Vitamin D – Explored
Vitamin D is a hormone that regulates several important processes in our bodies.
Some of its most important actions in the body are:
- Calcium, Phosphorous & Bone Metabolism
- Muscle Function
- Regulates Cell Proliferation, Differentiation, Apoptosis & Angiogenesis
- Decreases cellular proliferation and induces terminal differentiation in normal and cancer cells
- Immunomodulation: When exposed to pathogens immune cells activate vitamin D which in turn activates antimicrobial peptides
- Helps to Regulate blood pressure via RAAS System
- Increases insulin secretion thereby reduces blood glucose
Regulation of Calcium absorption and metabolism..
-> Regulation of Cell Proliferation and Differentiation..
-> Regulation of bone cell metabolism / bone mineralisation (calcium and phosphorous homeostasis…
Immune, Endocrine and Cardiovascular systems
Cell differentiation and growth
Skin stores 7 Dehydrocholesterol + UVB from Sunlight –>
Formation of Previtamin D3 –>
Non Enzymatic conversion of Previtamin D3 to Vitamin D3 (Cholecalciferol) in lower layer of skin –>
Vitamin D3 – Cholecalciferol –> Enters bloodstream –>
Liver – 25 hydroxyvitamin D3 – Calcidiol –>
Kidney – 1α,25-dihydroxyvitamin D3 – Calcitriol
WRITE MORE ABOUT IT IN DETAIL – MAYBE IMAGE
WHAT IS 7 DEHYDROCHOLESTEROL? HOW DOES IT GET TO SKIN? HOW MUCH IS IN SKIN? DOES IT EVERY RUN LOW / OUT?
WHAT IS PROCESS THAT CHANGES IT TO PREVITAMIN D3? UVB.. HOW? HOW IS PREVITAMIN CHANGED INTO CHOLECALCIFEROL? NON ENZYMATIC.. HOW? ETC. IS CHOLECALCIFEROL LOOSED INTO THE BLOOD THEN? HOW?
The two most important factors that govern the generation of pre-vitamin D3 are the quantity (intensity) and quality (appropriate wavelength) of the UVB irradiation reaching the 7-dehydrocholesterol deep in the stratum basale and stratum spinosum. Another important consideration is the quantity of 7-dehydrocholesterol present in the skin. Under normal circumstances, ample quantities of 7-dehydrocholesterol (about 25–50 ug/cm2 of skin) are available in the stratum spinosum and stratum basale of human skin to meet the body’s vitamin D requirements.
A vitamin D blood test measures the level of 25(OH)D in your blood (CALCIDIOL)
Absorption of Calcium from Gut
Immune modulation / enhancing
Growth and Dev – Gene regulation
The biological actions of calcitriol, involve regulation of gene expression at the transcriptional level, and are mediated through binding to a vitamin D receptor (VDR), located primarily in the nuclei of target cells (Jones et al., 1998; Jurutka et al., 2001)
The classical actions of vitamin D—which by itself is inactive—are due to the functions of the active metabolite, calcitriol
Absorption, Storage & Transport:
Synthesised in the skin upon exposure to sunlight. Metabolised in the liver and kidneys into active form – 1α,25-dihydroxyvitamin D.
NEED DETAILED WRITE UP ABOUT THE PROCESS OF ABSORPTION AND METABOLISM / STORAGE / TRANSPORT / EXCRETION ETC
HOW IS RELEASED FROM SKIN? HOW IS IT STORED? WHAT INIATES STORAGE? WHAT STOPS IT…
HOW DOES LOW FAT LEVELS (EXTREME) OR HIGH FAT ELEVELS (IN BLOOD, IN BODY TISSUES, IN DIET) EFFECT THE STORAGE AND UTILISATION?
What happens to all the excess cholecaciferol when lots of sun exposure?
What happens when calcitriol goes low and sunlight and diet intake is low – is cholescalciferol mobilised from fat storage? How?
“25OHD, the precursor of calcitriol, is the major circulating form of vitamin D; it circulates bound to a specific plasma carrier protein, vitamin D binding protein (DBP). DBP also transports vitamin D and calcitriol.”
Two enzymatic hydroxylation reactions – liver & kidney
Liver: 25-hydroxylase (most likely cytochrome P450 2R1 [CYP2R1]) which forms 25-hydroxyvitamin D (hereafter referred to as 25OHD)
Kidney: The second reaction takes place in the kidney, mediated by 1α-hydroxylase (CYP27B1), which converts 25OHD to the biologically active hormone, calcitriol (1,25-dihydroxyvitamin D)
The 1α-hydroxylase gene is also expressed in several extra-renal tissues, but its contribution to calcitriol formation in these tissues is unknown.
25OHD, the precursor of calcitriol, is the major circulating form of vitamin D; it circulates bound to a specific plasma carrier protein, vitamin D binding protein (DBP). DBP also transports vitamin D and calcitriol.
The renal synthesis of calcitriol is tightly regulated by two counter-acting hormones, with up-regulation via parathyroid hormone (PTH) and down-regulation via fibroblast-like growth factor-23 (FGF23) (Galitzer et al., 2008; Bergwitz and Juppner, 2010).
Low serum phosphorus levels stimulate calcitriol synthesis, whereas high serum phosphorus levels inhibit it
Following its synthesis in the kidney, calcitriol binds to DBP to be transported to target organs.
HOW ARE THESE ENZYMES MADE? WHERE? WHAT DO THEY DEPEND ON? WHAT ELSE DO THEY DEPEND ON? DIET?
Vitamin D Receptor (VDR)
DO ALL CELLS HAVE?
Normal Plasma Level
Normal (homeostatic level) 75 – 250 nmol/L
Marginally deficient 51 – 74 nmol/L plasma levels
Severely deficient – plasma levels <50 nmol/L
Reference Range is approximately
PLANT, ANIMAL, GOOD ONES, D2 IN PLANTS (MUSHROOMS UVB – HOW NOT GOOD REFERENCE STUDY)
Adult Male 15ug/Day
Adult Female 15ug/Day
1000IU/Day recommended in winter months (temperate climates)
Tolerable upper intake:
Tolerable upper intake level (UL) – 4000IU/Day
50000IU/Day leads to Hypercalcaemia
10000IU/Day is possibly toxic
Deficiency Signs and Symptoms
Bone demineralisation to elevate blood calcium to homeostatic levels
Muscle Weakness and Pain
Risk Factors for Deficiency
LATTITUDES THEY LIVE IN, DARKER SKIN, OVERUSE OF CLOTHING / SUNBLOCK, LOW DIET INTAKE (VEGAN)
impaired bile acid release or pancreatic insufficiency
Toxicity Signs and Symptoms
Calcification of Organs including kidneys and heart
Atopic Dermatitis, IBD, CVD: Hypertension, CHF.
GET NUTRIENT DRUG HERB INTERACTION BOOK.
cholestyramine (Questran), colestipol (Colestid), orlistat (Xenical), and mineral oil
phenytoin (Dilantin), fosphenytoin (Cerebyx), phenobarbital (Luminal), carbamazepine (Tegretol), and rifampin (Rimactane
proton-pump inhibitors (omeprazole, lansoprazole) might interfere with calcium absorption and increase the risk of fracture such that patients are advised to take calcium and vitamin D supplements (
HIV treatment drugs
cytostatic agents (cell growth inhibitors) may also increase the degradation of 25-hydroxyvitamin D and 1α,25-hydroxyvitamin D in cancer patients under chemotherapy (6
Hypercalcemia may also reduce the effectiveness of verapamil (Calan) and diltiazem (Cardizem) in atrial fibrillation (
ANY INFO IN BNF?