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D-lactic acidosis

D-lactic acidosis
Michael Emmett, MD
Biff F Palmer, MD
Section Editor:
Richard H Sterns, MD
Deputy Editor:
John P Forman, MD, MSc
Literature review current through: Dec 2022. | This topic last updated: Dec 06, 2021.

INTRODUCTION — D-lactic acidosis is an unusual form of lactic acidosis that can occur in patients with short bowel syndrome. It has also been described in patients who receive or ingest large amounts of propylene glycol and in patients with diabetic ketoacidosis. D-lactic acid is the stereoisomer of L-lactic acid, which is the principal isomer produced by humans and the acid responsible for most forms of lactic acidosis.

The pathogenesis, clinical manifestations, diagnosis, and treatment of D-lactic acidosis are presented here. The causes, diagnosis, and treatment of lactic acidosis (ie, L-lactic acidosis) are discussed separately:

(See "Causes of lactic acidosis".)

(See "Approach to the adult with metabolic acidosis".)

(See "Bicarbonate therapy in lactic acidosis".)

PATHOGENESIS — Accumulation of D-lactic acid occurs primarily in three settings:

In a patient with short bowel syndrome after consumption of a carbohydrate load

In a patient who receives or ingests a large amount of propylene glycol

In a patient with diabetic ketoacidosis

In patients with jejunoileal bypass, small bowel resection, or other causes of the short bowel syndrome, glucose, starch, and other carbohydrates delivered to the colon can be metabolized by bacteria to D-lactic acid, which is then absorbed [1-6]. D-lactate is not metabolized by L-lactate dehydrogenase, the enzyme that catalyzes the conversion of the physiologically occurring L-lactate into pyruvate. Thus, D-lactate is slowly metabolized in humans. Although it is excreted in the urine, significant accumulation in body fluids can occur and generates metabolic acidosis.

Two factors tend to contribute to the overproduction of D-lactic acid in patients with short bowel syndrome [3] (see "Pathophysiology of short bowel syndrome"):

Overgrowth of gram-positive anaerobes, such as lactobacilli, can produce large amounts of both L-lactate and D-lactate.

Glucose and other carbohydrates are normally absorbed by the small bowel. If the small bowel is bypassed, removed, or diseased, then delivery of these substances to the colon increases.

D-lactic acid is also a metabolic product of propylene glycol metabolism. A variety of medications are dissolved in propylene glycol to make them suitable for intravenous infusion. When these medications are infused at a rapid rate, the propylene glycol may accumulate. This generates an osmolal gap. An anion gap acidosis may also develop and is generated by the metabolic products of propylene glycol, which include several strong organic acids, one of which is D-lactic acid. Most reported cases are due to the infusion of high doses of lorazepam or diazepam [7,8].

D-lactic acid may also accumulate and contribute to the anion gap acidosis of diabetic ketoacidosis. One group has reported that concentrations of D-lactic acid often exceed 2 mEq/L in these patients and may reach the 8 to 10 mEq/L range [9]. The D-lactic acid is presumably derived from methylglyoxal, a metabolite of both acetone and dihydroxyacetone phosphate, which may accumulate in patients with diabetic ketoacidosis.

Slight elevations of D-lactate levels have also been documented in some patients with cystic fibrosis [10] and in patients with intestinal ischemia [11], although the degree of elevation is not sufficient to be detected as a metabolic acidosis or increased anion gap. These disorders may increase D-lactate absorption from the gastrointestinal tract.

CLINICAL MANIFESTATIONS — Patients with short bowel syndrome frequently have chronically elevated, but low-grade, serum concentrations of D-lactate that are not sufficient to induce symptoms [12]. In some patients, however, carbohydrate loading leads to severe and symptomatic D-lactic acidosis. These patients typically present with episodic metabolic acidosis (usually occurring after high-carbohydrate meals) and characteristic neurologic abnormalities including confusion, cerebellar ataxia, slurred speech, and loss of memory (table 1) [1-3,13]. In a review of 29 reported cases, all exhibited some degree of altered mental status [13]. Affected patients may complain of feeling drunk or appear to be drunk in the absence of ethanol intake.

Neurologic symptoms in acidotic patients with short bowel syndrome do not correlate with plasma or cerebrospinal concentrations of D-lactate; in addition, it has not been possible to reproduce neurologic symptoms in normal subjects by administering D-lactate. Thus, it seems more likely that symptoms are caused by other toxins produced in the colon that are generated and absorbed in parallel with D-lactate, rather than by D-lactate itself [3,13].

DIAGNOSIS — The diagnosis of D-lactic acidosis should be strongly considered in a patient with an otherwise unexplained metabolic acidosis (high anion gap or hyperchloremic) in addition to one or more of the following [13]:

Short bowel or other malabsorption syndrome such as an ileojejunal bypass

Acidosis that is preceded by carbohydrate-rich food intake and resolves with its discontinuation

Characteristic neurologic symptoms and signs

High-dose infusion of intravenous medications dissolved in propylene glycol or propylene glycol ingestion

The diagnosis can be confirmed with special enzymatic assays that use D-lactate dehydrogenase. The standard enzymatic laboratory assay for lactate will not detect D-lactate, because it uses L-lactate dehydrogenase. Chromatographic assays are not stereospecific, and these will measure both D- and L-lactate [1,2]. Urine D-lactate levels can also be quantitated, and these measurements are commercially available.

When D-lactic acidosis develops, the increase in the anion gap may be less than the fall in the plasma bicarbonate concentration (ie, patients may have both a high anion gap and hyperchloremic metabolic acidosis or, rarely, a pure hyperchloremic metabolic acidosis). The development of a hyperchloremic acidosis is related to the stereospecificity of the sodium-L-lactate cotransporter in the luminal membrane of the proximal tubule, resulting in less efficient reabsorption of filtered D-lactate. When D-lactic acid enters the extracellular fluid, the dissociated hydrogen ion reacts with bicarbonate to generate carbon dioxide and water. The bicarbonate concentration falls, and the D-lactate concentration increases, thereby producing an anion gap acidosis. However, because D-lactate is not efficiently reabsorbed by the kidney, the rapid excretion of D-lactate into the urine with sodium or potassium (rather than hydrogen or ammonium ions) leads to a reduction in the extracellular fluid volume and an increase in renal retention of dietary sodium chloride. The net effect of the combined extracellular fluid volume contraction, sodium chloride retention, and loss of D-lactate is the conversion of an anion gap acidosis to a hyperchloremic (normal gap) acidosis. This process is comparable to the indirect loss of sodium bicarbonate from the body fluids, as occurs with watery diarrhea or during the recovery phase of ketoacidosis.

The loss of sodium or potassium with D-lactate in the stool can also contribute to this process [3]. (See "The delta anion gap/delta HCO3 ratio in patients with a high anion gap metabolic acidosis".)

The evaluation of a patient with suspected D-lactic acidosis can be aided by determination of the urine anion and osmolar gaps:

The excretion of sodium and/or potassium with D-lactate into the urine will generate a large, positive urine anion gap (ie, the concentration of the measured urinary cations [sodium and potassium] will exceed the concentration of the measured urinary anion [chloride]). The combination of a hyperchloremic metabolic acidosis and a positive urine anion gap may lead to the incorrect conclusion that urine ammonium excretion is reduced, prompting a misdiagnosis of renal tubular acidosis [14]. (See "Urine anion and osmolal gaps in metabolic acidosis", section on 'Urine anion gap'.)

However, in patients with D-lactic acidosis, urinary ammonium excretion will increase in response to the acidosis, but the ammonium may be excreted with the D-lactate anion instead of chloride. As described above, this situation makes the urine anion gap calculation an invalid indicator of the urine ammonium concentration. The urine osmolar gap can be used to detect this elevation in ammonium excretion, even in settings in which unmeasured anions (such as D-lactate) are excreted with ammonium, sodium, and potassium. Thus, measurement of the urine osmolal gap can help distinguish renal tubular acidosis (in which ammonium excretion is low) from other causes of hyperchloremic acidosis. (See "Urine anion and osmolal gaps in metabolic acidosis", section on 'Urine osmolal gap'.)

TREATMENT — Sodium bicarbonate can be administered when D-lactic acidosis and acidemia are severe. Oral antimicrobial agents (such as metronidazole, neomycin, or vancomycin) can be used when D-lactic acidosis develops in patients with short bowel syndrome. These antimicrobials decrease the number of D-lactate-producing organisms [1-3].

A low-carbohydrate diet (or the use of starch polymers rather than simple sugars) is also helpful because it diminishes carbohydrate delivery to the colon [3,15]. Although antimicrobials are sometimes helpful, as noted above, they can also occasionally precipitate D-lactic acidosis in susceptible subjects by causing an overgrowth of lactobacilli [16]. Limiting D-lactic acidosis generation caused by the rapid infusion of propylene glycol can be achieved by slowing or stopping the infusion.

Several young patients with recurrent D-lactic acidosis have been successfully treated with fecal transplantation [17,18].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fluid and electrolyte disorders in adults".)


Pathogenesis – D-lactic acidosis can occur in patients with jejunoileal bypass, small bowel resection, or other causes of the short bowel syndrome. Overgrowth of gram-positive anaerobes and excessive delivery of glucose and starch to the colon generate excessive production of D-lactic acid. D-lactic acidosis can also occur when large amounts of propylene glycol are either rapidly infused or ingested. D-lactate may also accumulate in patients with diabetic ketoacidosis. (See 'Pathogenesis' above.)

Clinical features – In patients with short bowel syndrome, D-lactic acidosis typically presents with episodic metabolic acidosis after high-carbohydrate meals associated with confusion, cerebellar ataxia, slurred speech, and loss of memory. (See 'Clinical manifestations' above.)

Diagnosis – D-lactic acidosis should be considered in patients with an otherwise unexplained metabolic acidosis (either high anion gap or hyperchloremic) and characteristic history/signs/symptoms. Confirmation of the diagnosis requires a special assay because the standard assay for lactate uses L-lactate dehydrogenase, which will not detect D-lactate. The plasma anion gap increase may not be proportional to the decrease in serum bicarbonate, because D-lactate is more readily excreted into the urine than L-lactate. This occurs because the renal tubules preferentially reabsorb L-lactate compared with D-lactate. The loss of D-lactate with sodium or potassium, combined with retention of dietary sodium chloride, reduces the serum anion gap and generates a hyperchloremic acidosis. The excretion of sodium and potassium with D-lactate also increases the urine anion gap and can potentially prompt an incorrect diagnosis of renal tubular acidosis. However, measurement of the urine osmolal gap will better reflect the urine ammonium concentration in such patients. (See 'Diagnosis' above.)

TreatmentSodium bicarbonate can be administered when D-lactic acidosis and acidemia are severe. Oral antimicrobial agents (such as metronidazole, neomycin, or vancomycin) can be utilized when D-lactic acidosis develops in patients with short bowel syndrome. A low-carbohydrate diet (or the use of starch polymers rather than simple sugars) is also helpful because it diminishes carbohydrate delivery to the colon. When D-lactic acidosis is caused by rapid infusion of propylene glycol, the infusion should be slowed or stopped. (See 'Treatment' above.)

  1. Stolberg L, Rolfe R, Gitlin N, et al. d-Lactic acidosis due to abnormal gut flora: diagnosis and treatment of two cases. N Engl J Med 1982; 306:1344.
  2. Oh MS, Uribarri J, Carroll HJ. Electrolyte case vignette: a case of unusual organic acidosis. Am J Kidney Dis 1988; 11:80.
  3. Halperin ML, Kamel KS. D-lactic acidosis: turning sugar into acids in the gastrointestinal tract. Kidney Int 1996; 49:1.
  4. Bongaerts G, Bakkeren J, Severijnen R, et al. Lactobacilli and acidosis in children with short small bowel. J Pediatr Gastroenterol Nutr 2000; 30:288.
  5. Uchida H, Yamamoto H, Kisaki Y, et al. D-lactic acidosis in short-bowel syndrome managed with antibiotics and probiotics. J Pediatr Surg 2004; 39:634.
  6. Bianchetti DGAM, Amelio GS, Lava SAG, et al. D-lactic acidosis in humans: systematic literature review. Pediatr Nephrol 2018; 33:673.
  7. Jorens PG, Demey HE, Schepens PJ, et al. Unusual D-lactic acid acidosis from propylene glycol metabolism in overdose. J Toxicol Clin Toxicol 2004; 42:163.
  8. Tsao YT, Tsai WC, Yang SP. A life-threatening double gap metabolic acidosis. Am J Emerg Med 2008; 26:385.e5.
  9. Lu J, Zello GA, Randell E, et al. Closing the anion gap: contribution of D-lactate to diabetic ketoacidosis. Clin Chim Acta 2011; 412:286.
  10. Więcek S, Chudek J, Woś H, et al. Serum Level of D-Lactate in Patients with Cystic Fibrosis: Preliminary Data. Dis Markers 2018; 2018:5940893.
  11. Shi H, Wu B, Wan J, et al. The role of serum intestinal fatty acid binding protein levels and D-lactate levels in the diagnosis of acute intestinal ischemia. Clin Res Hepatol Gastroenterol 2015; 39:373.
  12. Bongaerts G, Tolboom J, Naber T, et al. D-lactic acidemia and aciduria in pediatric and adult patients with short bowel syndrome. Clin Chem 1995; 41:107.
  13. Uribarri J, Oh MS, Carroll HJ. D-lactic acidosis. A review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore) 1998; 77:73.
  14. Narula RK, El Shafei A, Ramaiah D, Schmitz PG. D-lactic acidosis 23 years after jejuno-ileal bypass. Am J Kidney Dis 2000; 36:E9.
  15. Mayne AJ, Handy DJ, Preece MA, et al. Dietary management of D-lactic acidosis in short bowel syndrome. Arch Dis Child 1990; 65:229.
  16. Coronado BE, Opal SM, Yoburn DC. Antibiotic-induced D-lactic acidosis. Ann Intern Med 1995; 122:839.
  17. Bulik-Sullivan EC, Roy S, Elliott RJ, et al. Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis. J Pediatr Gastroenterol Nutr 2018; 67:483.
  18. Davidovics ZH, Vance K, Etienne N, Hyams JS. Fecal Transplantation Successfully Treats Recurrent D-Lactic Acidosis in a Child With Short Bowel Syndrome. JPEN J Parenter Enteral Nutr 2017; 41:896.
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