A fixture of bathroom cabinets for decades, paracetamol is best known for lowering fevers, dulling headaches and taking the edge off hangovers. More recently, it has also been the subject of controversy, with the Trump administration suggesting that taking it during pregnancy may increase the risk of autism — a claim widely disputed by researchers.
Yet a growing body of research suggests that this humble tablet, first synthesised in the 19th century, may actually be far more helpful than is widely recognised.
Beyond its familiar uses, there is evidence that the drug — also known as acetaminophen and sold under the brand name Tylenol in the US — reduces the incidence of acute kidney injury after cardiac surgery. It may also prevent a deadly complication of malaria, a disease that claims about 600,000 lives each year, most of them children under the age of five in sub-Saharan Africa, and help patients with the kind of crush injuries often suffered in earthquakes and war zones.
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Discovered in the late 1800s and introduced widely in the 1950s, paracetamol quickly became a popular painkiller, prized for its reliability and safety compared with aspirin or opioids. For decades, however, scientists did not understand how it worked, only that it did. Something of an enigma, it provided fertile ground for researchers, some of whom now have uncovered the potential for surprising applications.
Among them is Kevin Moore, a professor at University College London and the Royal Free London NHS Foundation Trust. In the 1990s, he was part of a group that identified the mechanism by which paracetamol could prevent kidney failure caused by severe crush injuries to muscles elsewhere in the body. “The results were staggering,” he said.
Professor Kevin Moore
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Photographs from that early study tell the story. Kidneys from rats given doses of paracetamol remained healthy, while those from control rodents that did not get the drug were badly damaged. Other studies have since built on those findings, suggesting that the drug can also protect against blackwater fever, a potentially fatal complication of malaria.
For blackwater fever and trauma injuries, kidney damage comes about via a similar process. In malaria, a parasite destroys red blood cells. This releases a flood of haemoglobin, the protein in red blood cells that carries oxygen. When muscles are crushed a similar protein, myoglobin, is released.
Both haemoglobin and myoglobin contain iron, which can exist in several states, which differ in their electrical charge. Normally, iron switches safely between the ferrous (Fe²⁺) and ferric (Fe³⁺) forms. But a sudden release of the proteins from damaged red blood cells or injured muscle can overwhelm the body’s ability to safely process them.
As a result, the iron may be pushed into a highly reactive state known as ferryl (Fe⁴⁺). In this form, the proteins become potent oxidising agents, generating destructive molecules that act like corrosive sparks in the kidneys, damaging the organ and leading to acute renal failure.
Introduced to the market in the 1950s, paracetamol is considered much safer than aspirin or opioids
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Paracetamol, it turns out, acts as a kind of chemical fire extinguisher. It reduces ferryl iron back to the safer ferric or ferrous forms, preventing the cascade of oxidative injury. In effect, it calms the reactive proteins, allowing the kidneys to continue functioning even amid the onslaught of trauma or malaria.
Moore’s original paper, published in the Proceedings of the National Academy of Sciences in 2010, challenged long-standing dogma about kidney injury. The findings have since been borne out in more than half a dozen studies of malaria and two studies of patients undergoing cardiac surgery.
A drug often thought of as mundane may in fact turn out to save lives in some of the world’s deadliest conditions. Moore calls it “a good news story” at a time when paracetamol risks becoming better known for controversy than as a potential cure.
“Since there are 600,000 deaths per year from malaria, just a 10 per cent reduction in mortality would save more than 1,000 lives every week — and at a cost of pennies,” he said.
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