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Vitamin D

Terms Used
Ergocalciferol = D2
Cholecalciferol = D3

• 25, OH Cholecalciferol = Calcidiol


• 1,25, (OH)2 Cholecalciferol = Calcitriol

• Plant source = Ergocalciferol or D2 (sold commercially)


• Animal source = 7 dehydrocholesterol
Vitamin D Facts
• Unique vitamin because it:
• Is synthesized in the body with
adequate sun exposure
• Functions as a hormone
• Chemical structures
• D2 (ergocalciferol)
• D3 (cholecalciferol)
Structure and synthesis
1. Cholesterol from
endogenous production or
diet
2. In skin, cholesterol oxidized
to 7-dehydrocholesterol
3. With UV light, 7-
dehydrocholesterol 1 2 3
converted to precalciferol
(pre-D3)
4. With time (and body
temperature), precalciferol
isomerized to cholecalciferol 4 Addition of
double
5. Resulting in cutaneous bond
production of D3
Vitamin D Absorption

• Dietary vitamin D requires no digestion


– Absorbed from micelle by passive diffusion with help from
fat and bile salts
• Most absorbed in jejunum
• Incorporated into chylomicron for transport into
lymphatic system, then blood
Transport and Storage

• Transport
• D3 from diet: initially transported by chylomicron
 Also transported by vitamin D-binding protein (DBP) to extra
hepatic tissues
 Chylomicron remnants deliver remainder to the liver
• D3 from skin is carried by DBP

• Storage
• Storage in blood (largest single pool), muscle and adipose
tissue
Functions
Wide range of functions
• Cell differentiation, proliferation and growth
• Insulin secretion
(Limited data in humans suggest that insufficient vitamin
D levels may have an adverse effect on insulin secretion
and glucose tolerance in type 2 diabetes)

• Immune system function


• Blood pressure regulation
• Calcium homeostasis
Vitamin D Functions and Mechanisms of
Action
Teller (parathyroid)

Bank-safety deposit
box (bone)

Body Guard #2
enterocyte

Body Guard #1
Kidneys

• You are low on cash (Ca++); you know your cash is at


the bank
• You go to the teller to get some, she sends out a
message (PTH) to body guard #1 and he releases the
secret code (renal hydroxylase) this turns the ‘$25s’ into
$1s (calcitriol) . Body guard #1 relays the $1s to body
guard #2 and the safety deposit box. All three release
the cash. You are now not broke
Vitamin D Functions and Mechanisms of Action

• Serum calcium homeostasis


– Effects on kidneys, small intestine, and bone
• Calcitriol synthesis
– Stimulated in response to changes in serum calcium
concentrations and the release of PTH
– Normal serum calcium: 8.5–10.5 mg/dL (2.12–2.62
mmol/L)
– Hypocalcemia (less than 8.5 mg/dL)
Vitamin D Transport, Metabolism, and Storage

• Vitamin D made in the skin


– Diffuses and picked up by vitamin D-binding protein
(DBP) for transport
• Metabolized to 25-OH D in liver
• 25-OH D secreted into blood, transported by DBP
• Converted to 1,25-(OH)2 D (calcitriol) in kidneys
– Calcitriol released into blood
Vitamin D Functions and Mechanisms of Action

• Serum calcium homeostasis


– Actions to decrease serum calcium
– Calcitriol indirectly involved through effects on PTH
• Phosphorus homeostasis
– Calcitriol enables phosphorus absorption in the intestine
– Calcitriol promotes resorption of phosphorus out of bone
and into blood
Vitamin D Functions and Mechanisms of Action

• Cell differentiation, proliferation, and growth


• Calcitriol and muscle
– Myopathy linked to deficiency
• Other roles
– Several cardioprotective functions
– Autoimmune conditions
• Interactions with other nutrients
– Calcium, phosphorus, and vitamin K
Functions: cell differentiation
Interactions

• Calcium and phosphorus


Adequate vitamin D is key to regulation of these two
minerals

• Vitamin K
Because both vitamin D and vitamin K are related to
calcium metabolism, an interaction is possible
Metabolism and Excretion

• A variety of metabolites can be formed from


calcitriol through hydroxylation, oxidation,
cleavage of side chains, etc.

• The majority of metabolites are excreted in


feces
• Metabolites also secreted in bile
Vitamin D

• RDA first set in 2010


– 600 IU (15 μg) vitamin D: ages 1–70
– 800 IU (20 μg) vitamin D: those over 70

• Obtainable by 5–15 minutes sun exposure daily


Food Sources of Vitamin D
Vitamin D

• Assessment of nutriture

– Serum 25-OH D concentrations


 Less than 20 ng/mL indicates deficiency
 21–29 ng/mL indicates insufficiency
Deficiency

• Individuals at risk
• Exclusively breastfed
• Dark skin
• Older
• Limited skin exposure outdoors
• Heavy sunscreen use
• Fat malabsorption
• Inflammatory bowel disease
• Obese
Deficiency
• Rickets
• Insufficient mineralization of bone in children
• Seizures and growth retardation
• Results
• Malformed long bones of leg
• Rachitic rosary
• Curvature of the spine
• Deformed chest and pelvis
Deficiency
Toxicity
• Individuals at risk
• Individuals consuming cod liver oil or other vitamin D-
rich supplement
• Intakes above UL of 100 ug (4000 IU)
• Risk of hypervitaminosis D
• Due to dietary intake (supplements), not sunlight
• Results in excessively high blood calcium levels
• Major acute symptoms include nausea, vomiting, poor
appetite
• Main chronic symptom is calcification of soft tissues

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