Vitamin D - A Novel Therapy for Chronic Diseases?

The historical background of vitamin D for well-being dates to the beginning of the twentieth century. There are two types of vitamin D; ergocalciferol (D2) and cholecalciferol (D3). While D3 is mostly produced in the skin when exposed to sunshine, vitamin D2 is sourced from plant sources and is frequently utilized in fortified meals and supplements. The recommended form of vitamin D for supplementation is D3 since it has a greater potency in elevating and sustaining blood levels of the nutrient. The biochemistry of vitamin D is centered on how it becomes activated in the kidneys and liver to become its active form, which controls the metabolism of phosphorus and calcium. Although ideal serum levels might vary based on personal health considerations, recommended values generally lie between 20 and 50 ng/mL. Egg yolks, fortified dairy products, and fatty fish are good dietary sources of vitamin D; nevertheless, obtaining a sufficient intake only through food may be difficult, necessitating supplementation. However, overindulgence can result in toxicity, which is defined by hypercalcemia and associated symptoms including nausea and weakness. This emphasizes the significance of moderation in supplementing. Because vitamin D is fat-soluble, the body will keep excess rather than quickly excrete it, therefore taking too many supplements can be harmful. While vitamin D is essential for many body processes, getting the right amount of it without running the risk of negative side effects is crucial.

The gut microbiota, a complex bacterial community within the gastrointestinal system, critically regulates human physiology. This article explores the complex interactions between the gut microbiota and vitamin D, impacting immunity and overall health. Vitamin D plays a role in immunological modulation, cell proliferation, and maintaining intestinal balance highlighting the intricate connections between gut microbiota and vitamin D in the gastrointestinal system. Recent research indicates that vitamin D receptors in the gastrointestinal tract may influence the gut microbiota's composition. Dysbiosis, an imbalance in the gut microbiota, is linked to various illnesses, including autoimmune diseases and metabolic disorders. This section examines the effects of low vitamin D levels on immunity, associating insufficient amounts with increased susceptibility to infections and autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and Hashimoto's thyroiditis. Conversely, studies demonstrate that immune function relies on maintaining adequate vitamin D levels, particularly through calcitriol, the active form of vitamin D, regulating innate and adaptive immunity. Epidemiological research supports the hypothesis that sufficient vitamin D levels could reduce the prevalence of illnesses, including autoimmune diseases and osteoporosis. The chapter underscores the potential preventive benefits of adequate vitamin D intake, reviewing data from research on multiple sclerosis, Hashimoto's illness, and rheumatoid arthritis.

In conclusion, this exploration highlights vitamin D's critical role in immune system performance, gut health, and microbiota composition. While existing studies suggest the potential benefits of vitamin D for autoimmune illnesses, further research is imperative to establish conclusive evidence, especially regarding vitamin D supplementation for these ailments

This chapter examines the latest research findings on the association between vitamin D levels and insulin resistance (IR) in various populations, including pregnant and postpartum women, children and adolescents, and individuals with certain health conditions such as diabetes, obesity, multiple sclerosis (MS), polycystic ovary syndrome (PCOS), non-alcoholic fatty liver disease (NAFLD), diabetic kidney disease (DKD), and diabetic peripheral neuropathy (DPN). Existing evidence suggests that Vitamin D plays a crucial role as an immunomodulator, affecting important human disorders like insulin resistance, glucose homeostasis, and mineral and bone metabolism. Extensive evidence suggests that vitamin D has a substantial impact on the development of insulin resistance (IR), through its influence on different gene variants related to vitamin D and the metabolic and immunological pathways associated with it. Supplementing with vitamin D can be beneficial in properly managing and enhancing insulin resistance. Diverse research approaches have yielded both favorable and unfavorable results on the correlation between vitamin D and insulin resistance (IR). Further research is recommended to clarify the correlation between vitamin D and insulin function, as well as to determine any variations in this association among different age groups, genders, and illnesses.

Vitamin D is an essential micronutrient crucial for various physiological functions in humans, notably impacting calcium metabolism, skeletal integrity, immune response, and cellular proliferation and differentiation. While predominantly synthesized through sunlight exposure, dietary intake, and supplementation also contribute to its availability. Vitamin D deficiency has been implicated as a potential risk factor for atherosclerosis, cardiorespiratory distress, and cardiovascular diseases (CVDs), including sudden cardiac death, hypertension, and stroke. Observational studies have indicated an inverse correlation between circulating vitamin D levels and the incidence of CVDs; however, causality remains ambiguous. Some evidence suggests a potential cardioprotective effect of vitamin D supplementation, however, further investigation is warranted to elucidate its precise role in cardiovascular health. This review aims to comprehensively present existing literature on the relationship between vitamin D status and CVDs.

Irritable bowel syndrome (IBS) is a common gastrointestinal condition characterized by abnormal bowel habits (diarrhea, constipation, or both), poor mental health, and a reduced quality of life. Although commonly diagnosed through the Rome IV criteria, a universally agreed-upon diagnostic standard for IBS is yet to be established. Several therapeutic modalities are commonly employed to treat IBS, but the lack of a distinct biomarker for the condition makes it challenging for healthcare providers to evaluate the effectiveness of treatments. Elimination diets such as the low FODMAP diet may provide benefits to patients with IBS, however, the accompanying increased risk of nutritional deficiencies may worsen the condition’s symptoms. Vitamin D (VD) supplementation may reduce symptom intensity and enhance the overall quality of life for individuals with IBS through several postulated mechanisms of action, including possible influence on gut microbiota and serotonin levels. This chapter reviews the current evidence from observational studies, systematic reviews, and meta-analyses of randomized controlled trials linking VD deficiency and/or supplementation with IBS. Four observational studies found a connection between diagnosed IBS and patients' vitamin D levels, along with a correlation with symptom severity, while two studies showed contradictory results. Systematic reviews and metaanalyses suggest a positive association between vitamin D supplementation and the relief of IBS symptoms as well as improvements in mental health. Despite these encouraging results, further large-scale clinical trials are needed to establish conclusive findings and enhance clinical approaches for effectively managing IBS.

This chapter discusses the relationship between vitamin D and depression, shedding light on the physiological functions of the unique characteristics of vitamin D, its synthesis, and its role in extraskeletal activities apart from its established function in bone metabolism. It further delves into the global prevalence of vitamin D deficiency and the rising incidence of depression worldwide. The link between vitamin D and depression is presented emphasizing the potential roles of vitamin D in neuromuscular and immune function. The document also discusses the purported mechanisms underlying the relationship between vitamin D and depression, including neuroinflammation, imbalance in calcium homeostasis, and deficiency in neurotransmitters. Furthermore, the document presents a comprehensive review of the existing literature on the topic, citing multiple studies and reviews to support the discussed findings. It covers various aspects, including the molecular basis of vitamin D, its impact on neurobehavioral health, and its association with depressive symptoms across different age groups primarily fetal origins, children, adolescents, adults, and older adults. Many studies suggest a possible connection between depression and vitamin D insufficiency, but the exact nature of this relationship and whether the supplementation of vitamin D could effectively treat depression remains ambiguous. Given that the link between vitamin D and depression has attracted attention, further well-designed trials are needed to establish causality, elucidate the practical consequences, and address the existing discrepancies and limitations in the evidence.

Melanoma, a malignant tumor of the skin, is a major health concern worldwide, with increased incidence rates especially among fair-skinned individuals. This section investigates the complex connection between vitamin D and melanoma, offering insight to vitamin D's numerous functions in both skin health and prevention of cancer. Vitamin D, which is largely synthesized in the skin in response to ultraviolet B (UVB) radiation, has important activities beyond mineral homeostasis, such as immunological regulation and tumor suppression. Considering its potential preventive effects, the processes behind vitamin D's influence on the likelihood of melanoma and progression are complex and require further research. Observational studies indicate a possible adverse link between vitamin D levels and melanoma risk, while causality and appropriate supplementing regimens are unclear. Genetic differences in vitamin D receptors and metabolic enzymes may also influence an individual's vulnerability to melanoma. Melanoma risk reduction strategies include a broad approach, including limiting UV exposure, supplementing the diet, and considering genetics. This review summarizes the current investigation into vitamin D's complex interaction with melanoma, emphasizing the necessity for comprehensive measures to maximize its efficacy in melanoma prevention and care. 

Vitamin D insufficiency is prevalent among pregnant women and infants worldwide. Expectant mothers with a heightened risk of vitamin D deficiency may have notably low levels of 25-hydroxyvitamin D (25(OH)D) in their newborns, raising the likelihood of nutritional rickets. Numerous observational studies suggest a link between inadequate vitamin D levels during pregnancy and various adverse perinatal outcomes such as hypertensive disorders (like preeclampsia), restricted fetal growth, and premature birth. Nevertheless, the limited number of large-scale randomized controlled trials (RCTs) conducted so far have produced conflicting findings regarding the effectiveness of vitamin D supplementation in enhancing perinatal outcomes.