Jyrki Tillonen

Poor dental status increases acetaldehyde production from ethanol in saliva: a possible link to increased oral cancer risk among heavy drinkers

Epidemiological data support evidence that poor dental status increases oral cavity cancer risk especially among heavy alcohol consumers, but the causality of this finding is unclear. The enzymatic conversion of ethanol by the physiological oral microflora may lead to an accumulation of the highly carcinogenic intermediate acetaldehyde. This study was conducted to evaluate the role of dental status on the microbial production of acetaldehyde from ethanol in saliva. The microbial acetaldehyde production from ethanol was related to the dental score in 132 volunteers. After adjustment for smoking, alcohol consumption, age and gender, poor dental status was shown to lead to an approximately twofold increase in salivary acetaldehyde production from ethanol (P=0.02). Our results could be an important factor underlying the role of poor dental hygiene and status in oral cancer risk associated with ethanol drinking.

Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency.

High alcohol and low folate intake are independent risk factors for colorectal cancer. Acetaldehyde has been postulated to be a factor responsible for ethanol‐associated carcinogenesis. High levels of acetaldehyde accumulate in the large intestine via the microbial oxidation of alcohol. Acetaldehyde degrades folate in vitro. Thus, it is possible that high intracolonic acetaldehyde levels break down folate in the colon. Our aim was to test the effect of high alcohol and acetaldehyde concentrations in the gut on systemic and local intestinal folate levels in rats. Twenty rats received 3 g/kg of ethanol twice a day for 2 weeks with or without concomitant ciprofloxacin administration. Twenty control rats received saline with or without ciprofloxacin. All rats were fed a diet with normal folate content. Alcohol treatment led to very high intracolonic acetaldehyde levels (387 ± 185 μM), which were markedly decreased by concomitant ciprofloxacin treatment (21 ± 4 μM). Erythrocyte, serum and small intestinal folate levels were unaffected by alcohol treatment. Alcohol administration decreased significantly colonic mucosal folate levels by 48%, and this effect was prevented by ciprofloxacin. We conclude that alcohol administration for 2 weeks leads to local folate deficiency of colonic mucosa in rats, most probably via the degradation of folate by the high levels of acetaldehyde microbially produced from ethanol. Our findings offer a unique explanation for the increased risk of colonic cancer associated with alcohol intake and folate deficiency. Int. J. Cancer 86:169–173, 2000.

Hypochlorhydria induced by a proton pump inhibitor leads to intragastric microbial production of acetaldehyde from ethanol.

Acetaldehyde, produced locally in the digestive tract, has recently been shown to be carcinogenic in humans.

Lack of Disulfiram-Like Reaction with Metronidazole and Ethanol

BACKGROUND: Metronidazole, an effective antianaerobic agent, has been reported to have aversive properties when ingested with ethanol. This is thought to be due to the blocking of hepatic aldehyde dehydrogenase (ALDH) enzyme followed by the accumulation of acetaldehyde in the blood. However, based on animal studies and on only 10 human case reports, the existence of metronidazole-related disulfiram-like reaction has recently been questioned. OBJECTIVE: To investigate the possible disulfiram-like properties of metronidazole and ethanol in human volunteers. METHODS: Of 12 healthy male volunteers in this double-blind study, one-half received metronidazole for 5 days and the other half received placebo. All volunteers received ethanol 0.4 g/kg at the beginning of the study. Repeated blood samples were taken every 20 minutes for 4 hours, and blood acetaldehyde and ethanol concentrations were determined. Blood pressure, heart rate, and skin temperature were also measured every 20 minutes for objective signs of a possible disulfiram-like reaction. Volunteers also completed a questionnaire focusing on the subjective signs of disulfiram-like reaction. RESULTS: Metronidazole did not raise blood acetaldehyde or have any objective or subjective adverse effects when used together with ethanol. CONCLUSIONS: This study shows that metronidazole does not have an effect on blood acetaldehyde concentrations when ingested with ethanol and does not have any objective or subjective disulfiram-like properties. However, it is possible that disulfiram-like reaction can occur in some subgroups and by other mechanisms than the inhibition of hepatic ALDH.