Infections and Autoimmunity—The Immune System and Vitamin D: A Systematic Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(17), P. 3842 - 3842

Published: Sept. 2, 2023

Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections developing autoimmunity. This systematic review examines vitamin D’s mechanisms effects on enhancing innate acquired immunity against microbes preventing The study evaluated the quality evidence regarding biology, physiology, aspects human health related autoimmunity peer-reviewed journal articles published English. search analyses followed PRISMA guidelines. Data strongly suggested that serum concentrations more than 50 ng/mL is associated with significant risk reduction viral bacterial infections, sepsis, Most adequately powered, well-designed, randomized controlled trials sufficient duration supported substantial benefits D. Virtually all studies failed conclude or were ambiguous had major design errors. Treatment deficiency costs less 0.01% cost investigation worsening comorbidities hypovitaminosis Despite cost-benefits, prevalence remains high worldwide. was clear among those who died COVID-19 2020/21—most severe deficiency. Yet, lack direction agencies insurance companies using as an adjunct therapy astonishing. confirmed keeping individual’s above (125 nmol/L) (and 40 population) reduces community outbreaks, autoimmune disorders. Maintaining such 97.5% people achievable through daily safe sun exposure (except countries far equator during winter) taking between 5000 8000 IU supplements (average dose, for non-obese adults, ~70 90 IU/kg body weight). Those gastrointestinal malabsorption, obesity, medications increase catabolism a few other specific disorders require much higher intake. evaluates non-classical actions D, particular emphasis infection immune system.

Language: Английский

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Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency

European Journal of Nutrition, Journal Year: 2023, Volume and Issue: 62(4), P. 1579 - 1597

Published: March 2, 2023

Language: Английский

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Physiological Basis for Using Vitamin D to Improve Health

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1542 - 1542

Published: May 26, 2023

Vitamin D is essential for life-its sufficiency improves metabolism, hormonal release, immune functions, and maintaining health. deficiency increases the vulnerability severity of type 2 diabetes, metabolic syndrome, cancer, obesity, infections. The active enzyme that generates vitamin [calcitriol: 1,25(OH)2D], CYP27B1 (1α-hydoxylase), its receptors (VDRs) are distributed ubiquitously in cells. Once calcitriol binds with VDRs, complexes translocated to nucleus interact responsive elements, up- or down-regulating expression over 1200 genes modulating physiological functions. Administration D3 correct metabolites at proper doses frequency longer periods would achieve intended benefits. While various tissues have different thresholds 25(OH)D concentrations, levels above 50 ng/mL necessary mitigate conditions such as infections/sepsis, reduce premature deaths. Cholecalciferol (D3) (not metabolites) should be used raise serum target concentration. In contrast, calcifediol [25(OH)D] raises concentrations rapidly agent choice emergencies infections, those who ICUs, insufficient hepatic 25-hydroxylase (CYP2R1) activity. maintain serum-ionized calcium concentration persons advanced renal failure hypoparathyroidism. Calcitriol is, however, ineffective most other conditions, including replacement therapy. Considering high costs higher incidence adverse effects due narrow therapeutic margins (ED50), 1α-vitamin analogs, 1α-(OH)D 1,25(OH)2D, not conditions. Calcifediol analogs cost 20 times more than D3-thus, they indicated a routine supplement hypovitaminosis D, osteoporosis, failure. Healthcare workers resist accepting inappropriate promotions, chronic osteoporosis infections-there no rationale doing so. Maintaining population's (above 40 ng/mL) supplements and/or daily sun exposure cost-effective way diseases sepsis, overcome viral epidemics pandemics, healthcare costs. Furthermore, overall health (hence reducing absenteeism), reduces cardiovascular decreases all-cause mortality, minimizes infection-related complications sepsis COVID-19-related hospitalizations Properly using illnesses costs: thus, it part clinical care.

Language: Английский

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Comparison of calcifediol with vitamin D for prevention or cure of vitamin D deficiency

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2023, Volume and Issue: 228, P. 106248 - 106248

Published: Jan. 13, 2023

Language: Английский

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Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 400 - 400

Published: Jan. 29, 2023

The immunomodulatory and metabolic effects of vitamin D receptor (VDR) activation have been considered beneficial in mitigating the susceptibility severity COVID-19 infection. Furthermore, D-binding protein (DBP) has pleiotropic on immune system that may influence inflammation associated with COVID-19. Multiple observational studies demonstrated an association between low levels serum 25-hydroxyvitamin risk However, impact supplementation as adjunctive treatment for based evidence from randomized clinical trials is unclear. Equally important certain variations genes involved pathway shown to affect function linked various outcomes, including cardio-metabolic disorders, autoimmune diseases, infections, cancers. This indicates inter-individual difference body response D. There also emerging common polymorphisms these COVID-19, although confidence findings limited by a small number participants. Further are needed address potential role VDR DBP pathophysiology which take into account genetic pathway.

Language: Английский

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Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19

Nutrients, Journal Year: 2022, Volume and Issue: 14(22), P. 4779 - 4779

Published: Nov. 11, 2022

Vitamin D deficiency is associated with a higher risk of SARS-CoV-2 infection and poor outcomes the COVID-19 disease. However, satisfactory mechanism explaining vitamin protective effects missing. Based on anti-inflammatory anti-oxidative properties classical novel (CYP11A1-derived) lumisterol hydroxymetabolites, we have proposed that they would attenuate self-amplifying damage in lungs other organs through mechanisms initiated by interactions corresponding nuclear receptors. These include VDR mediated inhibition NFκβ, inverse agonism RORγ ROS activation NRF2-dependent pathways. In addition, non-receptor actions related hydroxymetabolites active sites transcription machinery enzymes (Mpro;main protease RdRp;RNA dependent RNA polymerase). Furthermore, these metabolites could interfere binding RBD ACE2 interacting TMPRSS2. can cause conformational dynamical motion changes TMPRSS2, which affect TMPRSS2 to prime spike proteins. Therefore, novel, CYP11A1-derived, forms restrain both receptor-dependent independent mechanisms, identify them as excellent candidates for antiviral drug research educated use their precursors nutrients or supplements prevention attenuation

Language: Английский

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Vitamin D Deficiency Meets Hill’s Criteria for Causation in SARS-CoV-2 Susceptibility, Complications, and Mortality: A Systematic Review

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 599 - 599

Published: Feb. 6, 2025

Clinical trials consistently demonstrate an inverse correlation between serum 25-hydroxyvitamin D [25(OH)D; calcifediol] levels and the risk of symptomatic SARS-CoV-2 disease, complications, mortality. This systematic review (SR), guided by Bradford Hill’s causality criteria, analyzed 294 peer-reviewed manuscripts published December 2019 November 2024, focusing on plausibility, consistency, biological gradient. Evidence confirms that cholecalciferol (D3) calcifediol significantly reduce hospitalizations, mortality, with optimal effects above 50 ng/mL. While vitamin requires 3–4 days to act, shows within 24 h. Among 329 trials, only 11 (3%) showed no benefit due flawed designs. At USD 2/patient, D3 supplementation is far cheaper than hospitalization costs more effective standard interventions. SR establishes a strong relationship 25(OH)D vulnerability, meeting criteria. Vitamin infections, deaths ~50%, outperforming all patented, FDA-approved COVID-19 therapies. With over 300 confirming these findings, waiting for further studies unnecessary before incorporating them into clinical protocols. Health agencies scientific societies must recognize significance results incorporate prophylaxis early treatment protocols similar viral infections. Promoting safe sun exposure adequate communities maintain 40 ng/mL (therapeutic range: 40–80 ng/mL) strengthens immune systems, reduces hospitalizations deaths, lowers healthcare costs. When exceed 70 ng/mL, taking K2 (100 µg/day or 800 µg/week) alongside helps direct any excess calcium bones. The recommended dosage (approximately IU/kg body weight non-obese adult) 50–100 cost-effective disease prevention, ensuring health outcomes.

Language: Английский

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Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts

Nutrients, Journal Year: 2022, Volume and Issue: 14(17), P. 3584 - 3584

Published: Aug. 31, 2022

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk developing COVID-19 and -most importantly-with a higher severe dying. On other hand, supplementation during early phases been related to decreased length hospital stay, less frequent need for oxygen, reduced mortality rate in inpatients. This seems be particularly true when high dosages used. In light this evidence, further studies needed define best timing most effective dosage schedule.

Language: Английский

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Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 994 - 994

Published: March 23, 2023

Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart and stroke), type 2 diabetes, hypertension, kidney stroke, infectious acute respiratory tract COVID-19, influenza, pneumonia, well adverse pregnancy outcomes. The respective is based on ecological observational studies, randomized controlled trials, mechanistic Mendelian randomization studies. However, trials supplementation have largely failed to show benefits, probably due poor design analysis. In this work, we aim use best available beneficial estimate expected reduction in incidence mortality rates D-related Kingdom Saudi Arabia United Arab Emirates if minimum serum 25(OH)D concentrations were be raised 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% stroke 20 mortality, cancer depicted a promising raising 25(OH)D. Methods increase at population level could include food fortification with

Language: Английский

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Unveiling the Interplay—Vitamin D and ACE-2 Molecular Interactions in Mitigating Complications and Deaths from SARS-CoV-2

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 831 - 831

Published: Oct. 16, 2024

The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses circulation and mitigating inflammation. While reduces expression, vitamin D increases it, counteracting virus's harmful effects. Vitamin D's beneficial actions are mediated through complex molecular mechanisms involving innate adaptive immune systems. Meanwhile, status [25(OH)D concentration] is inversely correlated severity, complications, mortality rates from COVID-19. This study explores which inhibits replication, including suppression transcription enzymes, reduced inflammation oxidative stress, increased expression antibodies antimicrobial peptides. Both hypovitaminosis elevate renin levels, rate-limiting step renin-angiotensin-aldosterone system (RAS); it ACE-1 but expression. imbalance leads to elevated levels pro-inflammatory, pro-coagulatory, vasoconstricting peptide angiotensin-II (Ang-II), leading widespread It also causes membrane permeability, allowing fluid infiltrate soft tissues, lungs, vascular system. In contrast, sufficient suppress reducing RAS activity, lowering ACE-1, increasing levels. cleaves Ang-II generate Ang

Language: Английский

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