by CORT on JULY 2, 2009
Dr. Logan is a board certified naturopathic physician who graduated magna cum laude from the State University of New York. An invited faculty member at the Harvard School of Continuing Medical Education and published researcher he is the author of “The Brain Diet” and the co-author with Dr. Alison Bested of a recently updated book on chronic fatigue syndrome (ME/CFS) – “Hope and Help for Chronic Fatigue Syndrome.”
He was willing to follow up a substantial comment he made to the “H2S Creator Speaks” blog with this full interview.
Questions asked by Cort are underlined. This is an excellent article that really gets into specifics, addressing the gut/probiotic issue specifically for those with ME/CFS.
A good number of chronic fatigue syndrome patients do experience gut pain but gut pain has never been considered the main or even a main symptom of the disease. It’s easy to see how something like there irritable bowel syndrome could emanate from the gut but given the sometimes enormous debility found in this disease shouldn’t we be in a lot more gut pain than we are if this disease is indeed centered in the gut? The gut is after all a very sensitive area is it not – it doesn’t take much to make gut problems very obvious to the person suffering from them.
Indeed gut pain is not chief among the constellation of CFS symptoms. Yet the vast majority of CFS patients do experience some degree of gut related symptoms and indeed there are many other gastrointestinal (GI) signs and symptoms in CFS that are not pain-specific. For example, alternating constipation, diarrhea, bloating and so-called functional dyspepsia (upper GI discomfort soon after meals) may not involve significant pain per se, however they indicate that not all is right in the GI tract.
It is also true that there may be issues with certain gut bacteria that, while producing no overt gut symptoms, they are still capable of provoking a body-wide immune response and intestinal permeability. From animal studies, we know that even a tiny amount of undesirable bacteria in the gut, at levels not even high enough to cause an overt immune response, can activate brain areas involved in emotions and ultimately influence behavior itself. While we are a long way from confirming that CFS is centered in the gut, early suggestions indicate that gut microbes may be the tail wagging the dog.
On another very basic note – if we are all producing enough hydrogen sulfide gas this disease shouldn’t we all be belching and otherwise releasing enormous amounts of rotten egg smelling gas?
No, not necessarily. It would only take miniscule amounts of H2S gaining access through the gut wall to cause fatigue and a host of other brain and body-wide symptoms. Small amounts of H2S can cause cognitive difficulties, and of particular interest to CFS symptoms, problems with tuning out unwanted environmental stimuli…the sort of “tired but wired” symptoms of CFS. Normally we can clear H2S quite efficiently, breaking it down with enzymatic activity and releasing it through the lungs. Yet there are many unknowns about H2S, including the amount of gut H2S the normal person can tolerate. In addition to the emerging work from Dr K DeMeirleir indicating that there are elevated H2S-producing gut flora in CFS, it may also be the case that in CFS there is a deficit in H2S disposal.
A common remedy for bacterial overgrowth in the gastrointestinal system involves antibiotics. Yet antibiotics, paradoxically, are sometimes blamed for setting the stage for bacterial overgrowth in the first place. Many people are not surprisingly skeptical about taking antibiotics because of this. How do you go about ensuring that you’re not just making the problem worse?
Indeed, there have been studies showing that antibiotics have reduced small intestinal bacterial overgrowth (SIBO) and improves a variety of symptoms (including brain-related symptoms) in CFS and fibromyalgia. Yet, these are very small studies of small duration. What happens when the antibiotics are stopped and the patients are followed in the long term? We do not know. Given that antibiotics and overuse of acid-blocking medications set the stage for SIBO, I would be inclined to worry about using antibiotics as a means of clearing SIBO. I would be more inclined to use probiotics and enteric-coated peppermint oil.
There are quite a few different kinds of probiotics on the market that feature different kinds of bacteria. Are there certain kinds of bacteria that may be more helpful for the kinds of gastrointestinal issues that chronic fatigue syndrome (ME/CFS) patients face?
Yes, the benefits appear to be strain-specific. If it is for symptoms that resemble that of irritable bowel syndrome (IBS) then I would suggest 2 strains of bacteria that have been shown to be helpful for gut-related symptoms – Align (Bifidobacteria infantis 35624) and LactoFlamX (Lactobacillus plantarum 299V). In our University of Toronto study, we used a probiotic made by the Japanese company Yakult. The strain, Lactobacillus casei Shirota had been found previously to improve mental outlook in healthy volunteers who had the lowest baseline mood scores. It also lowers propionate production in the gut.
Recently propionate has been the focus of research in autism; once it gains entry to the brain, it can alter behavior. It is too early to tell, however I feel that bifidobacteria strains such as Align will become the probiotic of choice for CFS. Align has been shown to reduce inflammation systemically, beyond the gut. It also does not contribute to the lactate load in the gut. What was not really emphasized in the reporting of Dr K DeMeirleir’s research is that his team also found elevated lactate producing bacteria and certain Lactobacilli are major manufacturers of D and L lactate.
If I understand you correctly its possible that strains of Lactobaccilus bacteria that are frequently found in probiotic preparations could exacerbate lactic acid production. Apparently Lactobaccillus acidophilus turns sugars into lactic acid.
Yes, but not all Lactobacillus strains produce the undesirable D-Lactate (for example, the well-researched Lactobacillus GG does not produce D-Lactate, but most strains of Lactobacillus have not been investigated for D-Lactate production. Its time to map that out properly).
It’s generally true that L.acidophilus does turn sugars into lactic acid, but not all Lactobacillus strains produce the D-Lactate; the L-Lactate can be cleared with a fair amount of ease by most.
Do you recommend staying away from the traditional formulations (L acidophilus)?
Most probiotics marketed under the umbrella term “acidophilus” have not been researched for health outcomes (let alone stability!) and we have no idea of their D-Lactate potential. It is known from studies in short bowel syndrome that unspecified strains of L. acidophilus can be major promoters of D-Lactate.
Kefir has a different bacterial makeup than yogurt. I did read that kefir grains make it deeper into the gut. What about kefir?
Great question! There have been two studies that have looked at D-Lactate production in fermented milk, commercial yogurts and kefir. Interestingly the kefir did not form D-Lactate, yogurt had high concentrations of D-Lactate (over 40%).
When you get to the store shelf there are probiotics that don’t need refrigeration, that do need refrigeration, that have X million or even billion bacteria ‘at the time of bottling’, that are in liquid or capsule form, etc. Dr. De Meirleir some years ago stated he was simply looking for a probiotics that was strong enough to fit ME/CFS patients needs. I noticed that Prohealth recently advertised a product that has over 50 billion bifidobacteria organisms in one capsule (at over a dollar a capsule). Do you have any advice to offer on specific types of probiotics for chronic fatigue syndrome (ME/CFS) patients?
Until the research shows otherwise I would choose Align for the reasons cited above. There are very good clinical studies to support the product in IBS.
If you do take probiotics are there any supplements that can help boost probiotics effects?
In recent years so-called prebiotics have been touted for boosting levels of Lactobacillus and Bifidobacteria in the gut. It is quite clear that prebiotics (inulin, chicory root, fructo-olligosaccharides) can increase both Lactobacillus and Bifidobacteria, however it remains unknown if they are also promoting undesirable bacteria as well. There have been hints that they can.
There are now two causes of concern for CFS patients and prebiotics – i. prebiotics have been shown to promote intestinal permeability, irritate the gut lining (this is a massive problem, especially when considering the new studies from Dr Michael Maes who documnented intestinal permeability in CFS) ii. prebiotics can increase the amount of lactate produced in the gut (now that we know there is already excess lactate production and/or inadequate lactate clearance, this is an obvious caveat).
On a personal level your conjecture that fiber induced fermentation in the gut could be associated with increased anxiety and aggression was intriguing since I’ve always felt that ’edginess’ is a key factor in my version of ME/CFS. But how do fiber induced problems in the gut translate into central nervous system problems? A study by Dr. Shungu has suggested increased lactate production in the brain may be occurring in ME/CFS patients; could this have anything to do with lactate production in the gut?
When too much fermentable fiber shows up in the large intestine there is a massive uptick in the production of D-lactate. Since, in CFS, we now know there is already over-production of D-lactate the blanket statements to eat more fiber may not be well suited to CFS. For example, animal studies show that excessive D-lactate production, due to excess fermentable carbohydrates showing up in the distant portion s of the gut, can increase aggressive an anxious behavior. It completely throws them off.
The same phenomenon has been written up numerous times in cases of short bowel syndrome. These are individuals who have had a portion of the small intestine removed, they are more prone to the over-fermentation of fiber-rich carbohydrates in the large intestine and an excess amount of D-lactate is produced. They can experience brain fog, lowered mood state, hypothamic dysfunction and anxiety when transient elevations in D-lactate occur.
Since we know that CFS patients have both bacterial overgrowth and excess D-lactate production (and/or lack of D-lactate clearance) a similar situation may be occurring. Ultimately, excess prebiotics and even excess Lactobacillus strains may worsen the situation in short bowel syndrome, and perhaps CFS as well.
I was very interested in Dr Shungu’s work as well. It certainly suggests that if excess lactate is making it to the brain (and we already know that systemic lactate can cause anxiety in adults with no history of anxiety) it can have multiple implications. Obviously, we have just begun to scratch the surface of this research, however in moving forward we should be very selective of the stains we use for CFS clinical trials.
Your statement that ‘fiber restricted’ diets can be helpful in this disease is a little jarring to hear given all the emphasis these days on high-fiber diets. You also noted that a fiber restricted diet cut the production of hydrogen and methane gas by more than half in one study. What is a restricted fiber diet look like? Are certain types of fiber worse than others?
Yes, while most adults and children in developed nations may need more fiber, those of us with CFS may actually be adding fuel to the fire. An elemental (liquid food) diet has been shown to help eradicate small intestinal bacterial overgrowth and gut excess H2S production. At this point we need more concrete studies although the soluble fiber in oats, barley, rye and root vegetables will be more likely to fuel fermentation and increase lactate production.
You noted that excessive fermentation in the large intestine can lead to the overproduction of lactic acid yet fermented lactic acid producing vegetable products such as sauerkraut, pickles and miso (as well as yogurt) are also sometimes recommended for gut issues. Do you recommend against using those products?
No, generally these would be good choices if not in excess. There is a difference between foods that have been fermented, and foods that are awaiting fermentation by our own bacteria. Still, excessive dairy sugars arriving in the lower gut may be an issue and dairy has been associated with problems in short bowel syndrome with excess D-lactate production.
If someone goes on a fiber-restricted diet how soon should they know if it is working for them?
Within a few weeks
What tests can patients take to assess the status of their small intestine with regards to bacterial overgrowth, hydrogen sulfide gas production, leaky gut and fiber problems?
In addition to Dr K DeM’s exciting new H2S urine test, there is also a test for small intestinal bacterial overgrowth…it is called the lactulose-hydrogen breath test. Similar tests are available for assessment of intestinal permeability. In North America, Genova Diagnostics does the small intestinal bacterial overgrowth and intestinal permeability tests.
There are blood tests for D-lactate; however, by the time a CFS patient sets up the testing the lactate may return to normal. That test is unique in that it is all about timing. Hopefully we will see some clinical investigations in CFS with patients consuming prebiotics and/or decent portions of fermentable carbohydrates and then evaluating both blood and urine lactate in the hours that follow.
A study by Dr. Burnett several years ago suggested that chronic fatigue syndrome patients often suffer from ‘reduced gastric emptying’ it seems to refer to food products remaining in the gastrointestinal system for longer than normal. Would this contribute to fermentation and bacterial overgrowth problems ?
It would certainly contribute to the upper gut symptoms after a meal. It also hints that there are electrical problems on GI tract in general. If there are any problems along the line, it can lead to stasis. We need more work in this area. What may be happening is similar to the folks with short bowel syndrome (although CFS patients may have a structurally intact small intestine, the SIBO may make it a functionally poor portion of the organ) where food material may be passing through the small intestine and then literally get “dumped” into the large intestine. When this happens with fructose, for those who do not absorb fructose well and it speeds through the upper gut, there is massive fermentation and mood related symptoms!
One of the beneficial aspects of enteric-coated peppermint oil is that it helps regulate peristalsis. This is almost certainly why most of the dozen plus trials of ECPO (alone or combined with caraway seed oil) in IBS and functional dyspepsia have shown good results.
Can one to some extent assess one’s bowel health simply by noting the consistency and quality of one’s bowel movements? That is could you say that someone who has one regular well formed bowel movement a day which was not accompanied by gas probably did not have problems with fermentation/hydrogen sulfide gas production?
A regular, well-formed bowel movement will not exclude a potential problem with gut flora alterations. I would be much more inclined to work with the tests available. While these breath test and intestinal permeability tests are imperfect (and the new H2S test requires outside validation), they would tell us much more than bowel movements when it comes to the internal consequences of undesirable bacteria.
I’ve always noticed that abstaining from food is helpful for me for short periods. On the converse many ME/CFS patients experience a considerable letdown 10 minutes or so after they eat. It seems that food does make a difference but this is occurring long before, one would think, food reaches the gut. Do you have any idea what’s going on here?
A period of fasting may be lessening the load of lactate, propionate and H2S…but is not going to be the Rx here. I am not sure about the quick exacerbation of symptoms. I have heard from a number of patients that symptoms are worsened within an hour, and this may be indicative of the small intestinal bacteria having a feast in the upper gut. The ensuing increased intestinal permeability allows unwanted material to pass through the gut wall and fire up the flames of low-grade inflammation.
For more on this topic I would urge visitors to your blog to further investigate the work of Dr Michael Maes and colleagues who have been doing great work in CFS, gut flora and intestinal permeability.
Are there any books you recommend on irritable bowel syndrome or the gastrointestinal system for ME/CFS patients?
I have yet to find one that is specifically suited to the needs and complexities of CFS. The problem is that CFS patients don’t have IBS per se, and the approaches don’t always apply.
The findings in the CFS-GI connection (Drs K DeM, Maes in Europe, Dr Bested in Canada) are so new that a well-rounded gut-specific resource is still some distance away – hopefully soon, but we really need clinical trials to validate specific avenues of approach. As exciting as these gut findings have been, it is important to underscore that we are still on the bridge between hypotheses and true clinical guidance in CFS.
Thanks Cort for your dedication and hard work to the amazing, resilient community of medical underdogs, the CFS patients.
Dr. Logan’s website contains articles, his books, recommended supplements and ‘power foods’, links and more.
Additional Follow-Up Comments by Alan Logan July 6, 2009 at 4:42 am
Fructose and Powerfoods
Yes, the powerfoods section listed on my website is directed at brain health for the general population and is definitely not a CFS-oriented list. I would concur that too much fructose can cause problems. Dr Max Ledochowski has authored 4 or 5 studies on what happens when fructose escapes absorption from the small intestine and gets dumped into the colon…depressive symptoms, brain fog and much lower blood tryptophan levels. Correcting this via a low-fructose diet has been shown to improve mood etc. Interestingly, only about 1/2 of those with fructose malabsorption present with the overt gut symptoms.
Diet and Fruits
My only concern with removal of all fruits is that we also take away much needed dietary antioxidants from the deeply colored berries. Blueberry and bilberry actually have anti-microbial properties that may be to the advanatge of CFS patients and cherries have significant anti-inflammatory activity…CFS patients are under increased oxidative stress, have lower levels of antioxidants due to the high demand, and in most studies, dietary antioxidants win vs. those from supplements. Consideration of some very small servings of berries is still warranted in my opinion.
The other concern with nuts, yes, absolutely no doubt they can be a source of sensitivity.
Candida and yeast can’t be ruled out of this emerging equation of gut flora. Over the years the Candida story has been, in my opinion, over-played. Still, there was a study in the journal Family Practice in 2001 which showed that in adults with “unexplained medical conditions” (symptoms typically over-lapped with CFS) Nystatin was helpful. There were significant improvements in anxiety, cognition, depressive symptoms and insomnia. Recently Dr Evengard’s team in Sweden found that Candida levels are much higher in stool during the early stages of CFS and are lower when patients are “in remission”. Since we know that stress and antibiotics can increase Candida in the gut, it possible that once established, it becomes a secondary contributing factor.
The dose used in the Sullivan probiotic study was 10 to the 8th power CFU twice daily…this was not a particularly high dose. The VSL#3 mentioned has a massive 450 billion CFU per sachet…and it is the kitchen sink of a variety of different strains. It may help some, however I know of cases where anxiety increased after taking the product, it may be a D-lactate connection.
Gut Ph and D-Lactate –
As Cort knows, we had this interview before the full text of the Dr K D paper on D-Lactate bacteria and CFS was released. Within the paper they note that alkaline therapy might be a future Rx in CFS. It would seem to make sense…we have high levels of acid-producing bacteria so it would appear rational to increase the pH and make it more alkaline.
However, the gut is a complex environment and a study by Jiang in Digestive Diseases and Sciences (1997) showed that raising the gut pH in the alkaline direction increases D-lactate production. In the same study they also showed that if you really want to lower D-Lactate production, add Bifidobacteria to the mix. Bottom line, we have much to learn about gut pH.
It has been shown since the 1920s that oral alkaline solutions can encourage small intestinal bacterial overgrowth and subsequent intestinal permeability (Arnold. Am J Hygiene 1928). Since CFS patients have both SIBO and intestinal permability, it is highly doubtful that alkaline solutions will be the answer.
No financial ties
I should have said that I have no financial ties to Align or any other probiotic company.
Thanks for all the comments and feedback.