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Science (New York, N.Y.) Apr 2024A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater...
A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.
Topics: Animals; Female; Humans; Male; Mice; Bacteroides fragilis; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Immunotherapy; Intestinal Mucosa; Mice, Inbred C57BL; Neoplasms; Vitamin D; Diet; Cell Line, Tumor; Calcifediol; Vitamin D-Binding Protein
PubMed: 38662827
DOI: 10.1126/science.adh7954 -
Nutrients May 2020Vitamin D deficiency is a global health problem due to its high prevalence and its negative consequences on musculoskeletal and extra-skeletal health. In our comparative... (Review)
Review
Vitamin D deficiency is a global health problem due to its high prevalence and its negative consequences on musculoskeletal and extra-skeletal health. In our comparative review of the two exogenous vitamin D supplementation options most used in our care setting, we found that cholecalciferol has more scientific evidence with positive results than calcifediol in musculoskeletal diseases and that it is the form of vitamin D of choice in the most accepted and internationally recognized clinical guidelines on the management of osteoporosis. Cholecalciferol, unlike calcifediol, guarantees an exact dosage in IU (International Units) of vitamin D and has pharmacokinetic properties that allow either daily or even weekly, fortnightly, or monthly administration in its equivalent doses, which can facilitate adherence to treatment. Regardless of the pattern of administration, cholecalciferol may be more likely to achieve serum levels of 25(OH)D (25-hydroxy-vitamin D) of 30-50 ng/mL, an interval considered optimal for maximum benefit at the lowest risk. In summary, the form of vitamin D of choice for exogenous supplementation should be cholecalciferol, with calcifediol reserved for patients with liver failure or severe intestinal malabsorption syndromes.
Topics: Animals; Calcifediol; Cholecalciferol; Dietary Supplements; Humans; Musculoskeletal System; Osteoporosis; Vitamin D; Vitamin D Deficiency
PubMed: 32486496
DOI: 10.3390/nu12061617 -
Nutrients Mar 2022Vitamin D deficiency is the main cause of nutritional rickets in children and osteomalacia in adults. There is consensus that nutritional access to vitamin D can be... (Review)
Review
Vitamin D deficiency is the main cause of nutritional rickets in children and osteomalacia in adults. There is consensus that nutritional access to vitamin D can be estimated by measuring serum concentrations of 25OHD and vitamin D deficiency can thus be considered as calcifediol deficiency. However, the threshold for vitamin D/calcifediol sufficiency remains a matter of debate. Vitamin D/calcifediol deficiency has been associated with musculoskeletal effects but also multiple adverse extra-skeletal consequences. If these consequences improve or if they can be treated with vitamin D supplementation is still unclear. Observational studies suggest a higher infection risk in people with low calcifediol levels. There is also a consistent association between serum calcifediol and cardiovascular events and deaths, but large-scale, long-term intervention studies did not show any benefit on cardiovascular outcomes from supplementation, at least not in subjects without clear vitamin D deficiency. Cancer risk also did not change with vitamin D treatment, although there are some data that higher serum calcifediol is associated with longer survival in cancer patients. In pregnant women, vitamin D supplementation decreases the risk of pre-eclampsia, gestational diabetes mellitus, and low birth weight. Although preclinical studies showed that the vitamin D endocrine system plays a role in certain neural cells as well as brain structure and function, there is no evidence to support a beneficial effect of vitamin D in neurodegenerative diseases. Vitamin D supplementation may marginally affect overall mortality risk especially in elderly subjects with low serum calcifediol concentrations.
Topics: Aged; Calcifediol; Child; Cholecalciferol; Female; Humans; Pregnancy; Risk Factors; Vitamin D; Vitamin D Deficiency
PubMed: 35334824
DOI: 10.3390/nu14061168 -
Nutrients Apr 2019Recent evidence revealed extra skeleton activity of vitamin D, including prevention from cardiometabolic diseases and cancer development as well as anti-inflammatory... (Review)
Review
Recent evidence revealed extra skeleton activity of vitamin D, including prevention from cardiometabolic diseases and cancer development as well as anti-inflammatory properties. It is worth noting that vitamin D deficiency is very common and may be associated with the pathogenesis of insulin-resistance-related diseases, including obesity and diabetes. This review aims to provide molecular mechanisms showing how vitamin D deficiency may be involved in the insulin resistance formation. The PUBMED database and published reference lists were searched to find studies published between 1980 and 2019. It was identified that molecular action of vitamin D is involved in maintaining the normal resting levels of ROS and Ca, not only in pancreatic β-cells, but also in insulin responsive tissues. Both genomic and non-genomic action of vitamin D is directed towards insulin signaling. Thereby, vitamin D reduces the extent of pathologies associated with insulin resistance such as oxidative stress and inflammation. More recently, it was also shown that vitamin D prevents epigenetic alterations associated with insulin resistance and diabetes. In conclusion, vitamin D deficiency is one of the factors accelerating insulin resistance formation. The results of basic and clinical research support beneficial action of vitamin D in the reduction of insulin resistance and related pathologies.
Topics: Calcifediol; Gene Expression Regulation; Humans; Insulin; Insulin Resistance; Vitamin D; Vitamin D Deficiency
PubMed: 30959886
DOI: 10.3390/nu11040794 -
International Journal of Molecular... Dec 2020A high prevalence of vitamin D (calcidiol) serum deficiency has been described in several autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis... (Review)
Review
A high prevalence of vitamin D (calcidiol) serum deficiency has been described in several autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (AR), and systemic lupus erythematosus (SLE). Vitamin D is a potent immunonutrient that through its main metabolite calcitriol, regulates the immunomodulation of macrophages, dendritic cells, T and B lymphocytes, which express the vitamin D receptor (VDR), and they produce and respond to calcitriol. Genetic association studies have shown that up to 65% of vitamin D serum variance may be explained due to genetic background. The 90% of genetic variability takes place in the form of single nucleotide polymorphisms (SNPs), and SNPs in genes related to vitamin D metabolism have been linked to influence the calcidiol serum levels, such as in the vitamin D binding protein (VDBP; rs2282679 ), 25-hydroxylase (rs10751657 ), 1α-hydroxylase (rs10877012, ) and the vitamin D receptor ( (rs2228570), (rs1544410), (rs7975232), and (rs731236) . Therefore, the aim of this comprehensive literature review was to discuss the current findings of functional SNPs in , , , and associated to genetic risk, and the most common clinical features of MS, RA, and SLE.
Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Autoimmune Diseases; Autoimmunity; Calcifediol; Cholestanetriol 26-Monooxygenase; Cytochrome P450 Family 2; Gene Frequency; Genetics, Population; Haplotypes; Humans; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Risk Factors; Vitamin D-Binding Protein
PubMed: 33348854
DOI: 10.3390/ijms21249626 -
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 -
International Journal of Molecular... Feb 2023Vitamin D is necessary for the normal functioning of many organs, including the thyroid gland. It is, therefore, not surprising that vitamin D deficiency is considered a... (Review)
Review
Vitamin D is necessary for the normal functioning of many organs, including the thyroid gland. It is, therefore, not surprising that vitamin D deficiency is considered a risk factor for the development of many thyroid disorders, including autoimmune thyroid diseases and thyroid cancer. However, the interaction between vitamin D and thyroid function is still not fully understood. This review discusses studies involving human subjects that (1) compared vitamin D status (primarily determined by serum calcidiol (25-hydroxyvitamin D [25(OH)D]) levels) with thyroid function assessed by thyroid stimulating hormone (TSH), thyroid hormones, and anti-thyroid antibody levels; and (2) evaluated the effect of vitamin D supplementation on thyroid function. Due to the many inconsistencies in the results between the studies, it is still difficult to draw a definite conclusion on how vitamin D status affects thyroid function. Studies in healthy participants observed either a negative correlation or no association between TSH and 25(OH)D levels, while the results for thyroid hormones showed high variability. Many studies have observed a negative association between anti-thyroid antibodies and 25(OH)D levels, but equally many studies have failed to observe such an association. Regarding the studies that examined the effect of vitamin D supplementation on thyroid function, almost all observed a decrease in anti-thyroid antibody levels after vitamin D supplementation. Factors that could contribute to the high variability between the studies are the use of different assays for the measurement of serum 25(OH)D levels and the confounding effects of sex, age, body-mass index, dietary habits, smoking, and the time of year when the samples were collected. In conclusion, additional studies with larger numbers of participants are needed to fully understand the effect of vitamin D on thyroid function.
Topics: Humans; Thyroid Gland; Vitamin D; Vitamins; Vitamin D Deficiency; Thyroid Hormones; Thyrotropin; Calcifediol
PubMed: 36835005
DOI: 10.3390/ijms24043586 -
Nutrients Apr 2022Currently, there is abundant scientific evidence showing that the vitamin D endocrine system (VDES) is a highly complex endocrine system with multiple actions in... (Review)
Review
Currently, there is abundant scientific evidence showing that the vitamin D endocrine system (VDES) is a highly complex endocrine system with multiple actions in different regions of the body. The unequivocal presence of vitamin D receptors in different tissues related to fertility, and to specific aspects of women's health such as pregnancy, undoubtedly implies functions of this steroid hormone in both male and female fertility and establishes relationships with different outcomes of human gestation. In order to review the role of the VDES in human fertility, we evaluated the relationships established between 25-hydroxyvitamin D (calcifediol) deficiency and in vitro fertilization, as well as aspects related to ovarian reserve and fertility, and commonly diagnosed endocrinopathies such as polycystic ovary disease. Likewise, we briefly reviewed the relationships between calcifediol deficiency and uterine fibroids, as well as the role that treatment may have in improving human fertility. Finally, the best scientific evidence available on the consequences of calcifediol deficiency during pregnancy is reviewed in relation to those aspects that have accumulated the most scientific literature to date, such as the relationship with the weight of the newborn at the time of delivery, the appearance of preeclampsia, and the risk of developing gestational diabetes and its final consequences for the pregnancy. To date, there is no definitive consensus on the necessary dose for treatment of calcifediol deficiency in the therapeutic management of infertility or during pregnancy. Large prospective clinical intervention studies are needed to clarify the benefits associated with this supplementation and the optimal dose to use in each situation. Although most intervention studies to date have been conducted with cholecalciferol, due to its much longer history of use in daily care, the use of calcifediol to alleviate 25-hydroxyvitamin D deficiency seems safe, even during pregnancy. The unequivocal presence of vitamin D receptors in very different tissues related to human fertility, both male and female, as well as in structures typical of pregnancy, allows us to investigate the crucial role that this steroid hormone has in specific aspects of women's health, such as pregnancy and the ability to conceive. Well-designed clinical studies are needed to elucidate the necessary dose and the best form of treatment to resolve the very common calcifediol deficiency in women of reproductive age.
Topics: Calcifediol; Female; Fertility; Hormones; Humans; Infant, Newborn; Male; Pregnancy; Prospective Studies; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency; Vitamins; Women's Health
PubMed: 35565788
DOI: 10.3390/nu14091820 -
The Journal of Clinical Endocrinology... Apr 2017Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Vitamin D deficiency disproportionately affects nonwhite individuals. Controversy persists over how to best restore low 25D levels, and how to best define vitamin D status [total (protein bound plus free) vs free 25D].
OBJECTIVE
To assess the effects of vitamin D3 (cholecalciferol, or D3) vs 25-hydroxyvitamin D3 (calcifediol, or 25D3) on total and free 25D in a multiethnic cohort of adults, and whether change in parathyroid hormone (PTH) is more strongly associated with total vs free 25D.
DESIGN
Sixteen-week randomized controlled trial. Biochemistries at 0, 4, 8, and 16 weeks.
SETTING
Academic medical center.
PARTICIPANTS
Thirty-five adults ≥18 years of age with 25D levels <20 ng/mL.
INTERVENTION
Sixty micrograms (2400 IU)/d of D3 or 20 μg/d of 25D3.
MAIN OUTCOME MEASURES
Total and free 25D, and PTH.
RESULTS
Baseline total (16.2 ± 3.7 vs 17.0 ± 2.5 ng/mL; P = 0.4) and free (4.2 ± 0.8 vs 4.7 ± 1.0 pg/mL; P = 0.2) 25D were similar between D3 and 25D3 groups, respectively; 25D3 increased total (+25.5 vs +13.8 ng/mL; P = 0.001) and free (+6.6 vs +3.5 pg/mL; P = 0.03) 25D more than D3. By 4 weeks, 87.5% of 25D3 participants had total 25D levels ≥30 ng/mL, compared with 23.1% of D3 participants (P = 0.001). Change in PTH was associated with both total (P = 0.01) and free 25D (P = 0.04).
CONCLUSIONS
25D3 increased total and free 25D levels more rapidly than D3, regardless of race/ethnicity. Free and total 25D were similarly associated with change in PTH.
Topics: Adult; Calcifediol; Calcium; Cholecalciferol; Female; Humans; Male; Middle Aged; Parathyroid Hormone; Vitamin D; Vitamin D Deficiency; Young Adult
PubMed: 28187226
DOI: 10.1210/jc.2016-3919 -
The British Journal of Dermatology Nov 2019Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status.
OBJECTIVES
To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday.
METHODS
The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D [25(OH)D ] was assessed by high-performance liquid chromatography-tandem mass spectrometry.
RESULTS
Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D (28·0 ± 16·5 nmol L ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L 25(OH)D , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L 25(OH)D .
CONCLUSIONS
Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission.
Topics: Administration, Cutaneous; Adult; Calcifediol; Female; Healthy Volunteers; Holidays; Humans; Male; Middle Aged; Poland; Skin; Skin Neoplasms; Spain; Sun Protection Factor; Sunburn; Sunlight; Sunscreening Agents; Treatment Outcome; Ultraviolet Rays
PubMed: 31069787
DOI: 10.1111/bjd.17888