Modifiable Lifestyle Factors Research Articles

Association of Risk Factors with Diabetes Mellitus in Rural Areas of Nawabshah City: A Case-Control Study

Background: Type 2 Diabetes Mellitus (T2DM) is a growing global health concern, particularly in rural regions of low- and middle-income countries where healthcare access and preventive strategies are limited. Despite increasing prevalence, the distribution of lifestyle and metabolic risk factors in rural Pakistani populations remains underexplored. Objective: To investigate the association between modifiable lifestyle and metabolic risk factors—specifically sedentary behavior, dietary habits, smoking, alcohol use, and obesity—and the risk of T2DM among young adults in rural areas of Nawabshah. Methods: This observational case-control study was conducted among 716 participants (346 cases, 370 controls) aged 18–45 years residing in rural Nawabshah. Cases included individuals clinically diagnosed with T2DM, while age- and sex-matched controls had no diabetes history. Data were collected using structured questionnaires, anthropometric measurements, and random capillary blood glucose (RCBG) tests. Ethical approval was obtained, and the study complied with the Declaration of Helsinki. Statistical analysis was performed using SPSS Version 26, employing chi-square and t-tests to evaluate group differences. Results: A sedentary lifestyle (70.2% vs. 51.4%, p = 0.007), dietary risk (90.8% vs. 60.8%, p = 0.01), smoking (20.2% vs. 13.5%, p = 0.019), overweight (25.7% vs. 19.2%, p = 0.036), and moderate obesity (19.1% vs. 10.8%, p = 0.003) were significantly more prevalent among T2DM cases than controls, indicating clinically relevant associations. Conclusion: Sedentary behavior, unhealthy diet, smoking, and obesity were strongly linked with increased T2DM risk in rural young adults, underscoring the urgent need for community-based preventive interventions in underserved populations.

Prevalence and Associated Factors of Sarcopenic Obesity Among Nursing Home Residents: A Cross-Sectional Multi-Centre Study.

Obesity and sarcopenia are prevalent among older adults and associated with adverse health outcomes. The aims of the present study were to assess the prevalence of sarcopenic obesity, to evaluate the co-occurence of sarcopenia, obesity and malnutrition (risk) and to assess the association between specific characteristics and sarcopenic obesity/probable sarcopenic obesity in nursing home residents. Three hundred eighty-seven nursing home residents with low to moderate care requirements from 20 nursing homes in Slovenia participated in the cross-sectional NutriCare study. Data on general patient characteristics, physical activity, usual dietary intake (estimated by a 2 × 24 h dietary recall and a food frequency questionnaire), malnutrition (risk) status (Mini Nutritional Assessment [MNA]), laboratory parameters, hand grip strength and body composition (estimated via BIA) were collected. Obesity was defined as a high body fat percentage. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People2 (EWGSOP2) criteria. Descriptive statistics were used to characterise the sample. Uni- and multivariable binary logistic regression analyses were performed to explore associations between the predictor variables and sarcopenic obesity. The prevalence of obesity was 90.7% according to high fat mass and 38.3% according to BMI (≥ 30). Prevalences were 27.6% (sarcopenia) and 24.5% (sarcopenic obesity), respectively. Probable sarcopenic obesity (low hand grip strength combined with obesity) was found in 37.6% of participants. A co-occurence of malnutrition (risk) and sarcopenia was present in 11.9%, whereas a combination of malnutrition (risk) and obesity was found in 28.2%. In 9.6% of the participants, a combination of all three phenomena-sarcopenia, obesity and malnutrition (risk)-was identified. The multivariable logistic regression model shows that higher age (OR 1.07; CI 1.02, 1.11), male sex (OR 2.3; CI 1.22, 4.5) and higher energy intake (OR 1.13; CI 1.04, 1.22) were significantly associated with sarcopenic obesity. Male sex (OR 2.30; CI 1.33, 3.98), higher age (OR 1.07; CI 1.03, 1.11), higher care requirements (OR 2.14; CI 1.20, 3.79), lower MNA score (OR 0.88; CI 0.80, 0.97) and metabolic equivalent of tasks (MET minutes/week) (OR 0.99; CI 0.98, 1.00) were significantly associated with probable sarcopenic obesity. The study indicates a notable prevalence of obesity and sarcopenic obesity among nursing home residents with lower to moderate care dependency. These findings underscore the importance of optimising nutritional intake and other modifiable lifestyle factors associated with such health conditions and implementing them into targeted, individualised interventions to reduce the risk of obesity and sarcopenic obesity and to improve health outcomes.

Association Between Healthy Dietary Patterns and Chronic Kidney Disease in Patients with Diabetes: Findings from Korean National Health and Nutrition Examination Survey 2019–2021

Background/Objectives: Although a healthy dietary pattern is a modifiable lifestyle factor in the prevention of chronic kidney disease (CKD), studies that investigate the association between a healthy diet and prevalent CKD in patients with diabetes, using the Korean Healthy Eating Index (KHEI), are lacking. Methods: This cross-sectional study included 1991 patients with diabetes from the eighth Korean National Health and Nutrition Examination Survey 2019–2021. A higher KHEI indicated healthier eating habits. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin–creatinine ratio ≥ 30 mg/g. The risk of prevalent CKD was evaluated according to the median KHEI value using logistic regression analysis adjusted for various clinicodemographic characteristics. Each KHEI component score was compared between those with and those without CKD, using the Student’s t-test. Results: Participants with a higher KHEI were older, with higher proportions of women, non-smokers, and non-alcoholics. A higher KHEI was significantly associated with a lower risk of prevalent CKD (adjusted odds ratio [aOR], 0.73 [0.58–0.93]). Subgroup analysis revealed stronger associations in those without hypertension status (aOR, 0.57 [0.37–0.87]) with at least high school education (aOR, 0.56 [0.38–0.81]). Moreover, patients with diabetes and CKD had significantly lower KHEI, particularly in the adequacy category components, including breakfast consumption, total fruit intake, and dairy product intake. Conclusions: A healthier dietary pattern was associated with a lower risk of prevalent CKD in patients with diabetes. Dietary intervention, which recommends the intake of breakfast, fruits, and dairy products, may be an effective strategy for CKD prevention.

Uncovering key factors in weight loss effectiveness through machine learning.

One of the main challenges in weight loss is the dramatic interindividual variability in response to treatment. We aim to systematically identify factors relevant to weight loss effectiveness using machine learning (ML). We studied 1810 participants in the ONTIME program, which is based on cognitive-behavioral therapy for obesity (CBT-OB). We assessed 138 variables representing participants' characteristics, clinical history, metabolic status, dietary intake, physical activity, sleep habits, chronotype, emotional eating, and social and environmental barriers to losing weight. We used XGBoost (extreme gradient boosting) to predict treatment response and SHAP (SHapley Additive exPlanations) to identify the most relevant factors for weight loss effectiveness. The total weight loss was 8.45% of the initial weight, the rate of weight loss was 543 g/wk., and attrition was 33%. Treatment duration (mean ± SD: 14.33 ± 8.61 weeks) and initial BMI (28.9 ± 3.33) were crucial factors for all three outcomes. The lack of motivation emerged as the most significant barrier to total weight loss and also influenced the rate of weight loss and attrition. Participants who maintained their motivation lost 1.4% more of their initial body weight than those who lost motivation during treatment (P < 0.0001). The second and third critical factors for decreased total weight loss were lower "self-monitoring" and "eating habits during treatment" (particularly higher snacking). Higher physical activity was a key variable for the greater rate of weight loss. Machine learning analysis revealed key modifiable lifestyle factors during treatment, highlighting avenues for targeted interventions in future weight loss programs. Specifically, interventions should prioritize strategies to sustain motivation, address snacking behaviors, and enhance self-monitoring techniques. Further research is warranted to evaluate the efficacy of these strategies in improving weight loss outcomes. clinicaltrials.gov: NCT02829619.

Genetic predisposition to adiposity and type 2 diabetes: the role of lifestyle, and phenotypic adiposity.

Genetic predisposition to adiposity is associated with type 2 diabetes (T2D), even in the absence of phenotypic adiposity (obesity and central obesity). We aimed to quantify the overall contribution of obesity and modifiable lifestyle factors to the association between genetic predisposition to adiposity, and the development of T2D. This prospective cohort study involved 220,703 white British participants from the UK Biobank. It examined the associations between genetic predisposition to adiposity (body mass index polygenic risk; BMI-PRS and waist: hip ratio; WHR-PRS) and incident T2D, as well as interactions and mediation via lifestyle factors (diet quality, physical activity levels, total energy intake, sleep duration, and smoking and alcohol intake) and phenotypic adiposity. People with high phenotypic adiposity and high adiposity PRS values (>1 standard deviation above the mean) had the highest risk of incident T2D (versus non-obese/central obese and non-high PRS). This was the case for BMI-PRS (hazard ratio or HR = 3.72) and WHR-PRS (HR=4.17). Lifestyle factors explained 30.5% of the BMI-PRS/T2D association (2.0% mediation; 28.5% effect modification) and lifestyle and obesity, together, explained 92.1% (78.8% mediation; 13.3% effect modification). Lifestyle factors explained 20.4% of the association with WHR-PRS/T2D (3.4% mediation; 17.0% effect modification) and lifestyle and central obesity, together, explained 72.8% (41.1% mediation; 31.7% effect modification). Whilst phenotypic adiposity explains a large proportion of the association between BMI/WHR-PRS and T2D, modifiable lifestyle factors also make contributions. Promoting healthy lifestyles among people prone to adiposity is important in reducing the global burden of T2D.

Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.

Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.

Traumatic brain injury persistently increases the incidence of both ischemic and hemorrhagic strokes: Potential mechanisms.

Traumatic brain injury persistently increases the incidence of both ischemic and hemorrhagic strokes: Potential mechanisms.

Composite lifestyle, genetic risk, blood biomarkers, and risk of suicide attempts: a prospective cohort study.

Composite lifestyle, genetic risk, blood biomarkers, and risk of suicide attempts: a prospective cohort study.

Circulating microRNAs and alcohol consumption in the multiethnic cohort study.

Circulating microRNAs and alcohol consumption in the multiethnic cohort study.

Observational and genetic evidence highlight the association of modifiable risk factors with the incidence and severity of neuroimmunological disorders.

Observational and genetic evidence highlight the association of modifiable risk factors with the incidence and severity of neuroimmunological disorders.

The Influence of Diet and Physical Activity on Periodontal Health: A Narrative Review

Periodontal diseases, including gingivitis and periodontitis, are chronic inflammatory conditions that compromise the supporting structures of the teeth, often leading to tooth loss and contributing to systemic comorbidities. Increasing evidence underscores the critical role of modifiable lifestyle factors, particularly diet and physical activity, in influencing periodontal health. This narrative review critically evaluates the current body of literature regarding the impact of dietary constituents and physical activity on the periodontium, with a focus on the molecular mechanisms, key biomarkers, and clinical implications. It aims to provide a deeper understanding of the complex interactions between nutrition, exercise, and periodontal health with potential implications for clinical management and preventive strategies.

Dietary Patterns and Brain Health in Middle-Aged and Older Adults: A Narrative Review

Diet has a profound impact on brain health, particularly in middle-aged and older adults, who are at increased risk of cognitive decline and neurodegenerative diseases. Various dietary patterns, including the Mediterranean diet (MedDiet), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets, have been linked to improved cognitive function. While the relative effectiveness of these diets on brain health is generally supported by evidence, variability in study results suggests that further research is needed to fully understand their effects across diverse populations. The objective of this descriptive narrative review is to examine the role of dietary patterns in supporting brain health in aging populations and to propose practical dietary strategies for promoting cognitive well-being. A comprehensive review of the existing literature was conducted on PubMed in October 2024, with no restrictions on language, publication date (1966–2024), or geographic location. A total of 18 articles were included in this review, covering the years 2013–2023. Studies assessing the impact of the MedDiet, DASH, MIND, and Western diets on cognitive function in middle-aged and older adults were prioritized. The research findings were synthesized to identify common and unique recommendations across these dietary patterns. The MedDiet consistently showed beneficial effects on cognitive health, including improved memory, processing speed, and long-term protection against neurodegenerative conditions. The DASH and MIND diets demonstrated potential benefits, particularly for specific cognitive domains, but the results were more mixed and inconclusive. In contrast, adherence to a Western diet was associated with negative cognitive outcomes, including cognitive decline and smaller brain volumes. These findings underscore the importance of adopting healthy dietary patterns as a modifiable lifestyle factor to support cognitive aging and inform future public health strategies and clinical guidelines.

Cognitive-and lifestyle-related microstructural variation in the ageing human hippocampus.

Age-related hippocampal alterations often accompany cognitive decline, a significant risk factor for dementias. Modifiable lifestyle factors may help preserve hippocampal neural tissue and slow neurodegeneration and potentially promote cognition in old age. Here, we sought to identify the relationship between lifestyle and cognition in the context of the hippocampal microstructure across the lifespan. We used data from 494 subjects (36-100years old) without cognitive impairment from the Human Connectome Project-Ageing study. We estimated hippocampal microstructure using myelin-sensitive (T1w/T2w ratio), inflammation-sensitive (MD) and fibre-sensitive (FA) MRI markers. We identified microstructural-lifestyle/-cognition using non-negative matrix factorization to integrate MRI measures into a multivariate spatial signature of hippocampal microstructure covariance followed by partial least squares analysis. Our results reveal that the preservation of axon density and myelin in regions corresponding to subicular regions and CA1 to CA3 regions are negatively associated with age, and is associated with improved performance in executive function tasks, however, this is also associated with a decreased performance in memory tasks. We also show that microstructure is preserved across the hippocampus when there is normal hearing levels, physical fitness and insulin levels and this is negatively associated with age in the presence of cardiovascular risk factors like high body mass index, blood pressure, triglycerides and blood glucose that are in turn associated with hippocampal neurodegeneration. Taken together, our results suggest that lifestyle factors like normal hearing, physical fitness and normal insulin levels may help preserve hippocampal microstructure which may be useful in maintaining optimum performance on executive function tasks and potentially other modes of cognition.

Multiomics Analysis of a Micronutrient-Rich Dietary Pattern and the Aging Genotype 9p21 on the Plasma Proteome of Young Adults.

Background: Diet is one of the most significant modifiable lifestyle factors influencing human health, contributing to both morbidity and mortality. Genetic variations in the pleiotropic 9p21 risk locus further shape premature aging, disease susceptibility, and have been strongly linked to cardiovascular disease (CVD), metabolic disorders, certain cancers, and neurodegenerative conditions. However, given that this region was discovered based on Genome-Wide Association Studies, the mechanisms by which 9p21 exerts its effects remain poorly understood and its interactions with diet and biomarkers are insufficiently explored. Methods: This study investigated the association between the rs2383206 SNP in 9p21, dietary patterns, and plasma proteomic biomarkers in a multi-ethnic cohort of 1280 young adults from the Toronto Nutrigenomics and Health Study. Participants' dietary intake was assessed using a validated food frequency questionnaire, and dietary patterns were categorized using principal component analysis. Plasma proteomics analyses quantified 54 abundant proteins involved in the cardiometabolic and inflammatory pathways. Genotyping identified individuals who were homozygous for the 9p21 risk allele (GG), known to confer the highest susceptibility risk to premature aging and multiple chronic diseases. Results: A significant interaction was observed between the 9p21 genotype and adherence to a micronutrient-rich Prudent dietary pattern for eight plasma proteins (α1 Antichymotrypsin, Complement C4 β chain, Complement C4 γ chain, Complement C9, Fibrinogen α chain, Hemopexin, and Serum amyloid P-component). However, only Complement C4-γ showed a pattern consistent with the risks associated with the 9p21 genotype and adherence to a Prudent diet. Individuals with the high-risk GG genotype had significantly higher concentrations of Complement C4-γ, but only among those with a low adherence to a Prudent diet. Conclusions: These findings suggest that Prudent dietary patterns rich in micronutrients may counteract genetic-mediated proinflammatory susceptibility by modulating key proteomic biomarkers in young adults, highlighting the potential for tailored dietary interventions to mitigate disease risk. This study also introduces a novel framework for post hoc micronutrient resolution within dietary pattern analysis, offering a new lens to interpret nutrient synergies in gene-diet interaction research.

Abstract 6198: Framework for Pacific Island Cancer and Obesity Across the Lifespan: PICOLI, A multi-dataset analysis approach

Abstract Background: Pacific Islanders experience disproportionate rates of obesity and cancer, contributing to morbidity and mortality. Comprehensive analyses examining obesity and cancer across age groups are limited. Objective: We propose to develop a framework identify and harmonize existing datasets to assess lifestyle factors, obesity, and cancer across various age groups, with a focus on Pacific Islander populations. Methods: We have identified several key datasets for this analysis, including the the Children’s Healthy Living Program (CHL), Pacific Islands Cohort on Cardiometabolic Health (PICCAH), Breast Cancer Risk Project (BRISK), and Multiethnic Cohort Study (MEC). These datasets contain approximately 22, 000 participants from 2-80 years old, which capture essential factors, such as body mass index, physical activity levels, dietary habits, sleep behavior, tobacco use, and cancer incidence. Expected Outcomes: The framework will guide future research to provide insights between lifestyle factors, obesity, and cancer risk that evolve throughout life. Anticipated identification of consistent patterns across age groups and potential modifiable lifestyle factors associated with reduced cancer risk. We will contribute valuable knowledge about the long-term effects of lifestyle factors on obesity and cancer risk in Pacific populations. Inform public health strategies tailored to address significant health disparities in this population. Conclusion: Developing this analytical framework aims to bridge current gaps in understanding the complex relationships between lifestyle factors, obesity, and cancer risk among Pacific Islanders, ultimately contributing to improved health outcomes. Future researchers can apply this framework to existing datasets, facilitating comprehensive analyses across age groups and potentially guiding targeted interventions. Table 1. Key Datasets for Pacific Island Cancer and Obesity Across the Lifespan Study Study Name Children’s Healthy Living Program (CHL) Pacific Islands Cohort on Cardiometabolic Health (PICCAH) Breast Cancer Risk Project (BRISK) Multiethnic Cohort(MEC) Participants, n 1, 263 500 dyads 245 ∼20, 000 Age, years 2 - 8y 4 - 10y &amp; 21 - 50y (biological adult parents) 25 - 80y 45 - 79y Study Design Cross-sectional and Randomized Controlled Trial Cohort Case Control Cohort Location CNMI, Guam, Hawaii Guam CNMI, Guam Hawaii Health Outcome Obesity, Acanthosis nigricans Obesity, Diabetes, Acanthosis nigricans Breast Cancer, Diabetes All Cancers, Diabetes Measured Anthropometry Height, weight, waist circumference Height, weight, waist circumference Height, weight, waist circumference Height, weight, waist circumference Lifestyle Measures Diet, physical activity, sleep Diet, physical activity, sleep, tobacco use Diet, physical activity, tobacco use Diet, physical activity, sleep, tobacco use Citation Format: Ashley B. Yamanaka, Michelle B. Laguana, Marie Chong, Rachael T. Leon Guerrero, Rachel Novotny, Grazyna Badowski, Lynne R. Wilkens. Framework for Pacific Island Cancer and Obesity Across the Lifespan: PICOLI, A multi-dataset analysis approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6198.

Interaction of Genetics and Dietary Patterns Scored by the High Healthy Eating Index in Hyperhomocysteinaemia Influencing Cardiovascular Disease Risk.

Hyperhomocysteinaemia has been associated with increased cardiovascular disease (CVD) risk, but the complex interplay between genetic determinants and modifiable lifestyle factors in modulating homocysteine (HC) levels remains incompletely understood. We aimed to investigate the aetiology of hyperhomocysteinaemia by examining the interactions between genetic predisposition, dietary patterns and other lifestyle factors and their potential associations with metabolic syndrome (MetS) and CVD risk. Cross-sectional analysis from the Korean Genome and Epidemiology Study, a hospital-based cohort conducted by the Korean Centers for Disease Control and Prevention from 2012 to 2016. Korean adults (n = 62 743, aged 40-79 years) were categorised into Low-HC (n = 53 450) and High-HC (n = 9293) groups based on a 15 μM serum homocysteine cutoff. Demographic, anthropometric and biochemical data were analysed. Genome-wide association and gene-environment interaction models explored genetic variants influencing hyperhomocysteinaemia and their interplay with lifestyle factors, including nutrient intake. Multivariable logistic regression assessed associations between hyperhomocysteinaemia and metabolic/CVD risks, adjusting for covariates. Genetic variant-environment interaction analyses identified genetic determinants and their interactions with diet/lifestyle. The High-HC group exhibited an elevated MetS risk. Hyperhomocysteinaemia was correlated with liver damage, inflammation and CVD risks. Low vitamin B12 intake (< 5.4 μg/day) showed a stronger association with hyperhomocysteinaemia than low folate intake (< 350 μg/day), with combined deficiencies exacerbating hyperhomocysteinaemia. An inverse relationship was observed between hyperhomocysteinaemia and healthy eating indices like Asian balanced and plant-based diets. Variants in MTHFR, NOX4, PLOD1, MIIP, PAX6 and CBS genes, involved in methionine/cysteine metabolism, exhibited differential expression in skeletal muscle, liver and adipose tissues. High polygenic risk scores interacted with poor diet quality, excess energy intake, a high glycemic index, smoking and heavy alcohol consumption to contribute to hyperhomocysteinaemia. In conclusion, these findings elucidate the complex interplay between genetics, diet and lifestyle in modulating homocysteine levels, providing insights for personalised nutrition strategies to mitigate CVD risk.

Parental Transmission of Type 2 Diabetes Risk in Offspring: A Prospective Family-Based Cohort Study in Northern China.

Background: While parental type 2 diabetes (T2D) is a known risk factor for offspring T2D, the differential impact of maternal versus paternal transmission remains debated. Methods: This prospective family-based cohort study enrolled 4508 diabetes-free adults from Northern China with a median 7.32-year follow-up. Using Cox proportional hazards models, we examined parent-of-origin effects on T2D incidence, adjusting for lifestyle, adiposity, and metabolic covariates. Results: Parental T2D conferred elevated offspring risk (adjusted HR = 1.82, 95% CI:1.44-2.30), and was predominantly driven by maternal transmission. Maternal T2D was robustly associated with offspring risk (HR = 1.89, 95% CI: 1.47-2.43), whereas paternal T2D showed no significant effect (HR = 1.27, 95% CI: 0.88-1.84). Offspring with only maternal T2D history exhibited the highest risk (HR = 2.55, 95% CI: 1.87-3.50; p = 4.70 × 10-9), persisting after full adjustment, while no significant association was observed for paternal diabetes. Lifestyle modified this association: healthy diet (diet score > 2 vs. ≤2: HR = 1.34 vs. 2.76; pinteraction = 9.10 × 10-4) and regular exercise (regular vs. unregular: HR = 1.13 vs. 2.10; pinteraction = 4.20 × 10-2) attenuated maternal transmission. Conclusions: Maternal T2D confers greater intergenerational risk than paternal T2D, with modifiable lifestyle factors mitigating this association. These findings highlight the importance of integrating maternal diabetes history into clinical risk stratification tools and prioritizing lifestyle interventions in the offspring of affected mothers to mitigate inherited risk.

Disease Severity and Disparities in Black and White People with Multiple Sclerosis: Sociodemographic and Modifiable Lifestyle Factors in a New York Population (P4-1.007)

Disease Severity and Disparities in Black and White People with Multiple Sclerosis: Sociodemographic and Modifiable Lifestyle Factors in a New York Population (P4-1.007)

Dietary riboflavin (vitamin B2) intake and osteoporosis in U.S. female adults: unveiling of association and exploration of potential molecular mechanisms

BackgroundOsteoporosis characterized by deteriorating bone loss is becoming one of the serious health problems globally. Vitamin B2, also known as riboflavin, exhibiting multiple prominent physiological traits such as antioxidant effects, reducing lipid peroxidation and regulating glutathione redox cycle, allows it to be a potential agent to improve bone loss. However, the relationship between dietary vitamin B2 intake and osteoporosis remains unelucidated. The objective of this study was to explore the association between the dietary intake of vitamin B2 and bone loss in the U.S. female adults using the National Health and Nutrition Examination Survey (NHANES) database.MethodsFemale participants with complete information on dietary vitamin B2 intake, dual-energy X-ray absorptiometry, and other essential covariates from NHANES database were included in the current study. Multivariable logistic regression and linear regression analyses were conducted to assess the relationships of dietary vitamin B2 intake with osteoporosis and bone mineral density (BMD) levels, respectively. Subgroup analyses, interaction tests, and restricted cubic spline (RCS) regression analyses were further used to verify the stability, robustness and potential nonlinearity of the association. Mediation analysis was performed to probe the role of serum alkaline phosphatase (ALP) in the aforementioned relationship, and the network pharmacology analysis was also conducted to determine the potential pathways and key targets for vitamin B2 regulating bone health.ResultsA total of 4, 241 female participants from four NHANES cycles were included in this study. After multivariate adjustment, the intake of vitamin B2 was beneficially associated with reduced risk for femur osteoporosis (ORQ4 vs. Q1=0.613; 95%CI: 0.454–0.829). A higher intake of vitamin B2 (quartile 4) was significantly correlated with decreased risk of reduced femoral BMD levels, with the β being 0.020 (95%CI: 0.007–0.033), 0.015 (95%CI: 0.002–0.027), 0.020 (95%CI: 0.009–0.031) and 0.022 (95%CI: 0.006–0.037) for the BMD of total femur, femoral neck, trochanter, and intertrochanter, respectively (all P value < 0.05). Covariate total MET was found to modify the association between vitamin B2 intake and osteoporosis (P interaction = 0.0364), with the aforementioned relationship being more pronounced in the subgroup of insufficiently active individuals. Furthermore, RCS analysis revealed that vitamin B2 intake was positively and linearly associated with reduced risk for femoral OP and increased BMD levels of total femur, trochanter and intertrochanter, while positively and nonlinearly correlated with increased BMD level of femoral neck. Additionally, the association between vitamin B2 intake, osteoporosis and BMD levels was mediated by ALP, with a mediation proportion of 12.43%, 7.58%, 12.17%, 7.64%, and 6.99% for OP, total femur, femoral neck, trochanter, and intertrochanter BMD, respectively. Finally, network pharmacology analysis indicated that vitamin B2 regulating bone health mainly through pathways like HIF-1 signaling pathway, longevity regulating pathway, p53 signaling pathway, etc.ConclusionsHigher intake of vitamin B2 is positively associated with reduced risks for femoral osteoporosis and bone loss. Vitamin B2 may represent a modifiable lifestyle factor for the prevention and management of osteoporosis.

Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes.

Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) and dementia. We examined whether an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer's, or vascular dementia, and investigated whether differences in potentially modifiable lifestyle factors in the mid- to late-life period may attenuate this risk. A prospective cohort study of 365 782 participants free from dementia for at least 5 years after baseline assessment was conducted within the UK Biobank cohort. Genetic risk was assessed using a genomewide polygenic risk score (PRS) for CAD and lifestyle risk using a modified version of the American Heart Association's Life's Essential 8 Lifestyle Risk Score (LRS). Higher values for both scores were deemed to represent increased risk. Primary outcomes were incident all-cause, Alzheimer's, and vascular dementia diagnoses obtained from self-report and electronic health records. Secondary outcomes were neuroimaging phenotypes measured in 32 028 participants recalled for magnetic resonance imaging. Sensitivity analyses were conducted to test the extent by which biological and behavioral risk factors contributed to observed associations. A total of 8870 cases of all-cause dementia were observed over a median 13.9-year follow-up. Both genetic (PRS) and lifestyle (LRS) risk scores for CAD were associated with a modestly elevated risk of all-cause dementia (subhazard ratio per SD increase, 1.10 [1.08, 1.12], P<0.001, for PRS and 1.04 [1.02, 1.06], P=0.006, for LRS). This risk appeared largely attributable to underlying vascular dementia diagnoses (subhazard ratio, 1.16 [1.11, 1.21], P<0.001 for PRS and 1.15 [1.09, 1.22], P<0.001, for LRS), because Alzheimer's disease was found to demonstrate moderate associations with PRS alone (subhazard ratio, 1.09 [1.06, 1.13]; P<0.001). LRS was found to have an additive rather than interactive effect with PRS, with individuals in the highest tertiles for both genetic and lifestyle risk for CAD ≈70% more likely to develop vascular dementia during follow-up compared with those in the lowest tertiles for both (subhazard ratio, 1.71 [1.39, 2.11]; P<0.001). This was substantially attenuated in those with a low LRS at baseline, however, regardless of underlying genetic risk (30% reduction for low versus high LRS tertile regardless of PRS tertile; P<0.001 for all). In a subset of individuals recalled for neuroimaging assessments, those in the highest tertiles for genetic and lifestyle risk for CAD demonstrated a ≈25% greater volume of white matter hyperintensities than those in the lowest risk tertiles, but showed little difference in gray matter or hippocampal volumes. Sensitivity analyses identified associations between both biological and behavioral risk scores with white matter hyperintensity burden and vascular dementia, whereas some Alzheimer's dementia associations showed seemingly paradoxical relationships. Individuals who are genetically predisposed to developing CAD also face an increased risk of developing dementia in old age. This risk is reduced in those demonstrating healthy lifestyle profiles earlier in the lifespan, particularly in those who may be at an increased risk of developing dementia caused by an underlying vascular pathology.