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

Abstract

Background: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of D-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of D-lactic acidosis (D-la).

Methods: D-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurological symptoms and high D-lactate levels. Fifty-nine D-la episodes were included in the qualitative synthesis comparing D-la symptoms with ME/CFS diagnostic criteria. A narrative review of D-la mechanisms and relevance for ME/CFS was provided.

Results: The majority of neurological disturbances reported in D-la episodes overlapped with ME/CFS symptoms. Of these, the most frequently reported D-la symptoms were motor disturbances that appear more prominent during severe presentations of ME/CFS. Both patient groups shared a history of gastrointestinal abnormalities and evidence of bacterial dysbiosis, although only preliminary evidence supported the role of lactate-producing bacteria in ME/CFS.

Limitations: Interpretation of results are constrained by both the breadth of symptoms included in ME/CFS diagnostic criteria and the conservative methodology used for D-la symptom classification. Several pathophysiological mechanisms in ME/CFS were not examined.

Conclusions: Shared symptomatology and underlying microbiota-gut-brain interactions raise the possibility of a continuum of acute (D-la) versus chronic (ME/CFS) presentations related to D-lactate absorption. Measurement of D-lactate in ME/CFS is needed to effectively evaluate whether subclinical D-lactate levels affect neurological symptoms in this clinical population.

Keywords: Acidosis, lactic; Dysbiosis; Encephalomyelitis, myalgic; Fatigue syndrome, chronic; Microbiota-gut–brain; Neurological symptoms.

Fig. 1

PRISMA flowchart of systematic search and article selection. Asterisk eligibility criteria included episodes of d-lactic acidosis where both neurological symptoms and d-lactate levels were reported

Fig. 2

Percentages of d-lactic acidosis (d-la) episodes that reported ME/CFS matching and ambiguous/other neurological impairments. Total percentages are reported for neurocognitive symptoms (B1), pain (B2), sleep disturbance (B3), neurosensory and perceptual disturbances (B4a), motor disturbances (B4b), speech symptoms, and altered consciousness. N.B. The same episode may be represented multiple times for both matching and ambiguous/other symptom groups across all neurological impairment subcategories

Fig. 3

Proposed continuum of d-lactic acidosis and ME/CFS symptoms. A continuum showing, from left to right; distinct myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms, shared and distinct d-lactic acidosis (d-la) symptoms. Continuum also shows chronic compared to acute presentations

Fig. 4

Overview of mechanisms in d-lactic acidosis. Legend. Summary of contextual factors, triggers and proposed mechanisms leading to d-lactic acidosis (d-la). A presentation of d-la requires an increase in d-lactate absorption. The proposed mechanisms of increased d-lactate production can be through (1) bacterial dysbiosis and/or (2) endogenous production of d-lactate. Simultaneous to the increased absorption, patients who present with d-la also require (3) slowed metabolism of d-lactate. Hence, the d-lactate production exceeds the body’s metabolic and/or excretion capacity. Short bowel syndrome (SBS); d-2-hydroxy acid dehydrogenase (d-2-HDH); adenosine triphosphate (ATP); tricarboxylic acid (TCA)

Fig. 5

Proposed mechanisms of gut–brain interaction leading to neurological symptoms observed in d-lactic acidosis. Supporting and opposing evidence for proposed central nervous system (CNS) mechanisms are categorised according to direct effects of d-lactate, indirect effects of d-lactate and other possible mechanisms unrelated to d-lactate. Abbreviations: enteric nervous system (ENS); d-2-hydroxy acid dehydrogenase (d-2-HDH); adenosine triphosphate (ATP); short chain fatty acids (SCFA)