The nonlinear relationship and threshold effects of vitamin D on immune function in healthy adults remain unclear. This cross-sectional study of 316 healthy adults (January 2022 to June 2023) investigated associations between serum 25-hydroxyvitamin D (25(OH)D) concentrations and peripheral blood immune parameters (CD3+ T lymphocytes, CD4+ T cells, CD19+ B cells, and natural killer [NK] cells) quantified by flow cytometry. Restricted cubic spline and piecewise regression models evaluated nonlinear relationships and inflection points. Compared to the low 25(OH)D group (<28.45 ng/mL), the high group (>28.45 ng/mL) had higher NK cell counts (306.00 vs 272.50, P < .01) and percentages (15.52% vs 14.21%, P < .01), but lower CD3+ T cell percentage (69.99% vs 73.20%, P < .01). Multivariate regression confirmed that 25(OH)D was negatively associated with CD3+ T cell percentage (β = -0.16, P < .001), and positively with NK cell count (β = 3.62, P = .002) and NK cell percentage (β = 0.16, P < .001). Restricted cubic spline analyses revealed significant threshold effects, with inflection points at 40.94 ng/mL for CD3+ T cell percentage (P = .003), 37.86 ng/mL for NK cell count (P = .005), and 40.94 ng/mL for NK cell percentage (P = .022). Subgroup analyses showed stronger correlations in males and individuals 40 to 59 years of age (P < .05). Our findings suggest that vitamin D may exert threshold-dependent dual immunomodulatory effects-enhancing innate immunity (NK cells) while suppressing adaptive immune activation (CD3+ T cells). Higher 25(OH)D concentrations (around 40 ng/mL) were associated with distinct immune profiles in this healthy cohort. These associations may provide preliminary insights for future studies, although causal relationships cannot be inferred from this cross-sectional design.

Blueberries and n - 3 polyunsaturated fatty acids each can provide protection against inflammation and cardiometabolic disorders. However, the underlying mechanisms are not fully understood. We hypothesized that blueberry and docosahexaenoic acid (DHA) can suppress high fat (HF) meal-induced postprandial inflammation and improve endothelial function. Sixty-two healthy participants (age: 26.8 ± 1.2 y; BMI: 22.1 ± 1.2 kg/m[2]) consumed an isoenergetic breakfast (850 kcal) containing 34.7 g mostly animal fat (36% kcal), 25.3 g protein, and 111 g carbohydrate, with or without either 42.2 g blueberry powder (BBP) or 1.76 g DHA in a randomized, double-blind, placebo-controlled crossover intervention study. Blood samples were collected before and 1 h, 3 h and 6 h after breakfast. Monocyte activation, proinflammatory gene expression, cytokine production and endothelial function were assessed. Compared with the placebo control, DHA supplementation suppressed the HF breakfast-induced: expression of IL-1β by 21.6% (P < .01) and prostaglandin-endoperoxide synthase 2 (PTGS2, i.e., cyclooxygenase 2) by 22.8% (P < .01) at 6 h; plasma IL-1β production by 40.1 to 49.8% (P < .01) at 1-6 h; lipoprotein lipase (LPL)-treated blood IL-1β production by 40.9% (P < .0001) at 6 h; and total cholesterol/HDL cholesterol ratio by 2.2% (P < .01) at 3 h and 3.5% (P < .0001) at 6 h. BBP supplementation suppressed LPL-treated blood IL-1β production by 23.1% (P < .05) at 6 h. BBP and DHA also induced postprandial increases in reactive hyperemia index (RHI) scores relative to the fasting baselines, with DHA producing a 13.3% increase compared with placebo at 6 h (P < .05). In conclusion, supplementation with BBP or DHA suppressed the HF meal-induced postprandial inflammation but only DHA improved postprandial endothelial function. This study was registered at clinicaltrails.gov (NCT02472171).

In the current study, we have investigated the association between dietary nitrate (NO3)/nitrite (NO2) intakes and the incidence of hypertension (HTN). This study included a total of 1576 men and women (mean age of 36.4 ± 11.7 and 39% men) in the third (2006-2008) phase of the Tehran Lipid and Glucose Study and were followed up until 2018-2022. At the beginning of the study, a semiquantitative food frequency questionnaire was applied to measure dietary intakes of NO3 and NO2. Multivariable-adjusted Cox proportional hazard models for multiple variables were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incidence of HTN across different quartiles of NO3 and NO2 dietary intakes. Median (interquartile range) daily intake of NO3 and NO2 were 465 (253) mg/d and 9.6 (4.8) mg/d, which were mostly derived from plant-based sources (95.4% and 55.8%, respectively). Participants in the highest quartile of total and plant-based NO3 intake were associated with a significantly lower risk of HTN (HRQ4 vs. Q1= 0.46; 95% CI, 0.23-0.91; HRQ4 vs. Q1=0.44; 95% CI, 0.22-0.87, in total and plant-based sources, respectively). No significant association was found between animal-based NO3 intake and HTN incidence. The highest quartile of plant-based NO2 intake, compared to the lowest, was associated with a lower risk of HTN (HRQ4 vs. Q1 = 0.57; 95% CI, 0.31-0.99) and there was no significant association between animal-based NO2 intake and the risk of HTN. Higher intakes of total and plant-based NO3 and NO2, compared with lower intakes, were significantly associated with a lower risk of HTN.

Disruption of circadian rhythms worsens glycemic control and cardiovascular health. Conversely, evidence suggests that optimizing circadian rhythms by eating earlier in the day, practicing intermittent fasting, and/or getting sufficient sunlight or bright light during the daytime improves cardiometabolic health. Here, we describe the protocol for a 2 × 2 randomized controlled trial testing whether two chronotherapies-early time-restricted eating (eTRE) and/or daytime bright light therapy (BLT)-can improve glycemic control, diurnal rhythms, and overall health in adults with type 2 diabetes (T2D). We will randomize 344 adults with insulin-independent T2D to 1 of 4 groups: (1) control, (2) eTRE, (3) daytime BLT, or (4) eTRE + daytime BLT. Participants in the eTRE groups will eat within an 8-hour window ending by 17:00, while those in the BLT group will receive bright light for 90 min/day before 15:00 and use blue-light-blocking glasses and blackout curtains at night. The intensive phase of the intervention is 16 weeks, with follow-up at the 1-year mark. The primary outcome is glycemic control as measured by HbA1c and 24-hour glucose, supplemented by additional assessments of glucose metabolism. Secondary outcomes are the diurnal melatonin and cortisol rhythms and the diurnal variation in glucose uptake. Tertiary outcomes include body mass, body composition, resting energy expenditure, cardiovascular risk factors, sleep parameters, quality of life, and psychological health. To our knowledge, this is the largest study to date of TRE in people with T2D and the largest study to test whether daytime bright light therapy can improve cardiometabolic health. Trial Registration: This trial was registered at clinicaltrials.gov (NCT04155619).

Most studies on vitamin E and immunity have focused on tocopherols, but the tocotrienol-rich fraction (TRF) from palm oil may exert stronger immunomodulatory effects. This study investigated the effect of various TRF doses on the immune response to influenza immunisation in healthy adults. We hypothesized daily supplementation with lower doses of TRF can boost immune response to the influenza vaccine in healthy Individuals. In a double-blind placebo-controlled trial, 150 participants (≥18 years) were randomised to receive placebo or TRF (50, 100, 200, or 400 mg) daily for 2 months, with vaccination on day 28. Blood samples collected on days 0, 28, and 56 were analyzed for humoral and cellular immunity, antioxidant status, and plasma concentrations of vitamin E. TRF significantly augmented anti-influenza antibody production across all doses, with the 400 mg group exhibiting the highest titers. A selective Th1-type immune response was observed, characterized by significant IFN-γ production upon restimulation in all TRF-supplemented groups compared with placebo. Plasma IL-12 was elevated in the highest dose, whereas the amount of EBI3 produced increased across a broader range of doses compared to placebo. TRF supplementation was associated with increased antioxidant enzyme activities and stable malondialdehyde activity. Elevated α-tocopherol concentrations observed, primarily at higher doses. Supplementation with TRF can enhance immune response to influenza immunisation by modulating humoral, Th1 responses and improving antioxidant status. Critically, antibody production increased similarly across all TRF doses, suggesting that lower doses may offer a cost-effective strategy for supporting humoral immunity, while higher doses provide broader immunomodulatory benefits.

Cardiometabolic diseases (CMDs) are a cluster of interconnected disorders encompassing both metabolic and cardiovascular diseases (CVDs). With their rising prevalence, these conditions represent a pressing global health challenge. Recent therapeutic strategies emphasize comprehensive approaches toward CMD management. Hydroxytyrosol (HT) is a prominent bioactive phenolic compound found in olives and olive oil. It demonstrates protective effects against metabolic syndrome, type 2 diabetes, and CVD by targeting multiple overlapping pathways involved in oxidative stress, inflammation, and lipid metabolism. As such, HT exhibits pleiotropic activity across the CMD spectrum, making it a promising dietary adjunct for managing these disorders. This review examines HT's ability to interrupt the progression of CMDs, from early metabolic dysfunction to atherosclerosis and advanced CVD complications, with a focus on the underlying molecular mechanisms. It also highlights current limitations and proposes future research directions to fully elucidate the effects of HT and its translational potential.

Vitamin D deficiency remains a major public health concern among adolescents, particularly in low- and middle-income countries. This study assessed vitamin D status and examined socioeconomic, dietary, and lifestyle factors associated with vitamin D deficiency among adolescent girls in India. A cross-sectional study was conducted among 1009 girls aged 11 to 18 years attending government schools. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured to determine vitamin D status, and information on dietary intake, socioeconomic characteristics, anthropometric indicators, clinical symptoms, and lifestyle factors was collected using standardized procedures. Vitamin D deficiency (<20 ng/mL) was identified in 50.0% of participants, while 37.9% were classified as insufficient (20-29 ng/mL), 11.0% as sufficient (30-100 ng/mL), and 1.1% as having concentrations above 100 ng/mL. A substantial proportion of participants reported dietary intakes below recommended levels for energy, protein, fat, calcium, and vitamin D. Multivariable logistic regression analyses indicated that lower socioeconomic status and inadequate dietary vitamin D intake were independently associated with an increased likelihood of vitamin D deficiency. Other dietary, clinical, and lifestyle factors showed weaker or nonsignificant associations after adjustment for potential confounders. These findings indicate that hypovitaminosis D is highly prevalent among adolescent girls in India and highlight the important contribution of modifiable dietary and socioeconomic factors to vitamin D status. Strategies aimed at improving dietary vitamin D intake and addressing nutritional inequalities may contribute to reducing the burden of vitamin D deficiency in this vulnerable population.

Adherence to the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet, which emphasizes fruit and vegetables and thereby carotenoid intake, is associated with better cognitive health in older adults. However, as neurodegeneration is thought to progress over decades, adopting such a dietary pattern in young adulthood may help prevent its initiation and progression. The aim of this study was to determine whether scores on the MIND diet screener predict skin carotenoid scores in college students, as a measure of construct validity. Participants completed a modified 14-item MIND diet screener and an item on weekly egg intake. Skin carotenoids were assessed using pressure-mediated reflective spectroscopy by Veggie Meter, and the data were analyzed using Pearson correlations. Participants (n = 293; 62.5% female; 20.0 ± 2.0 years) scored 8.3 ± 2.1 on the screener, indicating suboptimal adherence to the MIND dietary pattern, and skin carotenoid scores averaged 305 ± 90. MIND diet screener score predicted skin carotenoid score (r = 0.327; CI 0.220-0.425; P < .001), strengthened by adding the egg intake item (r = 0.353; CI 0.249-0.450; P < .001), and was highest in those consuming ≥7 eggs/wk (r = 0.50). Two dietary patterns emerged from clustering analysis, differentiated by intakes of leafy greens, other vegetables, berries, beans, and nuts. In conclusion, the MIND diet screener score predicts skin carotenoid content in young adults, supporting the tool's validity; however, frequent egg intake strongly moderated the relationship. Egg intake should be considered when interpreting skin carotenoid scores and included in future iterations of the MIND diet screener.

Imbalance of maternal diets can impair offspring development and contribute to congenital anomalies of the kidney and urinary tract (CAKUT). Excess maternal methionine intake is known to impair fetal development. The placenta serves as a crucial interface for maternal-fetal exchange and may contribute to these adverse outcomes. We hypothesize that excess methionine intake during pregnancy in mice increases the incidence of CAKUT in offspring. Therefore, we established a mouse model of 10% (w/w) methionine intake during pregnancy from Embryonic Day 8.5 to11.5 (E8.5-E11.5) and assessed the kidney phenotype. Crucial kidney developmental pathways were analyzed by RT-qPCR and immunofluorescence at E11.5. Changes in methionine metabolism in maternal plasma and placental tissues at E11.5 were analyzed using liquid chromatography-tandem mass spectrometry, and placental RNA-seq was performed. Offspring from dams exposed to excess methionine exhibited increased incidence of CAKUT (relative risk = 4.15, 95% confidence interval: 1.40-12.34, P = .010), primarily presenting as hydronephrosis and/or duplex collecting system. E11.5 embryonic kidneys showed shorter common nephric duct and decreased activity of the Gdnf/Ret/p-Akt pathway. At E11.5, homocysteine was elevated in the placentas, together with decreased mRNA expression of key metabolic enzymes betaine-homocysteine S-methyltransferase (Bhmt) and cystathionine γ-lyase (Cth) in the placentas. Concurrently, RNA-seq of E11.5 placentas revealed alterations in immune-inflammatory and vascular-related pathways. Overall, excessive maternal methionine intake in mice increased the incidence of CAKUT in offspring, which may be associated with altered activity of the Gdnf/Ret/PI3K/p-Akt pathway in embryonic kidneys as well as elevated placental homocysteine.

Bitter foods are linked to health benefits, but a comprehensive evaluation of dietary bitterness remains limited. This study quantified dietary bitterness and examined its relationship with nutritional quality. This secondary analysis of the 2011-12 National Nutrition and Physical Activity Survey (NNPAS) combined dietary data from 8975 Australian adults with an established sensory food database. The bitterness of foods consumed was calculated by multiplying the bitterness of each food by the grams consumed (bitterness intensity), then summing to estimate the total bitterness of an individual's diet. Tertiles of bitterness were created, and ANOVA with a Bonferroni post hoc test was used to compare individual characteristics and food and nutrient intakes between groups. We hypothesized that more bitter diets might exhibit a more favorable nutritional profile. Age was the strongest predictor of dietary bitterness (β = 0.26), with older adults consuming more bitter diets (P < .001). Compared to the least bitter diets, those with the most bitter diets had higher intakes of vegetables (+30%), fruits (+34%), wholegrain cereals (+36%), and low-fat dairy (+57.2%), and lower intake of refined cereal (-18.0%) P < .001. Beverages contributed more to dietary bitterness than solid foods (87% vs 13%; P < .001), particularly in the most bitter diets (94.6% vs 79.7%; P < .001). Higher intakes of tea/coffee (+285%) and milk (+6%), and lower soft drink (-16%) and juice (-10%) consumption characterized the most bitter diets (P < .001). Dietary bitterness may serve as an indicator of diet quality. Promoting bitter diets requires consideration of both individual characteristics and preferences for bitter foods and beverages.

Skin carotenoid score (SCS) as measured using pressure-mediated reflection spectroscopy has been validated among adults with normal and overweight body mass index, with little validation research among adults with obesity. Therefore, the purpose of this exploratory study was to examine the validity of SCS as an approximation of fruit and vegetable intake among adults with obesity. We used samples from adults with obesity from three prior studies: The first study examined the validity of SCS among 213 adults, 34 with obesity; the second, examined sensitivity of SCS to a β-carotene-rich juice intervention among 162 adults, 14 with obesity; the third examined changes in inflammatory markers in a 3-week lycopene-rich juice intervention, among 25 participants with obesity. Correlations between SCS and plasma carotenoids, and between SCS and self-reported FV and carotenoid intake were calculated using SAS 9.4. There was a positive association between SCS and plasma carotenoids (r = 0.30, P = .009), and between SCS and self-reported FV (r = 0.33, P = .004) and total carotenoid (r = 0.44, P < .001) intake in adults with obesity. In this small, secondary data analysis, the association between SCS and self-reported total FV intake among adults with obesity was similar to that among normal- and overweight adults in prior studies. The correlation between SCS and total plasma carotenoid concentrations among adults with obesity was weaker than that among normal- and overweight adults in prior studies. More work is needed to understand the associations between SCS and plasma carotenoid concentrations among adults with obesity.

Vitamin D is of vital importance for bone health and also regulates inflammatory cytokines. It is possible that physical activity could influence serum 25-hidroxyvitamin D concentrations (25(OH)D), and it has been suggested that exercise can increase serum 25(OH)D concentration. We hypothesized that regular exercise enables the body to absorb and use vitamin D more effectively, leading to lower concentrations of inflammatory cytokines. This is a cross-sectional population-based study, conducted with 712 adults aged 20 to 59 years living in the urban area of Viçosa, Minas Gerais, Brazil. Sociodemographic, anthropometric, behavioral and biochemical variables were collected. Multiple linear regression models (crude and adjusted) were used to determine associations between 25(OH)D concentration and inflammatory biomarkers. In the multiple linear regression models, it can be observed that for each unit increase in the concentration of 25(OH)D, there was an average decrease in the inflammatory biomarkers. Physical activity concentrations was considered an effect modifier of the association between serum 25(OH)D concentrations and some cytokines, and participants whose PAL was greater than 150 minutes tended to have lower concentrations of IL-6, IL-10, TNF-α and IL-12p70 when plasma 25(OH)D concentration was increased. In conclusion, higher 25(OH)D concentrations were associated with lower concentrations of inflammatory biomarkers in Brazilian adults. Furthermore, physical activity served as a significant effect modifier of this association, enhancing the reduction of pro-inflammatory cytokines.

This study investigated the inhibitory effects of a standardized Kaempferia parviflora ethanol extract (KPE) on muscle atrophy in high-fat diet (HFD)-induced obese mice. We hypothesized that KPE would ameliorate HFD-induced muscle atrophy in association with changes in muscle protein homeostasis and mitochondrial biogenesis. To test this, male C57BL/6J mice were fed an HFD for 6 weeks to induce obesity and skeletal muscle atrophy, followed by oral administration of KPE (100 or 200 mg/kg/d) for 8 weeks. KPE significantly attenuated HFD-induced muscle atrophy by increasing muscle mass, muscle strength, and exercise capacity. In the gastrocnemius muscle, KPE reduced the expression of pro-inflammatory cytokine genes and suppressed muscle protein degradation by inhibiting the expression of E3 ubiquitin ligases and autophagy-related genes. In addition, KPE enhanced mitochondrial biogenesis-related gene expression and muscle protein synthesis, accompanied by modulation of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway. These findings suggest that KPE alleviates muscle atrophy in HFD-induced C57BL/6J obese mice by inhibiting pro-inflammatory cytokines and muscle protein degradation while stimulating mitochondrial biogenesis and muscle protein synthesis.

Nutrition transition in sub-Saharan Africa (SSA) is accompanied by significant changes in dietary intakes. This systematic review reported data-driven dietary patterns (DPs) and their associations with health outcomes and sociodemographic factors among adults in SSA. Observational studies published between January 1990 and December 2024 were retrieved from Web of Science, EMBASE, PubMed, Google Scholar, African Journals Online, Semantic Scholar, and African Index Medicus, between January 29 and 31, 2025. Non-English articles and studies exclusively including diet-modified adults were excluded. Quality of studies was assessed using the NHLBI quality assessment tool. Narrative synthesis of findings from 24 studies out of 2630 retrieved was conducted. Two broad themes of DPs emerged: food group-based (carbohydrate, proteins, fruits/vegetables, assorted foods and snacks/beverages-based patterns) and context-based (traditional, Western, healthy, and transitional-based patterns). Healthy, fruit- and vegetable-based DPs were inversely associated with obesity, hypertension, and diabetes, whereas Western, snack/beverage-, carbohydrate-, fat-, and protein-based patterns were associated with chronic disease outcomes. Traditional DPs were also linked to obesity. Women, younger adults, urban residents, and individuals with higher education showed greater adherence to Western DPs, whereas rural and lower socioeconomic groups adhered more to traditional DPs. The coexistence of traditional and Western DPs, alongside the predominance of individual food groups, highlights an ongoing nutrition transition, increasing vulnerability to noncommunicable diseases in SSA. Underrepresentation of some subregions and countries in the available evidence may limit the generalizability and policy relevance of these findings across SSA. There is, therefore, a need to scale up research on data-driven DPs to inform region-specific nutrition policies and promote healthier dietary intake across SSA.