How methanol poisons

Starting on a Wednesday morning in June, 225 people were admitted to four hospitals in the southern Indian state of Tamil Nadu. Their symptoms included vomiting, stomachache, headache, diarrhea, and eye irritation.

To support the medical staff, the government brought in extra doctors from nearby medical schools. Yet 65 of the 225 patients did not survive. Their cause of death was the same—they had all consumed methanol-laced illicit liquor, purchased from local bootleggers.

“The victims included men and women; essentially, the poor. Most of them worked as manual or agricultural laborers, and they consumed the spurious liquor because it’s cheap,” says M. S. Prasanth, the top government official in the district of Kallakurichi, where the incident occurred. “It’s a problem controlling methanol. A detailed inquiry has been ordered by the Tamil Nadu government to probe the tragedy.”

Methanol poisoning is a global public health problem. According to data collected by Doctors without Borders, over 950 incidents of mass methanol poisoning have been reported since 1998, affecting over 28,500 people and killing nearly 13,500 in countries including Australia, Cambodia, Canada, China, Libya, Nigeria, Norway, Russia, and Turkey.

So far this year, more than 250 people have died from such poisoning worldwide, including almost 100 in India, according to Doctors without Borders. While methanol has been mixed in various kinds of alcohol in tragedies around the world, in most cases in India, the brew has been homemade liquor: producers have added methanol to regular alcohol to strengthen its intoxicating effects or increase its volume.

James Manor, emeritus professor of commonwealth studies at the University of London, says methanol has caused every liquor poisoning around the world since 1945. Manor says such instances keep repeating because some governments ban distilled liquor, often for ideological reasons, causing people who can’t afford underground market liquor to turn to bootlegged products. Other nations, meanwhile, tax regular alcohol heavily, making it too expensive for lower-income people and prompting them to turn to cheaper illicit liquor.

“Methanol has a number of industrial uses, and uses in people’s homes. So it is always going to be available on the market. There is no point in banning it. What is needed is to keep it out of mixtures of liquor for consumption,” says Manor, who wrote a book on a 1981 illicit liquor disaster in India that killed more than 300. “As long as no cheap type of distilled liquor is available to poor people, they will buy risky liquor from criminals.”

A ‘chemical Trojan horse’

Ethanol and methanol are alcohols with similar tastes and smells. When ingested, both lead to intoxication. But the structural difference in the molecules—ethanol has two carbon atoms, and methanol has one—leads to significantly different metabolism and effects, says A. Wallace Hayes, an adjunct professor at the University of South Florida’s Institute for Integrative Toxicology.

“Low levels of methanol are found in the human body and are maintained by physiological and metabolic clearance mechanisms,” Hayes says. Methanol is also found in low concentrations in fruit juices, dried legumes, filbert nuts, and vegetables such as potatoes, onions, and celery. But higher concentrations can be dangerous.

“As little as 1 g of methanol per kilogram of body weight can be fatal, and permanent visual damage can occur with the ingestion of 30 mL of methanol,” says Douglas J. Lanska, a neurologist and honorary fellow in the Department of Neurology at the University of Wisconsin School of Medicine and Public Health.

The human liver uses the same enzyme pathways to metabolize both methanol and ethanol, Lanska says. The difference lies in the metabolites of methanol, which are much more toxic than those of ethanol.

Lanska says that when the liver metabolizes ethanol, the most important enzyme pathway involves alcohol dehydrogenase (ADH), which converts ethanol to acetaldehyde, a chemical that contributes to the symptoms of a hangover. Acetaldehyde is then metabolized by aldehyde dehydrogenase into acetate before being broken down into carbon dioxide and water.

In contrast, ADH converts methanol to formaldehyde, and then aldehyde dehydrogenase converts formaldehyde to formic acid. “Methanol itself is not very toxic, but it is converted in the body to very toxic chemicals: formaldehyde and formic acid,” Lanska says.

Like acetate, formic acid breaks down into CO₂ and water, according to Peter Pressman, a food toxicology expert and professor at the University of Maine. But with formic acid, the process is very slow, and the acid may accumulate in the body, resulting in metabolic acidosis, Pressman says.

Methanol’s metabolites, particularly formic acid, also cause eye damage by interrupting the mitochondrial function in the optic nerve. They also affect the basal ganglia—brain structures that serve many functions, including the coordination of reward, emotional, and motor pathways. “Hemorrhagic and nonhemorrhagic damage are seen in cases of severe methanol intoxication,” Pressman says.

He calls the methanol poisoning process ironic, as the liver, while trying to detoxify methanol, produces the potent toxin formic acid. To Lanska, the process is a classic example of lethal synthesis, or a chemical Trojan horse—a seemingly benign chemical that secretly hides factors that can prove fatal for its consumer.

The challenges of diagnosis and treatment

In Karunapuram, a small village that was the epicenter of the Kallakurichi illicit liquor tragedy, almost every home lost a breadwinner to methanol-laced alcohol. Poongudi, an auxiliary nurse midwife, told the Hindu, an Indian daily, that her husband, Anandan, was addicted to the brew, which a bootlegger sold in their village, even though locals complained to the police about him on several occasions. After consuming the spurious liquor, Anandan first reported breathlessness but was rushed to the hospital only after he started experiencing loss of sight. His condition deteriorated soon thereafter, and he died.

“The symptoms of alcohol poisoning and methanol poisoning are the same, except for the blurring of vision caused by methanol,” says Prasanth, the Kallakurichi official. “But by the time blurring of vision is noticed, it’s too late.”

In cases of methanol poisoning, prompt medical care is essential to avoid permanent neurological complications and death, Lanska says. But because methanol and ethanol exhibit the same initial symptoms, misdiagnosis is common.

According to a 2022 paper, the symptoms of methanol poisoning develop gradually, owing to the slow metabolism of methanol in the liver. The body eliminates ethanol 6.5 times faster than methanol. As early as 4 h after methanol intoxication, people usually exhibit symptoms similar to ethanol poisoning, including headache, abdominal pain, nausea, vomiting, and general weakness. These symptoms are followed by an asymptomatic period of about 10–12 h. Severe nervous system dysfunction doesn’t appear until 12–24 h after exposure to methanol, and vision problems appear within 12–48 h in about half the cases.

“Moreover, animal studies have shown that despite almost complete metabolism and removal of methanol from the body, the concentration of formic acid simultaneously tends to persist, causing further tissue damage,” the study notes.

Knut Erik Hovda, a physician at Oslo University Hospital, says health-care personnel often know little about methanol poisoning, and the problem gets limited attention, as it mainly involves lower-income people. Diagnosis, too, is difficult, he says, because accurate methanol analysis requires sophisticated laboratory equipment and skills.

“Patients are often diagnosed with other conditions, or they just die or experience blindness and/or brain damage of varying degree,” says Hovda, who has developed a bedside diagnostic test to detect methanol poisoning. “The prototype is finished,” he says about the test, “but we have struggled for years to find investors who can help us get to the market.”

In lower-income countries, access to emergency health care is also a problem, Hayes says, as “terribly overcrowded and overburdened hospitals and clinics are the norm, and access is further limited by distance and poor transportation.” He also puts some responsibility on the stigma and prohibition attached to alcohol consumption in some traditions, as they prevent patients from admitting to having consumed alcohol.

Even if methanol poisoning is diagnosed accurately and quickly, the treatment process is riddled with challenges. According to Manor, most doctors do not know that an antidote to methanol is ethanol. “Ethanol competes well with methanol in the body to prevent methanol from breaking down into its component parts. A patient who has consumed methanol should be given pure alcohol or ethanol to drink in quantity,” Manor says.

Fomepizole is another effective treatment for methanol poisoning. Pressman says both antidotes work via competitive inhibition. Ethanol and fomepizole are both metabolized by ADH, and the enzyme has a higher affinity for the two antidotes than it does for methanol. ADH’s affinity for ethanol is at least 10 times what it is for methanol, and its affinity for fomepizole is 500–1,000 times what it is for ethanol.

“However, the use of fomepizole is limited because of its cost and lack of availability, especially in resource-scarce and austere environments . . ., which is typically where catastrophic methanol toxicity occurs,” Pressman says.

The business of adulteration

The market research firm Euromonitor International estimates that illicit alcoholic beverages account for over 25% of the total alcohol consumed each year in the 24 countries it reviewed in Latin America, Africa, and eastern Europe, generating more than $19.4 billion in sales. “These products are responsible for hundreds of cases of death and illness due to accidental methanol intoxication, millions of dollars used to fund other criminal activities, and the fiscal loss of billions of dollars in unpaid taxes,” the company’s white paper notes.

Yet methanol isn’t going away, Hayes says. It is central to the production of acetic acid and other important chemicals like formaldehyde, which is further used to produce plywood, adhesives, and insulation materials. Methanol is used to make fuels, deicing and disinfection products, and solvents. It’s also used in the defense and pharmacological industries and for producing plastics, synthetic fabrics, dyes, and fungicides, Hayes says.

And methanol is cheap. According to NITI Aayog, a public policy think tank of the Indian government, ethanol costs 54–75 cents per liter in India, depending on its source, which includes molasses, damaged grains, rice, and cane juice. Methanol, at less than 24 cents per liter, costs less than half as much.

Because methanol is so cheap and ubiquitous, experts like Manor say governments in countries where alcohol is legal must make at least one type of distilled liquor available cheaply to avoid liquor tragedies among lower-income people. “But almost no government has done that, mainly because they need revenues,” he says.

The recent illicit liquor tragedy in Tamil Nadu came a year after two such instances claimed a total of 22 lives in the same state. Prasanth says tragedies like these keep repeating because a 200 mL pack of illicit liquor costs about 72 cents in Kallakurichi, much less than legal liquor. Even one of the cheapest liquors in India, known as country liquor or Indian-made Indian liquor, costs more than three times as much.

“It’s the price difference,” Prasanth says.

Puja Changoiwala is an Indian journalist and author.