Background: The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D₃ (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study. Objective: To investigate the effects of vitamin D₃ and/or n-3 FAs on changes in systemic inflammatory biomarkers including pro- and anti-inflammatory cytokines over a 4-year period in the VITAL sub-cohort with in-person evaluations at the Center for Clinical Investigations (CCI) in Boston. Design: Serum levels of four inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, interleukin-10, and tumor necrosis factor-α) were measured in a total of 2713 samples from those 1054 VITAL/CCI participants (aged 64.9 ± 6.5 years, 49% female, 84% white, and 9% black) at baseline, year 2, and year 4 follow-up visits. Results: In multiple-adjusted models, vitamin D₃ supplementation decreased serum hs-CRP levels by 19% at 2-year follow-up (nominal p = 0.007; p-value after multiple comparison adjustment = 0.028), but not at 4-year follow-up (nominal and adjusted p-values > 0.05). The effects of vitamin D₃ on other inflammatory markers were not statistically significant either at year 2 or year 4 (all adjusted p-values > 0.05). Marine n-3 FAs were not significantly associated with changes of all the above inflammatory markers either at years 2 and 4, after multiple comparison adjustment (all p-values > 0.05). Conclusions: Vitamin D₃ supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, but not other inflammatory biomarkers at year 2 or year 4, while n-3 FAs with or without vitamin D₃ did not significantly affect these biomarkers at either time point. Our findings support a potential role of vitamin D supplementation in modulating the chronic inflammatory process, systemic inflammation, and possibly autoimmune disease progression.

Sphingolipid metabolism plays a critical role in cell growth regulation, lipid regulation, neurodevelopment, type 2 diabetes, and cancer. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation. In this study, we tested the hypothesis that vitamin D supplementation would alter circulating long-chain ceramides and related metabolites involved in sphingolipid metabolism in humans. We carried out a post-hoc analysis of a previously conducted randomized, placebo-controlled clinical trial in 70 overweight/obese African-Americans, who were randomly assigned into four groups of 600, 2000, 4000 IU/day of vitamin D₃ supplements or placebo for 16 weeks. The metabolites were measured in 64 subjects (aged 26.0 ± 9.4 years, 17% male). Serum levels of N-stearoyl-sphingosine (d18:1/18:0) (C18Cer) and stearoyl sphingomyelin (d18:1/18:0) (C18SM) were significantly increased after vitamin D₃ supplementation (ps < 0.05) in a dose–response fashion. The effects of 600, 2000, and 4000 IU/day vitamin D₃ supplementation on C18Cer were 0.44 (p = 0.049), 0.52 (p = 0.016), and 0.58 (p = 0.008), respectively. The effects of three dosages on C18SM were 0.30 (p = 0.222), 0.61 (p = 0.009), and 0.68 (p = 0.004), respectively. This was accompanied by the significant correlations between serum 25-hydroxyvitamin D₃ [25(OH)D] concentration and those two metabolites (ps < 0.05). Vitamin D₃ supplementations increase serum levels of C18Cer and C18SM in a dose–response fashion among overweight/obese African Americans.

Background: Adult studies have suggested that magnesium intake may regulate C-reactive protein (CRP) and muscle mass, known risk factors for cardiometabolic diseases. Given the large deficiencies in magnesium intake in adolescents, we aimed to investigate sex and race differences in dietary magnesium intake and test the hypothesis that lower magnesium intake is associated with higher CRP and lower muscle mass. Methods: A total of 766 black and white adolescents, 14 to 18 years old (51% black; 50% female) were previously recruited. Diet was assessed with four to seven independent 24-h recalls. Body composition was measured by dual-energy X-ray absorptiometry. High-sensitivity CRP (hs-CRP), leptin, resistin, and adiponectin were measured using fasting blood samples by ELISA. Results: There were sex and race differences in the daily consumption of magnesium. The average daily magnesium intakes were 200.66 ± 7.09 mg and 205.03 ± 7.05 mg for males and females, respectively, far below the recommended amounts of 410 mg for males and 360 mg for females. White subjects (217.95 ± 6.81 mg/day) consumed more than black subjects (187.75 ± 6.92 mg/day). Almost none of the adolescents met the recommendations. Adjusted multiple linear regressions revealed that lower magnesium intake was associated with higher hs-CRP and lower fat-free mass (FFM) (p-values < 0.05). Higher hs-CRP was associated with lower FFM. Moreover, an interaction between magnesium intake and hs-CRP on FFM was identified (p-value < 0.05). Lower magnesium intake amplified the inverse relationships between hs-CRP and FFM (p-values < 0.05). Conclusion: Magnesium consumption in our adolescents was far below daily recommended levels with male and black subjects consuming less than female and white subjects. Lower magnesium intake was associated with higher CRP and lower muscle mass. Low magnesium intake may also augment the inverse relationship between CRP and FFM.

Blood pressure variability (BPV) is linked to cardiovascular disease (CVD) and systemic inflammation in adults, but its relevance in young, healthy populations remains unclear. This study examined the association between short-term BPV and inflammatory markers in 447 normotensive participants (mean age, 22.9 years) from the Georgia Stress and Heart (GSH) study, a cohort of Non-Hispanic Black and White individuals. Participants underwent 24 h ambulatory blood pressure monitoring and assessment of serum inflammatory markers, including hs-CRP, IFN-γ, IL-6, and TNF-α. BPV was quantified using average real variability (ARV), and generalized estimating equations (GEEs) were used to evaluate associations, adjusting for age, sex, race, and mean blood pressure. Diastolic BPV was significantly, positively associated with hs-CRP and TNF-α, whereas systolic BPV was not associated with any inflammatory marker. Specifically, 24 h diastolic BPV was positively associated with hs-CRP (p = 0.001) and TNF-α (p = 0.015), while daytime diastolic BPV was positively associated with hs-CRP (p = 0.002). Nighttime diastolic BPV was positively associated with both hs-CRP (p = 0.020) and TNF-α (p = 0.007). No significant associations were found between BPV and IL-6 or IFN-γ. These findings suggest diastolic BPV may be a marker of low-grade inflammation in healthy young adults and could represent an early cardiovascular risk factor that warrants longitudinal study.

Cognitive–motor integration is the coordination of cognitive and motor processes; it is commonly impaired among people living with dementia (PWD) and may be improved through exercise. This pilot randomized controlled trial (1:1) aimed to determine the effect of 6 months of exercise on cognitive–motor integration compared to usual care in n = 42 PWD at two residential care facilities. Participants completed single- and dual-task standing (30 s of standing while counting backward by 1 s), walking (4 m walk while naming words), and timed-up-and-go (TUG) tests (TUG with a category task), measured using APDM inertial sensors at baseline and 6 months (age = 82 years, 35% female, Montreal Cognitive Assessment = 10.2 ± 5.9, NCT05488951). The adapted Otago Exercise Program involved 60 min of lower-body strength and balance exercises and walking 3x/week for 6 months. Usual care involved regular social activities and healthcare appointments. Exercise provoked increased single-task stride length and increased dual-task TUG turn velocity compared to usual care (p < 0.05). Usual care may reduce the ability to appropriately select cautious gait, as the usual care group exhibited faster dual-task gait speed at 6 months compared to the OEP plus usual care (p < 0.05), which was faster than their single-task gait speed. Our results support implementing the OEP to improve cognitive–motor integration in PWD.