An estimated 5.5 million people died of heart conditions linked to lead poisoning in 2019 - more than the number killed by outdoor air pollution over the same period. That's according to a recent study in the journal Lancet Planetary Health. The number is substantially higher than previous estimates. According to a 2021 World Health Organization (WHO) report there were roughly 900 000 deaths linked to lead exposure in 2019.
The researchers also found that exposure to lead (a powerful neurotoxin) causes more harm to children's intellectual development than previously thought. The paper estimates that in developing countries, where the condition is most prevalent, a child with average levels of lead exposure loses nearly six IQ points from the metal in their first five years of life (average IQ is 100).
While only about 2% of those living in wealthy countries have lead poisoning, the situation is very different for those in poorer parts of the world. A 2021 study found that nearly half of all children living across 34 low-and-middle income countries have lead poisoning - which is typically defined as a person having at least five micrograms of lead per 100ml of blood.
It's estimated that the average child in South Africa is well above this threshold - at about 5·59 micrograms. And worryingly, the metal can still cause harm below the clinical threshold. Indeed, any increase in a person's blood-lead levels is associated with greater health risks, even at the lowest detectable levels.
Part of the reason that lead poisoning is so widespread is that the metal is used in a wide range of everyday commercial products, and poorer countries typically have fewer well-enforced laws to regulate its use. Products include certain paints, ceramic glazes, cosmetics, traditional medicines, spices, lead-acid batteries, bullets and fishing sinkers.
The metal can make its way from these products into people's bodies through a number of routes. In some cases - like with alternative medicines or spices - people directly ingest contaminated goods. In others, people breathe in lead dust, which can be generated by unregulated industrial practices. For instance if lead-acid battery recyclers lack proper safety and environmental standards - as is often the case in developing countries - recyclers may simply pour lead-based battery solution onto the ground, contaminating the soil.
Children are most at risk. For one, they're more likely to put items that contain lead in their mouths, like toys covered in lead paint, or even a thumb coated in lead dust. Secondly, they're closer to the ground and therefore breathe in more lead-contaminated dust. The theme of this year's WHO-backed International Lead Poisoning Prevention Week was "End childhood lead poisoning".
After it's ingested or inhaled, some lead is excreted, while the rest is absorbed into the bones, teeth and blood. Children absorb more of the metal than adults and once it's in the blood, lead can be distributed to various organs in the body. This includes the heart as well as the brain, where it can interfere with neurotransmitter systems involved in learning and memory.
No threshold
The new study in Lancet Planetary Health adds to a growing body of evidence that global lead exposure is far more detrimental to human health than previously thought. While people began understanding that lead was poisonous several thousand years ago, it was only recently that evidence accumulated showing that even tiny amounts of lead can cause damage.
Part of the reason is simply because we didn't have data on low-level exposure until recently, explains Bjorn Larsen, the study's lead author. Most people in industrialised countries had very high blood-lead levels during most of the 20th century. For instance, in the late-1970s the average American child had about 15 micrograms of lead per 100ml of blood, which is about 25 times the average today, and three times the present-day threshold for lead poisoning. A major reason was leaded gasoline, which was introduced in the 1920s and phased out from the 1970s onward.
Thus, says Larsen, testing the effects of blood-lead levels that we would now perceive as low wasn't always possible. For instance, to show that even one or two micrograms of lead per 100ml of blood is harmful, researchers would need to compare people at this (very low) level to those with no lead to observe if they come off worse. But if almost everyone is above two micrograms, this becomes close to impossible as there isn't anyone to test. And in the absence of data, some simply assumed that the metal was only problematic above a particular threshold.
Bruce Lanphear, a professor of public health at Simon Fraser University, was the lead author of a seminal 2005 paper that showed that lead was associated with declines in IQ even below the clinical threshold set at the time (10 micrograms of lead per 100ml of blood). He explains that by the mid-1990s, when 95% of people were below that threshold, many felt that lead was no longer much of an issue: "my advisors at that point said get out of this line of research, the problem seems to be going away and there won't be any funding for it. And they were right about one of those two things - I haven't gotten much funding," Lanphear says.
As blood-lead levels continued to drop and scientists like Lanphear could study the effects of lead on children's intellectual development at lower levels, a new consensus emerged. Larsen explains: "Now people are willing to say that in all likelihood the correct way to estimate things is that there is some effect on IQ as soon as we can detect lead in the blood - even at the lowest level these effects start". Indeed, according to a WHO factsheet, "there is no known safe blood-lead concentration".
Not only that, adds Lanphear, but research shows that "proportionately, we see greater harms - greater reductions in IQ - at the lowest measurable lead levels". In other words, the more lead you have in your body, the worse it is, but going from one microgram of lead per 100ml of blood to two micrograms causes more additional harm than going from 15 micrograms to 16. Thus, it's strangely only through the decline in lead poisoning that its most pernicious effects have been revealed.
Lead 'poisons' our cells
As more data is gathered, estimates of the harm caused by lead are constantly being revised upward. The finding that lead is linked to 5.5 million cardiovascular deaths a year is over six times the number previously determined by a 2019 study. It should be noted however that the new estimate is relatively uncertain - the researchers estimate the real value is most likely in the range 2.3 to 8.3 million.
Part of the reason for the updated estimates is that the 2019 research had only looked at the effects of lead on blood pressure, while the new paper considers a wide variety of cardiovascular problems associated with lead.
According to a statement by the American Heart Association from earlier this year these effects include injury to the cells that line the blood vessels, oxidative stress (which can result in cell and tissue damage) and coronary heart disease, which is when the blood flow is restricted, increasing the risk of a stroke or heart attack.
Gervasio Lamas, Chief of cardiology at Mount Sinai Medical Centre and the lead author of the statement, explains that heavy metals like lead can erode cardiovascular health through two broad channels: "one is that toxic metals typically will end up replacing essential metals or ions in vital cellular reactions," he says.
For instance, lead replaces the calcium in our cells, a mineral which is involved in keeping our hearts pumping, our blood clotting and our heart muscles properly functioning. By removing calcium, lead "poisons these cells," says Lamas.
He tells Spotlight that the other main route is that toxic metals often interfere with our antioxidant mechanisms. Antioxidants are molecules which deactivate harmful free radicals (chemicals that can attack our cells and DNA). Lead disrupts these antioxidant defences, he says. As a result, free radicals build up, which may cause the blood vessels to harden (called atherosclerosis), blocking blood flow.
Different strands of evidence point in the same direction
To arrive at the conclusion that 5.5 million people died from lead-induced heart conditions, Larsen and his colleague relied on two large observational studies from the United States (where there is lots of data). These studies measured the blood-lead levels of thousands of people and looked at what happened to them over time. They showed that those who had more lead in their blood were more likely to die of heart complications at a younger age, even when controlling for lots of other factors.
Larsen and his colleagues used estimates from these studies to develop a model which calculates the increase in a person's risk of dying of heart disease at different levels of lead exposure. They then plugged in the blood-lead levels that we observe among people around the world to estimate how much cardiovascular death the metal is linked to.
One contention that emerges from research like this is whether it really shows cause and effect. As Lamas notes, "the populations that are most affected by high lead levels are [more likely] to be underprivileged in some way. They are often either poor or have access to less healthcare or live in areas that are more generally contaminated - things that you would expect would in any case cause [health] problems for them".
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When we find that people who have more lead in their blood die of heart disease more often, this may be due to one of these other factors.
But according to Lamas, there are a number of reasons to be confident that lead is actually the driver of heart disease. The first is that when observational studies (like the ones discussed above) measure the relationship between people's lead levels and cardiovascular disease, they control for a range of other risk factors, including their socioeconomic status. "Even when you do that, lead still sticks out like a big sore thumb," Lamas notes.
The other reason is that there are lots of different sources of evidence that all find lead damages cardiovascular health: "there are direct experiments where patients or animals are infused with lead and those show that arterial function [i.e. the ability of our arteries to transport blood] is diminished," Lamas explains.
Finally, Lamas points to the results of a randomised clinical trial which he and his colleagues published in 2013. In it, they took over 1700 patients who had recently suffered from a heart attack and randomly split them into different groups. One group received a treatment for lead poisoning called EDTA chelation. This is an intravenous medicine that binds with toxic metals in the body before being urinated out. Those who didn't receive the chelation therapy got a placebo drug.
Five years later, those who got chelation therapy appeared to be better off. They performed better than the placebo group when measured by a composite index that combines factors like patients' risk of dying and their need to return to hospital for further procedures.
With so many different kinds of research pointing in the same direction, Lamas believes the evidence that lead plays a causal role in heart disease is about as conclusive as in the case of high cholesterol.
And if lead truly is killing 5.5 million people through heart conditions each year, this places it among the top risk factors for cardiovascular disease globally. Despite this, lead poisoning along with exposure to other toxic metals, remains a remarkably overlooked issue. Lamas explains, "at the individual physician level - sitting across from a patient - I'm the only cardiologist I know who routinely checks lead, mercury, arsenic and cadmium".
Note: This is part one of a two-part Spotlight special series on lead poisoning.
