Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumours and kill cancer cells, according to a new study by researchers from the University of Chicago.
The research, published in Nature, also shows that cancer patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting potential as a nutritional complement to conventional cancer therapy. Although trans fatty acids that are industrially produced are known to be harmful to health, natural ones such as TVA are linked to health benefits. But the researchers don’t envision prescribing diets packed with red meat and cheese – rather, TVA would be a supplement.
“There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, professor of medicine at UChicago and one of the senior authors. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumour immunity by activating an important immune pathway.”
Searching for nutrients that activate immune cells
Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, they started with a database of around 700 known metabolites that come from food and assembled a ‘blood nutrient’ compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumour immunity by activating CD8+ T cells, which are critical for killing cancerous or virally infected cells.
After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.
Feeding mice a diet enriched with TVA significantly reduced the tumour growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumours.
The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, professor of chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumour fighting ability.
Finally, working with other researchers, the team analysed blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested leukaemia cell lines and saw that TVA enhanced the ability of an immunotherapy drug to kill leukaemia cells.
TVA as a supplement
The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimised amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.
“There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.
‘The new research also highlights the promise of this ‘metabolomic’ approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.
“After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level — I find that really amazing and intriguing.”
Reducing the dose of a widely used COVID booster vaccine produces a similar immune response in adults to a full-dose with fewer side effects, according to a new study published in The Lancet Regional Health – Western Pacific. The research found that a half dose of a Pfizer COVID booster vaccine elicited a non-inferior immune response to a full dose in Mongolian adults who previously had AstraZeneca or Sinopharm COVID shots. But it found half-dose boosting may be less effective in adults primed with the Sputnik V COVID vaccine.
The research, led by Murdoch Children’s Research Institute (MCRI) and the National Centre for Communicable Diseases in Mongolia, is part of an international clinical trial investigating the different COVID booster shot approaches to help guide future vaccination strategies.
The first batch of findings, and involving 601 participants over 18 years old from Mongolia, reports on the initial responses seen 28-days after vaccination. The study is the first of its kind to assess and compare COVID-19 vaccines widely used in low- and middle-income countries.
MCRI Professor Kim Mulholland, who also sits on the WHO SAGE committee, said the study found that fractional doses elicited an immune response that was non-inferior to a full dose with fewer side effects and was less costly.
“Fractional dosing may improve COVID booster acceptability and uptake and reduce the per-dose cost of COVID-19 booster programs,” he said. “Policymakers and immunisation advisory committees can draw upon this data to make flexible boosting schedules decisions.”
The study found that participants receiving a half dose reported fewer local reactions than those receiving full doses (60% versus 72%) including less pain and tenderness. They also reported fewer systemic reactions (25% vs 32%) including less fevers, vomiting, diarrhoea and headaches.
The cohort will be followed up at six and 12 months with the data to answer key questions on other aspects of the immune response including the rate of waning and breakthrough infections.
The burden of heat-related mortality during the summer of 2022 in Europe may have exceeded 70 000 deaths according to a study led by the Barcelona Institute for Global Health (ISGlobal). The authors of the study, published in The Lancet Regional Health – Europe, revised upwards initial estimates of the mortality associated with record temperatures in 2022 on the European continent.
In an earlier study, the same team used epidemiological models applied to weekly temperature and mortality data in 823 regions in 35 European countries and estimated the number of heat-related premature deaths in 2022 to be 62 862. In that study, the authors acknowledged that the use of weekly data would be expected to underestimate heat-related mortality, and pointed out that daily time-series data are required to accurately estimate the impact of high temperatures on mortality.
The objective of the new study was to develop a theoretical framework that could quantify the errors inherent to aggregated data, such as weekly and monthly temperature and mortality time-series. Models based on temporally aggregated data are useful because the data are available in real-time, allowing analysis of the health hazard within a few days. The researchers aggregated daily temperatures and mortality records from 147 regions in 16 European countries. They then analysed and compared the estimates of heat- and cold-related mortality by different levels of aggregation: daily, weekly, 2-weekly and monthly.
Analysis revealed differences in epidemiological estimates according to the time scale of aggregation. In particular, it was found that weekly, 2-weekly and monthly models underestimated the effects of heat and cold as compared to the daily model, and that the degree of underestimation increased with the length of the aggregation period. Specifically, for the period 1998–2004, the daily model estimated an annual cold and heat-related mortality of 290 104 and 39 434 premature deaths, respectively, while the weekly model underestimated these numbers by 8.56% and 21.56%, respectively.
“It is important to note that the differences were very small during periods of extreme cold and heat, such as the summer of 2003, when the underestimation by the weekly data model was only 4.62%,” explains Joan Ballester Claramunt, the ISGlobal researcher who leads the European Research Council’s EARLY-ADAPT project.
The team used this theoretical framework to revise the mortality burden attributed to the record temperatures experienced in 2022 in their earlier study. According to the calculations made using the new methodological approach, that study underestimated the heat-related mortality by 10.28%, which would mean that the actual heat-related mortality burden in 2022, estimated using the daily data model, was 70,066 deaths, and not 62,862 deaths as originally estimated.
Weekly data to analyse short-term effects of temperatures
“In general, we do not find models based on monthly aggregated data useful for estimating the short-term effects of ambient temperatures,” explains Ballester. “However, models based on weekly data do offer sufficient precision in mortality estimates to be useful in real-time practice in epidemiological surveillance and to inform public policies such as, for example, the activation of emergency plans for reducing the impact of heat waves and cold spells.”
It is an advantage in this area of research to be able to use weekly data since investigators often encounter bureaucratic obstacles that make it difficult or impossible to design large-scale epidemiological studies based on daily data. According to Ballester, when daily data is not available, the use of weekly data, which are easily accessible for Europe in real time, is a solution that can offer “a good approximation of the estimates obtained using the daily data model.”
A new intervention for men with urinary problems trialled across GP practices has shown a sustained reduction in symptoms. Findings from the University of Bristol-led Treating Urinary Symptoms in Men in Primary Healthcare (TRIUMPH) study, involving over 1000 participants and 30 GP practices, have been published in the BMJ. The study was funded by the National Institute for Health and Care Research (NIHR).
The severity and prevalence of lower urinary tract symptoms [LUTS] in men increases with age (up to 30% in men over 65 years), with greater numbers likely to be affected as the population ages. Symptoms can have a substantial impact on quality of life but can also influenced by lifestyle factors.
Current therapies recommended by NICE (National Institute for Health and Care Excellence) include bladder training, controlling fluid intake and lifestyle advice. However, there is a lack of evidence on their effectiveness, and provision by GP practices varies.
Bristol Medical School researchers sought to trial whether a new intervention, comprising a healthcare professional consultation and an information booklet providing conservative and lifestyle guidance, could be more effective than usual care.
Study findings
The team recruited 1077 adult men, each suffering with troublesome urinary tract symptoms between June 2018 and August 2019. Participants were split with 524 in the intervention arm and 553 in the usual care arm. Participants in the intervention arm were directed to relevant sections of the booklet by general practice nurses/healthcare assistants or research nurses following urinary symptom assessment, with subsequent contacts over 12 weeks to ask how the participant was managing.
Overall, the study’s findings showed a range of troublesome urinary tract symptoms improved over 12 months in a population of men with moderate symptom severity, using a standardised booklet and manualised approach to symptom management. Analyses of symptoms in each trial arm found the intervention achieved a greater reduction in symptoms than usual care, and that the difference was maintained in the longer term
Consultant Urologist, Professor Marcus Drake, the study’s Chief Investigator, said: “The assessment of male lower urinary tract symptoms and use of conservative treatments in primary care are inconsistent. Until now, there was limited evidence that conservative treatments are effective, despite their recommendation in national guidelines. The TRIUMPH study aimed to address this need in primary care.
“Implementation of this intervention as management in primary care, has the potential to improve care and reduce drug prescriptions. Our study also found the intervention can be delivered by practice nurses or healthcare assistants rather than GPs.”
Dr Jon Rees, GP Partner at Tyntesfield Medical Group, and Chair of the Primary Care Urology Society, added: “In primary care we have often traditionally relied upon pharmaceutical management for men with bothersome urinary symptoms – the TRIUMPH study emphasises the importance of discussing conservative measures with all of these patients – for some men, this will be all that is required, for others these measures can act as an adjunct to any medication prescribed.
“Many men will prefer to avoid long-term medication, so an understanding of the potential benefits of the interventions used in the study is a vital part of the toolkit for any clinician managing these patients.”
Professor Matthew Ridd, at University of Bristol, said: “This is a ‘bread-and-butter’ problem seen by GPs every day and it is great to now have evidence for something other than tablets. It has the additional advantage that it can be done by a practice nurse, freeing up GP time.”
Eating more ultra-processed foods (UPFs) may be associated with a higher risk of developing cancers of the upper aerodigestive tract (ie, the mouth, throat and oesophagus), according to a new study in the European Journal of Nutrition. The authors of this study, led by the University of Bristol and the International Agency for Research on Cancer (IARC), say that obesity associated with the consumption of UPFs may not be the only factor to blame.
Several studies have identified an association between UPF consumption and cancer, including a recent study which looked at the association between UPFs and 34 different cancers in the largest cohort study in Europe, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which followed 450 111 adults who for approximately 14 years.
As more evidence emerges about the associations between eating UPFs and adverse health outcomes, researchers from the Bristol Medical School and IARC wanted to explore this further.
Since many UPFs have an unhealthy nutritional profile, the team sought to establish whether the association between UPF consumption and head and neck cancer and oesophageal adenocarcinoma in EPIC could be explained by an increase in body fat.
Results from the team’s analyses showed that eating 10% more UPFs is associated with a 23% higher risk of head and neck cancer and a 24% higher risk of oesophageal adenocarcinoma in EPIC.
Increased body fat only explained a small proportion of the statistical association between UPF consumption and the risk of these upper-aerodigestive tract cancers.
Fernanda Morales-Berstein, a Wellcome Trust PhD student at the University of Bristol and the study’s lead author, explained: “UPFs have been associated with excess weight and increased body fat in several observational studies. This makes sense, as they are generally tasty, convenient and cheap, favouring the consumption of large portions and an excessive number of calories. However, it was interesting that in our study the link between eating UPFs and upper-aerodigestive tract cancer didn’t seem to be greatly explained by body mass index and waist-to-hip ratio.”
The authors suggest that other mechanisms could explain the association.
For example, additives including emulsifiers and artificial sweeteners which have been previously associated with disease risk, and contaminants from food packaging and the manufacturing process, may partly explain the link between UPF consumption and upper-aerodigestive tract cancer in this study.
Fernanda Morales-Berstein and colleagues did caution that the associations between UPF consumption and upper-aerodigestive tract cancers found in the study could be affected by certain types of bias.
This would explain why they found evidence of an association between higher UPF consumption and increased risk of accidental deaths, which is highly unlikely to be causal.
Inge Huybrechts, Team head of the Lifestyle exposures and interventions team at IARC, added: “Cohorts with long-term dietary follow-up intake assessments, considering also contemporary consumption habits, are needed to replicate these study’s findings, as the EPIC dietary data were collected in the 1990s, when the consumption of UPFs was still relatively low. As such associations may potentially be stronger in cohorts including recent dietary follow-up assessments.”
Further research is needed to identify other mechanisms, such as food additives and contaminants, which may explain the links observed.
However, based on the finding that body fat did not greatly explain the link between UPF consumption and upper-aerodigestive tract cancer risk in this study, Fernanda Morales-Berstein, suggested: “Focussing solely on weight loss treatment, such as semaglutide, is unlikely to greatly contribute to the prevention of upper-aerodigestive tract cancers related to eating UPFs.”
The World Health Organization (WHO) noted an upsurge of unidentified pneumonia-like respiratory illnesses among children in Northern China, and asked China for more information. This is significant as previous outbreaks of severe respiratory illnesses have started out in this fashion, but such WHO requests for more information on disease clusters are routine as part of its monitoring. No “unusual or novel pathogens” have been found, according to China, which attributed it to an increase in multiple pathogens and the lifting of COVID restrictions.
Earlier this month, China’s National Health Commission reported a nationwide increase in respiratory disease incidence, mostly among children. This increase was attributed to lifting of COVID restrictions and the arrival of the cold season, and due to circulating known pathogens including Mycoplasma pneumonia and RSV, which are known to affect children more than adults.
On 22 November 2023, the WHO identified media and ProMED reports about clusters of undiagnosed pneumonia in children’s hospitals in Beijing, Liaoning and other places in China. The WHO requested from China additional epidemiologic and clinical information, as well as lab results from these cases and data about recent trends in circulating respiratory pathogens.
The WHO held a teleconference with Chinese health authorities and received data indicating an increase in outpatient consultations and hospital admissions of children due to Mycoplasmapneumoniae pneumonia since May, and RSV, adenovirus and influenza virus since October. Some of these increases are earlier in the season than usual, but not unexpected given the lifting of COVID restrictions, as similarly experienced in other countries. No changes in the disease presentation were reported by the Chinese health authorities, who said no unusual or novel pathogens or unusual clinical presentations had been detected, but only the general increase in respiratory illnesses by known pathogens. Local hospitals had not been overloaded by new cases.
Risk assessment
In the current outbreak of respiratory illness, the reported symptoms are common to several respiratory diseases and, as of now, at the present time, Chinese surveillance and hospital systems report that the clinical manifestations are caused by known pathogens in circulation. M. pneumoniae is a common respiratory pathogen and a common cause of paediatric pneumonia, and is readily treated with antibiotics.
China has stepped up its influenza-like illness (ILI) and severe acute respiratory infections (SARI) sentinel surveillance system since mid-October, including for M. pneumoniae.
There is limited detailed information available to fully characterize the overall risk of these reported cases of respiratory illness in children. However, due to the arrival of the winter season, the increasing trend in respiratory illnesses is expected; co-circulation of respiratory viruses may increase burden on health care facilities.
According to surveillance data reported to WHO’s FluNet and published by the National Influenza Centre in China, ILI was above usual levels for this time of year and increasing in the northern provinces. Influenza detections were predominantly A(H3N2) and B/Victoria lineage viruses.
WHO advice
The WHO advice was for people in China to take measures against respiratory illnesses, including vaccines, masking and social distancing. It also does not recommend any specific measures for travellers to China.
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.”
