DOES ALCOHOL MAKE YOU FLUSH?

The Flushing Questionnaire
The flushing questionnaire consists of two questions:
(A) Do you have a tendency to develop facial flushing immediately after drinking a glass (about 180 ml) of beer?

(B) Did you have a tendency to develop facial flushing immediately after drinking a glass of beer in the first one or two years after you started drinking? For both questions, the choice of answers are: yes, no, or unknown.

If an individual answers yes to either question A or B, they are considered to be ALDH-2 deficient. The addition of question B is important because some individuals can become tolerant to the facial flushing effect.

The alcohol flushing response is a biomarker for ALDH2 deficiency. ALDH2-deficient patients have an increased risk for esophageal cancer if they drink even moderate amounts of alcohol. Because of the intensity of the symptoms, most people who have the alcohol flushing response are aware of it. Therefore clinicians can determine ALDH2 deficiency simply by asking about previous episodes of alcohol-induced flushing.

ALDH2-deficient patients can then be counseled to reduce alcohol consumption, and high-risk patients can be assessed for endoscopic cancer screening. The authors estimate that there are at least 540 million ALDH2-deficient individuals in the world, representing approximately 8% of the population. In a population of this size, even a small reduction in the incidence of esophageal cancer could result in a substantial reduction in esophageal cancer deaths worldwide.

Philip J. Brooks e al has documented that approximately 36% of East Asians (Japanese, Chinese, and Koreans) show a characteristic physiological response to drinking alcohol that includes facial flushing nausea, and tachycardia,

This so-called alcohol flushing response is predominantly due to an inherited deficiency in the enzyme aldehyde dehydrogenase 2 (ALDH2) found mostly in Asia but also present in the West.

Few are aware of the accumulating evidence that ALDH2-deficient individuals are at much higher risk of esophageal cancer (specifically squamous cell carcinoma) from alcohol consumption than individuals with fully active ALDH2.

Esophageal cancer is one of the deadliest cancers worldwide, with five-year survival rates of 15.6% in the United States, 12.3% in Europe, and 31.6% in Japan.
When detected early, esophageal cancer can be treated by endoscopic mucosectomy, a standard and relatively non-invasive procedure. However, once the cancer has grown large enough to penetrate the submucosal layer, the likelihood of lymph node metastasis increases significantly. Only about 20% of esophageal cancer patients survive three years after diagnosis, emphasizing the importance of disease prevention.

In view of the approximately 540 million ALDH2-deficient individuals in the world, many of whom now live in Western societies, even a small percent reduction in esophageal cancers due to a reduction in alcohol drinking would save many lives. Increasing evidence also points to the metabolism of ethanol by microorganisms in the oral cavity as an important source of acetaldehyde in saliva and, by extension, in the esophagus. Acetaldehyde levels in saliva are 10–20 times higher than in blood, due to the local formation of acetaldehyde by oral microorganisms. Importantly, ALDH2 heterozygotes have two to three times the acetaldehyde levels in their saliva compared to fully active ALDH2 individuals after a moderate dose of oral ethanol.

For patients at high risk of esophageal cancer, doctors should also consider endoscopy for early cancer detection.
Using a version of the health risk assessment that includes the flushing questionnaire as a major component, it has been estimated that approximately 58% of esophageal cancers in the population could be detected by screening.

Philip J. Brooks et al. The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption. PLoS Med 6(3): e1000050. doi:10.1371/journal.pmed.1000050