Fig 4 - uploaded by Michael F Holick
Content may be subject to copyright.
![Schematic representation of the synthesis and metabolism of vitamin D for regulating calcium, phosphorus and bone metabolism. During exposure to sunlight 7-dehydrocholesterol (7-DHC) in the skin is converted to previtamin D 3 (preD 3 ). PreD 3 immediately converts by a heat dependent process to vitamin D 3 . Excessive exposure to sunlight degrades previtamin D 3 and vitamin D 3 into inactive photoproducts. Vitamin D 2 and vitamin D 3 from dietary sources are incorporated into chylomicrons, transported by the lymphatic system into the venous circulation. Vitamin D (D represents D 2 or D 3 ) made in the skin or ingested in the diet can be stored in and then released from fat cells. Vitamin D in the circulation is bound to the vitamin D binding protein which transports it to the liver where vitamin D is converted by the vitamin D-25-hydroxylase (25-OHase) to 25-hydroxyvitamin D [25(OH)D]. This is the major circulating form of vitamin D that is used by clinicians to measure vitamin D status (although most reference laboratories report the normal range to be 20-100 ng/ml, the preferred healthful range is 30-60 ng/ml). 25(OH)D is biologically inactive and must be converted in the kidneys by the 25-hydroxyvitamin D-1α- hydroxylase (1-OHase) to its biologically active form 1,25-dihydroxyvitamin D [1,25(OH) 2 D]. Serum phosphorus, calcium, fibroblast growth factor (FGF-23) and other factors can either increase (+) or decrease (-) the renal production of 1,25(OH) 2 D. 1,25(OH) 2 D feedback regulates its own synthesis and decreases the synthesis and secretion of parathyroid hormone (PTH) in the parathyroid glands. 1,25(OH) 2 D increases the expression of the 25-hydroxyvitamin D-24-hydroxylase (24-OHase) to catabolize 1,25(OH) 2 D and 25(OH)D to the water soluble biologically inactive calcitroic acid which is excreted in the bile. 1,25(OH) 2 D enhances intestinal calcium absorption in the small intestine by stimulating the expression of the epithelial calcium channel (ECaC; also known as transient receptor potential cation channel sub family V member 6; TRPV6)) and the calbindin 9K (calcium binding protein; CaBP). 1,25(OH) 2 D is recognized by its receptor in osteoblasts causing an increase in the expression of receptor activator of NFκB ligand (RANKL). Its receptor RANK on the preosteoclast binds RANKL which induces the preosteoclast to become a mature osteoclast. The mature osteoclast removes calcium and phosphorus from the bone to maintain blood calcium and phosphorus levels. Adequate calcium and phosphorus levels promote the mineralization of the skeleton and maintain neuromuscular function. Holick copyright 2007. Reproduced with permission.](profile/Michael-Holick/publication/46008214/figure/fig4/AS:340523920445443@1458198637521/Fig-4-Schematic-representation-of-the-synthesis-and-metabolism-of-vitamin-D-for.png)
Schematic representation of the synthesis and metabolism of vitamin D for regulating calcium, phosphorus and bone metabolism. During exposure to sunlight 7-dehydrocholesterol (7-DHC) in the skin is converted to previtamin D 3 (preD 3 ). PreD 3 immediately converts by a heat dependent process to vitamin D 3 . Excessive exposure to sunlight degrades previtamin D 3 and vitamin D 3 into inactive photoproducts. Vitamin D 2 and vitamin D 3 from dietary sources are incorporated into chylomicrons, transported by the lymphatic system into the venous circulation. Vitamin D (D represents D 2 or D 3 ) made in the skin or ingested in the diet can be stored in and then released from fat cells. Vitamin D in the circulation is bound to the vitamin D binding protein which transports it to the liver where vitamin D is converted by the vitamin D-25-hydroxylase (25-OHase) to 25-hydroxyvitamin D [25(OH)D]. This is the major circulating form of vitamin D that is used by clinicians to measure vitamin D status (although most reference laboratories report the normal range to be 20-100 ng/ml, the preferred healthful range is 30-60 ng/ml). 25(OH)D is biologically inactive and must be converted in the kidneys by the 25-hydroxyvitamin D-1α- hydroxylase (1-OHase) to its biologically active form 1,25-dihydroxyvitamin D [1,25(OH) 2 D]. Serum phosphorus, calcium, fibroblast growth factor (FGF-23) and other factors can either increase (+) or decrease (-) the renal production of 1,25(OH) 2 D. 1,25(OH) 2 D feedback regulates its own synthesis and decreases the synthesis and secretion of parathyroid hormone (PTH) in the parathyroid glands. 1,25(OH) 2 D increases the expression of the 25-hydroxyvitamin D-24-hydroxylase (24-OHase) to catabolize 1,25(OH) 2 D and 25(OH)D to the water soluble biologically inactive calcitroic acid which is excreted in the bile. 1,25(OH) 2 D enhances intestinal calcium absorption in the small intestine by stimulating the expression of the epithelial calcium channel (ECaC; also known as transient receptor potential cation channel sub family V member 6; TRPV6)) and the calbindin 9K (calcium binding protein; CaBP). 1,25(OH) 2 D is recognized by its receptor in osteoblasts causing an increase in the expression of receptor activator of NFκB ligand (RANKL). Its receptor RANK on the preosteoclast binds RANKL which induces the preosteoclast to become a mature osteoclast. The mature osteoclast removes calcium and phosphorus from the bone to maintain blood calcium and phosphorus levels. Adequate calcium and phosphorus levels promote the mineralization of the skeleton and maintain neuromuscular function. Holick copyright 2007. Reproduced with permission.
Source publication
Vitamin D, the sunshine vitamin, has been important not only for the evolution of a healthy calcified vertebrate skeleton but it also evolved into a hormone that has a wide diversity of biologic effects. During exposure to sunlight the ultraviolet B radiation converts 7-dehydrocholesterol to previtamin D(3) which in turn rapidly isomerizes to vitam...
Contexts in source publication
Context 1
... It travels to the liver where it is converted to 25-hydroxyvitamin D [25(OH)D], which is considered to be the major circulating form of vitamin D that is measured to determine a person's vitamin D status [3,15]. However 25(OH)D is biologically inert and travels on the DBP to the kidneys where it is converted to 1,25-dihydroxyvitamin D [1,25(OH) (Fig. 4). Once formed 1,25(OH) 2 D bound to DBP enters the circulation and its free-form enters target tissues that regulate calcium and phosphorus metabolism. In the intestine 1,25(OH) 2 D interacts with its vitamin D receptor (VDR) to enhance the expression of an epithelial calcium channel which results in the enhanced transport of calcium ...
Context 2
... binding protein (calbindin9k) and other proteins that helps the transport of calcium through the intestinal absorptive cell to this the serosal side depositing it into the circulation [16]. When 1,25(OH) 2 D enters the skeleton it interacts with its VDR in the osteoblast to increase the expression of RANKL (receptor activator of NFκB ligand) [17] (Fig. 4). Monocytic preosteoclasts have the receptor RANK which interacts with RANKL causing signal transduction resulting in the forma- tion of multi-nucleated osteoclasts which are capable of releasing HCl to dissolve the bone mineral and collagenases to destroy the matrix releasing calcium into the circulation. 1,25(OH) 2 D also interacts ...
Context 3
... parathyroid hormone (PTH) production [1,15]. In the intestine 1,25(OH) 2 D stimulates phosphorus absorption. Thus the major physiologic functions of vitamin D are to maintain serum calcium and phosphorus in physio- logic acceptable ranges to support not only most metabolic functions but also to guarantee the mineralization of the skeleton (Fig. ...
Context 4
... osteoclasts to remove precious calcium stores from the skeleton. It also enhances the renal production of 1,25(OH) 2 D which in turn travels to the bone and intestine to regulate calcium metabolism. The increase in PTH also causes and internalization of the sodium-phosphorus cotransporter resulting in the loss of phosphorus into the urine [1,31] (Fig. ...
Citations
... According to Holick [13], children were classified into 'Sufficient' when serum vitamin D level is ranging between 30 and 100 ng / ml, 'Insufficient' when it is 20-30 ng / ml, and 'Deficient' less than 20 ng / ml. ...
Background Dental caries is one of the most common diseases of childhood. Evidence suggests that malnutrition and vitamin deficiency may increase the risk to dental caries. Aim This study aimed to determine the relationship between vitamin D and dental caries experience in children and whether vitamin D deficiency is a risk factor for tooth decay. Participants and methods A cross-sectional study was performed on 51 Egyptian children, aged from three to five years and diagnosed from Abo El-Resh Children's Hospital as 'Sufficient' , 'Insufficient' or 'Deficient' in vitamin D. Children were divided into 3 equal groups. A structured questionnaire, formed of four sections, was answered by the parents. Dental examination was performed under natural daylight. Caries index (dmf), for each group, was calculated then compared. The study was conducted from July 2019 to January 2020. Associations between dmf and different variables were assessed using independent t-test. Correlation between age and dmf was assessed using Spearman's rank order correlation coefficient. Multiple linear regression model was used to study the effect of different variables on caries. Results There was a weak positive correlation between age and dmf scores (β = 2.00; 95%CI, 0.73:3.26). Children playing outside experienced higher dmf (β = 1.29; 95%CI,-0.35:2.94) than those with no outside play. Children with 25(OH) D below 20 ng / ml had the highest dmfs (β = 1.01; 95%CI,-0.74:2.76). There was a significant association with teeth brushing; children not brushing their teeth showed significantly higher dmf (β =-2.21; 95%CI,-4.14:-0.28) than their counterparts. There were no significant associations of sex (β =-1.05; 95%CI,-2.68:0.59), fluoride tablets intake (β = 2.19; 95%CI,-1.25:5.63), dental visits (β =-1.43; 95%CI,-3.09:0.23), mothers' vitamin D intake during pregnancy (β = 0.71; 95%CI,-1.13:2.56), snacking (β =-1.18; 95%CI,-4.62:2.26) and parental education (β = 0.62; 95%CI,-1.18:2.42) with caries experience among the study population. Conclusion Vitamin D deficiency does not seem to be associated with dental caries experience of 3-5 years old Egyptian children. Out of the indicator variables, age and tooth brushing contributed significantly to the occurrence of dental caries among the study population.
... The food habits of the participants had five options for frequency of consumption ranging from "never" to "daily." Vitamin D was classified as follows: <20 ng/ml (50 nmol/L) as "deficient" and between 21 and 29 ng/ml (50-75 nmol/L) as "insufficient" (19). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated using the following formula: fasting insulin (microU/L) × fasting glucose (nmol/L)/22.5. ...
Introduction
India has a high prevalence of Vitamin D insufficiency among women of childbearing age. In this study, we aimed to evaluate the potential relationship between Vitamin D deficiency and gestational diabetes mellitus (GDM) and low birth weight (LBW) of newborns in the “Maternal antecedents of adiposity and studying the transgenerational role of hyperglycaemia and insulin” (MAASTHI) birth cohort.
Methods
A prospective cohort study involving 230 participants was conducted in public hospitals located in urban Bengaluru, India. Healthy pregnant women who visited these hospitals for antenatal care (ANC) and who were between 14 and 36 weeks of gestational age were recruited after obtaining their informed consent. An oral glucose tolerance test (OGTT) was administered between 24 and 36 weeks of pregnancy and blood samples were preserved at −80°C for Vitamin D analysis. Follow-up at birth included recording the child's birth weight.
Results
We found that 178 (77.4%) of the study participants were vitamin D deficient, 44 (19.1%) were diagnosed with GDM, and 64 (27.8%) gave birth to LBW babies. Women in the lowest quartile of serum Vitamin D levels had three times higher odds of developing GDM than women in the higher quartiles [OR = 3.22 (95% CI: 1.03, 10.07), p = 0.04] after adjusting for age, parity, socioeconomic status, season, and adiposity. For every one-unit increase in Vitamin D levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) decreased by nearly 18%. Furthermore, causal mediation analysis showed that a decrease in one unit of Vitamin D is associated with a decrease of 0.015 units of fasting blood sugar (FBS) and 0.019 units of postprandial blood sugar (PPBS) as it flows through the mediator variable insulin resistance. Vitamin D-deficient women were twice at risk of giving birth to LBW babies (OR 2.04, 95% CI 0.99, 4.19, p = 0.05).
Discussions
Low levels of Vitamin D during pregnancy are associated with a greater risk of pregnant women developing GDM and giving birth to LBW babies in urban Bengaluru.
... HDL, also called the "good" cholesterol due to it brings cholesterol from tissues to the liver, which removes it from the body. A low level of HDL cholesterol increases the risk of heart disease (78). ...
... Vitamin D, often referred to as the "sunshine vitamin," plays a crucial role in numerous physiological processes, including bone health, immune function, and inflammation regulation [5]. Emerging research has also suggested its involvement in T2DM pathophysiology. ...
This study investigates the relationship between vitamin D deficiency and uncontrolled type 2 diabetes mellitus (T2DM) indicated by elevated glycosylated hemoglobin (HbA1c) levels, alongside assessing the association between fasting C peptide levels and uncontrolled T2DM, considering their roles in β-cell function and insulin secretion. The study employs a cohort design, selecting individuals diagnosed with T2DM aged 18 years or older with baseline data on vitamin D, fasting C peptide, and HbA1c. Data were collected through electronic medical records and follow-up assessments at regular intervals. Binary logistic regression analyses were conducted to explore associations between exposure variables and uncontrolled T2DM. Significant associations were observed between vitamin D and C peptide levels with uncontrolled diabetes, with coefficients of -0.097 and -0.222, respectively. Higher vitamin D and C peptide levels are linked to a decreased likelihood of uncontrolled diabetes. In conclusion, there is a potential connection between vitamin D levels, C peptide levels, and uncontrolled diabetes mellitus (HbA1C > 7%), while higher levels of both vitamin D and C peptide appeared to correlate with a decreased likelihood of uncontrolled diabetes.
... In order to exert its hormonal activity, vitamin D undergoes two hydroxylation processes [6,20,21]. The first hydroxylation requires 25-hydroxylase, which facilitates the production of 25-hydroxyvitamin D 3 (25(OH)D 3 ) in the liver hepatocytes. ...
... The first hydroxylation requires 25-hydroxylase, which facilitates the production of 25-hydroxyvitamin D 3 (25(OH)D 3 ) in the liver hepatocytes. 25-hydroxyvitamin currently represents the standard marker for assessing vitamin D status in humans [21][22][23][24][25]. The second hydroxylation occurs in the proximal tubes in the kidneys and is performed using 1α-hydroxylase (CYP27B1), leading to the synthesis of calcitriol (1,25(OH) 2 D 3 ) [26]. ...
Vitamin D, a steroid hormone synthesized primarily in the skin upon exposure to ultraviolet light, is widely deficient across global populations. This study aimed to fill the data gap in Western Romania by measuring 25-hydroxy-vitamin D levels in a cohort of 7141 from Arad County. It was observed that women, younger adults (18–29 years), and older adults (70–79 years) had notably lower vitamin D levels compared to the average population. Additionally, there was a rise in vitamin D levels over the four-year span of 2018–2022, coinciding with the COVID-19 pandemic. Our research provides fresh data on those most susceptible to vitamin D deficiency and lays the groundwork for educational campaigns on vitamin D supplementation benefits.
... For those under 50, the daily requirement is 5 micrograms, while for those over 70, it is recommended to intake 15 micrograms daily (Nowson et al., 2012). A study conducted by Holick (2011) underscored the significance of maintaining adequate vitamin D levels, as insufficient vitamin D status can lead to the development of conditions like rickets in both children and adults. Research has indicated that inadequate vitamin D levels can potentially play a role in the development of various chronic conditions, including obesity and being overweight (Vranić et al., 2019). ...
... Vitamin D plays a critical role in bone development by maintaining calcium-phosphate homeostasis [1,2] and has a wide range of important biological functions in the body, including metabolism, growth, immunity, and the antioxidative status [3,4]. In pigs, vitamin D forms can be directly obtained from the dietary sources or produced in the body following the skin exposure to solar ultraviolet-B (UVB) [5][6][7][8]. ...
In the currently prevailing pig husbandry systems, the vitamin D status is almost exclusively dependent on dietary supply. Additional endogenous vitamin D production after exposure to ultraviolet-B (UVB) light might allow the animals to utilize minerals in a more efficient manner, as well as enable the production of functional vitamin D-enriched meat for human consumption. In this study, growing pigs (n = 16) were subjected to a control group or to a daily narrowband UVB exposure of 1 standard erythema dose (SED) for a period of 9 weeks until slaughter at a body weight of 105 kg. Transcriptomic profiling of liver with emphasis on the associated effects on vitamin D metabolism due to UVB exposure were evaluated via RNA sequencing. Serum was analyzed for vitamin D status and health parameters such as minerals and biochemical markers. The serum concentration of calcidiol, but not calcitriol, was significantly elevated in response to UVB exposure after 17 days on trial. No effects of UVB exposure were observed on growth performance and blood test results. At slaughter, the RNA sequencing analyses following daily UVB exposure revealed 703 differentially expressed genes (DEGs) in liver tissue (adjusted p-value < 0.01). Results showed that molecular pathways for vitamin D synthesis (CYP2R1) rather than cholesterol synthesis (DHCR7) were preferentially initiated in liver. Gene enrichment (p < 0.05) was observed for reduced cholesterol/steroid biosynthesis, SNARE interactions in vesicular transport, and CDC42 signaling. Taken together, dietary vitamin D supply can be complemented via endogenous production after UVB exposure in pig husbandry, which could be considered in the development of functional foods for human consumption.
... The prevalence of insufficient vitamin D levels across diverse populations and the potential association between inadequate vitamin D status and adverse health outcomes underscore the importance of addressing vitamin D deficiency as a significant public health issue [1][2][3][4]. Beyond its classical role in calcium homeostasis, emerging research indicates that vitamin D may have wider physiological implications, extending its impact on multiple organ systems and metabolic pathways [5,6]. Insufficient vitamin D levels are associated with a spectrum of adverse outcomes, including increased risks of osteoporosis, autoimmune diseases, cardiovascular disorders, and certain cancers [3]. ...
Vitamin D deficiency and its potential impact on testosterone levels have been subjects of scientific interest. This systematic review aims to evaluate the association between vitamin D deficiency and testosterone levels in adult males and examine the effects of vitamin D supplementation on testosterone. A comprehensive literature search was conducted in accordance with the PRISMA guidelines across PubMed, Google Scholar, and ScienceDirect. The inclusion criteria involved studies published in English between 2013 and 2023, which investigated the correlation between vitamin D and testosterone levels in adult males. The process of data extraction and synthesis encompassed various aspects, including study characteristics, participant demographics, measurement methods, and outcomes pertaining to the association. The initial search resulted in a pool of 354,235 articles. Through the application of relevant filters and the review of titles and abstracts, 48 articles were chosen for further assessment. Out of these, eight studies fulfilled the inclusion criteria and were ultimately incorporated into the final review. The included studies consisted of four cross-sectional studies, three randomized controlled trials (RCTs), and one analysis utilizing Mendelian randomization. The results showed heterogeneity among the studies, as some reported a positive correlation between vitamin D levels and testosterone, while others did not find a significant association. The effects of vitamin D supplementation on testosterone levels were inconclusive, with limited evidence of significant changes in total testosterone. However, potential influences on sex hormone-binding globulin and free testosterone levels were observed. To establish more definitive evidence regarding the impact of vitamin D on testosterone levels, there is a need for further well-designed, long-term RCTs that encompass diverse populations.
... Pale skin evolved approximately 8000 years ago among people who migrated north from Africa as an adaptation to maintain cutaneous vitamin D synthesis in environments with less sun exposure due to weaker sunlight 7 and also less skin exposure due to the clothing required in colder temperatures. 2 Vitamin D is important to several biological processes including calcium and phosphorous homeostasis, immune system modulation and maintenance of cardiovascular health, 8 thus, in geographies with limited sunlight, such as the northern parts of Europe, this genetic polymorphism presented a significant competitive advantage. Pale skin and northern European heritage are racialised as white, generally speaking. ...
... 5 Vitamin D is a principal micronutrient with great implications for human health. 6 Beside its well known role in maintaining bone health, vitamin D has been found to have other roles in the body. Studies in literature showed association between vitamin d levels and inflammatory markers. ...
