Vitamin D: The Conclusion and Future Prospective

Vitamin D plays a crucial role in the regulation of the immune system, with immunomodulatory effects that are key in the prevention of colorectal cancer (CRC). Over the past decades, research has shown that this steroid hormone impacts much more than bone health, significantly influencing immune responses. Vitamin D enhances immune organ functions such as the spleen and lymph nodes, and boosts T-cell activity, which is essential in defending the body against tumors. Additionally, vitamin D mitigates inflammatory responses closely linked to cancer development, reducing the inflammation that contributes to CRC. It acts via vitamin D receptors (VDRs) expressed on immune cells, modulating immune responses. Adequate vitamin D levels influence gene expression related to inflammation and cell proliferation, inhibiting tumor development. Vitamin D also activates mechanisms that suppress cancer cell survival, proliferation, migration, and metastasis. Low levels of vitamin D have been associated with an increased risk of CRC, with deficiency correlating with higher disease incidence. Lifestyle factors, such as a diet high in red meat and calories but low in fiber, fruits, and vegetables, as well as physical inactivity, contribute significantly to CRC risk. Insufficient calcium and vitamin D intake are also linked to disease occurrence and poorer clinical outcomes. Maintaining optimal vitamin D levels and adequate dietary intake is crucial in preventing CRC and improving patient prognosis. This review explores the role of vitamin D in immune regulation and summarizes findings from randomized clinical trials assessing the effects of vitamin D supplementation on CRC outcomes.

Military personnel experience energy deficit (total energy expenditure higher than energy intake), particularly during combat training and field exercises where exercising energy expenditures are high and energy intake is reduced. Low energy availability (energy intake minus exercising energy expenditure expressed relative to fat free mass) impairs endocrine function and bone health, as recognized in female athletes as the Female Athlete Triad syndrome. More recently, the Relative Energy Deficiency in Sport (RED-S) syndrome encompasses broader health outcomes, physical and cognitive performance, non-athletes, and men. This review summarizes the evidence for the effect of low energy availability and energy deficiency in military training and operations on health and performance outcomes. Energy availability is difficult to measure in free-living individuals but doubly labeled water studies demonstrate high total energy expenditures during military training; studies that have concurrently measured energy intake, or measured body composition changes with DXA, suggest severe and/or prolonged energy deficits. Military training in energy deficit disturbs endocrine and metabolic function, menstrual function, bone health, immune function, gastrointestinal health, iron status, mood, and physical and cognitive performance. There are more data for men than women, and little evidence on the chronic effects of repeated exposures to energy deficit. Military training impairs indices of health and performance, indicative of the Triad and RED-S, but the multi-stressor environment makes it difficult to isolate the independent effects of energy deficiency. Studies supplementing with energy to attenuate the energy deficit suggest an independent effect of energy deficiency in the disturbances to metabolic, endocrine and immune function, and physical performance, but randomized controlled trials are lacking.

Purpose: This whitepaper examines the chemical composition, synthesis, and sources of Vitamin D3, emphasizing the importance of optimal levels for overall well-being. It explores the role of Vitamin D3 in various physiological processes beyond bone health, including immune system support, anti-inflammatory effects, cardiovascular health, cancer prevention, mental well-being, autoimmune disease management, muscle function, weight management, hormone regulation, dental health, and skin health.
 Methodology: The document provides a comprehensive overview of natural and dietary sources of Vitamin D3, including supplements. It outlines the synthesis process in the human body, emphasizing the role of magnesium and key enzymes. Popular Vitamin D3 supplements in the U.S. market are also presented.
 Findings: Vitamin D3, recognized as the "sunshine vitamin," offers diverse health benefits across multiple systems in the human body. Its popularity stems from advantages beyond bone health, contributing to immune system modulation, anti-inflammatory effects, cardiovascular health, cancer prevention, mental health, autoimmune disease management, muscle function, weight management, hormone regulation, dental health, and skin health.
 Unique Contribution to Theory, Policy, and Practice: The paper contributes a comprehensive understanding of vitamin D3's multifaceted benefits, stressing the need for dietary intake and supplementation. It suggests potential implications for public health strategies, especially in regions with limited sunlight exposure.

Vitamin D, sometimes referred to as the "sunshine vitamin," provides a number of benefits beyond bone health. In men, it has a role in fertility, metabolic regulation, immunological modulation, and healthy aging. By analyzing its production, mechanisms, physiological functions, and specific effects on male health across several systems, this article aims to clarify the importance of vitamin D in preventative and therapeutic health measures. Vitamin D, previously linked to calcium and bone homeostasis, is now a crucial regulator in various physiological domains affecting men's health. This comprehensive review explores the production, metabolism, and several mechanisms of action of vitamin D, with particular attention to its impact on male fertility, metabolic syndrome, immunological regulation, aging, obesity, and chronic diseases such as type 2 diabetes and autoimmune disorders. According to recent studies, vitamin D receptors are found in male reproductive and metabolic organs, and adequate vitamin D levels are linked to improved musculoskeletal integrity, insulin sensitivity, hormonal balance, and semen quality. The study explores the impact of vitamin D deficiency, a prevalent issue in men globally, and suggests interventional strategies such as supplementation and lifestyle modifications. Vitamin D is a crucial regulator of male physiological and pathological processes, according to all available research, and as such, it merits more attention in clinical practice and public health policy.

Shift work has been increasingly associated with alterations in immune regulation and stress responses. Circadian alteration, sleep disruption, and occupational stressors collectively impair immune status. However, the specific association between shift work, psychological stress, and the immune function of monocytes, neutrophils and lymphocytes among female nurses is still not clear. The aim of our study is to evaluate the association between shift work, psychological stress, and immune cell functions in female nurses using a within-subject design. A cross-sectional, repeated-measures observational study with a within-subject design was conducted at a tertiary care hospital from March to July 2025 among eight female nurses aged 22–32 y. Blood sampling and psychological stress assessments (Perceived Stress Scale and Copenhagen Psychosocial Questionnaire) were conducted within 2 h after completion of each shift. Monocytes, neutrophils, lymphocytes, and plasma were isolated from the blood of the same participants after each shift for immune marker assessment. Stress scores were significantly higher after night shifts. Night shift samples showed increased oxidative stress and stress-related markers, reduced nitric oxide levels, decreased phagocytic activity, leads towards the pro-inflammatory state along with altered chemokine receptor expression. This study highlights the association between shift work, psychological stress, and altered immune function in female nurses. Lack of sleep data is a limitation, as sleep variability may influence stress and immune responses. Future studies with larger, more diverse cohorts and detailed sleep assessments are needed to confirm these findings across different healthcare settings.

Vitamin D, sometimes called the “sunshine vitamin” is produced in our skin in response to sunlight.It’s a fat-soluble vitamin in a family of compounds that includes vitamins D-1, D-2, and D-3.Our bodyproduces vitamin D naturally when it’s directly exposed to sunlight. Vitamin D has several importantfunctions. Perhaps the most vital are regulating the absorption of calcium and phosphorus, and facilitatingnormal immune system function. Getting a sufficient amount of vitamin D is important for normal growthand development of bones and teeth, as well as improved resistance against certain diseases. Nowadays,Vitamin D deficiency patients are identified in various medical fields and it is necessary to understand thesymptoms, pathophysiology and therapeutic measures to overcome the deficiency of this vitamin in variousage groups from pediatric to geriatric.

The resurgence in vitamin D-associated rickets and world-wide description of maternal and infant vitamin D deficiency highlights the need for global maternal and infant vitamin D recommendations and action to ensure vitamin D health during lactation. Direct infant vitamin D supplementation of at least 400 IU/day vitamin D will protect the majority of infants from vitamin D deficiency rickets by maintaining 25-hydroxyvitamin D status above 50 nmol/l regardless of race, season, latitude, or maternal vitamin D status. Additionally, the physiology of breast milk production comprises the mechanism required for the mother to supply vitamin D activity to her infant and, with adequate maternal vitamin D intake, a mother is able to supply her infant with the vitamin D required to match the status achieved with direct infant supplementation. As current multi-center, randomized, controlled trials are underway to identify the maternal vitamin D supplementation associated with safe, effective supplementation of the breastfed infant, studies to more accurately define infant vitamin D health also are occurring. Though the vitamin D status and dose to safely avoid vitamin D deficiency rickets are known, the vitamin D status and/or dose (infant and/or maternal) that optimizes infant bone health or immune function for both short- and long-term outcomes has yet to be identified. Current case series and cohort studies demonstrate that infant vitamin D health may be important in avoiding acute lower respiratory infection and diabetes mellitus type 1.

Tetraspanins are membrane organizing proteins that play a role in organizing the cell surface through the formation of subcellular domains consisting of tetraspanins and their partner proteins. These complexes are referred to as tetraspanin enriched microdomains (TEMs) or the tetraspanin web. The formation of TEMs allows for the regulation of a variety of cellular processes such as adhesion, migration, signaling, and cell fusion. Tetraspanin CD53 is a member of the tetraspanin superfamily expressed exclusively within the immune compartment. Amongst others, B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and natural killer cells have all been found to express high levels of this protein on their surface. Almost three decades ago it was reported that patients who lacked CD53 suffered from an increased susceptibility to pathogens resulting in the clinical manifestation of recurrent viral, bacterial, and fungal infections. This clearly suggests a vital and non-redundant role for CD53 in immune function. Yet, despite this striking finding, the specific functional roles of CD53 within the immune system have remained elusive. This review aims to provide a concise overview of the published literature concerning CD53 and reflect on the underappreciated role of this protein in immune cell regulation and function.

BackgroundPerilla frutescens seeds (PFS) are gaining recognition as a natural alternative to antibiotics in livestock, supporting sustainable farming and animal health. However, the underlying molecular mechanisms through which PFS influence host immune function and antioxidant capacity, especially via the gut-liver-muscle axis, remain largely unknown. This study employed an integrative multi-omics approach to elucidate how PFS supplementation modulates the microbiota-gut-liver-muscle axis and enhances immune and antioxidant functions in lambs.ResultsPFS supplementation markedly improved immune and antioxidant profiles, demonstrated by elevated serum levels of IL-10, IgM, IgG, GSH-PX, and SOD, and reductions in IL-1β, TNF-α, and MDA. Microbial analysis revealed elevated abundances of ruminal and intestinal taxa commonly associated with gut homeostasis and metabolic health (Christensenellaceae_R-7_group) and reduced levels of species with pathogenic or pro-inflammatory potential (Bacillus cereus and Clostridioides) in the ileum. Transcriptomic and metabolomic profiling of liver tissue indicated modulation of key inflammatory and bile acid signaling pathways, including the downregulation of TLR4, NLRP3, ATF3, CYP2J2, and LXR-α. PFS also increased hepatic concentrations of anti-inflammatory metabolites such as chlorquinaldol and indole-3-carboxaldehyde, while reducing levels of LysoPC(20:4) and phosphatidic acid. Correlation and mediation analyses revealed strong interconnections among gut microbiota, hepatic gene expression, lipid metabolites in liver and muscle, and systemic immune-antioxidant markers.ConclusionThese findings highlight the microbiota-gut-liver-muscle axis as a central mechanism through which PFS enhances immune function and antioxidant capacity in lambs. PFS supplementation represents a promising nutritional strategy to improve healthy lamb production, supporting the development of antibiotic-free and sustainable livestock systems.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40104-025-01317-3.

Probiotics play diverse roles in promoting health and well-being, encompassing gut microbiota balance, digestive health, immune function, gut barrier integrity, metabolic health, and mental well-being. With the beneficial effects of probiotics, individuals may improve their gastrointestinal health, boost immune function, and reduce the risk of various diseases. These probiotics compete with pathogens and support gut and immune homeostasis to help in the prevention and cure of gastrointestinal disease, immune disorders, diabetes, obesity, cancer and allergic disorders, etc. Probiotic-rich foods and supplements into the diet offer a proactive approach to maintaining overall health and optimizing the functioning of the gut. Probiotics help to maintain immune homeostasis and decrease the risk of inflammatory disorders and allergic conditions. Several probiotic strains are available on the market and are being consumed in the form of foods, supplements, or drugs for health benefits. Lactobacilli, Bifidobacteria, and Bacillus species are common probiotic strains.

MicroRNAs and immunity: Novel players in the regulation of normal immune function and inflammation

The vitamin D receptor is found on most cells, including active immune cells, implying that vitamin D has important biological functions beyond calcium metabolism and bone health. Although captive primates should be given a dietary source of vitamin D, under free-living conditions vitamin D is not a required nutrient, but rather is produced in skin when exposed to UV-B light. The circulating level of 25 hydroxyvitamin D (25-OH-D) considered adequate for humans is a topic of current controversy. Levels of circulating 25-OH-D sufficient for good health for macaques and other Old World anthropoids are assumed to be the same as human values, but data from free-living animals are scant. This study reports values for 25-OH-D and the active vitamin D metabolite, 1,25-dihydroxyvitamin D (1,25[OH]2 D) for wild, forest-ranging toque macaques (Macaca sinica) in Sri Lanka. Plasma samples were obtained from eight adult males, seven juvenile males, six young nulliparous females, nine adult females not pregnant or lactating, eleven lactating adult females, and four pregnant females. Mean values for the complete sample were 61.3 ± 4.0 ng/ml for 25-OH-D and 155.6 ± 8.7 pg/ml for 1,25[OH]2 D. There were no significant differences for either metabolite among age and sex classes, nor between lactating and non-reproductive females. Values from the literature for circulating 25-OH-D in captive macaques are three times higher than those found in this wild population, however, 1,25[OH]2 D values in captive animals were similar to the wild values. The data from this study indicate that anthropoid primates exposed to extensive sunlight will have circulating values of 25-OH-D generally above 30 ng/ml, providing some support for the Endocrine Society recommendations for humans. Current dietary vitamin D supplementation of captive macaques likely exceeds requirement. This may affect metabolism and immune function, with possible consequences for macaque health and biomedical research results.

In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH. A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and β-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans. In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group. This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood. ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389.

IntroductionImmune function is a vital physiological process that is often suppressed during times of resource scarcity due to investments in other physiological systems. While energy is the typical currency that has been examined in such trade-offs, limitations of other resources may similarly lead to trade-offs that affect immune function. Specifically, water is a critical resource with profound implications for organismal ecology, yet its availability can fluctuate at local, regional, and even global levels. Despite this, the effect of osmotic state on immune function has received little attention.ResultsUsing agglutination and lysis assays as measures of an organism’s plasma concentration of natural antibodies and capacity for foreign cell destruction, respectively, we tested the independent effects of osmotic state, digestive state, and energy balance on innate immune function in free-ranging and laboratory populations of the Gila monster, Heloderma suspectum. This desert-dwelling lizard experiences dehydration and energy resource fluctuations on a seasonal basis. Dehydration was expected to decrease innate immune function, yet we found that dehydration increased lysis and agglutination abilities in both lab and field studies, a relationship that was not simply an effect of an increased concentration of immune molecules. Laboratory-based differences in digestive state were not associated with lysis or agglutination metrics, although in our field population, a loss of fat stores was correlated with an increase in lysis.ConclusionsDepending on the life history of an organism, osmotic state may have a greater influence on immune function than energy availability. Thus, consideration of osmotic state as a factor influencing immune function will likely improve our understanding of ecoimmunology and the disease dynamics of a wide range of species.

The umbrella term "human gut microbiota" describes the complex ecosystem harboring our gut. It includes bacteria, viruses, protozoa, archaea, fungi, and yeasts. This taxonomic classification does not describe its functions, which encompass nutrients digestion and absorption, immune system regulation, and host metabolism. "Gut microbiome" indicates instead the genome belonging to these "microbes" actively involved in these functions. However, the interaction between the host genome and the microbial ones determines the fine functioning of our organism. We reviewed the data available in the scientific literature on the definition of gut microbiota, gut microbiome, and the data on human genes involved in the interaction with the latter. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, gut microbiome, human genes, immune function, and metabolism. Candidate human genes encoding enzymes, inflammatory cytokines, and proteins show similarity with those included in the gut microbiome. These findings have become available through newer artificial intelligence (AI) algorithms allowing big data analysis. From an evolutionary point of view, these pieces of evidence explain the strict and sophisticated interaction at the basis of human metabolism and immunity regulation in humans. They unravel more and more physiopathologic pathways included in human health and disease. Several lines of evidence also obtained through big data analysis support the bi-directional role of gut microbiome and human genome in host metabolism and immune system regulation.