VITAMIN D T Like a hormone Its Role in Calcium Homeostasis

How Does “D” Compare To Hormones? Vitamin D3 is not secreted by a classical endocrine gland, the active form of the hormone is released from the kidney and acts at distant sites or locally. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. Only a very small proportion of vitamin D remains in a free form in the circulation and has a serum t1/2 of about 5 hours

The skin Major organ 16 % of body weight ¼ th of blood supply nourish it Mirror of emotion Temperature control Infection control Nerves protection

Resorption and Remodeling Osteoclasts do this using HCL and ACID PHOSPHATASE to dissove bone matrix Remodeling Ostoblasts do this Collagen fibers and hydroxyapatite matrix

To Make Me D, Warm Me Up and Hydroxylate Me..3X!

So..Exposure to Sun and Then, Fortified Foods….Give Us the D We Need

How Does Vitamin D Facilitate Calcium Absorption in the Intestines??

IN THE INTESTINE It facilitates intestinal absorption of calcium, as well as stimulates absorption of phosphate and magnesium ions. In the absence of vitamin D, dietary calcium is not absorbed at all efficiently. Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood.

The vitamin D form, 1,25-dihydroxcholecalciferol [1,25(OH)2D3], 1. stimulates the synthesis of the epithelial calcium channels in the plasma membrane calcium pumps , and 2. induces the formation of the calbindins.

Vitamin D: Its Role is ABSORPTION of CALCIUM ,and to a lesser extent, Phosphorous, from the Small Intestine and Duodenum.

Once joined with ingested vitamin D, facilitate increased serum calcium levels . Shows Expressed Calbindins and How the facilitate transport of Calcium through the Membranes

Calcium Absorption Enhanced by Carrier Protein Calbindin

Calcium absorption is transport across the epithelial cell, which is greatly enhanced by the carrier protein calbindin, the synthesis of which is totally dependent on vitamin D

Calcitriol Raises Blood Calcium in 3 Ways: Increases Ca++ absorption by the small intestine. Increases Calcium (and Phosphate ) resorption from the skeleton. It binds to hematopoietic stem cells and causes differentiation of osteoclasts. 3. Weakly promotes the reabsorption of Calcium ions by the kidney cells (less calcium excreted)

Let’s Look A Bit Closer at RANK L

But, I thought Vitamin D HELPED US retain Calcium? Yes, It does. So, although there is some proliferation of osteoclasts the NET RESULT IS: CALCIUM ABSORPTION and REMODELING….Outweighs RESORPTION…. Because…

Vitamin D

Vitamin D is not strictly a vitamin. It can be synthesized in the skin. Under most conditions that is the major source of the vitamin. Dietary source required, only when sunlight exposure is inadequate .

Major Role Its main function is in the regulation of calcium absorption and homeostasis. Most of its actions are mediated by way of nuclear receptors that regulate gene expres­sion.

Role in regulating cell proliferation and differentiation There is some scientific evidence available now that intakes considerably higher than RDA maintain better calcium homeostasis, reduce the risk of insulin resistance, development of obesity and various cancers.

Vitamin D Is Synthesized in the Skin 7-Dehydrocholesterol (intermediate in the synthesis of cholesterol that accumulates in the skin) undergoes a nonenzymic reaction on exposure to ultraviolet light, yielding previtamin D.

Factors affecting Vit. D synthesis The amount of Vit D formed by the action of sunlight on the skin is dependent on Intensity of light Length of exposure Skin pigmentation

ABSORPTION This undergoes a further reaction over a period of hours to form cholecalciferol, which is absorbed into the bloodstream. In temperate climates, the plasma concentration of vitamin D is highest at the end of summer and lowest at the end of winter.

Metabolism Vitamin D Is Metabolized to the Active Metabolite, Calcitriol, in Liver & Kidney. Cholecalciferol, either synthesized in the skin or from food, undergoes two hydroxylations to yield the active metabolite, 1,25-dihydroxy vitamin D or calcitriol. This is released into the circulation bound to a vitamin D binding globulin, which is the main storage form of the vitamin.

Alternate product In the kidney, calcidiol undergoes either 1- hydroxylation to yield the active metabolite 1,25-dihydroxy-vitamin D (calcitriol), or 24-hydroxylation to yield a probably inactive metabolite, 24,25-dihydroxyvitamin D (24-hydroxycalcidiol).

Functions Vit D plays a major role in the regulation of calcium and phosphate metabolism by promoting their intestinal absorption, influencing the process of bone mineralization.

Functions Vitamin D exerts its anti ricket action by making the intestinal mucosa permeable to calcium and phosphorus and facilitating the active transport of calcium across cell membranes.

Vitamin D occurs in two forms “Vitamin D2” (ergocalciferol), chief Vit D precursor in plants is, ergostreol. 2 “Vitamin D3” (cholecalciferol), the main form occurring in animal cells and developing in skin on exposure to ultraviolet light from 7- dehydro cholesterol

Animal sources of Vit D Eggs Fish Liver oil Butter Fish

Stability Vit D is stable through storage, processing and cooking and is absorbed effectively from GIT Any abnormality in fat absorption may cause mal- absorption of Vit D

Metabolism Before it can function, Vit D3 must be activated by hydroxylation which takes place both in liver & kidney. The initial conversion in the liver results in 25-hydroxy cholecalciferol (cacidiol), the major circulating form of Vit D3.

Metabolism 2nd hydroxylation takes place in the proximal tubule of the kidney, giving rise to 1,25-dihydroxycholecalciferol or calcitriol. This form is then transported to bones, kidneys and intestines.

Recommended Daily Allowance 400 iu (10ug) of Vit D per day promote optimal calcium absorption and enhance growth Higher level is recommended for infants and children

Recommended Dietary Allowances Infants 0 – 0.5 10 g 0.5 – 1.0 10 g Children 1 – 3 10 g 4 – 6 10 g 7 – 10 10 g

Recommended Dietary Allowances Adults Male Female 11 – 14 10 10 15 – 18 10 10 19 – 22 7.5 7.5 23 – 50 5 5 51+ 5 5 Pregnancy + 5 Lactation + 5

Effects of deficiency A deficiency of Vit D causes impaired intestinal absorption of calcium and phosphorus and faulty mineralization of teeth and bones. 2. Skeletal malformation result from the inability of the softened bone to withstand weight bearing . In children this bone condition is termed rickets.

Effects of deficiency In adults this bone condition is termed as osteomalacia and is caused purely by lack of Vit D and calcium. Particularly prevalent among pregnant and lactating oriental women.

Effects of deficiency Other symptoms of rickets include Delayed closure of the fontanelles (suture lines in the skull) especially in premature infants Projection of sternum (pigeon breast). Spinal curvature and Bowing of the legs

Effects of deficiency Vit D is involved in neuro-muscular activity and its deficiency causes tetany characterized by convulsions, muscle twitching and sharp flexion of the wrest and ankle joint.

Effects of deficiency 4.This condition may also result from parathyroid disease or from insufficient dietary intake or intestinal absorption of calcium or Vit D 5. Dental caries are more prevalent among children with poor intakes of Vit D, calcium and phosphorus.

Toxic Effects Precisely not known It is potentially lethal vitamin. Toxicity symptoms include Polyurea Nocturia Weight loss Diarrhea & Nausea

Severe toxicity results in Calcification of soft tissues such as Blood vessels Heart Stomach Bronchi & Kidney