Prospective study of circulating metabolomic profiles and breast cancer incidence among predominantly premenopausal women.

Background: Associations between premenopausal plasma metabolites and breast cancer incidence are largely unknown.

Methods: We conducted a prospective, matched case-control study in which we measured pre-diagnostic metabolomic profiles among predominantly premenopausal women in the Nurses' Health Study II (n = 2010). Lipids, carbohydrates, and organic acid-related metabolites (n = 218) were profiled via liquid chromatography-tandem mass spectrometry.

Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function.

Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) have a substantial genetic basis, with APOE4 homozygotes increasingly recognized as a distinct genetic subtype. To identify genotype-specific metabolic pathways and modifiable risk factors, we integrated genetic, plasma metabolomic and dietary data from 4,215 women and 1,490 men in prospective cohorts. Here we show that the associations of 57 metabolites with dementia risk varied by APOE4 genotype or other AD/ADRD risk variants.

Prediagnostic Plasma Metabolomic Profiles Using NMR for Exfoliation Glaucoma Among US Health Professionals.

Background: Exfoliation glaucoma (XFG) represents a form of deleterious ocular aging of unclear etiology. We evaluated prediagnostic nuclear magnetic resonance (NMR)-based metabolites in relation to XFG risk, expanding on our prior findings of XFG-related metabotypes using liquid chromatography-mass spectrometry (LC-MS).

Methods: We identified 217 XFG cases and 217 matched controls nested within three prospective health professional cohorts with plasma collected a mean 11.

Amino acid intake, plasma metabolites, and incident type 2 diabetes risk: a systematic approach in prospective cohort studies.

Background: Amino acid (AA) intake is thought to be closely related to the etiology of type 2 diabetes (T2D), although few prospective human studies have examined the association. The study prospectively examined inter-relationships among the intake of all 20 AAs, blood metabolome, and T2D incidence.

Methods: Prospective associations between 20 individual AA intake and T2D were examined among 201,113 participants from the Health Professionals Follow-up Study (HPFS), Nurses' Health Study (NHS), and NHSII who did not have T2D, cardiovascular disease, or cancer at baseline.

Plasma and ovarian metabolomic responses to chronic stress in female mice.

Introduction: Chronic stress has been linked with higher risk of ovarian cancer and one posited pathway is through altered metabolism of amino acids, lipids, and other small molecule metabolites. However, the types of alterations that occur may not be uniform across tissue types.

Objectives: We aim to examine and compare the impacts of chronic stress on metabolomic changes in circulation and ovarian tissue.

Pyruvate and related energetic metabolites modulate resilience against high genetic risk for glaucoma.

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed.

Machine Learning on Prediagnostic Metabolite Data Identifies Etiologic Endotypes of Exfoliation Glaucoma in United States Health Professionals.

Purpose: Exfoliation glaucoma (XFG) etiology is poorly understood. Metabolomics-based etiologic endotypes of XFG may provide novel etiologic insights. We aimed to use unsupervised machine learning on prediagnostic plasma metabolites to characterize etiologic XFG endotypes.

Plasma metabolites associated with endometriosis in adolescents and young adults.

Study Question: What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults?

Summary Answer: Our findings show dysregulation of plasma metabolomic profiles in adolescents and young adults with endometriosis, revealing systemic elevation of fatty acyls and ceramides in endometriosis cases compared to controls.

What Is Known Already: Endometriosis is a gynecologic disease often presenting with severe pelvic pain impacting around 200 million reproductive-aged women worldwide. However, little is known about the pathophysiology and molecular features of endometriosis diagnosed during adolescence and young adulthood.

Persistent PTSD symptoms are associated with plasma metabolic alterations relevant to long-term health: A metabolome-wide investigation in women.

Background: Post-traumatic stress disorder (PTSD) is characterized by severe distress and associated with cardiometabolic diseases. Studies in military and clinical populations suggest that dysregulated metabolomic processes may be a key mechanism. Prior work identified and validated a metabolite-based distress score (MDS) linked with depression and anxiety and subsequent cardiometabolic diseases.

Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma.

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed.

Supplemental oxygen for pulmonary embolism (SO-PE): study protocol for a mechanistic, randomised, blinded, cross-over study.

Background: Acute pulmonary embolism (PE) mortality is linked to abrupt rises in pulmonary artery (PA) pressure due to mechanical obstruction and pulmonary vasoconstriction, leading to right ventricular (RV) dilation, increased RV wall tension and oxygen demand, but compromised right coronary artery oxygen supply. Oxygen is a known pulmonary vasodilator, and in preclinical animal models of PE, supplemental oxygen reduces PA pressures and improves RV function. However, the mechanisms driving these interactions, especially in humans, remain poorly understood.

Novel metabolomic predictors of incident colorectal cancer in men and women.

Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed prediagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) who provided blood between 1989 and 1995.

Longitudinal study of seafood and fish oil supplement intake and risk of persistent tinnitus.

Background: Persistent tinnitus is common, disabling, and difficult to treat. Diet has been implicated in tinnitus etiology, but studies are inconsistent, and longitudinal data are scarce. Seafood intake is associated with a lower risk of hearing loss, but the longitudinal association with tinnitus is unknown.

Pet Attachment and Anxiety and Depression in Middle-Aged and Older Women.

Importance: Understanding how attachment to pets can alleviate depression and anxiety offers valuable insights for developing preventive and therapeutic strategies, particularly for those with insecure attachment styles from childhood trauma.

Objective: To determine if a close bond with a pet is associated with reduced depression and anxiety, especially among women who experienced childhood abuse.

Design, Setting, And Participants: This cross-sectional study involved women who voluntarily enrolled in the Mind Body Study (MBS), a substudy of the Nurses' Health Study II (NHS2) focusing on psychosocial factors.

Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts.

There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities.

Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies.

Background: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity.

A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women.

Context: Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association.

Objective: To evaluate the association between a metabolomic signature for psychological distress and diabetes risk.

The metabolic potential of inflammatory and insulinaemic dietary patterns and risk of type 2 diabetes.

Aims/hypothesis: Diets with higher inflammatory and insulinaemic potential have been associated with an increased risk of type 2 diabetes. However, it remains unknown whether plasma metabolomic profiles related to proinflammatory/hyperinsulinaemic diets and to inflammatory/insulin biomarkers are associated with type 2 diabetes risk.

Methods: We analysed 6840 participants from the Nurses' Health Study and Health Professionals Follow-up Study to identify the plasma metabolome related to empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), four circulating inflammatory biomarkers and C-peptide.

Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank.

Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses' Health Studies, and Health Professionals' Follow-Up Study.

Sex differences in the polygenic architecture of hearing problems in adults.

Background: Hearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated by large-scale genetic studies.

The Role of Statins in the Prevention of Ovarian and Endometrial Cancers.

Ovarian and endometrial cancers are the most common gynecologic malignancies and emerging evidence suggests that lipid metabolism and subsequent inflammation are important etiologic factors for both tumors. Statins (HMG-CoA reductase inhibitors) are the most widely prescribed lipid-lowering drugs in the United States and are used by 25% of adults aged 40+ years. In addition to their cardio-protective actions, statins have anti-inflammatory effects and have demonstrated antiproliferative and apoptotic properties in cancer cell lines, supporting a potential role in cancer prevention.

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus: A Population-Based Case-Control Study.

Importance: Persistent tinnitus is common, disabling, and difficult to treat.

Objective: To evaluate the association between circulating metabolites and persistent tinnitus.

Design, Setting, And Participants: This was a population-based case-control study of 6477 women who were participants in the Nurses' Health Study (NHS) and NHS II with metabolomic profiles and tinnitus data.