What is Vitamin D?
This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Vitamin D is a fat-soluble vitamin that is crucial for maintaining various physiological functions in the human body. It is unique because it can be synthesized in the skin upon exposure to sunlight, specifically ultraviolet B (UVB) radiation, and can also be obtained from dietary sources. This article explores the multifaceted roles of vitamin D, its sources, metabolism, and its impact on health beyond its classical functions. Other names include: Alfacalcidol: 1-alpha-hydroxycholecalciferol, 1-alpha-hydroxycholécalciférol, 1 alpha (OH)D3.<br/> Calcifediol: 25-HCC, 25-hydroxycholecalciferol, 25-hydroxycholécalciferol , 25-hydroxyvitamin D3, 25-hydroxyvitamine D3, 25-OHCC, 25-OHD3, Calcifédiol.<br/> Calcipotriene : Calcipotriène, Calcipotriol.<br/> Calcitriol: 1,25-DHCC, 1,25-dihydroxycholecalciferol, 1,25-dihydroxycholécalciférol, 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamine D3, 1,25-diOHC, 1,25(OH)2D3, Eldecalcitol.<br/> Cholecalciferol: 7-déhydrocholestérol Activé, Activated 7-dehydrocholesterol, Cholécalciférol, Colecalciferol, Colécalciférol, Vitamin D3.<br/> Dihydrotachysterol: DHT, Dihydrotachystérol, dihydrotachysterol 2, dichysterol, Vitamine D3.<br/> Ergocalciferol: Activated Ergosterol, Calciferol, Ergocalciférol, Ergocalciferolum, Ergostérol Activé, Ergostérol Irradié, Irradiated Ergosterol, Viosterol, Viostérol, Vitamin D2, Vitamine D2.<br/> Paricalcitol: 19-nor-1,25-dihydroxyvitamin D2, 19-nor-1,25-dihydroxyvitamine D2, Paracalcin.<br/> Vitamina D, Vitamine D.
Sources of Vitamin D
The primary source of vitamin D is its synthesis in the skin through a chemical reaction dependent on sun exposure. In lesser amounts, it can be obtained from the diet, mostly from fatty fish, fish liver oil, and mushrooms7. Vitamin D3, or cholecalciferol, is synthesized in the skin and then undergoes hydroxylation in the liver and kidneys to become its active form, 1,25-dihydroxyvitamin D10.
Metabolism of Vitamin D
Vitamin D metabolism involves several steps. Initially, vitamin D3 is hydroxylated in the liver to form 25-hydroxyvitamin D (25(OH)D), which is the main circulating form and is used to determine vitamin D status. This is further hydroxylated in the kidneys to form 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form that exerts various biological effects10. The production of 1,25(OH)2D is regulated by parathyroid hormone (PTH) and calcium levels10.
Classical Functions
The classical functions of vitamin D are well-known and include the regulation of calcium and phosphorus homeostasis and the promotion of bone mineralization. Vitamin D facilitates the absorption of calcium from the gut, which is essential for maintaining healthy bones and preventing disorders such as rickets and osteomalacia9 10.
Immunomodulatory and Anti-inflammatory Roles
Vitamin D is also recognized for its immunomodulatory and anti-inflammatory properties. It plays a critical role in the modulation of the immune system by influencing both the innate and adaptive immune responses. The vitamin D receptor (VDR) is expressed in various immune cells, including B and T lymphocytes, monocytes, macrophages, and dendritic cells5. Vitamin D and VDR signaling have been shown to suppress autoimmunity and reduce inflammatory cytokine secretion5.
Impact on Autoimmune Diseases
There is growing evidence that vitamin D deficiency is associated with an increased risk of developing several autoimmune diseases. Studies have demonstrated an inverse relationship between vitamin D levels and the incidence of diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), type 1 diabetes, and rheumatoid arthritis1 2. Vitamin D supplementation has been suggested as a potential therapeutic strategy to modulate immune responses in these conditions1 2.
Cardiovascular Health
Vitamin D also plays a role in cardiovascular health. It regulates blood pressure by acting on endothelial cells and smooth muscle cells. Deficiency in vitamin D has been linked to various cardiovascular risk factors and a higher incidence of cardiovascular diseases (CVD)7. However, recent randomized controlled trials have not confirmed the benefits of vitamin D supplementation for CVD prevention, indicating that more research is needed in this area7.
Physical Performance
Vitamin D is essential for maintaining physical performance, particularly in athletes and active populations. It affects muscle strength and may participate in protein synthesis through the actions of the vitamin D receptor in muscle tissue. Poor vitamin D status has been associated with decreased muscle strength and increased risk of overuse injuries6.
Reproductive Health
Vitamin D also influences reproductive health. The vitamin D receptor and metabolizing enzymes are present in reproductive tissues, and deficiency in vitamin D has been linked to reproductive issues in both men and women. For instance, low levels of vitamin D are associated with polycystic ovary syndrome (PCOS) and poor semen quality4.
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Use of Vitamin D
Bone Health and Calcium Homeostasis
Vitamin D is essential for maintaining healthy bones by regulating calcium absorption, reducing calcium loss in urine, and mobilizing calcium from the skeleton1 4 5.
Immune System Modulation
Vitamin D modulates the immune system, influencing T cells, macrophages, and other immune cells. It has been shown to prevent or suppress autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes2 3 6 8 9.
Cardiovascular Health
Vitamin D plays a role in cardiovascular protection by regulating blood pressure and improving the function of cardiac, endothelial, and smooth muscle cells1.
Cancer Prevention and Treatment
Vitamin D has potential benefits in reducing the incidence and severity of certain cancers, including prostate, breast, colorectal cancers, and melanoma. It may act as a coadjuvant in cancer treatment1 6 7.
Mental Health
Vitamin D supplementation has been associated with reduced symptoms of depression and anxiety, particularly in individuals diagnosed with major depressive disorder1 10.
Infection and Inflammation
Vitamin D improves immunity, reduces inflammation, and lowers the risk and severity of infectious diseases, including respiratory infections and sepsis1 5 8.
Chronic Diseases
Adequate levels of vitamin D are linked to a lower risk of chronic diseases such as type 2 diabetes, metabolic syndrome, and obesity5.
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Adverse Effects of Vitamin D
Hypercalcemia and Hypercalciuria
Long-term high-dose Vitamin D supplementation increases the risk of hypercalcemia (elevated calcium levels in the blood) and hypercalciuria (elevated calcium levels in the urine)1 2.
The increased risk of hypercalcemia was observed in 37 studies (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01) and hypercalciuria in 14 studies (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03)2.
Kidney Stones
There is no significant increase in the risk of kidney stones with Vitamin D supplementation. Some studies even suggest a tendency for fewer kidney stones in the Vitamin D group compared to placebo1 2.
Noncalcemic Adverse Effects
Vitamin D supplementation does not significantly increase the risk of noncalcemic adverse effects such as gastrointestinal or dermatological symptoms3.
Withdrawal rates due to adverse effects were not significantly different between Vitamin D and placebo groups, except when calcium was co-supplemented3.
Cardiovascular Disease
Vitamin D supplementation does not reduce the risk of major adverse cardiovascular events, myocardial infarction, stroke, cardiovascular disease mortality, or all-cause mortality6.
Observational studies suggest an association between Vitamin D deficiency and increased cardiovascular risk, but supplementation does not appear to mitigate this risk7.
General Safety
Prolonged intake of Vitamin D3 at doses up to 100 microg/day (4000 IU/day) is considered safe, with no significant changes in serum calcium or urinary calcium excretion5.
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How has Vitamin D Improved Patient Outcomes?
Fibromyalgia and Quality of Life
Vitamin D supplementation improves physical function, emotional health, social function, and general health in fibromyalgia patients1.
Critical Illness
Vitamin D supplementation reduces the length of ICU stay and duration of mechanical ventilation in critically ill patients, though it does not significantly affect overall mortality2 6.
No significant improvement in hospital length of stay or ICU stay was observed in neurocritical care patients4.
Vitamin D supplementation does not significantly impact 28-day mortality, length of ICU stay, hospital stay, or duration of mechanical ventilation in critically ill adults7.
COVID-19
Regular bolus Vitamin D supplementation is associated with better survival and less severe outcomes in frail elderly COVID-19 patients3.
Cancer
Higher circulating levels of 25-hydroxyvitamin D are associated with better overall and progression-free survival in cancer patients5.
Acute Respiratory Failure
Vitamin D supplementation may reduce in-hospital and ICU mortality in patients with acute respiratory failure6.
Chronic Kidney Disease (CKD)
Vitamin D therapy does not significantly reduce all-cause mortality, cardiovascular death, or fracture risk in CKD patients, though it lowers serum parathyroid hormone and alkaline phosphatase levels8.
Coronary Artery Disease (CAD)
Vitamin D supplementation improves diastolic blood pressure and parathyroid hormone levels in CAD patients but does not significantly affect other cardiac outcomes9.
Tuberculosis
Vitamin D supplementation does not improve clinical outcomes or reduce mortality in tuberculosis patients10.
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Vitamin D Mechanisms of Action
VDR and RXR Interaction
Vitamin D exerts its effects by binding to the VDR, which then forms a heterodimer with the retinoid X receptor (RXR). This complex binds to vitamin D responsive elements in the DNA, regulating the transcription of various genes involved in calcium and phosphate homeostasis, bone remodeling, and other functions1 2 3 5 7.
Genomic and Non-Genomic Actions
The VDR/RXR complex regulates gene expression by recruiting coactivators or corepressors, affecting genes related to calcium absorption, bone mineralization, and renal reabsorption of calcium and phosphate. Additionally, vitamin D has non-genomic actions that influence cellular signaling pathways, such as the mitogen-activated protein kinase pathway, impacting muscle function and other cellular processes1 2 6 7.
Role in Calcium and Phosphate Homeostasis
Vitamin D is crucial for maintaining calcium and phosphate levels in the body. It stimulates intestinal calcium and phosphate absorption, mobilizes calcium from bones, and enhances renal reabsorption of calcium. These actions are mediated through the VDR in target tissues like the intestine, bone, and kidney1 3 5 7.
Immunomodulatory and Anti-Inflammatory Effects
Vitamin D has significant immunomodulatory effects, influencing the expression of junctional proteins, defensins, and mucins, which are crucial for maintaining epithelial barrier integrity. It also modulates inflammatory responses and affects gut microbiome composition, which is particularly relevant in conditions like inflammatory bowel diseases (IBD)4 8 9.
Extraskeletal Effects
Beyond its role in bone health, vitamin D influences various other physiological processes, including muscle function, cardiovascular health, and insulin sensitivity. It has been shown to inhibit cancer progression, modulate immune responses, and potentially play a role in preventing chronic diseases like type 2 diabetes and cardiovascular disorders2 6 9.
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Common Complaints Associated with Vitamin D Use
Psychological and Somatic Symptoms from Deficiency
Vitamin D deficiency (VDD) is associated with psychological symptoms such as irritability, anxiety, and difficulties in getting to sleep, particularly in children and adolescents1.
VDD in older adults is linked to sarcopenia, which involves the loss of muscle mass and strength, leading to increased risk of falls and disability5.
Symptoms of Vitamin D Toxicity
Vitamin D toxicity (VDT) can cause confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and dehydration. These symptoms are often related to severe hypercalcemia due to excessive long-term intake of vitamin D2 3.
In children, VDT is rare but can present with severe hypercalcemia, hypercalciuria, or nephrocalcinosis, often due to errors in manufacturing or prescription8.
Chronic Pain and Musculoskeletal Issues
Low levels of vitamin D are linked to chronic pain conditions, including osteomalacia-related pain and other types of chronic pain such as headaches, abdominal pain, knee pain, and back pain9.
Vitamin D deficiency is also associated with nonspecific musculoskeletal pain and periodontal disease in patients undergoing maintenance methadone treatment6.
Impact on Quality of Life in Cancer Patients
In adults with advanced cancer, vitamin D deficiency is common and associated with symptoms like fatigue and pain. Supplementation may improve these symptoms, although the evidence is still emerging7.
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Disclaimer
The content presented in this blog is generated by Consensus, an AI-powered academic search engine, and is based on publicly available scientific literature. While every effort is made to provide accurate, up-to-date, and well-researched information, the content is intended for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making any decisions regarding medical conditions, treatments, or medications. The AI system’s analysis may not cover all perspectives, emerging research, or individual cases, and it is not a substitute for professional expertise. Neither the blog publisher nor the developers of the AI-powered search engine are responsible for any actions taken based on the information provided in this content. Use of this information is at your own risk. Citations to the original scientific studies are included for reference, but these studies should be reviewed in full and interpreted with the guidance of a healthcare or research professional.
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