IPA, other experts roundly reject conclusions of 'brain fog' paper

The IPA’s official reaction to the paper was supplied to NutraIngredients-USA this morning. 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,”​ ​​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​.​

“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.

Source:​ Clinical and Translational Gastroenterology​
 Published online ahead of print: doi.org/10.1038/s41424-018-0030-7​​
 ​“Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.”
Authors: Satish Rao, Abdul Rehman, Siegfried Yu, Nicole Martinez de Andino