Vitamin D

Vitamin D3 Synthesis and Metabolism

- PTH increases CYP27B1 gene expression (kidney enzyme) - Negative feedback: as plasma [1,25(OH)2D] increases, decrease CYP27B1 and increase CYP24A1 (induces Vit D3 catabolism) - CYP27B supressed by FGF-23 NB: 25(OH)D is best measure of Vit D status

Vitamin D Toxicity

- toxicity of Vit D in the skin is impossible (photosensitive; degraded by increased exposure to sunlight) - excess intake of Vit D can lead to Vit D "intoxication" or "hypervitaminosis D" (leads to hypercalcemia and eventually soft tissue calcification...renal/cardiovascular damage)

Vitamin D2 vs. Vitamin D3 a) 20-40%

- Vit D2 found in plants (biological activity _____ (a) of that of Vit D3) - Vit D3 found in animals NB: It is rare to find naturally occurring active Vit D in foods.

Photobiology

- adequate [25(OH)D] may be obtainable by 5-15 mins sun exposure, 10am to 3pm, during summer - higher latitudes and during winter months, UVB photon path length too long for significant Vit D synthesis

Fat Soluble Vitamins a) Free unesterified b) Bile acids c) Chylomicrons d) Vitamin D

- digested/absorbed along w/ lipids - Vit D, E and carotenoids present mostly in _____ ______ (a) forms in foods - absorption assisted by ____ ____ (b) - transported into bloodstream in _____ (c) (lymphatic system) ; taken up during hydrolysis - stored in body lipids (variable amount) - CM remnants return to liver with remaining _____ (d)

RDA Across the Life Cycle

0 to 0.5 years: 10 mcg/day (400 IU)* 0.5 to 1 years: 10 mcg/day (400 IU)* 1 to 18 years: 15 mcg/day (600 IU) 19 to 50 years: 15 mcg/day (600 IU) Pregnant: 15 mcg/day (600 IU) Lactating: 15 mcg/day (600 IU) > 70 years: 20 mcg/day (800 IU) 1 mcg Vit D = 40 IU UL 25 to 40 mcg/day (1000 to 4000 IU): linked to hypercalcemia

Serum [25(OH)D] and Health a) 80 to 120 b) 30 to 60

1. <30 nmol/L (<12 ng/mL) - associated with Vit D deficiency (rickets in children; osteomalacia in adults) 2. 30 to 50 nmol/L (12 to 20 ng/mL) - generally considered inadequate for bone and overall health in healthy individuals 3. >50 nmol/L (>20 ng/mL) - generally considered adequate for bone and overall health in healthy individuals - optimal = ______ nmol/L (a) or ______ ng/mL (b) 4. >125 nmol/L (>50 ng/mL) - may be adverse events

Groups at Risk for Inadequacy

1. Breastfed infants (related to maternal intake) 2. Older adults 3. People with limited sun exposure 4. People with dark skin 5. People with fat malabsorption 6. People who are obese or who have undergone bypass surgery (serum levels may rise temporarily w/ wt loss)

Biological Function of Vitamin D

1. Calcium balance 2. Immunomodulation - Vit. D deficiency associated w/ increased risk of AID 3. Regulates cell-growth (Anti-proliferative effects) 4. Reduces hypertension by downregulating renin production

Food Sources of Vitamin D

1. Natural Sources - fatty fish - egg yolks - beef liver - some mushrooms 2. Fortified Food Products - cow's milk, yoghurt and soy beverages - OJ - RTE cereal - margarine - infant formula

Factors Affecting Vitamin D Synthesis from Sunlight

1. Skin Colour - increased skin pigmentation decreases production of pre-Vit D (melanin blocks UVB) 2. Aging - decreased [7 DHC] in epidermis leads to decreased capacity for skin to produce Vit D 3. Sunscreens - sublock absorbs UV radiation and diminishes Vit D production from skin 4. Clothing 5. Obesity - Vit D is lipid soluble and w/ increase AT over time, Vit D is stored and is less accessible (also, reduced sun exposure?)

Assessment of Vitamin D Status a) Serum [25(OH)D] b) ~ 15 days c) ~ 15 hours

1. ____ ____ (a) best indicator - biomarker of exposure - reflects Vit D from cutaneous/food sources and supps - long circulating half life = _______ (b) - does NOT indicate amount stored 2. 1,25(OH)2D not a good indicator - short half life _____ (c) - regulated by PTH, Ca, P - does not decrease until deficiency is severe

Role of Vitamin D in Calcium/Phosphate Metabolism and Balance a) Gene expression

Major role: 1,25(OH)2D helps maintain normal plasma [Ca] 1. Intestine - increases efficiency of Ca absorption (from basal of 10-15% to 30-80%); also increases P absorption 2. Bones/Kidneys - along w/ PTH, 1,25(OH)2D induces formation and activation of osteoclasts (mobilize Ca from bones (and increases renal distal tubule reabsorption of Ca NB: most of these effects are mediated through alterations in ____ ____ (a)

Vitamin D Deficiency in Adults

Osteomalacia: poor mineralization of the collagen matrix Symptoms: - osteopenia: decrease in opacity of the skeleton - increased risk of skeletal fractures - bone pain

Vitamin D Deficiency in Children

Rickets: failure of epiphyseal plates to close results in disorganization and hypertrophy of chondrocytes Symptoms: - softening of bones - short stature - bone deformities