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Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Nutrients Jul 2023Psoriasis is a chronic immune-dysregulated inflammatory disease and hypovitaminosis D is considered a risk factor. We conducted an online database search to review and... (Meta-Analysis)
Meta-Analysis Review
Psoriasis is a chronic immune-dysregulated inflammatory disease and hypovitaminosis D is considered a risk factor. We conducted an online database search to review and meta-analyze the relationship between vitamin D, other bone metabolism parameters, and psoriasis. The efficacy of oral vitamin D supplementation in improving Psoriasis Area and Severity Index (PASI) was also evaluated. Non-original articles, case reports, and animal studies were excluded. Bias risk was assessed according to the Cochrane Collaboration's tool and the Newcastle-Ottawa scale in randomized controlled trials (RCTs) and case-control studies, respectively. Unstandardized mean differences were used for data synthesis. Twenty-three studies reported serum 25 hydroxyvitamin D (25(OH)D) levels in 1876 psoriasis patients and 7532 controls. Psoriasis patients had significantly lower 25(OH)D levels than controls (21.0 ± 8.3 vs. 27.3 ± 9.8, < 0.00001). Conversely, 450 psoriasis patients had lower levels of parathormone than 417 controls (38.7 ± 12.8 vs. 43.7 ± 16.5, = 0.015). Four RCTs examined the effect of oral vitamin D supplementation on psoriasis for 173 patients and 160 patients were treated with placebo. No significant differences were found in PASI after 3, 6, and 12 months of supplementation. It is shown that 25(OH)D serum levels are significantly lower in psoriasis, but, although the granularity of RCT methodology may have influenced the pooled analysis, vitamin D supplementation did not seem to improve clinical manifestations.
Topics: Humans; Vitamin D; Vitamins; Psoriasis; Vitamin D Deficiency; Calcifediol; Dietary Supplements
PubMed: 37571324
DOI: 10.3390/nu15153387 -
Annals of Medicine Dec 2023Children's Vitamin D (VitD) fortification and supplementation are diminishing due to less outdoor exercise and insufficient VitD intake (low exogenous intake and... (Review)
Review
Children's Vitamin D (VitD) fortification and supplementation are diminishing due to less outdoor exercise and insufficient VitD intake (low exogenous intake and endogenous malabsorption induced by gastrointestinal disease). Consequently, children in many developed countries suffer from VitD deficiency, which may contribute to many paediatric disorders. Our review briefly introduced the metabolic process of VitD, summarized the role of VitD in paediatric diseases such as autism, obesity, rickets and asthma. We sought to identify the link between VitD deficiency and these diseases.
Topics: Child; Humans; Vitamin D Deficiency; Vitamin D; Vitamins; Obesity; Nutritional Status
PubMed: 36495273
DOI: 10.1080/07853890.2022.2154381 -
The Journal of Steroid Biochemistry and... Jul 2023In this review, we summarize the most recent advances in vitamin D cancer research to provide molecular clarity, as well as its translational trajectory across the... (Review)
Review
In this review, we summarize the most recent advances in vitamin D cancer research to provide molecular clarity, as well as its translational trajectory across the cancer landscape. Vitamin D is well known for its role in regulating mineral homeostasis; however, vitamin D deficiency has also been linked to the development and progression of a number of cancer types. Recent epigenomic, transcriptomic, and proteomic studies have revealed novel vitamin D-mediated biological mechanisms that regulate cancer cell self-renewal, differentiation, proliferation, transformation, and death. Tumor microenvironmental studies have also revealed dynamic relationships between the immune system and vitamin D's anti-neoplastic properties. These findings help to explain the large number of population-based studies that show clinicopathological correlations between circulating vitamin D levels and risk of cancer development and death. The majority of evidence suggests that low circulating vitamin D levels are associated with an increased risk of cancers, whereas supplementation alone or in combination with other chemo/immunotherapeutic drugs may improve clinical outcomes even further. These promising results still necessitate further research and development into novel approaches that target vitamin D signaling and metabolic systems to improve cancer outcomes.
Topics: Humans; Vitamin D; Proteomics; Vitamins; Neoplasms; Vitamin D Deficiency; Antineoplastic Agents; Receptors, Calcitriol
PubMed: 37054849
DOI: 10.1016/j.jsbmb.2023.106308 -
Journal of Bone and Mineral Research :... Oct 2023Vitamin D plays an important role in calcium homeostasis and many cellular processes. Although vitamin D supplements are widely recommended for community-dwelling... (Review)
Review
Vitamin D plays an important role in calcium homeostasis and many cellular processes. Although vitamin D supplements are widely recommended for community-dwelling adults, definitive data on whether these supplements benefit clinically important skeletal and extraskeletal outcomes have been conflicting. Although observational studies on effects of vitamin D on musculoskeletal and extraskeletal outcomes may be confounded by reverse causation, randomized controlled studies (RCTs) and Mendelian randomization (MR) studies can help to elucidate causation. In this review, we summarize the recent findings from large RCTs and/or MR studies of vitamin D on bone health and risk of fractures, falls, cancer, and cardiovascular disease, disorders of the immune system, multiple sclerosis, and mortality in community-dwelling adults. The primary analyses indicate that vitamin D supplementation does not decrease bone loss, fractures, falls, cancer incidence, hypertension, or cardiovascular risk in generally healthy populations. Large RCTs and meta-analyses suggest an effect of supplemental vitamin D on cancer mortality. The existence of extraskeletal benefits of vitamin D supplementations are best documented for the immune system especially in people with poor vitamin D status, autoimmune diseases, and multiple sclerosis. Accumulating evidence indicates that vitamin D may reduce all-cause mortality. These findings, in mostly vitamin D-replete populations, do not apply to older adults in residential communities or adults with vitamin D deficiency or osteoporosis. The focus of vitamin D supplementation should shift from widespread use in generally healthy populations to targeted vitamin D supplementation in select individuals, good nutritional approaches, and elimination of vitamin D deficiency globally. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Dietary Supplements; Fractures, Bone; Mendelian Randomization Analysis; Multiple Sclerosis; Neoplasms; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency; Adult
PubMed: 37483080
DOI: 10.1002/jbmr.4888 -
International Journal of Molecular... Oct 2023In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential... (Review)
Review
In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential hormone in regulating calcium/phosphorous balance and in the pathogenesis of inflammation, insulin resistance, and obesity. The main forms of vitamin D, Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are converted into the active form (1,25-dihydroxyvitamin D) thanks to two hydroxylations in the liver, kidney, pancreas, and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased, and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity, and cardiovascular disease. It is interesting to note that several long-term studies also revealed an inverse correlation between vitamin D levels and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects. While some studies demonstrated improvements in insulin sensitivity, glucose, and lipid metabolism, others revealed no significant effect on glycemic homeostasis and inflammation. This review aims to provide insight into the molecular basis of the relationship between vitamin D, insulin resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.
Topics: Pregnancy; Female; Humans; Vitamin D; Insulin Resistance; Metabolic Syndrome; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Insulin; Vitamin D Deficiency; Vitamins; Cholecalciferol; Obesity; Inflammation; Cytokines; Anti-Inflammatory Agents
PubMed: 37895163
DOI: 10.3390/ijms242015485 -
BMC Medicine Oct 2023Sedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been...
BACKGROUND
Sedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been investigated.
METHODS
We analyzed data from 2914 cancer survivors who participated in the National Health and Nutrition Examination Survey (2007-2018) and followed up with them until December 31, 2019. Sedentary behavior was assessed by self-reported daily hours of sitting, and vitamin D status was measured by serum total 25-hydroxyvitamin D (25(OH)D) levels.
RESULTS
Among 2914 cancer survivors, vitamin D deficiency was more prevalent in those with prolonged daily sitting time. During up to 13.2 years (median, 5.6 years) of follow-up, there were 676 deaths (cancer, 226; cardiovascular disease, 142; other causes, 308). The prolonged sitting time was associated with a higher risk of all-cause and noncancer mortality, and vitamin D deficiency was associated with a higher risk of all-cause and cancer mortality. Furthermore, cancer survivors with both prolonged sitting time (≥ 6 h/day) and vitamin D deficiency had a significantly higher risk of all-cause (HR, 2.05; 95% CI: 1.54-2.72), cancer (HR, 2.33; 95% CI, 1.47-3.70), and noncancer mortality (HR, 1.91; 95% CI, 1.33-2.74) than those with neither risk factor after adjustment for potential confounders.
CONCLUSIONS
In a nationally representative sample of U.S. cancer survivors, the joint presence of sedentary behavior and vitamin D deficiency was significantly associated with an increased risk of all-cause and cancer-specific mortality.
Topics: Humans; Cancer Survivors; Sedentary Behavior; Nutrition Surveys; Vitamin D; Vitamin D Deficiency; Risk Factors; Neoplasms
PubMed: 37904126
DOI: 10.1186/s12916-023-03118-9 -
The Journal of Clinical Endocrinology... Sep 2023Long COVID is an emerging syndrome affecting 50% to 70% of COVID-19 survivors that still lacks predicting factors.
CONTEXT
Long COVID is an emerging syndrome affecting 50% to 70% of COVID-19 survivors that still lacks predicting factors.
OBJECTIVE
Due to the extraskeletal effects of vitamin D, we retrospectively assessed the association between 25(OH) vitamin D levels and long COVID in COVID-19 survivors 6 months after hospitalization.
METHODS
Long COVID was defined according to NICE guidelines. Fifty long COVID and 50 non-long-COVID subjects matched on a 1:1 basis were enrolled from an outpatient clinic post-COVID cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin D/bone metabolism, and/or admission to the intensive care unit during hospitalization were exclusion criteria. 25(OH) Vitamin D was measured at hospital admission and 6 months after discharge.
RESULTS
We observed lower 25(OH) vitamin D levels, evaluated at follow-up, in subjects with long COVID than those without (20.1 vs 23.2 ng/mL, P = .03). Regarding the affected health areas evaluated in the entire cohort, we observed lower 25(OH) vitamin D levels in those with neurocognitive symptoms at follow-up (n = 7) than those without (n = 93) (14.6 vs 20.6 ng/mL, P = .042). In patients presenting vitamin D deficiency (<20 ng/mL), both at admission and at follow-up (n = 42), those affected by long COVID (n = 22) presented lower 25(OH) vitamin D levels at follow-up than those not affected (n = 20) (12.7 vs 15.2 ng/mL, P = .041). In multiple regression analyses, lower 25(OH) vitamin D levels at follow-up were the only variable significantly associated with long COVID in our cohort (P = .008, OR 1.09, CI 1.01-1.16).
CONCLUSION
COVID-19 survivors with long COVID have lower 25(OH) vitamin D levels than matched patients without long COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge. The role of vitamin D supplementation as a preventive strategy of COVID-19 sequelae should be tested in randomized controlled trials.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Retrospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins; Survivors
PubMed: 37051747
DOI: 10.1210/clinem/dgad207 -
Nutrients Jun 2023Vitamin D is a fat-soluble steroid hormone, acting through genomic and non-genomic mechanisms, obtainable via two main sources: diet and exposure to ultraviolet B rays...
Vitamin D is a fat-soluble steroid hormone, acting through genomic and non-genomic mechanisms, obtainable via two main sources: diet and exposure to ultraviolet B rays [...].
Topics: Humans; Vitamin D; Vitamins; Diet; Ultraviolet Rays; Vitamin D Deficiency
PubMed: 37447228
DOI: 10.3390/nu15132902