Tiny fragments of plastic known as nanoplastics interact with a particular protein that is naturally found in the brain, creating changes linked to Parkinson’s disease and some types of dementia, according to a Duke University-led study.
In Science Advances, the researchers report that the findings create a foundation for a new area of investigation, fuelled by the timely impact of environmental factors on human biology.
“Parkinson’s disease has been called the fastest growing neurological disorder in the world,” said principal investigator, Andrew West, PhD, professor at Duke University School of Medicine.
“Numerous lines of data suggest environmental factors might play a prominent role in Parkinson’s disease, but such factors have for the most part not been identified.”
Improperly disposed plastics have been shown to break into very small pieces and accumulate in water and food supplies, and were found in the blood of most adults in a recent study.
“Our study suggests that the emergence of micro and nanoplastics in the environment might represent a new toxin challenge with respect to Parkinson’s disease risk and progression,” West said.
“This is especially concerning given the predicted increase in concentrations of these contaminants in our water and food supplies.”
West and colleagues in Duke’s Nicholas School of the Environment and the Department of Chemistry at Trinity College of Arts and Sciences found that nanoparticles of the plastic polystyrene — typically found in single use items such as disposable drinking cups and cutlery — attract the accumulation of the protein known as alpha-synuclein.
West said the study’s most surprising findings are the tight bonds formed between the plastic and the protein within the area of the neuron where these accumulations are congregating, the lysosome.
Researchers said the plastic-protein accumulations happened across three different models performed in the study – in test tubes, cultured neurons, and mouse models of Parkinson’s disease.
West said that questions remain about how such interactions might be happening within humans and whether the type of plastic might play a role.
“While microplastic and nanoplastic contaminants are being closely evaluated for their potential impact in cancer and autoimmune diseases, the striking nature of the interactions we could observe in our models suggest a need for evaluating increasing nanoplastic contaminants on Parkinson’s disease and dementia risk and progression,” West said.
“The technology needed to monitor nanoplastics is still at the earliest possible stages and not ready yet to answer all the questions we have,” he said.
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.
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”.
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.
Air filtration systems do not reduce the risk of picking up viral infections, according to new research from the University of East Anglia. A new study published in Preventive Medicine reveals that technologies designed to make social interactions safer in indoor spaces are not effective in the real world. The team studied technologies including air filtration, germicidal lights and ionisers.
They looked at all the available evidence but found little to support hopes that these technologies can make air safe from respiratory or gastrointestinal infections.
Prof Paul Hunter said: “Air cleaners are designed to filter pollutants or contaminants out of the air that passes through them.
“When the Covid pandemic hit, many large companies and governments – including the NHS, the British military, and New York City and regional German governments – investigated installing this type of technology in a bid to reduce airborne virus particles in buildings and small spaces.
“But air treatment technologies can be expensive. So it’s reasonable to weigh up the benefits against costs, and to understand the current capabilities of such technologies.”
The research team studied evidence about whether air cleaning technologies make people safe from catching airborne respiratory or gastrointestinal infections. They analysed evidence about microbial infections or symptoms in people exposed or not to air treatment technologies in 32 studies, all conducted in real world settings like schools or care homes. So far none of the studies of air treatment started during the Covid era have been published.
‘Disappointing’ findings
Lead researcher Dr Julii Brainard said: “The kinds of technologies that we considered included filtration, germicidal lights, ionisers and any other way of safely removing viruses or deactivating them in breathable air.
“In short, we found no strong evidence that air treatment technologies are likely to protect people in real world settings.
“There is a lot of existing evidence that environmental and surface contamination can be reduced by several air treatment strategies, especially germicidal lights and high efficiency particulate air filtration (HEPA). But the combined evidence was that these technologies don’t stop or reduce illness.
“There was some weak evidence that the air treatment methods reduced likelihood of infection, but this evidence seems biased and imbalanced. We strongly suspect that there were some relevant studies with very minor or no effect but these were never published.
“Our findings are disappointing – but it is vital that public health decision makers have a full picture. Hopefully those studies that have been done during Covid will be published soon and we can make a more informed judgement about what the value of air treatment may have been during the pandemic.”
A recent study has revealed a new culprit in the formation of brain haemorrhages that does not involve injury to the blood vessels, as previously believed. In the first-of-its kind study, researchers led by the University of California, Irvine discovered that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, offering deeper insights into how they occur and identifying potential new therapeutic targets for treatment and prevention.
The findings, published in the Journal of Neuroinflammation, describe how the team was able to watch the process by which red blood cells stall in the brain capillaries and then observe how the haemorrhage happens.
Cerebral microbleeds are associated with a variety of conditions that occur at higher rates in older adults, including hypertension, Alzheimer’s disease and ischaemic stroke.
“We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop,” said co-corresponding author Dr Mark Fisher, professor of neurology in UCI’s School of Medicine.
“Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral haemorrhages that occurs at the capillary level.”
The team exposed red blood cells to a chemical called tert-butyl hydroperoxide that caused oxidative stress; the cells were then marked with a fluorescent label and injected into mice.
Using two different methods, the researchers observed the red blood cells getting stuck in the brain capillaries and then being cleared out in a process called endothelial erythrophagocytosis.
As they moved out of the capillaries, microglia inflammatory cells engulfed the red blood cells, which led to the formation of a brain haemorrhage.
“It has always been assumed that in order for cerebral haemorrhage to occur, blood vessels need to be injured or disrupted. We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development,” said co-corresponding author Xiangmin Xu, UCI professor of anatomy & neurobiology and director of the campus’s Center for Neural Circuit Mapping.
“We need to examine in detail the regulation of brain capillary clearance and also analyse how that process may be related to insufficient blood supply and ischaemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments.”
Ulcerative colitis is an inflammatory bowel disease that is prone to flareups, especially around feasts. New research in mice suggests that certain foods – especially those high in tryptophan, like turkey, pork, nuts and seeds – could reduce the risk of a colitis flare. It also helps explain why cigarette smokers are less likely to have colitis. The findings, published in Nature Communications, point to a noninvasive method of improving long-term colitis management, if the results are validated in people.
“Although there are some treatments for ulcerative colitis, not everyone responds to them,” says senior author Sangwon Kim, PhD, an assistant professor of immunology at Thomas Jefferson University.
“This disease has a huge impact on quality of life, and can lead to surgery to remove the colon or cancer.”
Since ulcerative colitis is caused by inflammation of the inner lining of the colon and rectum, Dr Kim and his colleagues looked for ways to calm the inflamed tissue.
They focused on a group of immune cells called T-regulatory (T-reg) cells, which can help break the cycle of inflammation. They reasoned that getting more T-reg cells to the colon might reduce the inflammation that causes colitis.
Dr Kim’s team thought about how to attract the T-reg cells, and found a specific receptor, CPR15, on the surface of T-reg cells that acts like a magnet for the colon. The more CPR15 the T-reg cells have, the more strongly they are attracted to the colon.
So they searched for molecules that could make T-reg cells produce more GPR15 to turn up the power of the magnet. They found tryptophan – specifically, one of the molecules that tryptophan breaks down into in the body – could increase these receptors called GPR15.
To test whether these molecules could control colitis, the researchers supplemented tryptophan in the diet of mice over a period of two weeks.
They saw a doubling in the amount of inflammation-suppressing T-reg cells in the colon tissue compared to mice that weren’t fed extra tryptophan.
Dr. Kim’s team also saw a reduction in colitis symptoms, which seemed to last for at least a week after tryptophan was removed from the diet.
“In human time that might translate to about a month of benefit,” explained Dr Kim.
However, when tryptophan was given to mice during a colitis flare, it provided little benefit, suggesting this dietary change might only be effective at preventing future flares rather than treating them.
In a chance finding, while looking for molecules that could increase GPR15, the researchers also stumbled across a molecule that helps explain why smoking seems to be protective against colitis. Researchers have long observed that people who smoke cigarettes have a lower incidence of ulcerative colitis than the general public.
Dr. Kim’s team found a molecule that is prevalent in smoke – from cigarettes and barbeque alike – that can also increase GPR15 levels on T-reg cells “Although both might help protect against colitis, tryptophan is obviously the much safer and healthier option,” says Dr Kim.
In the future, the researchers plan to test whether these results can be translated to people with colitis. Tryptophan supplement is considered safe, as long as the dose doesn’t exceed 100mg per day. Using the mouse data as a guide, Dr Kim expects that 100mg could be enough to see an effect in humans, and is planning further testing in clinical trials.
