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Scientists comment on the health effects of methanol, after several deaths in Laos due to methanol poisoning.
Professor Christer Hogstrand, Professor of Molecular Ecotoxicology, King’s College London, said:
“Methanol is not uncommon in home-distilled alcohol and if there is enough of it a person drinking it can go blind, get internal organ failure and even die. It is the metabolites which are the active toxic agents.
“Methanol is like the alcohol in our drinks – colourless and odourless – but its impact on humans can be deadly. It has a different carbon atom structure which completely changes how humans process it in the body, leading to these potentially fatal consequences.”
Dr Wayne Carter, Associate Professor, University of Nottingham, said:
“In standard alcoholic drinks, methanol would not be present but historically, the presence of methanol in alcoholic drinks can be masked by mixing with alcohol. Hence, if mixed with ethanol, it can go undetected until the toxic effects are felt – highlighting the potential for toxicity with fatal consequences. Similar to alcohol it is oxidised in the body, but the breakdown of methanol forms a strong and dangerous acid (formic acid) as well as a toxic product (formaldehyde, a cancer-causing chemical). Drinks spiked with methanol can cause blindness as well as damage to organs by metabolic acidosis. It varies between individuals but for some people, even low levels of methanol ingestion (as little as 15 mL of a 40% solution) can cause death.”
Prof Sir Colin Berry, Emeritus Professor of Pathology, Queen Mary University of London (QMUL), said:
“Methanol has been recognized as a human visual neurotoxin for more than a century (see Wood and Buller, 1904) and the clinical features of acute human methanol toxicity have been well documented. Products that contain methanol include windshield washer fluid, gas line antifreeze, carburettor cleaner, copy machine fluid, perfumes, food warming fuel, and other types of fuels.
“The ingestion of methanol is followed by metabolism to formaldehyde (by alcohol dehydrogenase) formic acid and by the subsequent production of formates. Formaldehyde, formic acid and formates are all agents of methanol toxicity, where they disrupt mitochondrial energy production.
“Initially, the symptoms of methanol intoxication are similar to those of ethanol intoxication, with an initial transient central nervous system depression, followed by disinhibition and ataxia. Following a latent period, patients may develop headache, nausea, vomiting, or epigastric pain with visual problems ranging from mild photophobia and misty or blurred vision to markedly reduced visual acuity with visual hallucinations (misty vision, snowstorm, dancing spots, flashes) and partial or total loss of vision, which may be unilateral. Gastro-intestinal bleeding may occur.
“In later stages, generally developing between 18 and 48 hours after methanol ingestion, drowsiness may progress to coma. Convulsions may occur, generally as a complication of the metabolic upset – there is formic acidaemia and an uncompensated metabolic acidosis.
“Susceptibility among persons to the acute effects of methanol is highly variable, and blindness has been reported after ingestion of as little as 4ml of methanol.”
Dr Christopher Morris, Senior Lecturer, Newcastle University, said:
“Methanol, unlike alcohol (or ethanol), gets converted in the body to several toxic compounds including formic acid, formate, and formaldehyde. Treatment has to be started very quickly as often the person recovers soon from the initial effects of the methanol which are similar to alcohol, but then the toxic by-products build up and start to have their harmful effects. Formate, which is the main toxin produced, acts in a similar way to cyanide and stops energy production in cells, and the brain seems to be very vulnerable to this. This leads to certain parts of the brain being damaged. The eyes are also directly affected and this can cause blindness which is found in many people exposed to high levels of methanol. Because the body also converts methanol to formic acid, this along with the effects of formate can cause the pH of the body to drop. This pH drop can damage various tissues and organs in the body, leading to organ failure and sadly death in severe cases.”
Prof Alastair Hay, Professor (Emeritus) of Environmental Toxicology, University of Leeds, said:
“The risk from methanol is twofold. Methanol breaks down in the body to formaldehyde and then formic acid. The formic acid upsets the acid /base balance in blood and the major consequence is initially the effect on someone’s breathing. There are effects on many other organs the kidney being one. The disturbance of acid/base balance and disrupted breathing will eventually affect the heart and it will stop functioning.
“Formaldehyde attacks nerves, particularly the optic nerve and blindness is a potential risk.
“Depending on the severity of poisoning, treatment may require dialysis to remove methanol from blood whilst at the same time keeping someone mildly drunk by administering ethanol.
“If the poisoning is not too severe, and only blood tests will determine this, ethanol alone may suffice.
“The principle behind administering ethanol is quite simple; it delays methanol metabolism. Both alcohols are broken down by the same liver enzyme alcohol dehydrogenase. But the enzyme prefers ethanol. So ethanol acts as a competitive inhibitor largely preventing methanol breakdown, but markedly slowing it down, allowing the body to vent methanol from the lungs and some through the kidneys, and a little through sweat. Avoiding the formation of toxic levels of formaldehyde is key.”
Prof Oliver Jones, Professor of Chemistry, RMIT University, said:
“Methanol toxicity is caused by the way it is processed (metabolised) by the body.
“Methanol itself is a type of alcohol, similar in structure to the ethanol in alcoholic drinks but far more toxic. Methanol’s chemical formula is CH3OH , while ethanol is C2H5OH.
“In the body Methanol is first acted on by an enzyme called alcohol dehydrogenase, which converts it to a compound called Formaldehyde (CH2O). Formaldehyde is then transformed by an enzyme called formaldehyde dehydrogenase to become formic acid (HCO2H), which becomes a formate ion (HCO2-) in the blood.
“It is the build-up of formic acid /formate in the blood that causes the toxicity. Formic acid blocks the action of another enzyme called cytochrome oxidase. This enzyme is critical to how the body uses oxygen to generate energy. If it stops working, cells cannot take up or use oxygen from the blood even when oxygen levels are normal. Lack of oxygen causes problems in a range of organs as the cells start to die. The build-up of formic acid in the blood also causes a condition called metabolic acidosis, which is a serious imbalance in electrolytes.
“Symptoms of methanol poisoning include vomiting, seizures and dizziness. The optic nerve seems to be particularly vulnerable to methanol toxicity, so there is the potential for temporary or permanent blindness, and even death.
“While thankfully rare, methanol poisoning is very serious, and treatment should be given at a hospital. Methanol poisoning is treated by stopping the alcohol dehydrogenase enzyme from creating toxic by-products. This can be accomplished by either using a drug to inhibit the enzyme directly or by giving the patient ethanol. In the latter case, the alcohol dehydrogenase enzyme is essentially too busy processing the ethanol to process the methanol into the dangerous byproducts. Dialysis of the blood to remove both the methanol and toxic breakdown products can also be an option.”
Declared interests
Prof Alastair Hay: I have no declarations of interest.
Prof Oliver Jones: I don’t have any competing interests to declare.
Prof Sir Colin Berry: No conflicts
Dr Christopher Morris: “I am a member of the Committee on Toxicity for the Food Standards Agency but not commenting as a member of COT, these are my views as an independent scientist.”
For all other experts, no reply to our request for DOIs was received.