big difference, because a lot of the GI effects are caused by a change in endorphins and chemicals, rather than direct contact.

Q: How long might the GI tract take to repair itself following a stem cell transplant?
A: It can take a while for the GI tract to completely recover. For something like ulcers, this takes about 12 weeks, but other issues can take as long as 24 months.

Q: Can probiotics help with any of the GI issues caused by amyloidosis?
A: This is an interesting question. To give a bit of background information, the average person has about 3 pounds of gut bacteria present, but we have little insight into what’s considered “normal,” as we can only culture about 20% of what’s there. It’s thought that every person has a very individual microbiome, as different as a fingerprint. The benefit of probiotics is that you are repopulating the good bacteria in the gut. There is good evidence that shows that probiotics can help with bloating and also good evidence taken from studies of the stool that shows that probiotics do a good job with rebalancing of bacteria. One issue with probiotics is that they are not regulated by the FDA currently, so there is a relatively loose threshold to which bacteria and how much of it the probiotics should contain. I tell people that are interested that it is worth a try, since they are relatively safe, but it may take 28 days to notice any difference. I recommend trying for about 6 weeks. Align and VSL#3 are two options that seem to have the most literature, so we like to recommend those.

Q: What are your recommendations for dealing with weight loss?
A: For folks that are losing weight due to their amyloidosis, we usually have them work with a nutritionist. Supplements and shakes are often recommended because they are more calorie-dense. We may also try antibiotics to lessen the small intestine bacteria to increase absorption.

Q: Is there any evidence to show that intermittent fasting might help with the GI issues in amyloidosis?
A: No evidence at present, but it is currently a hot topic. We are looking into this at Stanford in inflammatory bowel and reflux issues. Intermittent fasting, if you’re not familiar, is taking longer breaks between meals to break down fat more actively. Unfortunately there isn’t any information in amyloidosis specifically available, but other studies have shown it may help with bloating and reflux.

Q: Can there be amyloid deposits in the gallbladder?
A: It is reported but thought to be rare. We usually examine the stomach and bowels, so to confirm gall bladder involvement, we would need to biopsy and stain it, and we typically don’t. We have seen symptoms that can suggest involvement, such as gall stones or biliary dyskinesia, but since those are commonly reported outside of amyloidosis, it’s hard to know if the amyloid is to blame.

Q: Could a low FODMAP diet help with the GI issues in amyloidosis?
A: A low FODMAP diet aims to minimize eating foods which are gas producing and was designed to help with irritable bowel. FODMAP stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyps. Avoiding foods in those 5 categories may help relieve cramping, diarrhea, bloating, and gas. Foods to avoid would include: dairy products (milk and yogurt), wheat-based products (bread, cereal, crackers), beans and lentils, and some fruits and vegetables that can be gassy. Foods to consume on this diet include eggs and meat, almond milk, grains like rice or quinoa, and the less gas-causing produce. This diet is thought to help with bacteria overgrowth in the small bowel, but I don’t feel it would provide much relief for those with stomach or esophageal issues.

Q: Is there anything that could help with uncontrollable bowel movements and accidents? 
A: The uncontrollable bowel movements after eating is likely related to an exaggerated gastrocolic reflex (where stomach distention or gas-related distention triggers contractions). I would consider (a) trying a medication such as Bentyl or Levsin 15 minutes before food to block contractions, (b) moving to a low-gas (low FODMAP) diet, (c) a trial of antibiotics for small intestinal bacterial overgrowth, (d) pelvic floor physical therapy to strengthen the anal muscles to help minimize the accidents.

Q: What is the effect of Ninlaro on the digestive tract? 
A: Ninlaro can cause diarrhea, constipation, nausea & vomiting but if it working from an amyloid standpoint then we usually try to treat the symptoms rather than change the therapy. Ondansetron is a good option for nausea but can cause constipation. You could try a lower dose of ondansetron or try Phenergan, Compazine, ginger or cyproheptadine instead for nausea. If ondansetron works well, though, you may want to just add Miralax to help with the constipation.

Q: Is someone considered “laxative dependent” if they won’t have a bowel movement without daily Citrucel and Colace?
A: If Citrucel and Colace work, that is very reasonable to keep taking. Those are very gentle laxatives and have no long-term safety concerns. This is technically laxative-dependence but the safety of that regimen is excellent.

Q: Can GI problems be the inflammatory disease that caused AA amyloidosis?
A: Gastrointestinal inflammation is not thought to cause AA amyloidosis.

Q: What could someone do to avoid having diarrhea after eating fatty foods? Also what could prevent getting GERD (reflux) around midnight?
A: Diarrhea with fatty foods could be from a variety of causes, but malabsorption is probably most likely. Pancreatic insufficiency is also a potential. If you are having GERD around midnight, I would consider trying a Pepcid before dinner & before sleeping and raising the head of your bed a few inches. Occasionally, we will also use Gaviscon Double Action after dinner & before bedtime.

Q: Anything else to help with NOT getting Diarrhea besides benefiber, lomotil, and the BRAT method? 
A: Benefiber & Lomotil is a very reasonable regimen & seems like a very safe long-term option. You could consider a probiotic trial or trial of antibiotics for small intestinal bacterial overgrowth and potentially a low FODMAP diet.

Q: Colonoscopy and endoscopy should not be solely relied on to determine presence of amyloid?
A: Correct. Endoscopy & colonoscopy are specific for amyloid deposition if it is found on pathology but they are relatively insensitive for deposition other than at the mucosal layer. Neuropathic or muscle-related GI involvement won’t be seen with biopsies.

Q: Can you comment on abnormal gut microbiome in AL amyloidosis with GI symptoms? 
A: The microbiome is definitely implicated in GI symptoms & can be affected by amyloid therapies, most GI medications used, and potentially amyloid itself. I don’t know of any medical literature exploring that role specifically, but the microbiome likely plays a key potential role in GI symptoms & we do often (but not always) see improvement in symptoms with therapies directed at gut microbiome modulation (prebiotics, probiotics, antibiotics).

Q: Is there any issue with using docusate daily? Is there a difference for low-sodium patients between docusate sodium and docusate calcium?
A: No concern regarding docusate use long-term. It is perhaps the absolute safest medication from a GI standpoint. I am not sure with regards to the sodium load present in docusate, but I have personally only seen patients taking docusate sodium and suspect the sodium load is not high. Most of the papers looking at docusate are actually from the 50s and to my knowledge there is no efficacy data on docusate sodium versus docusate calcium.

Q: Why might an amyloidosis patient experience fecal incontinence associated with exercise right after a meal?
A: There is a reflex called the gastrocolic reflex where stomach distention/gas production triggers colon contractions and my guess if the symptoms right after a meal are probably related to that. We will sometimes try medications such as Bentyl or Levsin prior to meals to try to blunt this response. Fecal incontinence is often responsive as well to pelvic floor physical therapy & we see improvement on that front in approximately 70% of people with this. I would consider trying both measures.

Q: If there is GI involvement, is it likely that there is also nerve/ autonomic nervous system involvement as well?
A: If the GI involvement is neuropathic in origin, then the two usually link. Mucosal GI involvement may not be connected.

Q: How can a patient know if GI issues, such as lessened appetite, diarrhea, and constipation are from amyloidosis or simply associated with old age? 
A: This could relate to either TTR or normal age-related processes and it is often hard to separate. Constipation increases significantly after age 65, so it could be age-related or linked with medications – not necessarily amyloid-related.

Q: Are there any over the counter supplements that are recommended for GI tract involvement?
A: There are a number of over the counter supplements that we often employ. From an esophageal standpoint, Gaviscon Double Action is an option. From the stomach standpoint, Iberogast, ginger, peppermint and simethicone are all options. For small bowel, Iberogast and simethicone. For colon, any of the over the counter laxatives (Senna, magnesium-containing products, Miralax).

Q: Unintentional weight loss is often cited with amyloidosis but what about unintentional weight *gain*?
A: Weight gain is less typical with amyloid but can occur with decreased activity, as a side effect of medications or if dietary changes leads to more calorically-dense foods. It is less common though.

Q: Are there any other alternatives to the tincture of opium? Is it likely the amyloid deposits in a patient’s intestines will decrease, reducing the need for treatment?
A: I would continue with tincture of Opium if it is working & you are tolerating it well. While there are other options, I’m not sure anything else would be as safe or effective as what you are on now.  The hope is that with long-term suppression of amyloid production that there will be gradual improvement with time – that being said it is hard to say for certain & no way to predict.

Q: What percentage of patients do you treat with opium tincture? What dosage?
A: The overall percentage I treat with Opium has been low (< 5%) but I have been impressed by how well it has worked in those people that need it. I usually start at 0.3 2-3 times daily & then gradually increase as tolerated until finding the dose that works best. Normally 0.6 three times daily is about the norm, although I have gone higher on occasion.

Q: Has it been proven that a vegetarian diet can help with GI issues?
A: There is one paper that showed a vegetarian diet with alkaline water helped with reflux, but otherwise not much literature. That being said, I would imagine that a vegetarian diet low in processed foods would be good for almost all GI issues.

Q: Is it a problem to use Imodium & Loperamide on a daily basis?
A: No, there are no safety concerns.

Q: Can amyloidosis affect taste?
A: Taste can be affected by either amyloid deposition or as an adverse effect to some of the treatments.

If you have any questions about the information presented here, please email arc@arci.org