Growing up in Taiwan, Joseph Wu watched his parents and grandparents enjoy alcohol on occasion, their faces turning a glaring shade of red after only one or two drinks. When trying alcohol for himself years later, he experienced the phenomenon firsthand.
“My heart rate goes up to 130 beats per minute, I get facial flushing, and three to four hours later, I’ll probably get a headache,” said Wu, director of the Stanford Cardiovascular Institute and president of the American Heart Association, who studies the genetic mutation that causes what is known as alcohol flush reaction.
About 560 million people, or 8 percent of the global population, carry this mutation, with the vast majority being of East Asian descent — hence the nickname for the reaction, “Asian glow” or “Asian flush.”
An estimated 45 percent of East Asians get the “glow” when drinking. For some, the unpleasantness is enough to abstain from alcohol. Many others push through the discomfort, sometimes with the help of an antihistamine to lessen the effects.
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Experts such as Wu, however, say that people who experience alcohol flush reaction should drink as little as possible or ideally not at all. The redness and other symptoms may be thought of as a severe warning from the body that alcohol is extremely toxic to this individual, much more so than to many others.
The associated mutation, known as the ALDH2*2 variant, has been linked to a staggering number of diseases in those who consume moderate to large quantities of alcohol.
Higher risk of many diseases
Alcohol flush reaction seemed like a “nuisance and a discomfort” when I was younger, Wu said. “Like most people, I wasn’t aware of the medical implications,” he said.
“This is one of the most common hereditary disorders in the world, and people in our societies like to drink,” said Ronald G. Crystal, chair of genetic medicine at Weill Cornell Medical College. “But the combination of these two things puts these individuals at risk for cardiovascular disease, osteoporosis, esophageal cancer and more.”
For example, someone with the ALDH2*2 variant who drinks in moderation — defined as two drinks a day for men and one drink a day for women — has a risk of esophageal cancer 40 to 80 times higher than a person without the mutation who consumes the same amount.
It is a dose-dependent relationship, meaning that more drinks per day translates to an even greater risk. The ALDH2*2 variant does not influence esophageal cancer risk in nondrinkers.
The mutation has also been associated with an increased risk of head and neck cancers, gastric cancer, coronary artery disease, stroke and osteoporosis in East Asian populations.
What causes the alcohol flush reaction?
People with the ALDH2*2 variant lack a functional enzyme that helps the body break down alcohol. Alcohol is normally metabolized by the body in two steps. One enzyme converts alcohol into acetaldehyde, a compound significantly more toxic to humans than the alcohol itself. A second enzyme then quickly converts acetaldehyde into acetate, a compound that can be safely metabolized by the body.
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People with alcohol flush reaction produce a version of the second enzyme, mitochondrial aldehyde dehydrogenase 2 (ALDH2), that has very low activity. This ALDH2 deficiency leads to alcohol not being metabolized normally, and acetaldehyde — essentially, a poison — builds up in the blood.
“Acetaldehyde is classified as a Group 1 carcinogen by the World Health Organization, meaning it has been proven to cause cancer in humans,” said Che-Hong Chen, country director of the Stanford Center for Asian Health Research and Education. “Even with just two cans of beer, the amount of acetaldehyde in their blood is already reaching carcinogenic levels.”
In his laboratory, Chen uses a simple ethanol patch test to determine whether subjects have an ALDH2 deficiency. He applies ethanol to a Band-Aid and places it on their skin for 20 minutes. Acetaldehyde causes blood vessels to dilate — essentially, what causes the flushing to occur — and those with the mutation will have a red spot in that area. The ethanol patch test is approximately 70 to 90 percent accurate. To know for sure, individuals may take a DNA test from 23andMe or Ancestry.
Can an antihistamine help?
An antihistamine might prevent skin flushing, since it reduces blood vessel dilation, but the medication does nothing to lower acetaldehyde levels in the blood. Chen said that college students at his university commonly take Pepcid AC or Zantac before going out drinking to avoid the discomfort of Asian glow.
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“Taking a drug to prevent alcohol flush reaction basically numbs the unpleasant feeling so you can drink more, which is even more dangerous,” Chen said. “Think of it as your body having a pain sensation to tell you to stop drinking.”
Lack of awareness
The ALDH2*2 variant was thought to originate from a single founder in Southeast China who lived 2,000 to 3,000 years ago. From there, the mutation spread to other East Asian countries. Today, the proportion of carriers varies across countries such as South Korea (30 percent), China (35 percent), Japan (40 percent) and Taiwan (49 percent).
Alcohol intake continues to increase despite the widespread nature of alcohol flush reaction in these populations. The prevalence of drinkers in East Asia has risen from 48.4 percent in 1990 to 66.9 percent in 2017. South Korea notably has a binge-drinking problem, while China has seen a surge in alcohol consumption over the past three decades.
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East Asia has the largest absolute burden — measured in the number of years lost because of the disease — of alcohol-attributable cancer in the world. It is also the region with the greatest proportion of cancer cases that can be traced back to alcohol, at 5.7 percent. In comparison, North America has a proportion of 3 percent.
The biggest problem is a lack of awareness about the dangers of drinking with an ALDH2 deficiency, experts said.
“I’m a geneticist, and even I didn’t know about this mutation,” said Chen, who is an ALDH2*2 carrier. “When I visited my home country of Taiwan, I realized that so many people were unaware like me.”
Misconceptions include thinking that alcohol flush reaction is a mere inconvenience or even signifies a strong liver. Many people still believe that a moderate amount of alcohol is good for your health, which recent research shows is false.
Educating people about alcohol flush reaction
Chen founded a nonprofit organization in 2017 to inform the Taiwanese public about the health implications of alcohol flush reaction. The Taiwan Alcohol Intolerance Education Society collaborates with the government to promote education around ALDH2 deficiency and alcohol consumption. Together, they launched the first National Taiwan No Alcohol Day on May 9, 2019. In Mandarin, “5-9” is a hom*ophone for “no alcohol.”
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Research suggests that knowing one’s alcohol-related health risks is enough to reduce consumption, at least temporarily. A 2010 study of 200 Asian American young adults found that conveying genetic feedback and medical information specific to the ALDH2*2 variant resulted in significant reductions in 30-day drinking frequency and quantity.
“We don’t know if there are long-term effects, but I think that people knowing their genetic makeup is helpful,” said study author Tamara Wall, a psychologist at the University of California at San Diego. “People have to be aware that if they drink with this variant, they are putting themselves at greater risk than people without.”
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