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The synthesis of vitamin D3 (cholecalciferol, D3) occurs at the skin where pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 in response to sunlight exposure (ultraviolet B radiation). Vitamin D3, obtained from the isomerization of pre-vitamin D3 in the epidermal basal layers, or intestinal absorption of natural and fortified foods and supplements D2 (ergocalciferol) and D3, binds to vitamin D-binding protein (DBP) in the bloodstream, and is transported to the liver. D2 and D3 are hydroxylated by liver 25-hydroxylases. The resultant 25-hydroxycholecalciferol [25(OH)D] (calcifediol or calcidiol) is 1-hydroxylated in the kidney by 1α-hydroxylase. This yields the active secosteroid 1,25(OH)2D (calcitriol), which has different effects on various target tissues. The synthesis of 1,25(OH)2D from 25(OH)D is stimulated by the parathyroid hormone and suppressed by calcium, phosphate, and 1,25(OH)2D itself.
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Studies on vitamin/hormone D deficiency have received a vast amount of attention in recent years, particularly concerning recommendations, guidelines, and treatments. Moreover, vitamin D’s role as a hormone has been confirmed in various enzymatic, metabolic, physiological, and pathophysiological processes related to many organs and systems in the h...
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Context 1
... D3 is synthesized at a cutaneous level from 7-dehydrocholesterol (provitamin D) during exposure to ultraviolet rays of sunlight (wavelengths 290-320 nm). Previtamin D3 is thermally unstable and isomerizes into vitamin D3 (cholecalciferol) after a rearrangement of the triene structure of the molecule [17] (Figure 1). Exposure to UV radiation, amounting to 25% of the minimum erythematic dose (MED) over about a quarter of skin surface (face, hands, and arms) would produce the equivalent of 1000 IU of vitamin D [19]. ...
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Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of calcidiol monohydrate as a novel food (NF) pursuant to Regulation (EU) 2015/2283, including its bioavailability as a metabolite of vitamin D3 when added for nutritional purposes to food...
Citations
... It is a fat-soluble vitamin that also acts as a prohormone. It is a chemical secosteroid in nature and maintains the balance of calcium and phosphate ions in our body by promoting their absorption (1). Vitamin D can be acquired in two ways. ...
Vitamin D deficiency has emerged as a global health concern, affecting populations across various geographical and socioeconomic spectrums. This study, conducted at the National Institute of Nuclear Medicine and Allied Sciences (NINMAS) in Shahbag, Dhaka, investigates the prevalence and determinants of Vitamin D deficiency among 1,819 individuals who have visited for their regular health check-up. Utilizing retrospective data from the Laboratory Information System of the Chemiluminescence Immunoassay (CLIA) laboratory of In-vitro and Radiochemistry Division of NINMAS, we analyzed Vitamin D levels alongside demographic variables and seasonal fluctuations to elucidate patterns of deficiency within this cohort. Our findings reveal a widespread Vitamin D deficiency, with 62.1% of the studied population exhibiting levels below 20 ng/mL, indicative of deficiency. A gender disparity was evident, with females comprising 74.7% of those deficient, compared to 25.3% of males. The overall mean Vitamin D level was recorded at 19.73 ± 11.94 ng/mL, with a slight male predominance in Vitamin D concentrations (20.80 ± 11.48 ng/mL for males vs. 19.33 ± 12.11 ng/mL for females). Seasonal analysis further underscored higher Vitamin D levels during the summer months, pointing towards the impact of sun exposure on Vitamin D synthesis. Conclusively, the substantial prevalence of Vitamin D deficiency underscores an urgent need for comprehensive public health strategies aimed at addressing this issue within the Bangladeshi population. Strategies may include promoting dietary sources of Vitamin D, enhancing public awareness about the importance of sun exposure, and considering food fortification programs. Bangladesh J. Nuclear Med. 27(1): 89-94, 2024
... The study of the healthy general population of northern Taiwan showed that the predictors of vitamin D deficiency were female sex, lower age, high educational status, living in an urban area, and physical inactivity, while our study showed that female sex and early age at diagnosis were risk factors. Vitamin D is mainly synthesized in the skin upon exposure to sunlight, and 20% is obtained from dietary sources 26,30,36 . Previous studies found a high prevalence of vitamin D deficiency among patients with IBD 26,43,44 . ...
Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn’s disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.
... Es necesario la implementación de estudios observacionales que tengan en cuenta una población heterogénea y real. El tamizaje de vitamina D ha aumentado con los años, tomando como parámetro de deficiencia severa un resultado menor a 30 nmol/l, (16,17)pero no quiere decir que un valor de 30 o levemente superior represente un valor óptimo, sigue siendo deficiente solo cuando supera los 50 nmol/l pág. 9 se considera adecuado. Se ha reportado en Europa, Canadá y Estados Unidos hasta un 40% de la población con deficiencia y un 13% con deficiencia severa (6). ...
El apoyo hormonal con vitamina D como coadyuvante en la remodelación ósea en fracturas ha recibido una gran atención en los últimos años, particularmente por el déficit de vitamina D que ha llegado a ser un problema a nivel mundial asociado enfermedades musculoesqueléticas como la osteomalacia, osteopenia y empeoramiento de la osteoporosis. El efecto de la vitamina D sobre la homeostasis ósea se ha vuelto evidente en procesos enzimáticos, metabólicos y fisiológicos, es por esto que se cree que un déficit de la misma puede generar un retraso en la adecuada consolidación ósea en un paciente cuando presenta una fractura, hasta la fecha es poca la evidencia que existe sobre directrices y tratamiento con vitamina D como suplemento en fracturas para una adecuada remodelación ósea, los estudios existente son limitados y poco concluyentes. Teniendo en cuenta lo anterior se presenta un caso de una paciente con una fractura compleja de fémur a la cual se le inició suplementación dietaria con vitamina D como alternativa para su tratamiento.
... This active form is crucial for calcium absorption and bone health. The measurement of 25(OH)D is preferred in clinical settings because it has a longer half-life and reflects overall vitamin D reserves more accurately than the highly regulated 1,25(OH) 2 D [1,2]. ...
... Vitamin D, a fat-soluble vitamin, plays an important role in calcium homeostasis and bone metabolism [1][2][3]. Beyond these traditional roles, emerging evidence suggests a significant impact of vitamin D on the immune system, particularly in the prevention of infections [3][4][5]. Epidemiological studies have consistently shown a link between vitamin D deficiency and increased susceptibility to infectious diseases, including respiratory infections [6][7][8]. ...
Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This cross-sectional study, conducted from May 2022 to December 2023 in Timisoara, Romania, aimed to evaluate the potential influence of vitamin D supplementation on the incidence of respiratory infections among preschool-age children. This study examined 215 children over 18 months who were split into a group of patients with recurrent respiratory infections (n = 141) and another group of patients with only one respiratory tract infection in the past 12 months (n = 74). Patients were evaluated based on their serum vitamin D levels 25(OH)D, demographic characteristics, and health outcomes. The study identified that preschool-age children with recurrent infections had significantly lower mean vitamin D concentrations (24.5 ng/mL) compared to the control group (29.7 ng/mL, p < 0.001). Additionally, a higher proportion of vitamin D deficiency was observed among children with recurrent infections in the past 12 months. Notably, vitamin D supplementation above 600 IU/week significantly reduced the likelihood of respiratory infections, evidenced by an odds ratio of 0.523 (p < 0.001), indicating that preschool-age children receiving a dose of vitamin D higher than 600 IU/week were about half as likely to experience respiratory infections compared to those who did not. Furthermore, no significant associations were found between sun exposure, daily sunscreen use, and the incidence of respiratory infections. Conclusively, this study underscores the potential role of vitamin D in helping the immune system against respiratory infections in preschool-age children. The observed protective effect of vitamin D supplementation suggests a potential public health strategy to mitigate the incidence of respiratory infections in preschool children on top of the already known benefits.
... In the 12 studies included, we observed that lower baseline 25OHD levels increased the risk of developing diabetes by Figure 4 shows the association between lower baseline serum 25OHD levels and incident diabetes at follow-up after adjusting for potential confounders. The median number of adjustments in the multivariable analyses was 11 (range: [4][5][6][7][8][9][10][11][12][13][14][15][16][17], with all the studies including adiposity estimates, as fully detailed in Table 1. In the 12 studies included, we observed that lower baseline 25OHD levels increased the risk of developing diabetes by 19% (HR = 1.22; 95% CI: 1.12-1.33; ...
... The most recent meta-analysis by Pittas et al. [24] with a very rigorous and wellconducted design showed that supplementation with vitamin D reduced the risk for incident diabetes by 15% in adjusted analyses, reaching a reduction of 76% in participants maintaining 25-OHD levels ≥50 ng/mL vs. 20-29 ng/mL during follow-up. These results are outstanding; however, the meta-analysis included a population of adults or not very old people rather than older adults who are at greatest risk of both, hypovitaminosis D [14,25] and type 2 diabetes [1,26]. ...
... Several mechanisms may help explain our findings of a significant association between low vitamin D levels and an increased risk of incident diabetes, including vitamin D's modulation of insulin secretion [16,[53][54][55]; a reduction of insulin resistance with evidence of vitamin D receptor (VDR) presence in the major insulin-sensitive tissues, i.e., adipocytes [56], muscle [57], and hepatocytes [58]; improved insulin reactivity for glucose transport [59,60]; indirectly through the regulation of calcium [60][61][62][63][64] and magnesium [65][66][67] metabolism, essential for intracellular processes mediated by insulin; a reduction of chronic inflammation [67][68][69][70][71]; because most patients affected by type 2 diabetes are obese, they may have repression of the bioactivation of vitamin D by cytochrome P450 2R1 [72,73] leading to reduced production of 25OHD; and finally, vitamin D sequestration in excess adipose tissue may blunt vitamin D serum levels [14,74]. ...
Vitamin D deficiency is very common worldwide, particularly in old age, when people are at the highest risk of the negative adverse consequences of hypovitaminosis D. Additionally to the recognized functions in the regulation of calcium absorption, bone remodeling, and bone growth, vitamin D plays a key role as a hormone, which is supported by various enzymatic, physiological, metabolic, and pathophysiological processes related to various human organs and systems. Accruing evidence supports that vitamin D plays a key role in pancreatic islet dysfunction and insulin resistance in type 2 diabetes. From an epidemiological viewpoint, numerous studies suggest that the growing incidence of type 2 diabetes in humans may be linked to the global trend of prevalent vitamin D insufficiency. In the past, this association has raised discussions due to the equivocal results, which lately have been more convincing of the true role of vitamin D supplementation in the prevention of incident type 2 diabetes. Most meta-analyses evaluating this role have been conducted in adults or young older persons (50–60 years old), with only one focusing on older populations, even if this is the population at greater risk of both hypovitaminosis D and type 2 diabetes. Therefore, we conducted an update of the previous systematic review and meta-analysis examining whether hypovitaminosis D (low serum 25OHD levels) can predict incident diabetes in prospective longitudinal studies among older adults. We found that low 25OHD was associated with incident diabetes in older adults even after adjusting for several relevant potential confounders, confirming and updating the results of the only previous meta-analysis conducted in 2017.
... Vitamin D is a hormone, best known for its role in calcium and phosphate metabolism related to bone health [1,2]. Beyond its traditional role in bone metabolism, Vitamin D has diverse physiological functions and is thought to be involved in the suppression of immune-mediated diseases, infections, certain cancers, and cardiovascular disease [3]. ...
The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5–60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30–60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.
... p=0.014. Deficiency Vt.D was found in 63.6% of the total depressive adolescents and was significantly more than nondepressive adolescents 3. 8%, p<0.0001, with (B: 3.199, OR: 24.5,). Serum Vt.D level was significantly decreased in depressive adolescent median (IQR) 18.8(13.1₋28.9) ...
... Serotonin (5-HT) is a vital neurotransmitter in the central nervous system as well as a regulatory hormone that regulates a wide variety of physiological functions. Perhaps the most classically defined roles of 5-HT are central to mood, sleep, and anxiety management and peripheral to gastrointestinal motility modulation [8]. However, 5-HT has recently been recognized as an important metabolic hormone that contributes to glucose homeostasis and obesity, with a causal association between circulating 5-HT levels and metabolic disorders (9). ...
Vitamin D deficiency (Vt.D) is common in adolescents and is influenced by some factors, including puberty. It impacted serotonin levels, thus increasing the risk of depression. This study was conducted to assess the association between vitamin D deficiency and depression and its effect on adolescent students. A cross-sectional study of 130 adolescent students aged 12-18 years, between November 2023 to February 2024. This study investigated serum Vt.D, serotonin levels, and hematological indices such as (RBC, Hb, MCV, and MCH, of adolescents, in addition, it was dependent on the Beck Depression Inventory to calculate scales of depression. 130 adolescent students were enrolled aged 12-18, mean ± SD: 14.85±2.19. The results indicated that 77(59.2%) students had depression symptoms, median (IQR) of scores16(13₋21.5), and 53(40.8%) adolescents with non-depressed (scores 5(2.5₋7), who were considered as the control group, a statistically significant between these groups (p=0.035). Depression was significantly more prevalent in females 46(59.7%) than males 31(40.3%), p=0.014. Deficiency Vt.D was found in 63.6% of the total depressive adolescents and was significantly more than nondepressive adolescents 3.8%, p<0.0001, with (B: 3.199, OR: 24.5, 95%CI: 5.96 -100.74). Serum Vt.D level was significantly decreased in depressive adolescent median (IQR) 18.8(13.1 ₋28.9) ng/ml, compared with non-depressed 52.22(42.2₋62.4), (p< 0.0001), and its lowest in a type of severe depression 10.74±3.52. The depressive adolescent group had significantly lower serotonin levels in deficiency Vt.D status than non-depressive groups (143.39±60.91 vs. 314.05±46.11), p = 0.001). Correlations and linear regression analysis to predict the risk factors for depression scores showed a significant negative correlation with levels of Vt.D (r=0.786, B: -0.109, 95%CI: -0.15 to -0.065, p<0.0001), and serotonin (r=0.848, B: 0.003, 95%CI: -0.032 to -0.019, p<0.0001), respectively. Deficiency Vt.D is an important risk factor for adolescents, especially in females, and is associated with an increased risk of depression in adolescent students
... The most important steps of vitamin D metabolism are summarized in the simplified vitamin D flow chart shown in Figure 1. For detailed information on the complex metabolism of vitamin D, the reader is referred to current reviews [29][30][31][32]. For clarity, we refer to the essential form of vitamin D for humans, vitamin D 3 , also known as cholecalciferol, in the text below. ...
Clinical and preclinical studies have provided conflicting data on the postulated beneficial effects of vitamin D in patients with prostate cancer. In this opinion piece, we discuss reasons for discrepancies between preclinical and clinical vitamin D studies. Different criteria have been used as evidence for the key roles of vitamin D. Clinical studies report integrative cancer outcome criteria such as incidence and mortality in relation to vitamin D status over time. In contrast, preclinical vitamin D studies report molecular and cellular changes resulting from treatment with the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) in tissues. However, these reported changes in preclinical in vitro studies are often the result of treatment with biologically irrelevant high calcitriol concentrations. In typical experiments, the used calcitriol concentrations exceed the calcitriol concentrations in normal and malignant prostate tissue by 100 to 1000 times. This raises reasonable concerns regarding the postulated biological effects and mechanisms of these preclinical vitamin D approaches in relation to clinical relevance. This is not restricted to prostate cancer, as detailed data regarding the tissue-specific concentrations of vitamin D metabolites are currently lacking. The application of unnaturally high concentrations of calcitriol in preclinical studies appears to be a major reason why the results of preclinical in vitro studies hardly match up with outcomes of vitamin D-related clinical studies. Regarding future studies addressing these concerns, we suggest establishing reference ranges of tissue-specific vitamin D metabolites within various cancer entities, carrying out model studies on human cancer cells and patient-derived organoids with biologically relevant calcitriol concentrations, and lastly improving the design of vitamin D clinical trials where results from preclinical studies guide the protocols and endpoints within these trials.
... Then, pre-vitamin D3 can be isomerized to vitamin D3. Once formed, vitamin D enters the circulation and is metabolized first to 25 hydroxyvitamin D (25(OH)D) in the liver, then to the hormonal/active form 1,25-dihydroxyvitamin D (calcitriol) in the kidneys ( Figure 1) [1][2][3]. Vitamin D has numerous functions in the human body such as promoting calcium absorption in the gut, maintaining adequate serum calcium and phosphate concentrations, bone growth and remodeling, reducing inflammation, as well as modulation processes such as cell growth, neuromuscular and immune function, and glucose metabolism [4]. ...
The synthesis and absorption of Vitamin D play crucial roles in numerous bodily functions, yet deficiencies persist due to factors like insufficient sunlight exposure and dietary inadequacy. Research underscores the significance of lifestyle elements such as diet, sun exposure, and physical activity in maintaining optimal Vitamin D levels. Strategies aimed at tackling deficiencies emphasize supplementation alongside lifestyle adjustments, especially in regions with abundant sunlight like the Middle East and North Africa (MENA).
Despite the abundance of sunshine in the Arab world, there remains a prevalent issue of Vitamin D deficiency. This problem arises from various factors, including cultural practices such as traditional clothing covering most skin areas, which limit sun exposure, and environmental factors like air pollution that reduce UV penetration. Dietary habits and lifestyle choices also contribute to this deficiency.
Dealing with the ongoing pandemic requires a focused effort to enhance awareness. While some individuals may recognize common diseases caused by Vitamin D deficiency, such as rickets and osteomalacia, many remain unaware of the broader health risks associated with the condition, including non-skeletal manifestations. Additionally, there is a lack of understanding regarding the numerous hidden benefits of this hormone. Therefore, prioritizing educational initiatives that delve into these aspects is essential to effectively combat the current health crisis.
This literature review aims to report both skeletal and extraskeletal consequences of hypovitaminosis and briefly discuss the cause of paradoxical vitamin D deficiency in sunny regions like the MENA.
This was done by reviewing pertinent articles published between January 2000 and January 2024, sourced from databases such as PubMed, UpToDate, Scopus, and CINAHL, focusing exclusively on English language literature and using keywords such as “Vitamin D deficiency” and “Extraskeletal manifestations.”
... Vit D is a fat-soluble vitamin and is enzymatically converted in the liver to 25hydroxyvitamin D (25(OH)D), which is the main form of circulation of Vit D [1]. 25(OH)D is further hydroxylated in the kidney to 1,25(OH) 2 D, which is its active form. ...
Background:
Few studies have correlated maternal and neonatal Vit D (25(OH)D) levels at birth in Greece. We investigated this potential association, taking into account the administration or not of low doses (400-800 IU) of prenatal Vit D supplements. Our study contributes evidence not only to the small amount of existing literature regarding the above correlation, but also to the topic of maternal and neonatal vitamin D deficiency (VDD) during pregnancy in Mediterranean countries, such as Greece.
Methods:
A cross-sectional study was conducted on 248 neonates and their mothers from September 2019 to January 2022. Blood samples of 25(OH)D were studied at the time of delivery. Frequency counts and percentages were registered, and logistic regression was used to investigate the independent factors associated with maternal Vit D status. The Chi-square test and the Pearson coefficient were used to demonstrate a possible association between maternal and neonatal 25(OH)D levels.
Results:
Our findings show a high prevalence of VDD in Greek women and their newborns at birth. This was observed not only in women who did not receive Vit D supplements, but also in all the study groups, especially in the autumn and winter months. We observed that mothers who received low doses (400-800 IU) of prenatal Vit D supplements increased both their own 25(OH)D concentrations and those of their newborns; however, the latter did not seem to be completely covered by the prenatal administration of Vit D because, although their 25(OH)D concentrations increased, they never reached sufficient 25(OH)D levels, unlike their mothers who reached sufficient concentrations.
Conclusions:
Overall, this study highlights the strong association between maternal and neonatal 25(OH)D concentrations at the end of gestation. However, neonates tended to show even lower 25(OH)D concentrations relative to maternal 25(OH)D concentrations. The same phenomenon was observed irrespective of the administration of Vit D supplements during pregnancy. Moreover, this is what was observed concerning the administration of formulations with 400-800 IU of Vit D, which the doctors in our clinic used in the present study. In any case, more clinical studies related to the administration of higher doses of Vit D supplementation to pregnant women would lead to more reliable conclusions. Without a doubt, the measurement of maternal vitamin D status during pregnancy provides opportunities for preventive and therapeutic interventions in the mother-infant pair.
