Vitamin d

UNIVERSITY PUTRA MALAYSIA

FACULTY OF MEDICINE AND HEALTH SCIENCES

DEPARTMENT OF NUTRITION SCIENCES

VITAMIN D

MICRONUTRIENTS IN HEALTH AND DISEASE

By

Mohammed Ellulu

Introduction

Vitamin D is represented by:

1. cholecalciferol (vitamin D3)

2. ergocalciferols (vitamin D2) (in plant, fungi, yeast)

they are structurally similar, derived from the UV irradiation

of provitamin D sterols.

Vitamin D3 is produced by the action of sunlight on

7-dehydrocholesterol in the skin.

2

Structural differences of D2 and D3 3

In C-17 side chain, vitamin D2 has double bond and

additional methyl group.

Human activation 4

1. Endogenous or dietary origin of vitamin D will be

hydroxylated in the liver at carbon 25 to yield 25-

hydroxyvitamin D [25(OH)D].

2. This compound circulates in the blood and,

3. In the kidney, hydroxylation at the α-position of

carbon 1 to generate 1α,25-dihydroxyvitamin D

[1α,25(OH)2D].

The active form 5

The dihydroxylated vitamin D2 and D3 metabolites

are the active hormones.

Dietary sources 6

The proportion of vitamin D obtained from the diet

is very small compared with that synthesized in skin

in response to sunlight.

Fish-liver oils,

Fatty fish as sardines,

Eggs and dairy products,

Cereals, vegetables and fruit contain no vitamin D,

Meat and poultry contribute insignificant amounts.

Cutaneous synthesis 7

Vitamin D3 is synthesized in the skin from 7-

dehydrocholesterol (provitamin D3).

Provitamin D3 is converted photochemically to

previtamin D3, which converted to vitamin D3 by a

temperature-dependent process (non enzymatic).

The waveband of solar radiation responsible for the

conversion of the provitamin to the previtamin is

that between 290 and 315 nm, known as the UV-B

band (less than 290 does not reach the earth).

Factors affecting vitamin D3 production 8

1- Ageing

The skin becomes progressively thinner. The epidermal concentration of 7-dehydrocholesterol decreases.

Young adults produce 3 times more than elderly.

2- Degree of skin pigmentation

Skin pigmentation is a limiting factor for previtamin D3 synthesis because melanin competes with 7-dehydrocholesterol in absorbing UV-B radiation.

3- Use of sunscreens

Intestinal absorption and transport 9

Vitamin D is incorporated into chylomicrons, when

released, the chylomicrons convey the vitamin in the

mesenteric lymph to the systemic circulation.

In the lymph, an appreciable amount of the vitamin

D in the chylomicrons is transferred to the DBP.

After lipolysis of the chylomicrons, the vitamin D

remaining on the chylomicron remnants, and also the

vitamin D bound to protein, is initially taken up by

the liver.

Calcium and phosphate homeostasis 10

1α,25-Dihydroxyvitamin D restores low plasma concentrations of Ca2+ and Pi to normal by action at the three major targets; intestine, bone, kidney.

a) stimulates the intestinal absorption of Ca2+ and Pi by independent mechanisms,

b) stimulates the transport of Ca2+ (accompanied by Pi) from the bone fluid compartment to the extracellular fluid compartment,

c) facilitates the renal reabsorption of Ca2+. These three mechanisms provide calcium for bone mineralization and prevent hypocalcaemic tetany.

11

1α,25-Dihydroxyvitamin D3 regulates the synthesis

of two classes of calcium-binding proteins

(calbindins) found in mammalian intestine and

kidney.

An intestinal protein (calbindin-D9k) binds two

calcium ions per molecule,

A renal protein (calbindin-D28k) binds five to six

calcium ions per molecule.

Calcium and phosphate homeostasis

Intestinal calcium absorption 12

Calcium is present in foods and dietary supplements as relatively insoluble salts.

Calcium is absorbed only in ionized form, it must be released from the salts (mostly acidic medium).

On reaching the alkaline environment of the small intestine, some of the Ca2+ complex with minerals or other specific dietary constituents, thereby limiting calcium bioavailability.

Calcium absorption takes place by the translocation of luminal Ca2+ through the enterocytes (transcellular route) and between adjacent enterocytes via the tight junctions (paracellular route).

The calbindin-based diffusional-active

transport model 13

This transcellular pathway is a complex process

involving three steps:

(1) entry by movement of Ca2+ from lumen through

the brush-border membrane of the enterocyte,

(2) intracellular diffusion,

(3) extrusion from the cell across the basolateral

membrane. The major action of vitamin D in

regulating this process is on the steps involved in

Ca2+ movement beyond brush-border entry.

Intestinal phosphate absorption 14

Dietary phosphorus is a mixture of inorganic and organic phosphorus.

Phosphorus in meat and fish exists largely in the form of phosphoproteins and phospholipids (enzymatic hydrolysis).

80% of phosphorus in grains is found as phytic acid (bioavailability reduced).

Milk protein (casein) is highly phosphorylated.

Phosphate absorption takes place mainly in the jejunum by an energy-dependent transcellular route.

Vitamin D action on bone 15

1α,25(OH)2D3 is required for normal development and

mineralization of bone, and for bone remodelling.

The effect of 1α,25(OH)2D3 on bone is indirect, being

attributable to the increased availability of calcium and

phosphate for incorporation into bone that results from

the increased intestinal absorption.

Rickets can be cured in vitamin D-deficient rats by

increasing the calcium and phosphorus content of the

diet or by maintaining normal circulating concentrations

of these minerals through infusion.

Vitamin D action on bone 16

A major physiological function of 1α,25(OH)2D3 in calcium homeostasis is stimulation of bone resorption, which refers to localized bone dissolution by osteoclasts with resultant net calcium movement from bone to blood.

The hormone acts by increasing the expression of proteins essential to the resorptive process, proteins such as carbonic anhydrase.

The hormone also inhibits bone formation by decreasing alkaline phosphatase activity and collagen synthesis in osteoblasts and increasing the synthesis of osteocalcin, a potent inhibitor of mineralization.

Calcium homeostasis 17

Phosphate homeostasis 18

Unlike calcium, dietary phosphate usually exceeds the body’s nutritional requirement, therefore a major component of phosphate homeostasis is renal excretion. A diet that is low in phosphorus is likely to be low also in calcium, which complicates the picture of phosphate homeostasis.

A lowering of plasma phosphate will stimulate the kidney to release 1α,25(OH)2D3, which elicits rapid and long-term responses in the kidney, leading to increased renal reabsorption of phosphate.

The 1α,25(OH)2D3 will also increase the intestinal absorption of phosphate and calcium. The parathyroids will not be stimulated to produce PTH.

Effects of vitamin D on insulin secretion 19

1α,25-Dihydroxyvitamin D3 is considered to be a

modulator of insulin secretion;

Because…. vitamin D deficiency in rats is associated

with marked impairment of insulin secretion and the

insulin-secreting β-cells of the pancreas contain the

vitamin D-regulated protein calbindin-D28k.

Vitamin D-related diseases 20

Rickets

The classic vitamin D deficiency disease in children.

The disease is characterized by bow legs or knocks

knees, curvature of the spine, and pelvic and

thoracic bone deformities.

These deformities result from the mechanical stresses

of body weight and muscular activity applied to the

soft uncalcified bone.

Vitamin D-related diseases 21

Osteomalacia

In adults, when the skeleton is fully developed,

vitamin D is still necessary for the continuous

remodelling of bone.

During prolonged vitamin D deficiency, the newly

formed, uncalcified bone tissue gradually takes the

place of the older bone tissue and the weakened

bone structure is easily prone to fracture.

Toxicity 22

Hypervitaminosis D results from the excessive

consumption of vitamin D supplements, and not from

the consumption of usual diets.

Toxic concentrations of vitamin D have not resulted

from unlimited exposure to sunshine.

Vitamin D toxicity is due primarily to the

hypercalcaemia caused by the increased intestinal

absorption of calcium, together with increased

resorption of bone.

Possible Interactions with Vitamin D 23

Vitamin D levels may be increased by the following medications:

Estrogen: Hormone replacement therapy appears to increase vitamin D levels in the blood; this may have a beneficial effect on calcium and bone metabolism. In addition, use of vitamin D supplements in conjunction with estrogen increases bone mass more than ERT alone.

Isoniazid (INH): INH, a medication used to treat tuberculosis, may raise blood levels of vitamin D.

Thiazide: Diuretics in this class increase the activity of vitamin D and can lead to inappropriately high calcium levels in the blood.


Vitamin D levels may be decreased, or its absorption may be reduced, by the following medications:

Antacids: Taking antacids for long periods of time may alter the levels, metabolism, and availability of vitamin D.

Calcium channel blockers (as verapamil ): used to treat high (bp) and heart conditions, may decrease the production of vitamin D by the body.

Cholestyramine: cholesterol-lowering medication, known as a bile acid sequestrant, interferes with the absorption of vitamin D (as well as other fat-soluble vitamins).

Phenobarbital (anticonvulsant): may accelerate the body's use of vitamin D.


Weight loss products:

Orlistat, a medication used for weight loss, and

Olestra, a substance added to certain food products,

The both intended to bind to fat and prevent the absorption of fat and the associated calories.

Because of their effects on fat, orlistat and olestra may also prevent the absorption of fat-soluble vitamins such as vitamin D.

In addition, multivitamins with fat soluble vitamins will be prescribed with orlistat to the regimen.

Dietary requirement 26

The dietary requirement for vitamin D depends upon the amount of vitamin synthesized by solar irradiation of the skin.

Exposing hands, arms and face on a clear summer day for 10–15 min, two to three times a week, should yield sufficient cutaneous production of vitamin D to meet daily needs.

To maintain satisfactory plasma 25(OH)D levels without any input from skin irradiation, an oral input in the region of 10–15 μg of vitamin D per day would be required.

References 27

http://www.umm.edu/altmed/articles/vitamin-d-000995.htm#ixzz2R6E5HYwi.

Caballero B (2005). Encyclopaedia of Human Nutrition. Second Esition. Elsevier

Zempleni J, Rucker RB, McCormick DB, and Suttie JW (2007) Handbook of VITAMINS. Fourth Edition. Taylor & Francis Group.

Bender D (2003). Nutritional Biochemistry of the Vitamins. Second Edition. Cambridge University Press.

Health & Medicine

Vitamin d