scholarly journals Endocrinology, Vitamin D and the UK’s Covid-19 Disaster

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A274-A275
Author(s):  
David Coussmaker Anderson ◽  
David S Grimes
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Vitamin D3 ◽  
Influenza Pandemic ◽  
Endocrine System ◽  
Endocrine Function ◽  
Food Sources ◽  
Endocrine Control ◽  
Blood Calcium ◽  
Ionic Calcium

Abstract The formation of cholecalciferol (Vitamin D3) in skin depends on solar UVB to break the B ring of 7-dehydrocholesterol. Its discovery more than a century ago resulted from the identification of rickets as due to deficient sunshine in latitudes far from the equator, exacerbated by the air pollution, factory work and indoor living. Rickets resulted from defective endocrine control of blood calcium, and was accompanied by epidemic tuberculosis from failure of the D3-dependent first-line immune system. The influenza pandemic of 2018 revealed the need for D3 to fight viruses. Half a century later the systemic hormone role of 1,25(OH)D3 of renal origin, under control of PTH, was a major stimulus to understanding the mechanism of action via the VDR-RXR heterodimer. It was soon realised that 1,25(OH)D3 is also produced and acts locally in many organs and tissues provided that there are adequate reserves of the (protein-bound) blood storage form, 25(OH)D. This is the common pool for 1-hydroxylation by any cells that need local activation of VDR for induction of specific genes. In the case of the immune system, the trigger is foreign proteins recognised as ‘non-self’. Local production and action of 1,25(OH)D, and then its local destruction by 24-hydroxylation must all occur below the ‘endocrine radar’, so as not to interfere with systemic calcium control. Coronaviruses through their ‘spike’ protein are internalised by interacting with the ACE-2 receptor, which in turn is down-regulated by Vitamin D. In the process, 25(OH)D is hydroxylated to the active 1,25(OH)D, which must later be degraded to 1,24,25(OH)D. So it is to be expected that when 25(OH)D reserves are low at the onset of infection, they will fall further, allowing virus to enter the cells and trigger a cytokine storm and other damage. Blood PTH will rise to claim any residual 25(OH)D for the dominating systemic role in calcium homeostasis. It follows that intake of vitamin D3 should always be much more than the minimum claimed by the globally-active endocrine system. Unfortunately, the UK’s Specialised Advisory Committee on Nutrition (SACN), does not recognise this. It is dominated by nutritionists, even though food sources of D3 are for most non-existent, and of D2, the vegetable substitute, highly variable. The 400IU of D3 reluctantly recommended for those ‘at risk’, based on endocrinology alone, is grossly inadequate; 4,000IU daily is needed to maintain a blood 25(OH)D at more than 30 ng/ml (75 nmol/l), and provide sufficient reserve for its many autocrine and paracrine functions. The dangers of letting the dominant endocrine function of 1,25(OH)D in ionic calcium control dictate the level of D3 supplements, have once again been underlined by the Covid-19 disaster.

scholarly journals Biochemistry and metabolism of vitamin D / Biohemija i metabolizam vitamina D

2012 ◽  
Vol 31 (4) ◽  
pp. 309-315 ◽  
Author(s):  
Snežana Jovičić ◽  
Svetlana Ignjatović ◽  
Nada Majkić-Singh
Keyword(s):  
Vitamin D ◽  
Cytochrome P450 ◽  
Vitamin D3 ◽  
Mammalian Cells ◽  
Parent Compound ◽  
Endocrine System ◽  
Target Cells ◽  
Plasma Vitamin ◽  
Endocrine Gland ◽  
Target Organs

Summary Vitamin D is not technically a vitamin, since it is not an essential dietary factor. It is rather a prohormone produced photochemically in the skin from 7-dehydrocholesterol. Vitamin D and its metabolites may be categorized as either cholecalciferols or ergocalciferols. Cholecalciferol (vi - tamin D3) is the parent compound of the naturally occurring family and is produced in the skin from 7-dehydrocholesterol on exposure to the ultraviolet B portion of sunlight. Vitamin D2 (ergocalciferol), the parent compound of the other family, is manufactured by irradiation of ergosterol produced by yeasts and its potency is less than one-third of vitamin D3’s potency. The steps in the vitamin D endocrine system include the following: 1) the photoconversion of 7- dehydrocholesterol to vitamin D3 in the skin or dietary intake of vitamin D3; 2) metabolism of vitamin D3 by the liver to 25-hydroxyvitamin-D3 [25(OH)D3 ], the major form of vitamin D circulating in the blood compartment; 3) conversion of 25(OH)D3 by the kidney (functioning as an endocrine gland) to the hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 ]; 4) systemic transport of the dihydroxylated metabolite 1,25(OH)2D3 to distal target organs; and 5) binding of 1,25(OH)2D3 to a nuclear receptor (VDR) at target organs, followed by generation of appropriate biological responses. The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. Six cytochrome P450 (CYP) isoforms have been shown to hydroxylate vitamin D. Four of these, CYP27A1, CYP2R1, CYP3A4 and CYP2J3, are candidates for the enzyme vitamin D 25-hy - droxylase that is involved in the first step of activation. The highly regulated, renal enzyme 25-hydroxyvitamin D-1a-hy - dro xylase contains the component CYP27B1, which completes the activation pathway to the hormonal form 1,25(OH)2D3. A five-step inactivation pathway from 1,25(OH)2D3 to calcitroic acid is attributed to a single multifunctional CYP, CYP24A1, which is transcriptionally in du - ced in vitamin D target cells by the action of 1,25(OH)2D3. An additional key component in the operation of the vitamin D endocrine system is the plasma vitamin D binding protein (DBP), which carries vitamin D3 and its metabolites to their metabolism and target organs. DBP is a specific, high-affinity transport protein. It is synthesized by the liver and circulates in great excess, with fewer than 5% of the binding sites normally occupied. 1,25(OH)2D3, acts as a ligand for a nuclear transcription factor, vitamin D receptor - VDR, which like all other nuclear receptors, regulates gene transcription and cell function. The widespread presence of VDR, and the key activating (1a-hydroxylase, CYP27B1) and inactivating (24-hydroxylase, CYP24A1) en - zy mes in most mammalian cells means that the cells in these tissues have the potential to produce biological res pon ses, depending on the availability of appropriate amounts of vi - tamin D3. Thanks to this widespread presence of elements of vitamin D endocrine system, its biological features are being recognized outside bone tissue, i.e. calcium and pho - sphate metabolism.

Regulation of aromatase expression by 1α,25(OH)2 vitamin D3 in rat testicular cells

2011 ◽  
Vol 23 (5) ◽  
pp. 725 ◽  
Author(s):  
Leila Zanatta ◽  
Hélène Bouraïma-Lelong ◽  
Christelle Delalande ◽  
Fátima R. M. B. Silva ◽  
Serge Carreau
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Sertoli Cells ◽  
Endocrine System ◽  
Aromatase Gene ◽  
Testicular Cells ◽  
Pka Pathway ◽  
Aromatase Gene Expression

It is well known that the vitamin D endocrine system is involved in physiological and biochemical events in numerous tissues, especially gut, bone and kidney but also testis. Therefore, in this study the effect and mechanisms of action of 1α,25(OH)2 vitamin D3 (1,25D) on aromatase gene expression in immature rat Sertoli cells were evaluated. Vitamin D receptor transcripts were present in immature Sertoli cells as well as in adult testicular germ cells and somatic cells. The treatment of immature Sertoli cells with 100 nM 1,25D increased the amount of aromatase transcript, mainly in 30-day-old rats. The protein kinase A (PKA) blocker, H89, partially inhibited the 1,25D effect. The stimulation of aromatase gene expression in 30-day-old Sertoli cells by the agonist 1α,25(OH)2 lumisterol3, and the suppression of the 1,25D effect by the antagonists 1β,25(OH)2 vitamin D3 and (23S)-25-dehydro-1α (OH)-vitamin D3-26,23-lactone suggested, besides a genomic effect of 1,25D, the existence of non-genomic activation of the membrane-bound vitamin D receptor involving the PKA pathway.

scholarly journals Super-doses of dietary vitamin D3 intake in aged laying hens illustrates limitation of 24,25-dihydroxycholecalciferol conversion

2021 ◽  
Author(s):  
Matthew F. Warren ◽  
Pete M. Pitman ◽  
Dellila D. Hodgson ◽  
Kimberly A. Livingston
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Laying Hens ◽  
Dietary Vitamin ◽  
Plasma Vitamin ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Blood Calcium ◽  
Reduce Risk ◽  
Dietary Vitamin D

Background: Humans take vitamin D supplements to reduce risk of vitamin D deficiency and reduce the risk of osteoporosis. However, it is unclear how dietary super-dose (10,000x greater than requirement) can affect vitamin D status in aged animals. Aged laying hens could potentially be a model to compare with women in peri- or postmenopausal stages of life because their bone health is physiologically taxed from egg production and they are highly susceptible to osteoporosis. Objective: We investigated dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D status in aged laying hens in production. Methods: Forty-eight 68-wk old Hy-Line Brown laying hens were individually housed in cages with eight hens per dietary treatment for eleven weeks. Hens were randomly assigned to one of six groups of dietary vitamin D3 supplementation and fed ad libitum. Supplementation levels were 400 (recommended dosage for hens), 800, 7,400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At termination of the study, all hens were euthanized and we collected blood, feces, and tibia and humerus bones. Ionized (free) blood calcium, fecal calcium, bone calcium, and plasma vitamin D metabolites were measured. Results: We did not discern any dietary effects in tissue and fecal calcium. We observed that increasing dietary vitamin D3 increased plasma vitamin D3, 25-hydroxycholecalciferol, and 24,25-dihydroxycholecalciferol concentrations (p < 0.0001 for all 3 metabolites). We also observed super-dose fed hens had decreased kidney 24-hydroxylase expression (p = 0.0006). Conclusions: Although dietary vitamin D3 super-doses did not affect calcium status in our aged laying hens, it is possible there is an age-related effect of not being as sensitive to vitamin D efficacy. We suggest future research should explore how 24-hydroxylation mechanisms are affected by vitamin D supplementation. Further understanding of 24-hydroxylation can help ascertain ways to reduce risk of vitamin D toxicity.

Development of a mass spectrometry method for 1,25-dihydroxy vitamin D3 using immunoextraction sample preparation

2019 ◽  
Vol 56 (6) ◽  
pp. 646-653 ◽  
Author(s):  
Fiona M Ivison ◽  
Edward Hinchliffe ◽  
Neil Howarth ◽  
Mandy Pickersgill ◽  
Lesley Tetlow
Keyword(s):  
Mass Spectrometry ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Specific Method ◽  
Negative Bias ◽  
External Quality Assessment Scheme ◽  
Blood Calcium ◽  
Dihydroxyvitamin D ◽  
Limit Of Quantitation ◽  
1,25 Dihydroxy Vitamin D3

Background 1,25-Dihydroxy vitamin D3 (DHVD) is the active metabolite of vitamin D, required to maintain blood calcium concentrations. Measurement has proved challenging as it circulates in picomolar concentrations and must be differentiated from other dihydroxyvitamin D species. Clinically, it is essential to be able to determine the cause of hypercalcaemia, which may be due to DHVD excess. Methods The liquid chromatography-mass spectrometry (LCMS) assay which has been developed uses immunoextraction of 0.5 mL serum followed by Amplifex™ derivatization of the dried eluent, with the analysis using the SCIEX 6500+ instrument taking a run time of 11 min. Results The limit of quantitation was determined (15 pmol/L) and the method is linear up to at least 600 pmol/L. Repeatability ranged from 6.1% at 23 pmol/L to 2.5% at 172 pmol/L and intermediate imprecision was 15.6% at 26 pmol/L to 8.3% at 173 pmol/L. The method is unaffected by icterus, haemolysis or lipaemia. Good performance was achieved with the samples from the vitamin D external quality assessment scheme, demonstrating a negative bias compared with the all lab trimmed mean (average –13.8%) and the specific method group (average –7.75%). A negative bias was observed across the concentration range found in 78 patient samples in comparison to a commercial radioimmunoassay (mean –47.8%). This was not unexpected and is likely due to better specificity of the mass spectrometry assay and the lack of a commutable standard reference calibrator. Conclusions We have developed a sensitive and robust LCMS method for the analysis of DHVD in serum, utilizing immunoextraction and derivatization to provide specificity.

scholarly journals In Vitro Non-Genomic Effects of Calcifediol on Human Preosteoblastic Cells

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4227
Author(s):  
Simone Donati ◽  
Gaia Palmini ◽  
Cecilia Romagnoli ◽  
Cinzia Aurilia ◽  
Francesca Miglietta ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Active Form ◽  
Endocrine System ◽  
Human Adipose Tissue ◽  
Biologically Active ◽  
Cellular Processes ◽  
Genomic Effects ◽  
First Time

Several recent studies have demonstrated that the direct precursor of vitamin D3, the calcifediol [25(OH)D3], through the binding to the nuclear vitamin D receptor (VDR), is able to regulate the expression of many genes involved in several cellular processes. Considering that itself may function as a VDR ligand, although with a lower affinity, respect than the active form of vitamin D, we have assumed that 25(OH)D3 by binding the VDR could have a vitamin’s D3 activity such as activating non-genomic pathways, and in particular we selected mesenchymal stem cells derived from human adipose tissue (hADMSCs) for the in vitro assessment of the intracellular Ca2+ mobilization in response to 25(OH)D3. Our result reveals the ability of 25(OH)D3 to activate rapid, non-genomic pathways, such as an increase of intracellular Ca2+ levels, similar to what observed with the biologically active form of vitamin D3. hADMSCs loaded with Fluo-4 AM exhibited a rapid and sustained increase in intracellular Ca2+ concentration as a result of exposure to 10−5 M of 25(OH)D3. In this work, we show for the first time the in vitro ability of 25(OH)D3 to induce a rapid increase of intracellular Ca2+ levels in hADMSCs. These findings represent an important step to better understand the non-genomic effects of vitamin D3 and its role in endocrine system.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial

2020 ◽  
pp. 1-10
Author(s):  
Giuseppe Derosa ◽  
Angela D’Angelo ◽  
Chiara Martinotti ◽  
Maria Chiara Valentino ◽  
Sergio Di Matteo ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Metabolic Control ◽  
Vitamin D3 ◽  
Therapy Group ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Sign in / Sign up

Export Citation Format

Share Document