Too Much of a Good Thing? Can Probiotic Use Cause Bloating and Brain Fogginess?
I found a study that confirms the adage-everything in moderation, including moderation, regarding probiotic use. While they are very helpful and have been linked to improving numerous conditions, consuming too much may have unintended consequences. But the study provoked a scathing rebuke by the International Probiotics Association, and raised significant questions regarding the study’s methods and findings that probiotic use can result can result in disorienting brain fogginess as well as rapid, significant belly bloating.
In a published study of 30 patients, the 22 who reported problems like confusion and difficulty concentrating, in addition to their gas and bloating, were all taking probiotics, some several varieties.
When investigators looked further, they found large colonies of bacteria breeding in the patients' small intestines, and high levels of D-lactic acid being produced by the bacteria lactobacillus' fermentation of sugars in their food, says Dr. Satish S.C. Rao, director of neurogastroenterology/motility and the Digestive Health Clinical Research Center at the Medical College of Georgia at Augusta University.
D-lactic acid is known to be temporarily toxic to brain cells, interfering with cognition, thinking and sense of time. They found some patients had two to three times the normal amount of D-lactic acid in their blood. Some said their brain fogginess—which lasted from a half hour to many hours after eating—was so severe that they had to quit their jobs.
The report in the journal Clinical and Translational Gastroenterology appears to be the first time the connection has been made between brain fogginess, bacterial overgrowth in the small intestine, high levels of D-lactic acid in the gut and probiotic use, Rao says.
"What we now know is that probiotic bacteria have the unique capacity to break down sugar and produce D-lactic acid. So if you inadvertently colonize your small bowel with probiotic bacteria, then you have set the stage for potentially developing lactic acidosis and brain fogginess," Rao says.
While probiotics can be beneficial in some scenarios, like helping a patient restore his gut bacteria after taking antibiotics, the investigators advised caution against its excessive and indiscriminate use.
"Probiotics should be treated as a drug, not as a food supplement," Rao says, noting that many individuals self-prescribe the live bacteria, which are considered good for digestion and overall health.
Others have implicated probiotics in the production of D-lactic acid—and brain fogginess—in patients with a short bowel so their small intestine does not function properly, and in newborns fed formula containing the popular product. Short bowel syndrome results in a lot of undigested carbohydrates that are known to cause small intestinal bacterial overgrowth, or SIBO, and the high levels of D-lactic acid. Severe liver and kidney problems can produce similar problems.
Whether there was also a connection when the gut is intact was an unknown. "This is the first inroad," says Rao.
All patients experiencing brain fogginess took probiotics and SIBO was more common in the brain fogginess group as well, 68 percent compared to 28 percent, respectively. Patients with brain fogginess also had a higher prevalence of D-lactic acidosis, 77 versus 25 percent, respectively.
When brain-foggy patients stopped taking probiotics and took a course of antibiotics, their brain fogginess resolved.
Movement of food through the gastrointestinal tract was slow in one third of the brain foggy patients and one fourth of the other group. Slower passage, as well as things like obesity surgery, can increase the chance of bacterial buildup, or SIBO.
"Now that we can identify the problem, we can treat it," Rao says. Diagnosis includes breath, urine and blood tests to detect lactic acid, and an endoscopy that enables examination of fluid from the small intestines so the specific bacteria can be determined and the best antibiotics selected for treatment.
Normally there is not much D-lactic acid made in the small intestines, but probiotic use appears to change that. SIBO, which was present in most with brain fogginess, can cause bacteria to go into a feeding frenzy that ferments sugars resulting in production of uncomfortable things like hydrogen gas and methane that explain the bloating.
Probiotics added to that feeding frenzy the bacterium lactobacillus, which produces D-lactic acid as it breaks down sugars, The acid get absorbed in the blood and can reach the brain.
All those with brain fogginess, SIBO and/or D-lactic acidosis, were given antibiotics that targeted their bacterial population and asked to discontinue probiotics. Those without SIBO were asked to halt probiotics and stop eating yogurt, which is considered one of the best sources of probiotics. Those with SIBO and D-lactic acidosis but no brain fogginess also took antibiotics.
Following treatment, 70 percent of patients reported significant improvement in their symptoms and 85 percent said their brain fogginess was gone. Those without brain fogginess but with SIBO and high levels of D-lactic acid reported significant improvement in symptoms like bloating and cramping within three months.
Abdominal pain was the most common symptom in both groups and before treatment, six of those with brain fogginess reported a tremendous increase in their abdominal size within just a few minutes of eating.
All patients received extensive examination of their gastrointestinal tract, including a motility test, to rule out other potential causes of their symptoms. They filled out questionnaires about symptoms like abdominal pain, belching and gas and answered questions about related issues like antibiotic and probiotic use as well as food fads and yogurt consumption.
They were given carbohydrates followed by extensive metabolic testing looking at the impact on things like blood glucose and insulin levels. Levels of D-lactic acid and L-lactate acid, which results from our muscles' use of glucose as energy and can cause muscle cramps, also were measured.
Probiotic use may be particularly problematic for patients who have known problems with motility, as well as those taking opioids and proton pump inhibitors, which reduce stomach acid secretion and so the natural destruction of excessive bacteria.
Probiotics are supposed to work in the colon and not the small intestines or stomach, Rao says, so motility issues can result in problems with probiotic bacteria reaching the proper place. A wide variety of problems, from conditions like diabetes to drugs like antidepressants and minerals like iron, can slow movement and increase the possibility that probiotics will remain too long in the upper gut where they can cause harm, he says.
Probiotics definitely can help, for example, people who have gastroenteritis, or stomach flu, or are left with diarrhea and other problems after antibiotics wipe out their natural gut bacteria, Rao says.
"In those situations, we want to build up their bacterial flora so probiotics are ideal," he says.
Rao's pursuit of a possible connection between probiotics, brain fogginess and bloating started with a memorable patient who developed significant amounts of both problems within a minute of eating.
"It happened right in front of our eyes," Rao says of the dramatic abdominal distention. They knew the woman had diabetes, which can slow motility. When they looked in the blood and urine at a variety of metabolic compounds, they found the high levels of D-lactic acid and soon learned the patient used probiotics and regularly ate yogurt.
Next steps include additional studies in which the investigators better quantify and characterize the brain fogginess reported by patients and following patients for longer periods to ensure their problems remain resolved. Some patients in the current study required a couple of rounds of antibiotics, Rao notes.
Good food sources of probiotics include yogurt, sauerkraut, kimchi, kefir and dark chocolate, which are generally safe because of the small amounts of bacteria present, Rao says.
The 19-foot long small intestine has been a bit of an understudied organ, likely in part because it's hard to visualize via the mouth or anus, Rao says. "I think the small bowel can be a source of huge mystery," Rao says.
Your helpful gut bacteria, or microbiome, which are essential to things like a well-functioning immune system and general health, are largely in the large intestine and colon.
The IPA’s official reaction to the paper was supplied to NutraIngredients-USA. The statement was written by Dr Jessica Younes PhD, IPA’s scientific director, with contributions from Dr Artur Ouwehand, PhD, a research manager with DuPont Nutrition and Health.
The IPA’s scathing take on the study, which was written by clinicians from the Medical College of Georgia at Augustana University, was echoed by other prominent researchers and stakeholders in the probiotic field.
The paper, titled “Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis,” (link is external)was published in the journal Clinical and Translational Gastroenterology. The team, led by Dr. Satish Rao, MD, observed 38 patients, 30 of whom were suffering from symptoms of brain fogginess (BF) and excessive gas and bloating and were using probiotics. Dr Rao asserted that, “What we now know is that probiotic bacteria have the unique capacity to break down sugar and produce D-lactic acid. So if you inadvertently colonize your small bowel with probiotic bacteria, then you have set the stage for potentially developing lactic acidosis and brain fogginess.”
“Probiotics should be treated as a drug, not as a food supplement,” he concluded.
‘Brain fogginess’: Fashionable term or true condition?
First, to the subject of ‘brain fogginess.’ While this has become a fashionable diagnosis in recent years, there are still few, if any, hard diagnostic criteria associated with it. It seems to have become a synonym for ‘mental malaise.’
“Brain fogginess is very subjective, and different criteria are used to assess this,” said Dr Emeran Mayer, MC a professor of medicine at UCLA. Mayer is also an expert on brain gut interactions and has written the book The Mind Gut Connection (link is external).
“It is well known that patient reported outcomes are highly unreliable when uncorrelated with hard biological markers, which unfortunately don’t exist for BF [brain fogginess]. To standardize subjective reporting, validated questionnaires are required but these do not exist for BF nor was an attempt made by the authors to come to such standardization. Furthermore, no further assessment of any markers was performed after the discontinuation of probiotics and/or use of antibiotics which means that it is impossible to know if acidosis stopped after probiotic intake ceased,” the IPA statement said.
Can probiotics be associated with SIBO?
Secondly, the Rao paper failed to make an assessment of the different probiotics the patients were taking. These seemed to fall broadly into the Lactobacillus and Bifidobacterium groups. The problem is, no Bifidobacteria make D-lactate, and only a few organisms in the Lactobacillus group are known to do so. D-lactic acidosis is an unusual form of lactic acidosis that can occur in patients with short bowel syndrome.
“SIBO (Small Intestine Bacterial Overgrowth) is a controversial term. There are many patients who have an abnormal burp test who have absolutely no symptoms,” Dr Mayer said. “I certainly don’t believe that SIBO has any relationship to what they are calling brain fogginess.”
A paper in the World Journal of Gastroenterology hinted at the broad use of this term. “SIBO is a very heterogeneous syndrome characterised by an increased number and/or abnormal type of bacteria in the small bowel,” the researchers wrote.
“The aetiology of SIBO is usually complex,” those researchers continued. This renders suspect an attempt to assign the cause of this condition in a given patient to one factor—probiotics use.
“Normally, it’s mainly enzymatic activity in the small intestine and you don’t see high bacterial counts until you get close to the colon,” said Dr Michael Gänzle, PhD, of the University of Alberta. “I would tend to believe that the symptoms were there before these patients took the probiotics.”
“In scanning the paper I see no evidence of causality between probiotic use and the symptoms described. They don’t touch on the idea that the subjects may have been self-medicating with probiotics to counter the GI symptoms. They did not test withdrawal of probiotics alone to resolve symptoms,” said Dr Paul Forsythe, PhD, of McMaster University. Dr Forsythe is another world-renowned expert on the gut-brain connection.
No baseline measurements
“Baseline measurements of lactic acid were not performed so it is difficult to say if the patients were already in a state of acidosis before starting the study,” the IPA stated. “Interestingly enough, the same GI symptoms were reported in the BF and non-BF groups, yet the authors offer no explanation for this.”
Dr Dan Fabricant, PhD, president and CEO of the Natural Products Association, was also unstinting in his criticism of the work.
“To call this science is insulting to the thousands of scientific studies out there confirming the safe and effective use of probiotics. Consumers should always consult with their doctors or medical professionals before using probiotics, but to suggest they are making people confused or disoriented based on this laughable study is absurd,” he said.
Dr Fabricant noted that brain fogginess in a non medical condition that can be triggered by many different stimuli, such as fatigue, lack of sleep and dehydration.
Just let it go?
Dr Mayer said the study’s manifest shortcomings mean that people shouldn’t take it very seriously.
“I personally would say that this study does not confirm my experience with patients who come to me who are on probiotics or who I have started on probiotics. I think people should not really pay much attention to this,” he said.
But in the view of IPA and others, the damage has been done.
“Such claims are not only unfounded but draw attention to the imprecision employed in this study. Misleading the scientific community, popular press and above all consumers in this way is irresponsible and the authors should more clearly communicate the short comings of their work in light of the above criticisms. In this perspective, also the journal that published this work and the editor need to know their responsibility. Here, the peer-review process has clearly failed,” the IPA said.
“I would hope a single paper like this would not make a big difference, but you never know what gets stuck in the mind of the general population,” Dr Gänzle said.
Satish S. C. Rao et al. Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis, Clinical and Translational Gastroenterology (2018). DOI: 10.1038/s41424-018-0030-7