Dietary Nitrate and Nitrite Intake and Phosphate Biomarkers and Risk of Chronic Diseases

NCT07746310 | Completed

• 1 other identifier: 2025-02373
• Study Type: observational
• Target: 86,000
• Locations: 1 country
• Sites: 1

Brief Summary

Nitrate, nitrite, and phosphate (NO3, NO2, P) are at all age stages ubiquitous in our everyday foods, including naturally occurring and as food additives, and in our drinking water. These compounds are essential in maintaining human well-being and health, but they have also been linked to detrimental health effects including contribution to cancer initiation and artery calcification, making it difficult to evaluate their overall health impact. Therefore, the overarching aim of this project is to shed light on the potential dual effect of these compounds on a variety of chronic diseases (cardiovascular and respiratory diseases, gastrointestinal cancers) at different life stages and to further elucidate on the molecular mechanisms suggested to underly the pathogenesis of these disease outcomes. This will be achieved by using prospective, longitudinal population-based cohorts linked to comprehensive databases of NO3 and NO2 and using a biomarker of P while also integrating omics data on inflammatory and cardiometabolic biomarkers as well as the microbiome and urine bacterial metabolites. The project will be led by the PI and conducted by a team of PhD students and postdoc in close collaboration with relevant experts. It will be initiated early on and continued throughout a 4-year study period. With this research, the investigators attempt to provide the strongest scientific evidence with etiologically more relevant exposure-disease associations and to shape future health risk assessments.

Conditions

Healthy; Chronic Obstructive Airway Disease; Gastrointestinal Cancer; Cardiovascular Diseases; Asthma (Diagnosis)

Outcome Measures

Primary Outcomes (7)

• Gastrointestinal cancers incidence

  In SIMPLER cohorts

  Through study completion, an average of 25 years

• Cardiovascular diseases incidence

  In SIMPLER cohorts

  Through study completion, an average of 25 years

• Chronic obstructive pulmonary disease incidence

  In SIMPLER cohorts

  Through study completion, an average of 25 years

• Differential abundance of gut microbiota sequenced using DNBseq

  In SIMPLER cohorts and sequenced using DNBseq technology (BGI) and computationally analysed using both MetaPhlAn4 and CHAMP (CM HumAn Microbiome Profiler 2.0, Clinical Microbiomics)

  At baseline (time of sample collection)

• Asthma incidence

  In BAMSE cohort

  From birth through young adulthood (up to 24 years of age)

• Lung function (FEV1 and FVC)

  In BAMSE cohort and measured using spirometry according to the ATS/ERS spirometry criteria (at age 8 years using a 2200 Pulmonary Function Laboratory (SensorMedics), at 16 years of age using a Jaeger MasterScreen-IOS system (CareFusion Technologies), and at 24 years using a Vyaire Vyntus system (Vyaire Medical))

  Assessed every 8 years

• Concentrations of inflammatory biomarkers assessed by Olink Inflammation panel

  In BAMSE cohort, using the Olink Target 96 Inflammation panel, which measures relative protein levels reported as Normalized Protein eXpression (NPX) values on a log2 scale. All proteins included in the panel (approximately 92) will be analyzed individually in an exploratory manner.

  At 24 years of age

Secondary Outcomes (1)

• Urinary bacterial metabolite profiles assessed by non-targeted LC-HRMS

  At 24 years of age

Study Arms (3)

Swedish Mammography Cohort (SMC)

Cohort of Swedish Men (COSM)

Barn, Allergi, Miljö, Stockholm, Epidemiologi (BAMSE)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We plan to use data from two population-based and longitudinal cohorts of middle-aged to elderly women and men, parts of the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research (SIMPLER). The SMC was established in 1987-90 to which all women born in 1914-48, living in the counties of Uppsala and Västmanland in Sweden, were invited to participate in. In 1997, the COSM was established inviting all men born in 1918-1952 and living in Västmanland and Örebro counties in Sweden. Questionnaire information has been repeatedly collected in 1987-90, 1997, 2008/9, and in 2019. Clinical sub-cohorts (SMC-C and COSM-C) were established between 2003 and 2010. We will also use data from the population-based prospective birth cohort BAMSE. The cohort was established in 1994-96, when 4,089 newborn children in two areas in Stockholm were invited to participate in the study.

You may qualify if:

• SMC and COSM
• Born between 1914 and 1948 (SMC) or through 1952 (COSM)
• Residing in Västmanland and Uppsala counties (SMC)
• Residing in Västmanland and Örebro counties (COSM)
• BAMSE cohort
• All children born in certain areas of northern and central Stockholm between Feb 1994 and Nov 1996.

You may not qualify if:

• SMC and COSM
• Incorrect or missing national registration number
• Prevalent disease at baseline (depending on research question)
• Implausible energy intake
• BAMSE cohort
• The family planned to move within 1 year of the study start;
• Insufficient knowledge of the Swedish language;
• The family had a seriously ill child or
• an older sister or brother was already included in the study.

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Karolinska Institutet

Stockholm, Sweden

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Cardiovascular Diseases; Pulmonary Disease, Chronic Obstructive; Asthma; Disease

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 26 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: August 5, 2026
• Study Start: January 1, 1987
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)