Many people with digestive issues cannot tolerate probiotics. Some people mention that when they ingest probiotics, their brain fog worsens. Does the increase of cognitive issues from ingesting probiotics occur only from immune system up-regulation and die off, or could it be caused by something else? Increased D-lactate production might be your issue.

What is the Difference Between L-lactate and D-lactate?

Lactic acid bacteria in our gut produce both forms of lactate from carbohydrate fermentation.

L-lactate is produced in our body from lactic acid bacteria in our microbiome and is a natural byproduct produced during the Kreb’s cycle for metabolism. L-lactate is also up-regulated during exercise because of the increased need for mitochondrial energy and oxygen to support our muscles. L-lactate is oxidized back into glucose by our liver and is further used for energy production by our body. Finally, our brain can metabolize lactate for energy.1 2 3

D-lactate is produced in minute concentrations in human metabolism via the methylglyoxal pathway that converts acetone derivatives to glutathione. Larger quantities of D-lactate are only produced by lactic acid producing bacteria in our microbiome and by ingestion of substances that metabolize into D-lactate including propylene glycol. Usually, our body has little issue with the usual amounts of D-lactate that are produced by lactic acid bacteria that live within our gut. Minute amounts are produced by these bacteria unless there is a significant dysbiosis or severe carbohydrate malabsorption. D-lactate can be metabolized into pyruvate by our liver and kidney’s (by the enzyme D-2 hydroxy acid dehydrogenase) and what is left is eliminated in our urine by our kidney’s and in our stool. The main issue associated with D-lactate metabolism is that our body is slow in metabolizing it and if its concentrations increase quickly or in large amounts before we can metabolize it, toxicity occurs.4 5 6 7 8

Leaky Brain/Gut Worsens Symptoms

D-lactate acidosis does exist in medical literature but is an infrequent occurrence. It is documented to occur in short bowel syndrome, a medical condition where carbohydrate malabsorption occurs from the absence of the small intestine causing overgrown of lactic acid bacteria. It is also documented in people who have had a roux-en-y gastric bypass performed. Increased D-lactate production over time by D-lactate producing bacteria, combined with leaky gut and overburdened kidneys and liver creates lactic acidosis. Symptoms of D-lactate acidosis include:9 10 11 12 13

  • Altered mental status
  • Ataxia
  • Brain fog (cognitive issues)
  • Coma
  • Confusion
  • Delirium
  • Fatigue
  • Headaches
  • Memory loss
  • Reduction of mitochondrial function (fatigue, weakness)
  • Respiratory issues and failure
  • Slurred speech (dysarthria)
  • Syncope
  • Violent behavior

D-lactate acidosis has been diagnosed in people who have kidney and liver disease as well. D-lactate acidosis has also rarely been diagnosed in people suffering from severe leaky gut and in people diagnosed with IBD (inflammatory bowel disease).14

Is it possible for people who ingest D-lactate producing probiotics or fermented food that contains lactic acid bacteria to develop elevated D-lactate and cause issues similar to lactic acidosis? Possibly, if they have severe enough leaky gut and brain that allow the d-lactate to cross the intestinal barrier, not be metabolized by the liver, and cross the blood-brain barrier into the brain.15

Most of the studies, however, with D-lactate acidosis and SBS (short bowel syndrome) show that it takes awhile for the body to build up enough D-lactate from excessive carbohydrate fermentation to cause severe notable health issues. In most cases, the kidney’s and liver can metabolize normal amounts of D-lactate quick enough to reduce concentrations of it in the bloodstream before it causes issues. Finally, severe leaky gut and brain would also need to occur for side effects of excessive buildup D-lactate in the bloodstream to become symptomatic.16 17 18 19 20

Reduction of short-chain fatty acid production has been theorized in people with D-lactate producing dysbiosis which may contribute to the development of leaky gut. The short chain fatty acid butyrate is a potent anti-inflammatory agent which is produced by the probiotic microbiome. Butyrate feeds cells that make up the epithelium of the colon known as colonocytes, which improve the integrity of our gut junctions and reduce leaky gut. The reduction of short-chain fatty acid’s is also hypothesized to cause a reduction of neurotransmitters and propionic acid being produced by the gut microbiome causing motility issues and poor mitochondrial health.21

Many people have adverse side effects from ingesting probiotics that produce D-lactate. Bacteria that produce D-lactate include:22 23

  • Enterococcus faecalis
  • Lactobacillus acidophilus
  • Lactobacillus bulgaricus
  • Lactobacillus delbrueckii subsp lactis
  • Lactobacillus johnsonii
  • Lactobacillus fermentum
  • Lactobacillus plantarum
  • Lactobacillus reuteri
  • Leuconostoc
  • Pediococcus
  • Oenococcus
  • Weissella

Avoidance of the use of intravenous Ringer’s lactate might be useful as well since some formulations contain minute amounts of D-lactate. Finally, I would avoid the ingestion of anything containing propylene glycol if you believe you are suffering from D-lactate metabolism issues because it is metabolized into lactic acid by the body by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase for detoxification.24

So What Might be Done to Relieve D-lactate acidosis?

Enhancing the metabolism of D-lactate may help improve symptoms. Pyruvate derived from glucose is metabolized into lactate by the enzyme lactate dehydrogenase during anaerobic glycolysis. Pyruvate can also be metabolized into acetyl CoA by pyruvate dehydrogenase to produce adenosine triphosphate during aerobic glycolysis later. Lactate can also be metabolized into pyruvate as well. The B vitamin thiamine (vitamin B1) functions as a cofactor in mitochondrial oxidative decarboxylation, converting pyruvate to acetyl-CoA and α-ketoglutarate to succinyl-CoA for use in the citric acid (Krebs) cycle. In the absence of thiamine, pyruvate cannot enter the Krebs cycle and, instead, is converted to lactic acid. Oral or intravenous supplementation of thiamine may help favor the production of pyruvate instead of lactate, reducing the bodies load of lactate and improving energy by enhancing adenosine triphosphate production and mitochondrial function.25

In addition, severe reduction of dietary carbohydrates might be necessary for a short period to reduce the amount of lactate being produced by our body (through glycolysis) and microbiome. An extremely low carbohydrate diet (no more than ten grams daily) only consisting of meat, healthy sources of fat (pastured butter, ghee, extra virgin coconut oil, and extra virgin olive oil), herbs and spices, and low FODMAP and oxalate (dietary oxalates inhibit D-2 hydroxy acid dehydrogenase) vegetables might be needed to reduce the amount of lactate produced by the body and reduce its overall load. Diets that are very low in carbohydrates may worsen certain health issues and should be monitored by a health care professional. People who are suffering from adrenal fatigue or diabetics that are prone to ketoacidosis (which is seen in people suffering from D-lactate acidosis). I also do not recommend the ingestion of fermented foods in people with D-lactate metabolism issues which can increase overall lactic acid burden by the body.26 27

Maintaining proper hydration also helps improve the clearance of lactate by the kidneys.

Peoples sensitivities from ingesting D-lactate producing strain probiotics, however, might stem from other issues besides D-lactate sensitivity. However, if you suffer from headaches, brain fog, or fatigue when ingesting D-lactate producing probiotic strains, I would avoid them and search out a D-lactate free probiotic. Finally, if you are suffering from D-lactate metabolism issues I would recommend getting a microbiome test performed like GI MAP to know the contents of your microbiome and consulting with me to resolve your health issues.