Vitamin D

Hilarie StubbinsColleen Linehan

Chemical Name

• Calciferol

• Two main forms are Vitamin D2 and D3

– Ergocalciferol (D2)

– Cholecalciferol (D3)

Source: 1

Structure

• Derived from a steroid• Considered a seco-steroid because one of its

four rings is broken• Contains three intact rings (A, B, and D) with a

break between carbons 9 and 10 in the B ring

• Vitamin D2 and D3 have differing side chain structures

Source: 1

Vitamin D2

Vitamin D3

Vitamin D2 is obtained from plant sources

Vitamin D3 is obtained from the sun

Source: 1

Chief Functions

• The primary function of Vitamin D is to work with and help the body absorb and use calcium in order to sustain and build strong bones.

• Regulate immune system.

• Protection of the pancreas and stimulation of insulin.• Improve blood glucose control in those with a high

risk for diabetes.

Source: 1

Functions Cont.

• Diminishes the production of hormones associated with high blood pressure.

• Decreases LDL.• Increases HDL.

• Protective against autoimmune conditions:– Rheumatoid Arthritis– Type I Diabetes– Multiple Sclerosis

Source: 1

Metabolic Pathways

• Vitamin D3 begins in the skin by exposure to UV rays from sunlight.

• 7-dehydrocholesterol absorbs the photons from the UV radiation to stimulate previtamin D3.

• Thermal isomerization occurs to form vitamin D3.• This synthesis increases 25-OH D levels.• When Vitamin D2 is taken in, it is considered an

active substance.

Source: 2, 3

Metabolic Pathways Cont.

• Transported via chylomicrons.• Metabolic activation begins with the

hydroxylation of carbon 25.• Process occurs in the liver.• Hydroxylation cannot be regulated.• Indication of Vitamin D status is seen through

the plasma 25-OH D levels.

Source: 2, 3

Metabolic Pathways Cont.

• After the hydroxylation of Vitamin D, bioactivation occurs.

• Formed into 1, 25-dihydroxyvitamin D.

• Occurs in the kidneys.

Source: 2, 3

Vitamin D Transportation

• Transported into circulation by plasma proteins.• Most commonly bound to Vitamin D Binding

Protein (DBP).• DBP levels can be approximately 20x higher

than the total amount of vitamin D metabolites in plasma.

• This leaves limited access to target cells.

Source: 2, 3

Cont.

• The limited access reduces its susceptibility to hepatic metabolism and biliary excretion.

• This increases its circulating half-life.

• Predominately excreted through bile in the feces.

• Less than 30% is excreted through the urine.

Source: 1, 2, 3

Recommendations• Recommendations assume minimal sun

exposure RDAsInfants: 400 IU/dayChildren and adults, (ages 1-70), male and Female : 600 IU/day Adults 70+ : 800 IU/day

Pregnancy/lactating: 600 IU/day

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Factors affecting synthesis in skin

• Skin color/tone• Age • Latitudes• Season• Time of day• Clothing interference• Glass in windows

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Skin Color

• Persons with darker skin (due to their higher melanin content) require longer exposure to the sun than persons with lighter skin.

• This is because melanin blocks some of the UVB rays.

Source: 1

Age

• Older people with diminished organ function and 7-dehydrocholesterol content in the skin impair calcitrol production.

7-dehydrocholesterol: a cholesterol precursor

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Latitude

• At latitudes above 35degrees, the UVB photon path length is longer, and fewer UVB photons reach the Earth.– This results in less Vitamin D synthesis in the skin.

Source: 1

Season/Time of Day

• During spring, summer, and fall, exposure to sunlight for 5-15 minutes from the times of 10am-3pm is thought to provide sufficient amounts of vitamin D.

• In U.S.:1.5 IU/cm2/hour in winter6.0 IU/cm2/hour in summer Can be synthesized by skin.

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Deficiency

• Widespread throughout the United States and the World.

• Linked to several health conditions but most directly linked to rickets and osteomalacia

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Rickets

• Most common in children • Characterized by seizure, growth retardation,

and failure of bone to mineralize. • In deficient infants, the epiphyseal cartilage

grows and enlarges however, without replacement by bone matrix and minerals.

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Rickets Effects

• Effects are typically visible at wrists, ankles, and knees, which all enlarge.

• Long bones of legs bow, and knees knock as child grows and begins weight bearing activity.

• The spine becomes curved, and pelvic and thoracic deformities occur.– Characterized by costochondral beading at the

juncture of the ribs and cartilages.

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Osteomalacia

• Occurs in adults and some children• Characterized by bone demineralization• Results from prolonged elevations in blood

parathyroid hormone (PTH).• PTH promotes bone resorption and increased

urinary phosphorus excretion. • As bone turnover occurs, the bone matrix is

preserved but mineralization cannot occur.

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Osteomalacia

• Indicators of bone resorption include increased urinary excretion of bone collagen by-products such as:- Hydroxyproline- N-telopeptide- Pyridinoline- Deoxypyridinoline

• With insufficient serum calcium and phosphorous concentrations, the mineralization of bones cannot occur.

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Osteomalacia

• Progressive demineralization results in bone pain (throbbing or aching) and soft bones.

• Muscle weakness and general pain occur as well.

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Toxicity

• Tolerable Upper Intake = 4,000 IU for children, adolescents and adults.

• Vitamin D is one of the most likely vitamins to cause toxicity.

• Occurs with an intake of 10,000 IU/day for several months.

Source: 1

Toxicity

• Too much sunlight cannot cause toxicity – Only raises serum concentrations to ~100-

200nmol/L, whereas levels greater than 500nmol/l• Manifestions of toxicity include:– Hypercalccemia, calcinosis and the calcification of

the soft tissues including the heart, kidneys, lungs and blood vessels.

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Toxicity

• Additional effects include, hyperphosphatemia, hypertension, anorexia, nausea, weakness, headache, renal dysfunction, and sometime death.

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Significant Sources

• Provided by a small number of foods of animal origin.

• Liver (1 ug/3oz)• Eggs (1.1 ug/egg)• Fatty Fish- herring (2.4ug/3oz), salmon

11ug/3oz), tuna 1.7ug/3oz) and sardines (4.1ug/3oz)

• Small amounts in cheese and butter

Source: 1

Significant Sources

• Plant Origin-shitake mushrooms (0.5ug/1/2C)• Fortified sources:

– Milk– Yogurt– Cheese– Butter, margarine– Orange juice– Breads– Some cereals

• Supplements

Source: 1

References

1. Gropper SS, Smith JL. Advanced Nutrition and Human Metabolism, 6th ed. Belmont, CA: Wadsworth; 2013.

2. Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM (2012) 'Vitamin D metabolism, functions and needs: from science to health claims', Eur J Nutr, 52, pp. 429-441.

3. Dusso AS, Brown AJ, Slatopolsky E (2005) 'Vitamin D', Am J Physiol Renal Physiol, 289, pp. 8-22