Suche
Mein Konto
Relation
Rao S, Rehman A, Yu S, Andino NM. Brain fog, bloating and bloating: a link between SIBO, probiotics and metabolic acidosis.Clin Transl Gastroenterol. 2018;9(6):162.
Draft
Prospective observational study
Objective
To determine whether there are any associations between brain fog, abdominal symptoms, positive tests for small intestinal bacterial overgrowth (SIBO), and acidosis caused by circulating L-lactic acid or D-lactic acid in urine
Participant
Participants included consecutive adult patients referred to the authors' specialty clinic at the Medical College of Georgia at Augusta University over a 3-year period. Thirty-eight patients were evaluated. All patients presented with unexplained abdominal distension, bloating, and bloating; 30 had brain fog (BF) and 8 did not. Brain fog was defined as the presence of 2 or more of the following symptoms for more than 3 months during their initial clinic visit: mental confusion, clouding, impaired judgment, poor short-term memory, and difficulty concentrating. All participants had negative endoscopic and radiological tests.
Study parameters assessed
Participants were screened for SIBO with a glucose breath test (GBT) and duodenal aspiration/culture. Intestinal symptoms and gastrointestinal transit were also assessed. Metabolic assessments included blood L-lactic acid and ammonia levels and urine D-lactic acid levels.
The test for lactic acid is still considered a new diagnostic test. Blood and urine lactic acid levels were measured after an oral glucose challenge (simultaneously with GBT). L-lactic acid blood levels ≥ 2.2 mmol/L were considered positive and indicated acidosis. Urine samples for D-lactic acid were collected at baseline, 1 hour, and 3 hours during and after GBT and analyzed in a dedicated laboratory (Mayo Clinic Laboratories, Rochester, MN). D-lactic acid levels ≥ 0.22 mmol/L were considered abnormal and indicated acidosis.
Key insights
Gas, pain, bloating, and bloating were the most severe symptoms, and their prevalence was similar between groups. All 30 patients in the BF group had taken probiotics. Small intestinal bacterial overgrowth was more common in the BF group than in the non-BF group (68% vs. 28%;P=0.05). D-lactic acidosis was more common in the BF group than in the non-BF group (77% vs. 25%;P=0.006). Brain fog was reproduced in 66% (20/30) of patients during GBT. Gastrointestinal transit was slow in 33% (10/30) of patients with BF and in 25% (2/8) without BF. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF disappeared and gastrointestinal symptoms improved significantly in 77% (23/30) of the symptomatic group (P=0.005).
Practice implications
If the term D-lactic acidosis doesn't come to mind, don't worry; Until recently, the disease was considered rare in humans,1something only occasionally observed in ruminants, particularly cows.2It's not something you've forgotten; rather, it is something you have never heard of.
Bottom line: If your patients complain of bloating, bloating, and brain fog, ask if they are taking probiotics.
A single human case was first reported in 1979 by Oh et al. described in a patient with short bowel syndrome who presented with psychoneurological symptoms.3Over the years, occasional reports have been published that the condition occurred as a complication of bariatric surgery,4or most commonly short bowel syndrome.5The condition was considered very rare, one of those zebra diagnoses that should be considered in metabolic acidosis characterized by high anion gap encephalopathy.1It wasn't something to keep on the radar, at least not until this article.
The recent work by Rao et al. follows a preliminary study by the same authors. In a 2014 report, Rao and colleagues described 7 patients who presented with both unexplained abdominal distension and BF and consumed probiotics.6This new prospective study, building on the 2014 report, suggests that D-lactic acidosis is much more common than suspected, partly self-induced or self-inflicted by people taking over-the-counter (OTC) probiotics - which are ubiquitousLactobacilliandBifidobacteriumSpecies we have been promoting for a long time.
We need to go back for a second and check a little chemistry. Lactate exists in nature in 2 optical isomers, D-lactate or L-lactate. L-lactate is much more abundant in humans and other mammals, with blood concentrations 100 times higher than D-lactate. L-lactate is the only form produced in mammals. The trace amounts of D-lactate found in the blood are actually produced by carbohydrate-fermenting intestinal bacteria, includingLactobacillus sppandBifidobacterium sppwhich are capable of producing both stereoisomers in different proportions.7L-lactate is efficiently metabolized and broken down in the body, while D-lactate is not easily broken down and accumulates.8
Normal blood levels of D-lactate in healthy adults are low, ranging from 11 to 70 nmol/L. At elevated levels, defined as acidosis (>2.5-3.0 mmol/L; note the difference between nanomoles and millimoles), patients exhibit symptoms of ataxia, slurred speech, and confusion. Standard management consists of restriction of oral carbohydrates or fasting and use of nonabsorbable antibiotics to eliminate D-lactate-producing bacteria. However, D-lactic acidosis usually recurs and patients have to fast repeatedly to keep the problem at bay, affecting quality of life.9.10
A 2010 report describing a case of a 5-year-old girl in which supplemental probiotic intake was associated with D-lactate acidosis is perhaps the first mention of this potential possibility in the literature.11Until this report, no one had thought about it.
What this paper tells us is that this condition, D-lactic acidosis, may be more common than we ever suspected. No one would think of probiotics as a cause of disease - we think of them as a cure for many things. We would find them particularly useful for patients with bloating and bloating. Obviously, taking probiotics does not cause D-lactate acidosis in all people who take them.
The National Institutes of Health (NIH) reports that in 2017, 1.6% of U.S. adults, or about 3.9 million people, took probiotics.12Apparently this problem, if it exists at all, is still rare. There are people who express doubts as to whether this D-lactate acidosis is really a problem. A literature review published in August found no records of infants who became ill from probiotic supplementation.13
On the other hand, we are now obliged to know this symptom picture and include it in our differential diagnosis.
I think of previous patients. Because my practice focuses on oncology, most of our patients have been treated with chemotherapy before; Many of them complain of brain fog. A significant percentage of them regularly take probiotics to improve their health. Could we be confusing D-lactate acidosis with “chemo brain”? A clear symptom to remember and reported by Rao et al. What was reported was that brain fog was worsened by ingestion of sugar, in this case the glucose load used in the SIBO breath test. This symptom is so familiar to me that I wonder how many cases of D-lactic acidosis I may have missed over the years. In a bygone era we would have assumed that the symptom was due to thisCandida. Now we blame SIBO. In both cases we would prescribe probiotics.
We should note that the current study used a slightly lower D-lactate threshold to define the condition (2.5 vs. 3.0 mmol) than most reports, but remember that normal body levels are measured in nanomoles, not millimoles.14
Antibiotics have historically been the standard treatment for D-lactic acidosis. In some patients the disease has tended to recur or has proven resistant to antibiotics. There are reports of successful and lasting improvements after fecal transplants15,16or cocktails with specific strains of probiotic bacteria.17.18We don't have an easy way to differentiate between probiotic products to determine whether or not they produce D-lactate, so simply supplementing with more probiotics seems unwise.
Many patients and many colleagues will find this information difficult to accept. It is a new idea, and for many years we have promoted probiotic bacteria as such purely beneficial agents that it will be difficult for many to accept that they could have negative consequences.
Bottom line: If your patients complain of bloating, bloating, and brain fog, ask if they are taking probiotics. If so, ask if symptoms worsen after consuming sugar. If the answer is yes again, include D-lactic acidosis in your differential. One flaw in this current study is that patients didn't have to stop taking probiotics to see if they got better without antibiotics. Knowing my patient population, antibiotic treatment may not be their first choice. Still, stopping the probiotics and taking antibacterial herbs may be a reasonable first line of treatment to see if it controls symptoms.