Approaches to D-Lactic Acidosis

My last post cites a 2009 article that found:

“Faecal microbial flora of CFS patients and control subjects. The mean viable count of the total aerobic microbial flora for the CFS group (1.93×108 cfu/g) was significantly higher than the control group (1.09×108 cfu/g) (p<0.001). There was a significant predominance of Gram positive aerobic organisms in the faecal microbial flora of CFS patients. …This study confirms the previous observation (22), and those reported by other investigators (23) that there was a marked alteration of faecal microbial flora in a sub-group of CFS patients….. In this study the mean total count for Enterococcus and Streptococcus spp. for the CFS group was 52% of the total aerobic intestinal flora, which is significantly higher than the 12% seen in the control subjects (p<0.01). ” largely old hat to readers of this blog, a microbiome dysfunction.

But the study went on to some new interesting stuff, a possible mechanism:

“In this study the NMR-based metabolic profiles of the three intestinal micro-organisms, E. faecalis., S. sanguinis. and E. coli showed that the Gram positive bacteria (Enterococcus and Streptococcus spp.) produce more lactic acid than the Gram negative E. coli. Not surprisingly, these Gram positive bacteria were shown to lower the ambient pH of their environment in vitro as compared to that of E. coli. This suggests that when Enterococcus and Streptococcus spp. colonization in the intestinal tract is increased, the heightened intestinal permeability caused by increased lactic acid production may facilitate higher absorption of D-lactic acid into the bloodstream, henceforth perpetuating the symptoms of D-lactic acidosis. Increased intestinal permeability is also associated with endotoxin release from Gram negative enterobacteria, leading to inflammation, immune activation and oxidative stress, which are cardinal features in a large subset of CFS patients

This ties in well with observations, for example, some people getting relief by various breathing techniques intended to alter pH of the stomach and intestines.

So, putting on the blinkers and focusing solely on the overgrowth of Enterococcus and Streptococcus, how can someone impact this without getting antibiotics (in some countries, prescribing antibiotics for a condition that is not recognized as needing them, can cost a MD their license)?

  • “Among the plants chloroform and isoamyl alcohol extracts of Cumin ( Cuminum cyminum), Clove (Syzygium aromaticum) and Turmeric (Curcuma long Linn) had significant effect against … Streptococcus pyogenes” [2013]
  • “Cortex phellodendri showed antimicrobial activity against Streptococcus mutans, while Radix et rhizoma rhei was effective against Streptococcus mitis and Streptococcus sanguis. Fructus armeniaca mume had inhibitory effects againstStreptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis in vitro.” [2010] – most of these are Chinese/Japanese medicinal herbs
  • “eight herbal extracts could inhibit the growth of Streptococcus sanguinis. Jasmine, jiaogulan, and lemongrass were the most potent,” [2008]
  • ” (common Fig) F. carica and  (Olive leaf) Olea europaea leaves inhibited growth of… Streptococcus pyogenes” [2011]
  • “onion could inhibit E. coli, …   Streptococcus faecalis [1985] – not recommended because of impact on E.coli
  • ” Lemongrass, oregano and bay inhibited all organisms” [1999]
  • “especially those of Origanum glandulosum and  (Mediterranean thyme) Thymbra capitata with interesting minimum inhibitory concentration, biofilm inhibitory concentration, and biofilm eradication concentration values” [2014]

Early post on treating Enterococcus cites: Azadirachta indicaOcimum tenuiflorumMonolaurin. Streptococcus is associated with excessive histamine, see earlier post.  MedScape Article reveal no effective accepted treatment. A fuller article is (here JASN).

Brain Fog etc caused by lactic-acid

Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review [2017]

cites:

  • “Higher levels of d-lactate producing bacteria (such as Streptococcus and Enterococcus) have been identified in stool samples from patients with ME/CFS “
  • Shared with acidosis and ME/CFS “B1. Encephalopathy/Mental confusion/disorientation/dazed/Concentration difficulties/Slow processing and responding to questions/slow speech
    B2. Headaches/Muscle pain
    B3. Drowsiness/sleepiness/somnolence
    B4a. Blurred vision
    B4b. Weakness/hypotonic (lowered muscle tone)/flaccidity/impaired gait (staggering/wide/ataxic/unsteady/instability)/ataxia (movement and co-ordination difficulties)/impaired balance”

Antibiotic Approach

The prime bacteria to reduce are Enterococcus and Streptococcus. After the antibiotic, you want to have E.Coli back fill the spaces created by the above being killed.

Probiotic approach

“… Recently, considerable progress has been made in the isolation of these strictly anaerobic butyric acid-producing bacteria from the human gut. It has been shown … that lactic acid, produced in vitro by lactic acid bacteria, is used by some strictly anaerobic butyrate-producing bacteria of clostridial cluster XIVa for the production of high concentrations of butyric acid (Louis & Flint, 2009). This mechanism is called cross-feeding …” [Source]

This implies that miyarisan (clostridium-butyricum) should be of benefit.

E.coli probiotics (symbioflor-2, mutaflor) will displace the high producers and produce a lot less (around 2%) of what the high producers do.

“Lactomin[300 mg Lactobacillus acidophilus, 300 mg Bifidobacterium longum] was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis ” [2010]

Supplement Approach – Thiamine (Vitamin B1) and NAC

100 mg every 12 hours is reported to reverse this for other conditions.

  • Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients.” [1997]

B1 (at sufficient high dosages) have had major improvement of symptoms. See these posts also:

“We concluded that the patient had metabolic acidosis induced by accumulation of 5-oxoproline. We modified her antibiotic treatment, administered acetylcysteine (NAC), and her acidosis resolved.” [2016]

Classification

Cohen and Woods devised the following system in 1976 and it is still widely used:[1]

  • Type A: lactic acidosis occurs with clinical evidence of tissue hypoperfusion or hypoxia is likely what is seen in CFS. The hypoperfusion is well reported as a signature of CFS.

Testing for D-lactic Acidosis

This is a specialized test that is usually not done [Mayo Clinic] “Routine lactic acid determinations in blood will not reveal abnormalities because most lactic acid assays measure only L-lactate. Accordingly, D-lactate analysis must be specifically requested (eg, DLAC / D-Lactate, Plasma). ”

Word on Likely Dosage

The last article cited an article treating it. I noticed that often there was very high dosages.  My gut feeling (no evidence to back it up) is that for any of the above, we may well be talking 8 – 16 “00” capsules per day of each one, with a possible change of the herb/spice every 7 days. Remember we are talking about reducing from 52% to 12%, not a walk in the park.

As always, consult with your knowledgable medical professional before starting or changing supplements.

Probiotics to avoid

L. delbrueckii bulgaricus (ATC 11842) has a 26:7 ration of D-Lactic acid to L-Lactic Acid [Source]

Bottom Line

“Management includes correction of metabolic acidosis by intravenous bicarbonate, restriction of carbohydrates or fasting, and antibiotics to eliminate intestinal bacteria that produce D-lactic acid.” [2017]

“Main treatments are: 1) changing the abnormal intestinal flora with the administration of oral antibiotics, 2) attempt to diminish the quantity of substrate for intestinal fermentation by using the low-carbohydrate diet or enteral formulas containing fructose or starch instead of glucose as the main source of carbohydrate, 3) correction of the underlying abnormality by reanastomosing the intestine in case of intestinal bypass, 4) nonspecific therapy of acidosis with high doses of bicarbonate, 5) correction of the acidosis and simultaneous clearance of D-lactate with hemodialysis34). Antibiotics control symptoms and prevent recurrence of the syndrome in most patients, but in some patients acidosis recurs despite the antibiotic use. Antibiotics that have been tried include neomycin, vancomycin, ampicillin, kanamycin, and metronidazole. The optimum duration of antibiotic therapy is uncertain because the symptoms may recur in a few days after discontinuation of antibiotics in some patients, while others may remain without symptoms for several years in the absence of oral antibiotics4).” [2006]

B1, NAC and sodium bicarbonate taken together are a likely good starting point. Of the antibiotics listed above, I would opt for metronidazole because of the positive results reported in surveys of CFS patients, Probiotics would be any E.Coli probiotic. Any (or multiple) of the above herbs.