vitamin D

sources vitamin D

sunlight

- animal foods vitamin D3 form= cholecalciferol from Liver, beef, dairy, saltwater fish

- Plant origin vitamin D2 form = ergocalciferol from Mushrooms, yeast

cholesterol is precursor to

Cholecalciferol (vitamin D3) in formation from sunlight

Sun exposure for 10 - 40 min can produce

1,000IU/day

How is vitamin D absorbed from foods?

-requires no digestion other than digestion of food source

- Absorbed from micelle with help from fat and bile salts by passive diffusion

- Most absorbed in jejunun

- Incorporated into chylomicron for transport intolymphatic system then blood

transport of vitamin D (2 routes depending on source)

1. Dietary vitamin D

- Vitamin D2 or D3 incorporated into chylomicrons

- Chylomicrons enter lymphatic system

- Some vitamin D transferred to vitamin D binding protein (DBP)

- Chylomicrons enter portal blood and delivered to liver

- Vitamin D binds to DBP (vitamin D binding protein)

- Vitamin D-DBP is delivered to tissues

2. Cutaneous vitamin D3

- Diffuses through skin into blood stream

- Must pass through subcutaneous fat stores

- Excess adipose tissue (obesity) may reduce vitamin D

bioavailability

- Binds to vitamin D binding protein (DBP)

- Some vitamin D3 is directly released to tissues other than liver (Muscle, adipose tissue, etc.)

How is vitamin D activated?

1. In liver vitamin D is converted to 25-OH vitamin D by P450 hydroxylase (iron dependent enzyme) more substrate = less activity of enzyme

2. 25-OH vitamin D released into blood (Very little vitamin D stored in liver)

3. Plasma 25-OHD represents major storage form of vitamin D (circulates in blood not neccesarily "stored")

4. In kidney 25(OH)D is converted to 1,25 (OH) 2D (active form calcitriol)

5. 25 (OH)2 vitamin D released from kidney and travels to other target tissues (intestine, bone, muscle, pancreas, skin, brain etc.).

**Half life of 1,25 (OH)2 vitamin D is 4 - 5 hrs (Not a good measure of vitamin D status)

what converts 25(OH)D to 1,25 (OH) 2D

CYP27B1

converts circulating form 25(OH)D to 1,25 (OH) 2D (active form calcitriol) in the kidney

CYP27B1 is the same thing as

1-hydroxylase

25-OH vitamin D2 or 25-OH vitamin D3 concentrations reflect ?

- vitamin D status

- Half life is 1 to 3 weeks

- Most vitamin D is found in blood, also some storage found in

adipose tissue and muscle

further activation of vitamin D putting it all together

- 25-OH vitamin D bound to DBP while in blood

- Taken up by tissues especially kidney

- 25-OH vitamin D converted to 1, 25 (OH)2 vitamin D (calcitriol Active form of vi fountamin D) by Enzyme 1-hydroxylase

- Enzyme activity is increased byPTH when blood calcium levels are low and decreased by by dietary phosphorus

- if concentrations are high 25-OH vitamin D, is converted to 24, 25 (OH)2 vitamin D (less active form of vitamin D)

FUNCTIONS AND MECHANISMS OF VITAMIN D

1,25(OH) 2D (Calcitriol) has genomic and non-genomic mechanisms of action

1. Genomic mechanisms

- Affect transcription of vitamin D-regulated genes

- Causes blood calcium concentrations to increase

- Acts on bone, intestine and kidney

2. Non genomic mechanisms

- Cell differentiation, proliferation and growth

- Myopathy is linked to deficiency

- Activates signal transduction pathways

-increase calcium influx into cell

CALCITRIOL IN INTESTINE

- when blood calcium low PTH increases 1,25(OH)2D activation

- this Increases absorption of Ca++ and PO4

- Calbindin D9k synthesis increases and TRPV6 synthesis increases overall increasing Ca++ absorption

- Alkaline phosphatase activity increases and This increases PO4 absorption

CALCITRIOL IN KIDNEY

- when blood calcium low PTH increases 1,25(OH)2D activation

- increases re absorption of Ca++ in kidney

- increases Calbindin D28k synthesis

- increases blood ca++ concentrations

- lowers blood PO4 concentrations

calcitriol in bone

- when blood calcium low PTH increases 1,25(OH)2D activation

- calcitriol and PTH cause resorption of calcium from bone

-RANK-L stimulates osteoclasts to eat away at bone matrix releasing Ca++ and PO4

-calcitonin released if blood levels get to high

vitamin D interaction with other nutrients

needed for calcium

- iron needed for vitamin d activation

- works with vitamin k (vitmain k activates osteocalcin)

how is vitamin D excreted

- 1,25(OH)2D is deactivated by 24-hydroxylase converting it to 1,24,25(OH)3D in liver

- excreted mainly in bile (70%) and urine

vitamin D RDA's

18-70 600 ius

pregnancy and lactation 600 ius

70 + = 800 ius

What diseases are associated with vitamin D deficiency?

1. low ca++ and rickets (Failure of already formed bone to mineralize, growth retardation, seizures, long bones that buckle when walking begins)

2. Osteomalacia/osteopenia/osteoporosis (High PTH, bone resorption, soft bone, bone pain, bone fractures)

3. obesity can reduce sunlight vitamin D

4. dark skinned individuals more prone to vitamin D deficiency

vitamin d toxicity results in

- hypercalcemia, calcification of soft tissues, anorexia, nausea, vomiting

- UL set at 4,000 IU/day

vitamin d toxicity cant occur with excessive sun exposure

true (inactive forms are created when sun exposure is high)

How is vitamin D status assessed?

- plasma concentrations of 25(OH)D

-Has half-life of up to 3 weeks

-deficiency- less than 20 ng/ml (some say less than 30)