Agneta Åkesson

The hypothesis we will test is whether the prevalent exposure to the most widespread and persistent contaminants in food and drinking water compromise our health and contribute to the development of diseases of high public health relevance. These diseases include metabolic disturbances, cardiovascular disease (CVD), and cancer, as well as effects on prenatal development. Because accumulated data demonstrate that all these selected contaminants  are involved in various adverse pathophysiological processes, it is imperative to corroborate the indications of compromised health to correctly inform and tailor only the relevant preventive efforts. We will use a set of prospective study designs, nation-wide registers as well as cohorts and national infrastructures with biobanks of men and women and the specific research questions are: i) What are the associations between exposure to perfluorinated (PFAS)-contaminated public drinking water and child and maternal health? A Medial Birth Register-based study including &gt

300 000 births. ii) What are the associations between biomarkers of acrylamide and glycidol exposure and cancer of the breast, endometrium and colorectum in a case-cohort study? iii) What are the persistent organochlorine, PFAS, acrylamide and glycidol exposure-affected OMICS signatures (genomics, proteomics, metabolomics and lipidomics) and molecular pathways underlying disease development (myocardial infarction, stroke, and breast-, endometrial and colorectal cancer)?

Drinking water is one of our most important and most consumed foods. Drinking water can, however, be a source of substances that can have negative health effects. Studies have indicated a link between drinking water chlorination by-products and the risk of colorectal and bladder cancer, but with conflicting results. Chlorination is a cost-effective way to reduce pathogens, but today there are more cost-effective methods that do not add harmful substances. Increasing knowledge about possible health effects from chlorination would therefore contribute to change in the drinking water preparation and thus reduce the drinking water's contribution to ill health. The aim of the project is to study the connection between by-products from the drinking water chlorination and the risk of cancer in the adult population in Sweden. This will be done through a large-scale population-based study, in which cohort data from over 50,000 Swedish men and women will be linked to administrative registers and databases with drinking water analyzes. In the study, we have the opportunity to consider relevant risk factors at the individual level, and to map historical exposure by linking the individuals' migration patterns, drinking water analyzes and information on changes in the drinking water preparation. Previous studies in the field have shown contradictory results and the studies have also shown deficiencies, primarily with regard to the classification of exposure and that relevant risk factors for cancer have not been taken into account. With the proposed study, we therefore hope to be able to increase the knowledge of the connection between by-products from the drinking water chlorination and the risk of cancer. The possibility of connecting individual data via Swedish personal identification numbers means that we have a unique chance to consider relevant risk factors and historical exposure in a way that has not previously been possible. The study will be the largest of its kind.

Research problem and specific questionsUltra-processed foods (UPFs) have undergone extensive industrial processing and are proposed to delay satiety signaling, leading to overconsumption and weight gain. While high consumption of UPF is associated with obesity and non-communicable disease, there is no established causal relationship between the degree of food processing, independent of nutrient profile, and health outcomes. The overall aim of this project is to study the causal effects of a high UPF diet, compared to a nutrient-matched low UPF diet, on appetite and cardiometabolic health. In addition, biomarkers to assess UPF exposure will be identified. The specific research questions are:What is the impact of a 6-week high UPF intake, compared to a nutrient-matched low UPF intake, on appetite and markers of cardiometabolic health?Can intake of UPF be accurately assessed through a priori defined candidate food intake biomarkers or biomarker patterns?Data and methodWe will perform a randomized, crossover study, comparing high (&gt

90% of energy) and low (&lt

10% of energy) UPF intake, defined by the NOVA framework. All foods will be provided to participants. Diets will be matched on content of energy and macronutrients. N=40 participants will be randomized to the order of diets, each lasting 6 weeks. This design is chosen to maximize compliance and difference in UPF exposure, while maintaining equivalent nutrient intake. This will enable causal analyses of health effects of UPF, independent of nutrient intake.Societal relevance and utilizationDue to concerns regarding the health impact of UPFs, recommendations to limit UPF intake have been requested. However, evidence is insufficient to determine if food processing, overall or specific types, per se really is of public health concern. Unfounded recommendations to limit UPF intake would negatively impact those who rely on UPFs for convenience and low cost. The results of the proposed study can be used by both food industry and consumers, to inform future industrial development and consumption of UPF. In addition, the results will inform future dietary recommendations regarding UPF intake.Plan for project realizationRecruitment and intervention will be carried out during 2025-2026. Outcome assessments will include a wide range of cardiometabolic and appetite markers, measured in blood, urine and feces. In addition, biomarkers of UPF intake will be identified through both a priori and exploratory approaches.

Access to safe drinking water is a necessity for health and a human right. Per- and polyfluoroalkyl (PFAS) is a group of persistent environmental chemical contaminants that are widespread in the environment, including drinking water and sometimes at alarmingly high concentrations. PFAS exposure has been linked to a multitude of adverse outcomes, including immunotoxic effects such as decreased antibody response following vaccination. Data on infections, which are the clinically relevant endpoints of a decreased antibody response, are however scarce. Because most people in Sweden consume drinking water daily, and that the knowledge on drinking water production and distribution is high, Sweden is ideal for assessing drinking water-related health effects. The overall aim of this research proposal is to generate new knowledge on immune related health effects of PFAS in drinking water in women and children. The project comprises: i) a large scale register-based study assessing the association of PFAS in drinking water and the risk of infectious disease among pregnant women in Sweden, ii) a survey on children age 18 months and 4 years, evaluating the association of PFAS in food and drinking water as well as in biological specimens with risk of infections, and iii) a large register-based cohort of children (0-5 years, 2012-2022), assessing the association of toxico-kinetically modeled prenatal PFAS exposure and risk of subsequent infectious disease.

Everyone needs to consume food and drinking water, but sometimes these are sources of substances that can be directly harmful to health. An example is acrylamide and its metabolite glycidamide, which can be formed when carbohydrate-rich foods are heated, as well as glycidol, which occurs during the refining of vegetable oils. These substances are genotoxic and probably carcinogenic based on studies in rodents. Additionally, drinking water that is disinfected with chlorine may contain chlorination by-products that may also be genotoxic. We therefore want to evaluate the risk of developing certain forms of cancer when exposed to these substances. An epidemiological project based on established population-based cohorts with an associated biobank and commonly occurring forms of cancer. We will measure biomarkers of acrylamide, glycidamide and glycidol in blood and evaluate the risk of colorectal, breast and uterine cancer. We will also use data with levels of chlorination by-products in municipal drinking water and evaluate the risk of breast, uterine, liver and kidney cancer in over 50,000 cohort participants. The goal of the project is to evaluate whether commonly occurring contaminants in processed foods and drinking water increase the risk of certain forms of cancer. We hope to expand the knowledge and understanding of the development of these cancers linked to exposure to acrylamide, glycidamide, glycidol and chlorination byproducts. We hope to be able to fill the knowledge gaps that exist in the field, and thereby increase knowledge about, and the need for, preventive work to reduce the risk of cancer. The project can potentially lead to changes in routines about how food and drinking water are handled with clear prerequisites for success - given the need exists.

Acrylamide, a widespread food-processing contaminant, poses a major public health concern due to its high exposure level in the general population and its toxicity. While animal evidence shows that acrylamide causes neurological alterations and may play a role in cardiovascular disease, evidence in humans is lacking. Our project aims to investigate whether dietary acrylamide exposure, measured in blood, increases the risk of dementia, Alzheimer´s and Parkinson´s diseases and myocardial infarction. In addition, we aim to improve the understanding of the biological mechanisms underlying these associations integrating small compounds in blood (i.e., OMICS).In two population-based cohorts, the Cohort of 60-Year-Olds and the Swedish Mammography Cohort, acrylamide will be assessed in blood samples using a case-cohort design (around 1,740 individuals, 20-year follow-up). The results will be presented in four scientific publications using adequate data analysis. The project will run from 2024-2028.The project´s findings will help improve public health through safer food and better nutrition. If findings indicate that acrylamide increases the risk of these diseases, this will urge interventions to decrease acrylamide exposure via food production and consumption. In turn, this will help to reduce the burden of these diseases. Even findings showing null association will be equally relevant to avoid unnecessary and costly preventive measures.

The estimated exposure and reported serum levels of PFAS, show that parts of the general population exceed the tolerable weekly intake and the highest exposure occur in areas with contaminated drinking water. One of the main human health concerns associated with PFAS exposure is perturbation of blood lipid homeostasis observed in epidemiological studies. Current risk assessments are hampered by a lack of understanding on the mode of action and the potential causal relationship with cardiovascular disease. In addition, combined effects of PFAS mixtures remain largely unknown. In this project we will elucidate the lipidomic profiles (lipidomics) in human blood samples representing populations with high and low levels of exposure. We will also use a prospective nested case-control study to identify lipid profiles associated with an increased risk of cardiovascular disease. Identified biomarkers from the epidemiological studies will be compared with results from experimental in vitro studies using human hepatocytes (HepaRG). This cell model will also be used to study the cellular regulation of lipids in relation to various PFAS and human relevant mixtures. By integration of the benchmark dose-response modelling approach, results from epidemiological and experimental studies will be transferable to a regulatory context and relevant for retrospective risk assessments as well as for prospective safety evaluations.

Research problem and specific questions. Traffic noise is an environmental exposure of growing concern with mounting evidence of serious adverse health effects. At least one in five Europeans (approximately 113 million people) are exposed to noise levels exceeding the European Environment Agency indicator level linked to harmful health effects. Besides the increased risk of cardiovascular and metabolic effects, hearing loss, and sleep disturbance, more recent studies have indicated that prolonged exposure to noise might accelerate the risk of cognitive impairment, degenerative dementia, anxiety, and depression.  Data and Methods. We take advantage of the pre-existing data within the Nordic Studies on Occupational and Traffic Noise in Relation to Disease (NordSOUND) project, comprising over 185 000 adults from five Swedish and two Danish cohorts, to investigate whether exposure to traffic and occupational noise is related to dementia and mental health (depression, and anxiety) and to reveal potential mechanisms. We will adjust for individual- and area-level covariates to enable increased precision in the assessment of associations. We will also adjust for residential air pollution exposure and lack of greenness to explore the potential interactions.  Plan for project realization. The research group involved in the project is multidisciplinary, and the complementary expertise of the team members will guarantee a broad perspective considering clinical, social, and public health relevance as well as adequate methodological and management skills. A postdoc research fellow will implement the study plan, coordinated and supervised by project leader and senior researchers. Relevance. This collaborative research effort will address a considerable knowledge gap regarding noise exposure, dementia and mental health. Our results may have significant implications for risk assessment and public health policy, especially considering the recently relaxed noise guidelines in Sweden and the rapid urban growth.

Traffic noise is an environmental exposure of growing concern with mounting evidence of serious adverse health effects. At least one in five Europeans (113 million people) are exposed to noise levels exceeding the European Environment Agency indicator level linked to harmful health effects. Besides the increased risk of cardiovascular and metabolic effects, hearing loss, and sleep disturbance, recent studies have indicated that prolonged exposure to noise might accelerate the risk of cognitive impairment, dementia, anxiety, and depression.We take advantage of the pre-existing data within the Nordic Studies on Occupational and Traffic Noise in Relation to Disease (NordSOUND) project, comprising over 185 000 adults from 5 Swedish and 2 Danish cohorts, to investigate whether exposure to traffic and occupational noise is related to dementia and mental health (depression, and anxiety) and to reveal potential mechanisms. We will adjust for individual- and area-level covariates to enable increased precision in the assessment of associations. We will also adjust for residential air pollution exposure and lack of greenness to explore the potential interactions.This collaborative research effort will address a considerable knowledge gap regarding noise exposure, dementia and mental health. Our results may have significant implications for risk assessment and public health policy, especially considering the recently relaxed noise guidelines in Sweden and the rapid urban growth.