Search Results (237)

Background/Objectives: Childhood and adolescence are critical periods for bone mineral accrual and future skeletal reserve. Milk intake, sun exposure and caffeinated energy drink consumption are familiar lifestyle concepts, but they differ substantially in biological proximity and evidential strength. This structured narrative review critically evaluates these exposures in relation to peak bone mass accrual in youth. Methods: PubMed/MEDLINE, Scopus, Web of Science, the Cochrane Library and Google Scholar were searched from database inception to 23 June 2026. Search terms combined pediatric population terms with bone outcomes and exposure terms related to milk/dairy, calcium, vitamin D, sun exposure, physical activity, sleep, caffeine and energy drinks. A literature collection flowchart and a GRADE-informed evidence appraisal table are provided to improve transparency and clinical interpretability. Results: Evidence is strongest for adequate calcium intake, calcium-rich foods and weight-bearing physical activity as modifiable contributors to skeletal accrual. Vitamin D is essential for mineral homeostasis, but supplementation effects on bone density in otherwise healthy children are context-dependent and appear most relevant for deficiency prevention or treatment. Milk intake is best interpreted as a practical marker of calcium-rich dietary patterns rather than as the only route to calcium adequacy. Sun exposure is an indirect determinant of vitamin D status and is modified by season, latitude, skin pigmentation, clothing, sunscreen, adiposity and outdoor behavior. Direct evidence linking caffeinated energy drinks to impaired pediatric bone accrual is very limited. The relevance of caffeinated energy drink intake is better framed as indirect and hypothesis-generating, through possible displacement of calcium-rich beverages, sleep disruption and clustering with poorer lifestyle patterns. Conclusions: A prevention framework for pediatric bone health should emphasize calcium adequacy, avoidance of vitamin D deficiency, mechanical loading and correct pediatric DXA interpretation using Z-scores. Energy drinks can be included as a lifestyle concern, but conclusions should remain cautious because direct skeletal evidence is limited. Full article

Background: Data on the nutritional adequacy of unsupplemented vegetarians in Northeast China are limited. Methods: We compared dietary intake, body composition, and serum biomarkers among vegans, lacto-ovo-vegetarians, and omnivores. This cross-sectional study included 356 adults (all diet ≥ 2 years, no supplements). Dietary intake was assessed using a validated semi-quantitative FFQ, body composition by BIA, and serum biomarkers. Kruskal–Wallis tests with Bonferroni correction were used. Results: Vegans had lower BMI (22.0 vs. 24.6 kg/m²), body fat (24.5% vs. 28.0%), and visceral fat (0.65 vs. 1.05 L) than omnivores (all p < 0.002). Vegans consumed more fiber (38.5 vs. 18.0 g/d) and vitamin C (180 vs. 85 mg/d), but less vitamin B₁₂ (0.3 vs. 4.2 μg/d), vitamin D (0.5 vs. 3.2 μg/d), calcium (520 vs. 720 mg/d), iodine (65 vs. 130 μg/d), and selenium (45 vs. 85 μg/d). Serum vitamin B₁₂, 25-(OH)D, ferritin, and selenium were significantly lower in vegans, while homocysteine was higher. The proportion of vegans with dietary intake below the recommendation reached 100% for vitamin B₁₂ and 97% for vitamin D, whereas omnivores showed excessive sodium (75%) and SFA (70%) intake. Conclusions: In this Northeast China cohort, unsupplemented vegetarian diets offered favorable macronutrient profiles and body composition but were associated with a high prevalence of dietary intakes below recommendations for vitamin B₁₂, vitamin D, iodine, selenium, zinc, and calcium. These findings underscore the need for targeted supplementation and food fortification strategies for individuals adhering to plant-based diets without supplement use in this region. Full article

Background/Objectives: Hypocalcemia is a major transition-cow disorder in dairy cattle, with clinical and subclinical forms differing in detectability, severity, timing, and herd-level consequences. This systematic review integrates evidence on calcium (Ca) homeostasis, classification of clinical hypocalcemia (CHC) and subclinical hypocalcemia (SCH), diagnostic interpretation, risk factors, systemic effects, and preventive and therapeutic strategies in dairy cows. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, PubMed, ScienceDirect, SpringerLink, and CAB Abstracts were searched in February 2026 for 1994–2025 publications, and 23 reports were included in a qualitative synthesis; meta-analysis was not performed because of methodological and outcome heterogeneity. Results: The evidence indicates that hypocalcemia should be interpreted as a failure of homeorhetic adaptation to abrupt mammary Ca export rather than as a simple mineral deficiency. The parathyroid hormone–vitamin D axis, skeletal Ca mobilization, renal Ca conservation, intestinal Ca absorption, magnesium (Mg) status, dietary cation–anion difference (DCAD), dry matter intake, parity, and acid–base balance jointly determine whether blood Ca is maintained during early lactation. Total calcium (tCa) thresholds are useful decision aids for herd-level monitoring, but their interpretation depends on sampling time, parity, persistence pattern, clinical signs, and the relationship between tCa and ionized calcium (iCa). Subclinical hypocalcemia is most relevant when it is delayed, persistent, or occurs in high-risk cows because reduced Ca availability can impair smooth muscle function, feed intake, immune competence, uterine health, and metabolic resilience. Management should therefore combine prepartum ration control, Mg adequacy, DCAD and urine pH monitoring, selective Ca testing in high-risk cows, targeted oral Ca supplementation for standing cows, and intravenous Ca treatment for recumbent CHC cases. Conclusions: The evidence supports a risk-based, context-aware strategy rather than universal threshold-driven treatment. Full article

Coeliac disease is a chronic autoimmune enteropathy triggered by gluten consumption in genetically predisposed individuals. Given that lifelong adherence to a gluten-free diet (GFD) is the only effective treatment, the nutritional quality of commercially available gluten-free (GF) products is of particular importance. The aim of this study was to determine the nutritional content of selected GF products across multiple food categories available in the Greek market and compare them with their gluten-containing (GC) counterparts. In addition, the nutritional adequacy of a GFD for adults was assessed through an indicative 7-day dietary meal plan. A total of 228 food products (114 GF and 114 GC), categorized as charcuterie, starchy, bakery, confectionery, miscellaneous, meat-based, and plant-based, were included. Analysis of food label information revealed broadly comparable nutritional profiles with respect to energy, fat, saturated fat, carbohydrate, sugar, and sodium between GF and GC products. However, GF products contained less protein (7.31 ± 4.94 g vs. 9.86 ± 4.79 g, p < 0.001) and more dietary fibre (4.55 ± 3.05 g vs. 3.23 ± 2.21 g, p = 0.001). Analysis of the meal plan demonstrated that recommended intakes for all evaluated macronutrients and most micronutrients can be achieved while following a GFD with careful dietary planning. However, iron intake fell slightly below the recommended level for premenopausal women, while meeting vitamin D requirements remained challenging. Full article

Background/Objectives: Vitamin D deficiency is a global health concern, yet circulating 25-hydroxyvitamin D (25OHD) concentrations vary substantially across geographical regions and ancestral groups. Genetic predisposition may contribute to these differences. This systematic review aimed to synthesize evidence from genome-wide association studies (GWAS) on genetic variation associated with circulating 25OHD across populations from different ancestral backgrounds and to evaluate linkage disequilibrium (LD) between reported variants. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and the GWAS Catalog were searched to identify genome-wide association studies (GWAS) on circulating 25-hydroxyvitamin D (25OHD) concentrations. Studies were screened against predefined eligibility criteria, and data were extracted using a standardized framework. Methodological quality was assessed using a standardized tool, and study power adequacy was assessed formally. Genome-wide significant SNPs were extracted, and unique variants between studies were grouped by ancestry. Among these, dbSNP-indexed variants were grouped into genomic cluster windows and evaluated for LD structure. Results: Fifteen GWAS were included. Across these studies, 349 genome-wide significant SNP associations were identified, corresponding to 294 unique variants, of which 283 were indexed in dbSNP and retained for genomic and LD analyses. Variant discovery was dominated by large-scale European-ancestry studies, although African, Middle Eastern, East Asian, Hispanic/Latino, South Asian, and trans-ethnic studies also contributed signals. Some evidence of ancestry-specific variation was apparent, yet not conclusive due to lower study power in non-European cohorts. Variant aggregation was strongest at biologically relevant vitamin D loci, including GC, CYP2R1, DHCR7/NADSYN1, and FLG. Fifteen variants were replicated in at least two independent cohorts. LD-based clustering identified several high LD groups comprising variants identified across studies, with the strongest LD appearing between variants within established vitamin D-related loci, particularly GC, CYP2R1, DHCR7/NADSYN1, and FLG. Conclusions: Circulating 25OHD appears to be influenced by shared core loci involved in vitamin D metabolism, across ancestries. Although some evidence of ancestry-specific variation was identified, findings should be interpreted with caution, in light of the predominance of European-ancestry GWAS and scarcity of sufficiently powered GWAS for other ancestral populations. Larger GWAS in non-European populations are essential for improving ancestry-specific variant discovery and interpretation. Full article

Background and Objectives: Vitamin D deficiency is a pervasive public health issue in high-latitude regions, yet large-scale population data for the Baltic states remain sparse. This study aimed to determine the prevalence of vitamin D status and identify its primary determinants within a primary care setting in Lithuania. Materials and Methods: We conducted a retrospective cross-sectional analysis of serum 25-hydroxyvitamin D [25(OH)D] concentrations from 14,330 unique patients (aged 1–101 years) collected during 2025 at a major clinic in Vilnius. Vitamin D status was categorized according to the Central and Eastern European Expert Consensus thresholds. Results: The overall median 25(OH)D concentration was 68.3 nmol/L, placing it in the “insufficiency” range (50–75 nmol/L). Seasonality emerged as the most significant predictor of deficiency; multivariable logistic regression showed a maximal risk reduction in September (OR 0.33; 95% CI: 0.27–0.41) and August (OR 0.34) compared to January, while June and November provided no significant protection. Age-specific analysis revealed a non-linear “U-shaped” distribution: children aged 0–6 years had the highest levels (median ~87–91 nmol/L), likely due to rickets prophylaxis, whereas adolescents (12–18 years) exhibited the highest vulnerability, with approximately 80% suffering from deficiency or insufficiency. Males faced a 13.9% higher likelihood of deficiency than females (OR 1.14; p = 0.0036), potentially due to lower rates of elective supplementation. Conclusions: These findings suggest that current supplementation strategies successfully protect infants but fail to sustain adequacy through adolescence and adulthood, particularly during the “vitamin D winter.” Targeted public health interventions for adolescents and year-round monitoring are recommended to mitigate the high prevalence of suboptimal vitamin D status in Lithuania. Full article

Background/Objectives: Adequate micronutrient intake during pregnancy is critical for fetal development, yet whether pregnant women and healthcare professionals share consistent knowledge, beliefs, and supplementation practices remains poorly characterized. Methods: Two parallel cross-sectional surveys using identical core items were conducted at a German tertiary care center between April and November 2024. Pregnant women (n = 132) and healthcare professionals who initiated the survey (n = 105) completed anonymous QR-code-based questionnaires assessing micronutrient-related knowledge, perceived dietary adequacy, and supplementation practices or recommendation patterns. Comparative analyses were restricted to fully completed healthcare professional questionnaires (n = 80). Group differences were analyzed using chi-square or Fisher’s exact tests. Results: Healthcare professionals demonstrated higher knowledge levels across most micronutrients. Knowledge gaps were most pronounced for vitamin B12, with 53.0% of pregnant women unable to identify any fetal effect compared with 20.0% of providers (p < 0.001). Beliefs about dietary sufficiency were broadly aligned for folic acid (p = 0.452) and vitamin D (p > 0.999), but diverged markedly for vitamin B12, where 79.2% of providers considered dietary intake alone adequate compared with 47.3% of pregnant women (p < 0.001). Substantial differences were observed between patient-reported supplementation practices and provider-reported recommendation patterns: Vitamin B12 (70.0% vs. 3.8%), vitamin D (76.2% vs. 41.3%), omega-3 fatty acids (76.2% vs. 47.5%), and folic acid (98.5% vs. 81.3%; all p < 0.001). The internet was the most frequently cited information source among pregnant women (89.4%), while healthcare professionals reported using both scientific literature (75.0%) and internet-based resources (76.3%), the latter primarily for accessing professional and scientific information. Conclusions: Substantial patient–provider differences in micronutrient knowledge, beliefs, and supplementation practices persist even within a highly educated population at a tertiary care center. These findings suggest potential differences between patient-reported supplementation behavior and provider-reported recommendation practices, particularly for vitamin B12 and vitamin D. These findings suggest that more structured communication regarding micronutrient supplementation during pregnancy is needed. Full article

Background: Adequate nutrition during young adulthood is essential for health promotion, optimal physiological function, and the prevention of non-communicable diseases. However, evidence describing both nutrient adequacy and compliance with dietary recommendations in well-characterized samples of young adults remains limited. Therefore, the aim of the present study was to describe macronutrient and micronutrient adequacy and to quantify compliance with current dietary recommendations in young adults using an individualized energy-adjusted nutrient adequacy approach (NARm), and to explore sex differences to identify priority targets to inform tailored health promotion and public health nutrition strategies. Methods: This cross-sectional study included 74 young adults aged 18–45 years participating in the NutAF project. Dietary intake was assessed using a 5-day dietary record, including three weekdays and two weekend days. Modified nutrient adequacy ratios (NARm), adjusted according to individualized total daily energy expenditure, were calculated for macronutrients and micronutrients. The prevalence of compliance with current dietary recommendations was also determined. Differences between men and women were analyzed using independent samples t-tests. Results: Protein and total lipid intake levels exceeded recommended values in most participants, whereas carbohydrate adequacy was below recommendations. Regarding micronutrients, adequate intake was observed for several nutrients; however, low adequacy and low compliance rates were identified for calcium, folate, vitamin D, and omega-3 and omega-6 polyunsaturated fatty acids. No participants met the recommendations for vitamin D. No significant sex differences were observed for most nutrients. Conclusions: Despite intake levels above recommendations for some macronutrients, young adults included in this study exhibited inadequate intake and low compliance with current dietary recommendations for several key nutrients. No relevant sex differences were observed for most nutrients. These findings, obtained using an individualized energy-adjusted nutrient adequacy approach (NARm), underscore the need for targeted nutritional strategies, including nutrition education and micronutrient-focused interventions, aimed at improving dietary adequacy and supporting health promotion in this population. Full article

Background: An early menopause (by definition, menopause that occurs at a woman’s age 40 through 45) is often associated with certain changes in the body that can result in risks for health-related conditions, an extended period later. Thus, scientists have begun examining how vitamin D has been suggested to be associated with endocrine function regulating both hormones and reproductive function during this time. However, it is not yet clear as to whether or not vitamin D provides any benefit to women who have experienced an early menopause. Material and Methods: The data was collected from 272 women in this retrospective, observational study at The County Hospital, Department of Obstetrics and Gynecology, Arad. The method of grouping the sample included two stratifications into early and physiological menopause categories based on amenorrhoea for a minimum of 12 consecutive months. 25-hydroxyvitamin D (25(OH)D) levels were classified into three categories: deficiency (<20 ng/mL), insufficiency (21–29 ng/mL), or adequacy (≥30 ng/mL). Estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) hormone parameters were measured using standard immunoassays. The analysis employed correlation and regression to evaluate potential relationships between 25(OH)D levels and hormone parameters. Results: A significant proportion of the study group had a vitamin D deficiency. This was supported by the fact that only 24.27% of women were identified as having adequate levels of vitamin D, while the rest (62.03%) did not. Women in the early menopause group had a statistically significant negative relationship between estradiol and FSH (i.e., r = −0.29, p = 0.0016), as well as between progesterone and LH (i.e., r = −0.207, p = 0.026). There was not a statistically significant relationship between total sample vitamin D and estradiol (i.e., r = −0.038, p = 0.686) nor between vitamin D and progesterone (i.e., r = 0.031, p = 0.744). Women with vitamin D blood levels of 30 ng/mL or more showed a strong negative relationship between vitamin D and estradiol (r = −0.780; p = 0.0016) and a moderate positive relationship with progesterone (r = 0.534; p = 0.0104). However, these relationships were inconsistent in other groups. All group comparative analyses showed that women in the early menopause group had much lower estradiol levels than those in the physiological menopause group, regardless of whether they were classified based on their vitamin D levels (p < 0.0001). Conclusions: Women experiencing early or physiological menopause are at risk of having low vitamin D levels. However, our study results do not show a consistent relationship between serum 25(OH)D concentrations and serum estradiol or progesterone concentrations among the study population, suggesting that vitamin D is not a major factor influencing hormonal changes during menopause. These findings were inconsistent across analyses and should be interpreted cautiously. Overall, the results do not support a significant association between serum 25(OH)D concentrations and reproductive hormone levels in our study population. Full article

Background/Objectives: Adolescence is a critical life stage characterized by rapid growth, increased nutrient requirements, and the establishment of long-term healthy behaviors. Growing evidence suggests that nutritional inadequacies may persist even when conventional indicators such as body mass index (BMI) appear normal, reflecting hidden malnutrition, a condition characterized by micronutrient inadequacy despite adequate energy intake. This issue may be particularly relevant in structurally constrained environments. This study aimed to compare dietary intake and nutrient adequacy between adolescents residing in residential care institutions (RCIs) and those in the general population in Taiwan. Methods: A total of 248 adolescents were included in the analysis. Institutional data were collected in 2018 and compared with nationally representative data from the Nutrition and Health Survey in Taiwan (NAHSIT 2010–2012). To improve comparability, 1:1 propensity score matching (PSM) was applied based on age, sex, and geographic region. Nutrient intakes were evaluated according to the Taiwan Dietary Reference Intakes (DRIs). Results: Adolescents in RCIs demonstrated significantly lower energy and protein adequacy than their counterparts in the general population. Among boys aged 13–15 years, the proportion meeting protein adequacy was substantially lower in RCIs than in the general population (34.0% vs. 84.0%). Similarly, among girls aged 13–15 years, energy adequacy was markedly lower in RCIs (25.0% vs. 63.9%). In addition, inadequate intake of multiple micronutrients, particularly B vitamins and essential minerals, was observed. Despite these differences, BMI remained largely comparable between groups, indicating a mismatch between anthropometric status and underlying nutritional quality. Conclusions: These findings suggest that hidden nutritional vulnerability may persist even within structured institutional environments designed to ensure stable food provision. The results highlight the limitations of relying solely on anthropometric indicators to assess nutritional status and underscore the need for targeted nutritional strategies to improve dietary quality and reduce health inequalities in residential care settings. Full article

Background/Objectives: Healthy longevity depends on not only lifespan but also the maintenance of physiological, metabolic, physical, and cognitive functions throughout aging. Identifying early determinants of health is crucial for preventing age-related decline. This narrative review aims to synthesize current evidence on how diet and specific nutrients relate to these early risk factors and indicators of healthy longevity. Methods: A review was performed to identify the links between dietary factors, energy balance, and gut microbiota composition and normal body weight; blood cholesterol, pressure, and glucose; healthy sleep; an active lifestyle; and normal physical function and cognitive performance. Particular attention was given to Mediterranean and other plant-based dietary models as sources of key nutrients. Evidence from observational studies, randomized controlled trials, and meta-analyses was considered. Results: Across all markers, dietary quality and nutrient adequacy emerged as consistent determinants of health outcomes. Key nutrients were associated with favorable cardiometabolic, cognitive, and musculoskeletal functions, such as omega-3 fatty acids, fiber, vitamins D and B, minerals like magnesium and potassium, and polyphenols. Common nutrition gaps included insufficient intake of fiber, unsaturated fats, and micronutrients, which was often linked to a shift toward less plant-based diets. Gut microbiota diversity may mediate several of these associations, influencing metabolism, inflammation, sleep quality, and cognitive performance, although inter-individual variability and causal pathways remain incompletely understood. Conclusions: An integrated dietary approach emphasizing the consumption of whole and plant-rich foods, with moderate amounts of animal foods, supports multiple early markers, risk factors, and indicators of healthy longevity. The modulation of the gut microbiota through plant-based diets and fermented foods represents a promising strategy for maintaining health across aging trajectories. Full article

Traditional food systems have historically sustained nutrient adequacy under conditions of environmental variability and limited food diversity, yet their underlying nutritional mechanisms remain insufficiently integrated into contemporary nutrition science. This article attempts to provide a conceptual synthesis of how traditional dietary practices may function as informal nutrient optimization strategies. Drawing on evidence from nutrition science, food chemistry, and human physiology, it examines how food processing techniques (e.g., fermentation, soaking, germination, and thermal treatment), food pairing, and structural properties of foods influence nutrient bioavailability, absorption, and metabolic responses. Across diverse dietary contexts—including Mediterranean, agrarian cereal–legume, and East Asian-type patterns—recurring mechanisms emerge that can boost mineral solubility, improve protein digestibility and amino acid balance, facilitate vitamin absorption, and modulate glycemic responses. These effects are mediated not only by nutrient content but by interactions within the food structure and at the meal level. The synthesis supports a reframing of traditional diets as functional nutritional architectures in which processing and dietary configuration may enhance nutrient utilization efficiency. From this perspective, nutrient adequacy arises from coordinated structural features rather than from maximal nutrient density alone. The findings can be influential in contemporary nutrition research and policy, highlighting the need to move beyond reductionist intake-based models toward integrated approaches that account for bioavailability, metabolic handling, and dietary context. Several transferable principles of nutrient optimization are proposed, offering a framework for designing nutritionally efficient and resilient diets in modern settings. Full article

Muscle vulnerability occurs at both extremes of the human lifespan, although its biological significance differs substantially between developmental growth and late-life decline. During childhood and adolescence, insufficient muscle accretion reflects disruption of physiological anabolic trajectories driven by inadequate energy availability, inflammatory burden, endocrine imbalance, or disease-associated catabolism. In older adults, muscle deterioration is characterized by anabolic resistance, neuromuscular remodeling, chronic low-grade inflammation, and hormonal decline, culminating in sarcopenia and loss of functional independence. The absence of harmonized diagnostic frameworks across age groups limits direct translational extrapolation. A lifespan-informed perspective distinguishing growth-supportive from function-preserving nutritional approaches is, therefore, required. This narrative review examines how major classes of nutritional bioactive interact with molecular pathways regulating skeletal muscle homeostasis in fragile populations across the lifespan. The analysis encompasses energy adequacy, protein quantity and quality, amino acid-dependent anabolic signaling, vitamin D status, lipid-derived mediators, redox-modulating phytochemicals, and micronutrients supporting mitochondrial bioenergetics. In pediatric contexts, nutritional interventions primarily aim to restore anabolic permissiveness within a structurally intact growth environment. In aging individuals, strategies focus on mitigating anabolic resistance through optimized protein intake, correction of micronutrient insufficiencies, and integration with resistance exercise to preserve functional capacity. This narrative review emphasizes the need to distinguish mechanistic rationale from clinically validated interventions, as improvements in molecular pathways do not consistently translate into meaningful functional outcomes. Full article

Background/Objectives: Micronutrient malnutrition, particularly deficiencies in calcium, vitamin D, iron, zinc, and iodine, remains a significant public health issue among school-aged children in Morocco. Processed cheese, such as “The Laughing Cow” (TLC), has potential as a vehicle for fortification due to its widespread consumption and accessibility. This study aimed to evaluate the impact of fortified TLC on micronutrient intake and adequacy relative to the Recommended Dietary Allowances (RDA), among Moroccan children aged 6–12 years, and to explore differences in effects by socioeconomic status (SES). Methods: Data from the Moroccan Household Budget Survey (2013–2014) included 9266 children (39.4% TLC consumers). Dietary intake was assessed using 24 h recalls, and nutrient composition was analyzed using Ciqual 2020 tables and specialized software. Fortification scenarios were modelled to estimate potential impacts on micronutrient intake and compliance with RDAs. Results: Under the modelling scenarios, consumption of one portion/day of fortified TLC significantly improved RDAs compliance for iron, iodine, and zinc (p < 0.05). There was also an increase in RDA compliance for calcium and vitamin D, but differences were not significant. The impact of fortification on micronutrient intake and RDA compliance increased with socioeconomic status. Consumers of more than one portion/day showed the highest compliance with RDAs (p < 0.001). Fortification effects were consistent across age subgroups. Conclusions: Fortifying processed cheese represents a feasible strategy to address micronutrient deficiencies among Moroccan schoolchildren. This study highlights the potential of targeted fortification programmes to improve public health outcomes, particularly in vulnerable populations. Further research is needed to optimize fortification approaches and ensure sustainability. Full article

Background/Objectives: Metformin has been proposed as a potential treatment for hyperprolactinemia irrespective of etiology. Previous studies suggest that vitamin D deficiency attenuates the prolactin-lowering effect of metformin in women. This study examined whether vitamin D status modifies the effects of this agent on prolactin and other anterior pituitary hormones in men with iatrogenic hyperprolactinemia. Methods: Seventy-five adult men with antipsychotic-induced hyperprolactinemia and type 2 diabetes or prediabetes were enrolled. Participants were assigned to three equal groups based on vitamin D status and supplementation: vitamin D-naive men with sufficient levels (group 1), vitamin D-naive men with deficiency (group 2), and men with sufficient vitamin D levels receiving oral supplementation for at least six months (group 3). All participants received metformin (3 g/day) for six months. Plasma 25-hydroxyvitamin D, markers of glucose metabolism, total and monomeric prolactin, TSH, gonadotropins, ACTH, testosterone, and IGF-1 were measured at baseline and after treatment. Results: Baseline characteristics were comparable among groups except for 25-hydroxyvitamin D levels. Seventy participants completed the study. Metformin improved glycemic control and insulin sensitivity in all groups, with greater effects in men with sufficient vitamin D status. Reductions in total and monomeric prolactin were observed only in groups 1 and 3 and were associated with baseline prolactin concentrations and pretreatment 25-hydroxyvitamin D levels. These changes were accompanied by modest increases in LH and testosterone, and improvements in sexual functioning. Vitamin D levels and other hormonal parameters remained unchanged. The magnitude of the metformin effect did not differ between groups 1 and 3. Conclusions: Adequate vitamin D status is necessary for metformin to reduce prolactin levels in men with iatrogenic hyperprolactinemia. Full article