Chemicals are omnipresent today: they enter our bodies through food, air or the skin. But how do these complex mixtures of chemicals affect our health? In a study published in the journal Science, a research team from the Helmholtz Centre for Environmental Research (UFZ) has shown that chemicals that occur in complex mixtures and in concentration ratios as found in humans act together. Even if the concentrations of the individual substances were each below the effect threshold, the chemicals in the mixture showed a cumulative neurotoxic effect.
For their investigations, they used blood samples from pregnant women from the LiNA mother-child study (lifestyle and environmental factors and their influence on the newborn allergy risk), which has been running at the UFZ since 2006.
In our everyday lives, we are exposed to a wide variety of chemicals that are distributed and accumulate in our bodies. These are highly complex mixtures that can affect bodily functions and our health,” says Prof Beate Escher, Head of the UFZ Department of Cell Toxicology and Professor at the University of Tübingen. “It is known from environmental and water studies that the effects of chemicals add up when they occur in low concentrations in complex mixtures. Whether this is also the case in the human body has not yet been sufficiently investigated – this is precisely where our study comes in.”
The extensive research work was based on over 600 blood samples from pregnant women from the Leipzig mother-child cohort LiNA, which has been coordinated by the UFZ since 2006. The researchers first analysed the individual mixtures of chemicals present in these samples.
“We wanted to find out which chemicals were contained in the blood plasma and in what concentrations. We used a two-step extraction process to isolate as diverse chemical mixtures as possible,” says Georg Braun, postdoctoral researcher in Beate Escher’s working group and first author of the study. “Using mass spectrometry analyses, we searched for 1000 different chemicals that we knew could occur in the environment, could potentially be ingested by humans and could be relevant for adverse human health effects. Of these, we were able to quantify around 300 chemicals in several plasma samples.” This provided the researchers with information on the composition and concentration ratios of the chemical mixtures present in the 600 individual plasma samples.
The researchers used a prediction model to calculate the neurotoxic effects of the chemical mixtures. To test the predictions of the mixture effects experimentally, they used an established cellular bioassay based on human cells that indicates neurotoxic effects.
“We analysed individual chemicals as well as around 80 different, self-produced chemical mixtures in realistic concentration ratios. The extracts of the plasma samples were also tested,” says Georg Braun. The results were clear. “The laboratory experiments confirmed the predictions from the model: the effects of the chemicals add up in complex mixtures,” says environmental toxicologist Beate Escher. “Even if the individual concentrations of neurotoxic chemicals are so low that they are each below the effect threshold, there is still an effect on nerve-like cells in complex mixtures with many other chemicals.”
But what exactly do these results mean? “With our study, we were able to prove for the first time that what is known about the effects of chemical mixtures in the environment also applies to humans,” says Escher. “It is therefore imperative that we rethink risk assessment. Indicator substances alone are far from sufficient. In future, we must learn to think in terms of mixtures.” UFZ environmental immunologist and head of the LiNA study Dr Gunda Herberth adds: “It is becoming increasingly clear that many diseases such as allergies, immune system disorders, obesity or the development of the nervous system are linked to exposure to chemicals in the womb or in early childhood.”
The test method presented in this study – the extraction of chemical mixtures from human samples and their characterisation using chemical analysis combined with cell-based biotest systems – opens up new possibilities for researching the effects of complex chemical mixtures on human health. In future research projects, the scientists want to refine their test method and investigate the effects of chemical mixtures on other health-relevant endpoints such as immunotoxicity. In addition, they would like to uncover possible links between chemical exposure and the development of developmental disorders in children.
The foundation for healthy eating behaviour starts in infancy. Young children learn to regulate their appetite through a combination of biological, psychological, and sociological factors. In a new paper published in Social Science & Medicine, researchers at the University of Illinois Urbana-Champaign propose a model that explores these factors and their interactions, providing guidelines for better understanding childhood appetite self-regulation.
Appetite self-regulation is related to general self-regulation, but it specifically concerns an individual’s ability to regulate food intake, which affects healthy development and obesity risk. Children are born with a capacity to regulate appetite based on hunger and satiety signals, but with increased exposure to environmental factors, their eating is increasingly guided by psychological reasoning and motivations. Therefore, it is important to take a developmental perspective to trace changes in eating behaviours over time, Ju stated.
Ju and her colleagues provide a comprehensive framework based on the biopsychosocial pathways model, which outlines three interacting categories: Biological factors, including sensory experience, physiological hunger and satiety signals, brain-gut interaction, and the influence of the gut microbiome; psychological factors, including emotional self-regulation, cognitive control, stress regulation, and reward processing;and social factors, such as parental behaviour and feeding practices, culture, geographic location, and food insecurity.
The researchers combine this framework with temperamental theory to explore how the pathways are modified by individual temperament.
Children react differently to stimuli based on their psychological and emotional make up, Ju explained. For example, openness to novelty and positive anticipation can affect whether a child is willing to try new foods. If a parent pressures their child to eat, it could be counter-productive for a child with heightened sensitivity to negative affect, causing the child to consume less.
The model also takes children’s developmental stages into account. Infants have basic appetite regulation based on physiological cues. They gradually become more susceptible to external influences and by age 3-5, children begin to exhibit greater self-control and emotional regulation.
“By analysing the pathways outlined in our model, we can better understand the combined influences of multiple factors on children’s appetite self-regulation and their motivations to approach food,” Ju said. “For example, the presence of palatable food may not generate similar responses in everyone. Children could approach food as a reward, for pleasure-seeking, or to regulate emotions. The underlying motivations can be diverse, and they are influenced by external factors as well as temperamental characteristics.”
Socio-environmental influences include parent-child interactions around food, as well as non-food-related caregiver practices that can impact the child’s emotional regulation. The household food environment, cultural value of food intake, and food availability are also important factors, the researchers stated.
“If we understand the differential susceptibility to various factors, we can identify and modify the environmental influences that are particularly obesogenic based on children’s temperamental characteristics. Then we will be able to provide more refined approaches to support children’s healthy eating behaviour,” Ju explained.
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
In a peer-reviewed study believed to be the first of its kind published, a research team led by Johns Hopkins Medicine provides scientific evidence that a healthy diet may reduce the chance of low risk prostate cancer progressing to a more aggressive state in men undergoing active surveillance – a clinical option in which men with lower risk cancer are carefully monitored for progression in lieu of treatments that could have undesired side effects or complications.
The findings are reported in the journal JAMA Oncology.
“Many men diagnosed with low grade prostate cancer are interested in changes they can make to reduce the risk of their tumour becoming more aggressive, and the role of diet and nutrition is one of the most commonly asked questions,” says study co-senior author Bruce Trock, PhD, a professor of urology, epidemiology and oncology at the Johns Hopkins University School of Medicine, and director of the Brady Urological Institute’s epidemiology division. “These men are motivated to make changes that may improve their prognosis, which is why we began collecting data on their diets, lifestyles and exposures 20 years ago. Hopefully, these latest findings will enable us to develop some concrete steps they can take to reduce the risk of cancer progression.”
When a patient is found after a biopsy to have developed prostate cancer, the sampled cells are assigned to a grade group based on comparison normal prostate tissue. Grade groups range from 1 to 5, with grade group 1 indicating indolent cancer cells that don’t look very different than normal tissue and do not metastasise. At the other end of the scale, grade group 5 indicates cancer cells that are quite abnormal in appearance, and can grow and metastasise if untreated
During active surveillance, biopsies are performed at regular intervals to see if prostate cancer should be move it to a higher grade group. Called grade reclassification, this often leads to a recommendation for treatment. It also is a common way for researchers to evaluate the effectiveness of therapies and lifestyle modifications.
“While there have been previous research studies looking at diet and its relationship to prostate cancer, we believe that ours is the first to provide statistically significant evidence that a healthy diet is associated with a reduction in risk of prostate cancer progressing to a higher grade group, as shown by a reduction in the percentage of men on active surveillance experiencing grade reclassifications over time,” says study co-senior author Christian Pavlovich, MD, a professor in urologic oncology at the Johns Hopkins University School of Medicine and director of the Brady Urological Institute’s prostate cancer active surveillance program.
In the newly published study, the researchers prospectively evaluated the histories of 886 men (median age at diagnosis: 66) diagnosed with grade group 1 prostate cancer from January 2005 to February 2017, all of whom were in the Johns Hopkins Medicine active surveillance program and whom, at the time of enrolment, completed a validated food frequency survey regarding their usual dietary patterns. Of the participants, 55 were Black (6.2%), 803 (90.6%) were white and 28 (3.2%) identified as other races and ethnicities.
Based on their responses to the questionnaire, a Healthy Eating Index (HEI) score was calculated for each patient. The HEI ranges from 0 to 100.
“The HEI is a validated measure of overall diet quality, quantifying how well an individual’s dietary pattern adheres to the recommendations of the U.S. Department of Agriculture’s Dietary Guidelines for Americans,” says study lead author Zhuo Tony Su, MD. “We looked at each patient’s HEI score – as calculated from their dietary information recorded at enrolment in our active surveillance programme – and assessed whether men with a higher quality diet were less likely to experience grade reclassification in the years afterward.”
Su says the researchers also evaluated the patients using an energy-adjusted HEI (E-HEI) score that takes into account a person’s daily caloric intake.
Along with those two metrics, Su says, the researchers calculated scores for each study participant using the Dietary Inflammatory Index (DII) and the energy-adjusted DII (E-DII).
“The DII and E-DII scores assess the inflammatory or anti-inflammatory potential of any diet, so higher scores indicate a diet that may cause more inflammation, which in turn, may contribute to the development and progression of prostate cancer,” says Su. “We evaluated whether higher inflammatory potential was associated with increased risk of grade reclassification.”
By a follow-up assessment at 6.5 years after diagnosis, 187 men (21%) had been reclassified as grade group 2 or greater, of whom 55 (6%) had extreme grade reclassification to grade group 3 or greater.
“When our team looked at the HEI and E-HEI scores in relation to the grade reclassification rates, we found a statistically significant inverse association between adherence to a high quality diet – as indicated by high HEI and E-HEI scores – and the risk of grade reclassification during active surveillance,” says Trock. “In other words, the higher the HEI and E-HEI scores, the more reduced the risk that a low grade prostate cancer had progressed to a higher grade disease that mandated curative treatment.”
Pavlovich says for patients adhering to a high quality diet, every increase of 12.5 points in the HEI score was associated with an approximately 15% reduction in reclassification to grade group 2 or greater, and a 30% reduction in reclassification to grade group 3 or greater.
The researchers say their findings also indicate that lower inflammation potential is among several possible risk lowering mechanisms as a result of a higher quality diet. However, they did not find an association between grade reclassification and baseline DII/E-DII scores.
“This lack of association with DII/E-DII may indicate that inflammation plays a role in driving the progression from a healthy prostate to one with cancer,” says Trock. “Whereas, in men who already have prostate cancer, the more subtle biological change from a lower to higher grade may reflect other mechanisms potentially influenced by diet.”
The researchers report several limitations in their study, including diet data based on patient self-reporting, results subject to potential nonresponse bias (bias occurring when respondents and nonrespondents differ in ways that impact the research, making the sample population less representative of the whole population) and not accounting for dietary changes over time. Additionally, they say the study population, consisting predominantly of white men with grade group 1 disease at diagnosis, may not be generalisable to all patients.
“Our findings-to-date should be helpful for the counselling of men who choose to pursue active surveillance and are motivated to modify their behaviours, including quality of diet,” says Pavlovich. “However, to truly validate the association between higher quality diet and reduced risk of prostate cancer progression, future studies with more diverse populations are needed.”
Updated clinical recommendations, including lifestyle changes, prevention strategies and treatment options, to reduce the risk of a first stroke outlined in a new guideline from the American Stroke Association
Credit: American Heart Association
Healthy lifestyle behaviours, such as good nutrition, smoking cessation and being physically active, along with routine health screenings and managing risk factors for cardiovascular disease and stroke with medication, can help prevent individuals from having a first stroke. Screening for stroke risk and educating people on how to lower their chances of having a stroke ideally begin with their primary care professional and include evidence-based recommendations, according to a new clinical guideline from the American Stroke Association, and published in the journal Stroke.
“The most effective way to reduce the occurrence of a stroke and stroke-related death is to prevent the first stroke – referred to as primary prevention,” said Chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, professor and vice chair of research in the department of neurology at Wake Forest University School of Medicine. “Some populations have an elevated risk of stroke, whether it be due to genetics, lifestyle, biological factors and/or social determinants of health, and in some cases, people do not receive appropriate screening to identify their risk.”
The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 version and is a resource for clinicians in implementing a variety of prevention strategies for individuals with no prior history of stroke. The new guideline provides evidence-based recommendations for strategies to support brain health and prevent stroke throughout a person’s lifespan by improving healthy lifestyle behaviours and getting preventive care.
“This guideline is important because new discoveries have been made since the last update 10 years ago. Understanding which people are at increased risk of a first stroke and providing support to preserve heart and brain health can help prevent a first stroke,” said Bushnell.
Key stroke prevention recommendations include regular health screenings, identifying risk factors, lifestyle interventions and medications, when indicated.
Identifying and managing risk factors
Unidentified and unmanaged cardiovascular disease risk factors can cause damage to arteries, the brain and the heart years before cardiovascular disease and stroke occur. Primary care health professionals should promote brain health for patients through stroke prevention education, screenings and addressing risk factors from birth to old age.
Modifiable risk factors for stroke, such as high blood pressure, overweight and obesity, elevated cholesterol and elevated blood sugar, can be identified with physical exams and blood tests. These conditions should be addressed with healthy lifestyle and behavioural changes and may include medications for select patients. Antihypertensive medications to reduce blood pressure and statin medications to lower cholesterol can help to reduce the risk of first stroke in adults with increased cardiovascular disease risk and those receiving CVD care. A new recommendation is consideration of glucagon-like protein-1 (GLP-1) receptor agonist medications, which are FDA-approved to reduce the risk of cardiovascular disease in people with overweight or obesity and/or Type 2 diabetes.
Healthy lifestyle behaviours
The most common, treatable lifestyle behaviours that can help reduce stroke risk are detailed in the Association’s Life’s Essential 8 cardiovascular health metrics. They include healthy nutrition, regular physical activity, avoiding tobacco, healthy sleep and weight, controlling cholesterol, and managing blood pressure and blood sugar. The guideline recommends that adults with no prior cardiovascular disease, as well as those with increased risk, follow a Mediterranean dietary pattern. Mediterranean dietary programs have been shown to reduce the risk of stroke, especially when supplemented with nuts and olive oil.
Physical activity is also essential for stroke risk reduction and overall heart health. Physical activity can help to improve important health measures such as blood pressure, cholesterol, inflammatory markers, insulin resistance, endothelial function and weight. The guideline urges health care professionals to routinely screen patients for sedentary behaviour, a confirmed risk factor for stroke, and counsel them to engage in regular physical activity. The Association reinforces the U.S. Department of Health and Human Services Office of Disease Prevention and Health Promotion’s recommendation that adults get at least 150 minutes per week of moderate-intensity aerobic activity or 75 minutes per week of vigorous aerobic activity, or a combination of both, preferably spread throughout the week.
Health equity and stroke risk
New to the guideline is an emphasis on social determinants of health and the impact they have on stroke risk. Social determinants of health are non-medical factors, including education, economic stability, access to care, discrimination, structural racism and neighborhood factors (such as the lack of walkability, lower availability of healthy food and fewer health resources), that contribute to inequities in care and influence overall health. Health care professionals should ensure patient education is available for various educational and language levels, and advocate for their patients by choosing treatments and medications that are effective and affordable.
Health care professionals are also encouraged to connect patients to resources that help address health-related social needs such as food and housing insecurity, refer them to programs that support healthy lifestyle changes and direct them to support programs that may help defray health care costs including medication expenses.
New sex- and gender-specific recommendations
The guideline also includes some new gender- and sex-specific recommendations for women. Health professionals should screen for conditions that can increase a woman’s risk of stroke, including use of oral contraceptives, high blood pressure during pregnancy, other pregnancy complications such as premature birth, endometriosis, premature ovarian failure and early onset menopause. Treatment of elevated blood pressure during pregnancy and within six weeks of delivery is recommended to reduce the risk of maternal intracerebral haemorrhage.
Transgender women and gender-diverse individuals taking oestrogens for gender affirmation may also be at an increased risk of stroke. Evaluation and modification of any existing risk factors are needed to reduce the risk of stroke for these individuals.
“Implementing the recommendations in this guideline would make it possible to significantly reduce the risk of people having a first stroke. Most strategies that we recommend for preventing stroke will also help reduce the risk of dementia, another serious health condition related to vascular issues in the brain,” said Bushnell.
The writing group notes that writing recommendations focused on preventing a first stroke was challenging. There are limitations to some of the evidence that informed the guideline, including that many clinical trials enrolled adults who have already had a cardiovascular event that may include a stroke. The writing group also identified knowledge gaps to help inform topics for future research.
The guideline highlights the need for risk assessment in primary stroke prevention and includes the use of risk prediction tools to estimate risk for atherosclerotic cardiovascular disease so that patients receive timely prevention and treatment strategies. The Association has recently developed a new Predicting Risk of Cardiovascular Disease Events (PREVENT) risk calculator as a screening tool that can help inform preventive treatment decisions. The PREVENT calculator can estimate 10-year and 30-year stroke and heart disease risk in individuals starting at age 30 – a decade earlier than the Pooled Cohort Equations, another CVD risk calculator.
According to the American Stroke Association, learning the warning signs of stroke and preventative measures are the best way to avoid strokes and keep them from happening again. The abbreviation F.A.S.T. – for face drooping, arm weakness, speech difficulty, time to call 911 – is a useful tool to recognise the warning signs of stroke and when to call for help.
This guideline was prepared by the volunteer writing group on behalf of the American Stroke Association and is endorsed by the Preventive Cardiovascular Nurses Association and the Society for Vascular Surgery. The American College of Obstetricians and Gynecologists supports the clinical value of this document as an educational tool.
Since 1990, the American Stroke Association has translated scientific evidence into clinical practice guidelines with recommendations to improve cerebrovascular health. The “2024 Guideline for the Primary Prevention of Stroke” replaces the 2014 “Guidelines for the Primary Prevention of Stroke.” This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke. The Association supports the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts.
Those who wish to live to 100 cannot rely on chance. Instead, it is essential to keep biomarkers associated with ageing and disease in check. By the age of 60, it may already be too late.
Text by: Maja Lundbäck, first published in Medical Science No 3 2024
Swedes are increasingly living to older ages. Thirty years ago, 85-90- year-olds were rare, but now the majority reach that age ‒ and two percent even get to see 100 candles on their birthday cake.
“Centenarians are the age group that is increasing the most now,” says Karin Modig, Associate Professor at the Institute of Environmental Medicine at Karolinska Institutet, who researches ageing and health.
In a study published in the journal GeroScience, she and her colleagues show that it is possible to predict who has the greatest chance of becoming very old already during early ageing. The study is based on approximately 44 000 Swedes who underwent health examinations between 1985 and 1996, aged between 64 and 99. Of these, 1224 individuals lived to 100.
“The results suggest that becoming very old is not solely a matter of chance; it also seems to be linked to lifestyle,” says Karin Modig.
Known biomarkers
By looking at known biomarkers previously associated with ageing and disease, the researchers found that the centenarians had better health than their peers already in their 60s. All but two of twelve biomarkers examined could be linked to increased chances of reaching 100 years. Low iron levels reduce the chance, as does low total cholesterol, which can be a marker of disease processes in the body.
Four of the biomarkers stood out as particularly important: creatinine levels, which indicate kidneys health, were almost always normal at age 60 in those who lived to 100. The same was true for liver markers and uric acid levels, a marker for inflammatory processes. Individuals with the lowest uric acid levels had a four percent chance of living to 100, while those with the highest levels had a 1.5 percent chance. Blood sugar levels were also rarely above 6.5mmol/litrw.
The results suggest that it may be possible to increase one’s chances of living to 100 by changing your lifestyle, she believes.
“At the same time, life is not about living according to an algorithm; everyone must find their own balance between risk factors and health factors,’ she says.
