Endogenous Ethanol Production in a Child with Short Gut Syndrome

To the Editor: We recently reviewed the literature dealing with endogenous ethanol (EE) production in humans—the so-called auto-brewery syndrome (1). Our primary interest was litigation relating to driving under the influence of alcohol, in which EE production is sometimes used as a defense argument. In our review, we concluded that with few exceptions, the concentrations of EE in peripheral venous blood are vanishingly small (0.01–0.02 mg/dL) and therefore lack clinical or forensic significance. Indeed, any ethanol generated by microbiologic activity in the gut is effectively cleared when the portal venous blood passes through the liver for the first time (2). The abundance of hepatic alcohol dehydrogenase and the operation of Michaelis-Menten elimination kinetics should effectively clear low concentrations of ethanol entering the portal venous blood (3). Higher concentrations of EE might be generated in the gut of people with yeast overgrowth, particularly Candida albicans after carbohydrate-rich meals, and this has been reported uniquely in a number of Japanese patients (4). An abnormal yeast proliferation, food stagnation, and defective alcohol metabolizing enzymes in the liver might lead to higher concentrations of ethanol in the peripheral circulation. Pyruvate decarboxylase, a fungal enzyme lacking in humans, may produce elevated concentrations of acetaldehyde. Many Asians inherit an inactive form of the low km aldehyde dehydrogenase (ALDH), which converts acetaldehyde to acetate (5). A defective ALDH associated with higher hepatic concentrations of acetaldehyde could result in reduction of acetaldehyde to ethanol in a reversible NAD+/NADH reaction catalyzed by alcohol dehydrogenase (ADH). Dahshan and Donovan (6) describe the case of a 13-year-old girl with short bowel syndrome whose very high blood-ethanol concentrations (BACs) of 250 to 350 mg/dL (0.25–0.35 g/dl) were presumed secondary to endogenous synthesis in the gut. The BAC's were attributed to intestinal yeast overgrowth secondary to neonatal intestinal resection with intestinal blind loop syndrome. Recurrent episodes of disorientation and somnolence and a fruity odor on the breath suggested possible alcohol abuse. The girl's father monitored breath-alcohol concentration after carbohydrate-rich foods and the results supported the suspicion of EE production. We have several concerns about this report. First, the methods used to determine ethanol in blood and breath specimens are not mentioned. There are important differences between gas chromatographic and enzymatic procedures, which have an impact on this case. Gas chromatography (GC) is the preferred method because of its higher selectivity for ethanol, which allows positive identification by comparison of retention time with known standards. Mass spectral analysis would definitely prove the presence of ethanol. Enzymatic assays are less specific than GC for the analysis of ethanol. For example, both n-propanol and isopropanol are good substrates for ADH. Certain metabolic disturbances such as lactic acidosis create problems when automated enzymatic assays are used, which may lead to false positive test results (7–9). Indeed, the risk of hyperlactacidemia in short-gut syndrome was mentioned by Dahshan and Donovan, who found no measurable d-lactate in their patient. They failed, however, to report l–lactate, pyruvate, acetaldehyde, or other endogenous metabolites, all of which measurements are important to the assurance that EE is truly elevated in their patient. With respect to the breath alcohol testing performed by the girl's father, neither the name, the principle of operation, nor the source of the breath-alcohol analyzer was mentioned, and the authors do not report the specific results obtained, or whether they were consistent with the serum measurements. Breath-alcohol devices differ widely in reliability and selectivity for analysis of ethanol. The serum ethanol concentrations reported by Dahshan and Donovan are substantially greater than any prior reports of EE (4) and surgical models in animals have failed to produce this syndrome (10,11). Moreover, studies of patients with short bowel syndrome have noted that ethanol was not the cause of the neurologic manifestations in these patients (12). This report would have been more convincing if temporal variations or kinetics of EE production and degradation had been studied. The rate of elimination of EE from blood could have been compared with values in the literature (3), and the sufficiency of the substrate concentrations to produce this amount of ethanol could also have been evaluated (13). Use of two independent analytical methods or simultaneous identification of ethanol in blood and urine would have strengthened the report. Information about the girl's general state of health, her body weight, ethnic background, and whether she had any metabolic disorders such as diabetes, would have been useful information in evaluating this case report. While the patient's condition appears to have resolved after treatment with fluconazole, we do not believe that the data presented permit an unequivocal conclusion that EE was the cause. Based on the information provided in their report, we cannot accept the authors' position that ethanol was produced endogenously to such an extent that BACs of 250 to 350 mg/dL were reached. Selectivity of the analytical methods must be carefully considered. Finally, it seems unlikely that a 13-year-old girl could tolerate blood-alcohol concentrations as high as 250 to 350 mg/dL without suffering serious medical consequences such as acute alcohol poisoning. B. K. Logan A. W. Jones