Hydrogen Sulfide SIBO and Improvement In Interstitial Cystitis By Treating The Basics

Guest Case Study by Dr. Joe Mather

Initial Visits Nov and Dec 2019:

Kathy presents as a 62 y/o menopausal female who suffers from chronic constipation, heartburn and bloating that worsened after lumbar laminectomy in 2013. Since that time, she has been dependent on Norco to treat her chronic back pain and her health has deteriorated. She contacted me in distress after experiencing two hospitalizations for severe dehydration following episodes of nausea and diarrhea.

Has been treated for IBS conventionally without success. She has done research and believes that she has Hydrogen Sulfide (H2S) SIBO due to foul smelling gas and bloating. She is afraid that she will continue to worsen and need further hospitalizations if she is not able to improve medically.

She estimates that she has taken over 60 courses of antibiotics in her lifetime.

Medical History

• Chronic back pain
• Opioid dependence
• Metabolic: Hypertension, Chronic Kidney Disease, Pre-Diabetes
• Menopausal
• Obstructive Sleep Apnea (uses CPAP)
• Chronic Interstitial Cystitis

Polypharmacy

• Ambien, Atrantil, Celecoxib, Claritin, Cymbalta, Topical Diclofenac, Dicyclomine, Duloxetine, Flexeril, Gabapentin, Imitrex, Lortab, Magnesium, Promethazine, Ramilpril

Review of Symptoms

GI

• Constipation 7/10
• BM every other day, described as small pebbles, reliant on glycerin suppositories
• Heartburn, 10/10
• Reliant on PPIs
• Bloating, 10/10 “every time I eat after 30 mins”
• Diarrhea, occasionally, 5/10
• Abdominal pain, 6/10
• Chronic “sewer gas in my gut” with burps and flatulence

URINARY

• Urinary – Urge to urinate without urinary flow, bladder spasms, pain, dysuria. Occurs about 50% of the time. Using 5 mg valium suppositories which ease the pain.

MSK

• Joint pain, thumbs, knee.
• Chronic back pain 2/10 (with meds) – 6/10

NEURO

• Migraines since age 19, helped with Imitrex
• Brain Fog / Memory issues

LIFESTYLE

• Poor quality sleep
• Chronic stress
• Chronic pain

LAB AND IMAGING REVIEW

Elevated fasting blood glucose between 110-150

Dehydration with acute renal insufficiency in Oct

Mild, chronic elevated lactic acid

CT abdomen: Inflammation of the proximal small bowel

Impression:

Kathy came in with a pretty heavy list of medications and previously intractable Interstitial Cystitis and chronic pain. She was recently hospitalized. I felt confident that I could improve and help her GI symptoms as she hadn’t previously done any functional medicine work. I explained to her that while I wouldn’t promise other results, I frequently see improvements in other symptoms, especially brain fog, joint pain and IC when the gut heals.

Testing and Initial Recommendations (Dec 19)

Initial Treatment Recommendations

• Lifestyle improvement: I asked Kathy to commit to wearing her CPAP every night. I skipped right ahead to the paleo low FODMAP diet rather than starting with a paleo diet given her severe SIBO symptoms and recent hospitalizations.
• Supplements: I started with a class 1 probiotic, a class 2 / 3 probiotic, and a digestive enzyme blend before each meal.
  • I recommended that she use either Miralax or an herbal laxative regularly to provide relief from constipation. Severe constipation can worsen urinary symptoms due to physical compression on the bladder and urinary tract.
  • In order to reduce her reliance on Ambien and gabapentin I recommended that she try a sleep supplement a few times a week to help sleep.
  • Supplement list:
    • Lacto/Bifido Probiotic Blend 1 BID
      
    • Spore-based probiotic + s. boulardii 1 BID
      
    • Digestive enzyme with HCl 1 AC
      
    • (optional) Sleep supplement 2 AC
      
    • (optional) Motility support
      

Testing:

• Tests ordered: GI-MAP, Aerodiagnostics glucose breath test
• Rationale:
  • We considered beginning treatment without any lab testing. However, Kathy felt that no one had listened to her before and wanted to see if she had Hydrogen Sulfide SIBO.
  • No need to repeat blood work at this time. Kathy’s presentation was highly consistent with a GI dominated case so we opt to begin there and return to bloodwork later if needed.
    

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Email update (1 – 3 weeks later)

Subjective Assessment:

• “I have not had any additional SIBO spells since I saw you.” Doing well on diet and sleep, she questioned if fish oil supplement would be helpful for her health
• Sleep supplement causing heart to race

Impression:

• Kathy began responding quickly to my basic recommendations. When this happens, it is an indicator that I am addressing the right “root cause” and am on the right track.

Recommendations:

• Continue the basic program, stop sleep supplement, await labs.
• Added EPA/DHA capsules once to twice daily.
  

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Lab Interpretation and Treatment Evaluation (2 weeks later)

Subjective Assessment:

• “Overall my tummy is doing better. My acid is better.” Reduced prilosec to 3 weekly. BM is more regular using Miralax. General significant improvement, but still work to be done.
• Interstitial Cystitis – “I’m improving.” Symptoms improved by 50%. “I can eat iced tea, grapefruit, and orange. Migraines are significantly decreased.”
• Weight – down 12 pounds
• Diet – “I’m doing great.” Kathy expressed interest in adding some foods, especially cabbage.

Lab Interpretation:

• Glucose Breath Test
  
• GIMAP
  

Impression:

• Breath Test: Presumed Hydrogen Sulfide SIBO. In Kathy’s case, she had symptoms classic for SIBO but a normal breath test. In this setting, we first make sure that our patient actually drank the glucose or lactulose solution. If they did, then we consider the possibility that the gas that is being produced by their overgrowth is H2S, rather than H2.
• GI-MAP
  • Moderate Bacterial dysbiosis
  • Negative virus, yeast, parasites
  • Functional Markers: Elastase 224, Calprotectin 20

Recommendations:

• Meds: Stop Prilosec, if needed, use every other day
• Diet: Trial cabbage. Despite being higher in FODMAPS, Kathy was doing great on her diet, and will probably tolerate a small amount, making her life easier and her more likely to stick with the program.
• Supplements: Herbal antimicrobials + bismuth x 8 weeks
  
• 1g bismuth twice daily (OTC Pepto)
  

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Email: “I’m sick help”

Subjective Assessment: Email correspondence

• “I woke up this morning feeling badly. My abdomen is swollen, throwing up, hydrogen sulfide burps and feeling weak. The only thing I added was pumpkin seeds in the last 3 days. I have had an egg white omelette with orange colored bell pepper and some homemade bone broth today. I have thrown this up. Is there anything I can do or take?? I have 12.5 mg promethazine left from last time I was in the hospital for dehydration.”

Recommendations:

“This is most likely an intolerance to the FODMAPs in pumpkin seeds. Stop those completely along with any other nuts or seeds you are eating. Back off on cabbage for the moment if you have added this. Bone broth is very high in histamines, and some of my patients can’t tolerate this either. Hold this for now. I recommend fasting on water/herbal tea until this passes. Continue probiotics. Feel free to use promethazine as needed for nausea.”

Email – 1 week later

Subjective Assessment:

• 4 weeks into her program Kathy reports that she is generally pooping daily and has now lost 15 pounds. “This is the first time I have been off sugar in 10 years!!” She is hoping to begin adding more foods back into her diet.
• She continues to observe improvement in her IC symptoms: “Another interesting phenomena is IC diet restrictions like oranges, grapefruit, and iced tea have not aggravated my pelvic area as before, however I eat those sparingly.”
• She tells me that she never got around to starting bismuth.

Recommendations:

• Kathy’s flare of symptoms by adding pumpkin seeds 10 days ago tells me that she remains sensitive to FODMAPs. I recommended that she continue to go slow on the high FODMAP foods, and that she complete the first round of herbals before trying to add those back.
• With this point I had her add foods with the following idea in mind: “What foods do you miss the most or would make your life easier? Pick 2-3 of these and add them back one at a time in moderation.”

Email – 3 weeks later

Subjective Assessment:

• Reports acid and burning associated with the oregano oil despite taking them with food.

Recommendations:

• “If you are having significant discomfort with the oregano oil then please cut the dose back to 1 capsule twice daily. Keep other herbs at 2 capsules twice daily. If you are doing better at 1 capsule twice daily, then you can try 1 capsule 3x a day with food.”
• The best dose of supplement is the dose that the patient can tolerate. I don’t notice any difference in efficacy when smaller doses of antimicrobials are given over a longer period of time.
  

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Follow Up Visit (3 months later)

Subjective Assessment:

• In the interim, Kathy tells me that she moved. During this period, she did not follow a diet closely and “ate a lot of bad food for a while, but didn’t have a lot of symptoms.”
• She ended up using antimicrobials x 12 weeks all together.
• She is now interested in working on losing weight and improving her overall health.
• Review of Symptoms = “overall 90% better!”
  • GI: Bloating, abdominal pain gone. Heartburn 75% better. Having daily BMs.
  • Neuro: Brain Fog / Memory = “absolutely better!”
  • IC – 80% better, “probably if I dropped the caffeine again it would be 100%”

Recommendations:

• Diet:

  • Expand diet to Paleo with an emphasis on low glycemic index
  • For weight loss we choose to use a combination of tracking her weight and using a 16:8 time restricted eating with one 24 hour fast weekly.

• Supplements:

  • Hold digestive enzyme
  • Started a prokinetic:
    

• Medication:

  • Trial stopping omeprazole. Okay to use Zantac PRN.

• Next steps:

  • Bloodwork after one month of fasting program

Dr. Joe’s Comments

I wanted to highlight this case because it proved to me that our simple and practical approach can dramatically and quickly improve H2S without complicated interventions. In this case, bismuth wasn’t needed.

Kathy likely had H2S. Other practitioners have observed an association between H2S and IC. It was gratifying to see how well Kathy’s IC responded to this program.

Now that we have cleaned up her gut, Kathy is feeling better across the board. Moving forward, this will give her excellent momentum to keep making improvements to her health. Further work at reducing her weight and then improving her activity level will make it much more likely that her GI issues remain resolved.

Association of Frequency of Organic Food Consumption with Cancer Risk

JAMA Intern Med. 2018 Dec 1;178(12):1597-1606. doi: 10.1001/jamainternmed.2018.4357.

Study Purpose

• “To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults.”
• Previous research and case studies have demonstrated an increased risk of certain cancers for agricultural workers exposed to large amounts of pesticides. Food is the major source of pesticide exposure for the majority of the population.

Design, setting, and participants:

• Observational Prospective Study conducted in France
• 68,946 participants were classified according to their self-reported intake of organic food and were then followed for 5 years.
• The questionnaire asked participants to report their consumption of 16 different foods for which organic and non-organic options were readily available.

Main Results:

• “In this large cohort of French adults, we observed that a higher organic food score, reflecting a higher frequency of organic food consumption, was associated with a decreased risk of developing NHL and postmenopausal breast cancer, while no association was detected for other types of cancer.” NHL = non-Hodgkin’s Lymphoma
• Those with the highest frequency of organic food consumption had a 25% lower relative risk of being diagnosed as having cancer during follow-up compared with those with the lowest frequency.
• IMPORTANT: This inverse association was restricted to risk of postmenopausal breast cancer and lymphomas.

Authors Conclusion:

“If confirmed, our results appear to suggest that promoting organic food consumption in the general population could be a promising preventive strategy against cancer.”

Clinical Takeaways

• While we don’t want to cause anxiety and fear in our patients around food, this study adds to the data that food based pesticide intake is associated with certain types of cancer.
• This large and well-performed study adds to the body of literature pointing towards a link between pesticide consumption and cancer and is a good argument for choosing organic foods when possible. It is not specific enough to discourage non-organic fruit and vegetable consumption.

My Notes:

• Organic food intake is an inherently difficult area to measure, and the authors did not use a validated questionnaire proving that lower intake of organic food is an accurate reflection of pesticide exposure. However, in this case, other researchers have been able to prove that self reported intake of organic produce can predict urinary levels of organophosphates so they are probably on firm ground using this methodology.
• Considering that the alternative to questionnaires is either extremely expensive (multiple urinary tests) or invasive, (fat pad biopsies) we can hope that these types of studies are reproduced and the questionnaires refined.
• The findings of increased risk of lymphoma is consistent with findings from the Million Women Study in the UK which also linked organic food intake to a 21% lower relative risk of non-Hodgkin’s Lymphoma.
• Given the difficulty of crafting these types of questionnaire and the relatively short followup period, it is actually surprising that this was found. Most cancers develop slowly and epidemiological studies need to be conducted over a very long time to detect meaningful changes in risk.
• • This suggests that the actual effect of pesticide exposure may be even more significant that what was found here.
  • The questionnaire treated all types of non-organic food the same, and it is reasonable to expect that different foods carry different pesticide burdens. Further studies will hopefully clarify the risk that different pesticide exposures will cause.
    

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Efficacy of the Autoimmune Protocol Diet for Inflammatory Bowel Disease

Inflamm Bowel Dis. 2017 Nov;23(11):2054-2060. doi: 10.1097/MIB.0000000000001221

Study Purpose

• Pilot study to investigate the potential efficacy of the AIP diet in patients with active CD and UC

Study Design

• Adults with evidence of active IBD either via endoscopy, video capsule endoscopy, enterography or elevated calprotectin within 7 months. Patients were required to have Facebook accounts and email.
• Patients had advanced disease uncontrolled by medications.
  • 8 of the 9 participants with CD had active disease on endoscopic evaluation (with visible erosions or ulcers in diseased regions), 5 of whom had elevated calprotectin levels.
  • Mean IBD duration was 19 years (SD 14.6) and active biological use in 7 participants

Intervention:

• Began with 6 week staged elimination (grains, legumes, night-shades, dairy, eggs, coffee, alcohol, nuts and seeds, sugars, oils and food additives) followed by a 5-week maintenance phase where no reintroductions were allowed.
• Nutrient repletion was initiated for deficiencies in vitamin D (n = 3) and iron (n = 6).
• There were several supportive elements added to the AIP Diet
  • “The program also counseled participants on forming a support system, grocery shopping and food preparation, sleep and sleep hygiene, education regarding nutrient density and fermented foods, stress management, incorporation of bone broth and physical activity, and avoidance of nonsteroidal anti-inflammatory drugs.”
  • “Health and group-based coaching and dietary counseling were provided through individual email and a private Facebook group accessible by invited members only. Because participants began the study at the same time, they could communicate with one another through the Facebook group, but study investigators and staff were not part of this group.”

Main Results:

• “Clinical remission was achieved at week 6 by 11/15 (73%) study participants (6 CD and 5 UC), and all 11 maintained clinical remission during the maintenance phase of the study.”
• Improvements in other markers were also seen:
  • Mean total SIBDQ scores significantly improved
  • Mean partial Mayo score improved from 5.8 to 1.2, and this was sustained through week 11.

Authors Conclusion:

• “Our prospective observational study indicate that an AIP diet, involving an elimination phase followed by a maintenance phase, demonstrates preliminary efficacy in patients with active IBD. Our results support the use of dietary modification as an adjunct to IBD therapy.”

My Notes:

• This study has been helpful to my patients to prove to them that it is possible to put IBD into remission without the use of medication. I often print it out and highlight the fact that 73% of patients were able to achieve remission only 6 weeks into the diet.
• As much as I love this study, the title is misleading. This study doesn’t prove that the Elimination Diet itself is the reason for the dramatic improvement that was found. Participants were given health and diet counseling, vitamin D and iron replacement, and were placed within a community of patients with similar health issues where they could support each other.
• The beauty of this study is that it justifies a comprehensive and broad functional medicine approach, rather than a narrow focus on just the AIP diet.
• There was one complication which is a nice reminder that every program should be individualized.
  • “One participant with postoperative recurrence of ileal CD with known ileocolonic anastomotic stricture required hospitalization for partial small bowel obstruction approximately 3 weeks after study started. This was attributed to a significant increase in raw vegetables, salad, and meat consumption.”
    

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Eating Disorders in Adolescents with Chronic Gastrointestinal and Endocrine Diseases

Lancet Child Adolesc Health. 2019 Mar;3(3):181-189. doi: 10.1016/S2352-4642(18)30386-9. Epub 2019 Jan 10.

Study Purpose

• “Eating disorders are one of the most common chronic conditions in adolescents. The clinical symptoms can mimic those of other chronic diseases including gastrointestinal and endocrine disorders. However, an eating disorder can coexist with another chronic disease, making the diagnosis and management of both conditions challenging.”

Main Results:

• “More than 90% of patients with eating disorders present before the age of 25 years. Some other chronic medical conditions, including coeliac disease, inflam­matory bowel disease, diabetes, and thyroid disease, can also begin during adolescence and need to be dis­tinguished from an eating disorder.”
  • Those of us treating the above conditions need to be aware that eating disorders may be the underlying root cause of a patient’s symptoms, particularly when the patient is under age 25.
  • Nutritionally minded physicians will likely get a higher percentage of patients with eating disorders and recognizing when this is present will be critical to avoiding overtreatment.
• “Evidence is also growing implicating changes in the microbiome and gut–brain interactions in the cause and course of anorexia nervosa.”7
• “An elevated ESR or a low serum albumin concentration should raise suspicion of inflammatory bowel disease.”
  • A helpful reminder that inexpensive and basic markers can help us differentiate IBD from IBS in some patients.
• Low T3 is the most common thyroid function test seen in patients with malnutrition
• The authors remind us that some patients with eating disorders may be taking thyroid hormone in excess in an attempt to control their weight. When a patient has elevated thyroid hormone without goiter, negative thyroglobulin antibodies, with a decreased radioactive iodine uptake we should be suspicious that the patient does not have a true hyperthyroid pathology.

Authors Conclusion:

• “Eating disorders and some chronic gastrointestinal and endocrine diseases begin during adolescence and frequent­­ly present with similar symptoms. The conditions can be misdiagnosed inter­changeably, but they can also coexist, making manage­ment challenging.… Similarly, adolescents with chronic gastrointestinal and endocrine diseases should be screened for unhealthy methods of weight control.”

Rapid-Fire Research: Ultra-Concise Summaries of Noteworthy Studies

Effect of Coenzyme Q10 Supplementation on Clinical Features of Migraine: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials

Nutr Neurosci . 2019 Feb 6;1-8. doi: 10.1080/1028415X.2019.1572940. Online ahead of print.

• Objective: Coenzyme Q10 is an antioxidant and an essential mitochondrial cofactor which has been suggested to improve the clinical features of migraine. Several randomized clinical trials have examined the effects of Coenzyme Q10 on migraine with inconclusive results.
• Results: Four randomized clinical trials with 221 participants were included.
  • The daily oral CoQ10 supplementation dose varied from 100 to 400 mg.
  • Coenzyme Q10 supplementation significantly reduced the frequency of migraine attacks (weighted mean difference: -1.87 attacks/month, 95% CI: -2.69 to -1.05, p < 0.001)
  • Coenzyme Q10 supplementation had no significant effect on severity or duration of migraine attacks.
• Conclusion: Coenzyme Q10 supplementation may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks.
  

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Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis

Gastroenterology . 2020 May 8;S0016-5085(20)30609-0. doi: 10.1053/j.gastro.2020.05.016. Online ahead of print.

• Background: To examine the evidence between Celiac Disease and IBD
• Results:
  • “We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of celiac disease in patients with IBD vs controls and increased risk of IBD in patients with celiac disease vs controls.”
  • “There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with celiac disease vs controls (RR, 6.22; 95% CI, 2.44-15.84).”
• Conclusions:
  • “Our review found a nine-fold increased risk of IBD in CeD compared to controls, with a higher risk in Crohn’s disease than UC..”
    

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Safety and Feasibility of Various Fasting-Mimicking Diets Among People with Multiple Sclerosis

Mult Scler Relat Disord. 2020 May 6;42:102149. doi: 10.1016/j.msard.2020.102149. Online ahead of print.

• Background:
  • “Fasting-mimicking diets (FMD) have shown promise in experimental autoimmune encephalitis and are currently being investigated among people with multiple sclerosis (MS).”
  • This paper reviews three randomized controlled trial studies done between 2015 and 2017 on patients with MS and different FMDs.
• Objective:
  • 70 patients with MS finished one of three studies:
    • Study 1:  Eight weeks of continuous caloric restriction (78% of caloric needs 7 days / week) or intermittent caloric restriction (25% caloric needs 2 days /week)  or control (100% caloric needs 7 days / week) followed by 37 weeks of intermittent caloric restriction.
    • Study 2: Patients choose between 6 months of continuous caloric restriction or intermittent caloric restriction and further randomized to receive text messages to see if this would help improve adherence.
    • Study 3: Six months of time restricted feeding (16:8, 16 hours of fasting and 8 hours of eating all calories) vs no diet change.
• Results:
  • “Overall adherence to the calorie restriction diets was poor. When participants were tasked with maintaining a diet in a pragmatic setting, neither previously completed intense clinical support and education, nor weekly electronic communication throughout the diet period appeared to improve diet adherence.”
    • Texting did not improve adherence to the program.
  • “In contrast to calorie restriction, adherence to a time-restricted feeding (TRF) diet was relatively good.”
    • More evidence that TRF is easier in patients than simply reducing calories across the board.
  • “Participants in the pragmatic CR study had better self-reported adherence than those in ATAC-MS, which may be related to participant choice of intermittent versus continuous CR.”
    • Confirmation that letting patients have a say in their treatment improves adherence to recommendations.
  • Conclusion:
    • “These results provide evidence that continuous calorie restriction, intermittent calorie restriction and time-restricted feeding are safe among people with MS.”
    • No serious adverse events were reported. Fasting is a safe intervention even in chronically ill patients.

Practitioner Question of the Month

“Is it a bad idea to recommend the elemental diet to a patient with diabetes?”

Diabetes is not a contraindication to an elemental diet. A patient with insulin resistance secondary to GI dysbiosis may be significantly helped by the eradication of that dysbiosis.

You should be aware that the elemental diet will very quickly be converted into blood glucose, but this is not a reason to forgo the elemental diet. As with any diet or medication change in diabetics, increased monitoring of blood glucose for a short term is a good idea. This is especially true if your patient is insulin dependent, then any dietary change should be made with very close monitoring of their glucose. (I have found the Abbott FreeStyle Libre to be helpful for those patients interested in closely monitoring their glucose response to dietary or lifestyle interventions.)

One advantage of an elemental diet is that your patient may actually have a more stable blood sugar pattern than usual as the formula is sipped slowly throughout the day. Type 2 diabetics suffer large swings in blood sugar with meals that get larger throughout the day as their insulin reserve drops with each meal. Evidence is emerging that these large postprandial spikes are what cause microvascular damage.

You may consider a hybrid approach where your patient replaces breakfast and lunch with the formula and eats a regular (low carb) dinner.

A final consideration: One serving of Elemental Heal Low Carb is 19g of carbs. 5 servings a day will put your patient under 100g or carbs. I have treated many diabetics who were easily eating double that prior to seeing me!