FNH 351 - Bone Nutrients: Vitamin D

What are the chemical forms of vitamin D that are physiologically relevant?

1. ergocalciferol (vitamin D2)

2. cholecalciferol (vitamin D3)

what do the physiologically forms of vitamin D differ in? Which one can be converted to the active form?

differ only in side chains. both can be converted to active form and have same metabolic activity

what is vitamin D derived from?

steroids

what is the active form of vitamin D?

1,25-(OH)2-cholecalciferol (or 1,25-(OH)2-vitamin D3) = calcitriol

what examples of food sources of vitamin D?

Fatty fish, liver, shitake mushrooms, fortified products (milk, orange juice)

what forms of vitamin D is found in food?

• animal products – vitamin D3 / cholecalciferol

• plants – vitamin D2 / ergosterol

what forms of vitamin D are found in supplements and fortified foods?

• vitamin D2 / ergocalciferol

• vitamin D3 / cholecalciferol (more effective in increasing vitamin D status)

explain the digestion of vitamin D

there is none required

where does vitamin D absorption occur?

mostly jejunum

how is vitamin D absorbed?

• Absorbed in micelles by passive diffusion

• Incorporated into chylomicrons in enterocyte

• Chylomicrons → lymph → blood → vitamin D to extrahepatic tissues

• Chylomicron remnants → remaining vitamin D to the liver

what form of vitamin D is synthesized endogenously? what is it synthesized from?

vitamin D3 (cholecalciferol). synthesized from 7-dehydrocholesterol in skin upon exposure to UVB light

what prevents overproduction of vitamin D?

generation of inactive metabolites

what does endogenous synthesis of vitamin D depend on?

• Sunblocks and sunscreen use

• Skin pigment (lower with darker skin pigment)

• Aging (vitamin D synthesis decreases with age)

• Time of day

• Season

• Latitude

explain the transport of different forms of vitamin D

what happens to vitamin D in the liver?

most vitamin D gets converted. 25-hydroxylase converts vitamin D to active form (vitamin D3) - 25-hydroxyvitamin D3 (25-(OH)-D) and secreted into the blood circulation

what is the major circulating form of vitamin D?

Plasma 25-(OH)-D

how is 25-(OH)-D transported?

has to be bound to vitamin-D binding protein (DBP)

what is the major storage site of vitamin D?

blood

what is vitamin D converted to in the kidney?

converted into 1,25-(OH)2-D = active form of vitamin D (= hormone) by 1-alpha-hydroxylase

what regulates the conversion of vitamin D that occurs in the kidney?

• ↑ stimulated by parathyroid hormone (PTH), and low serum phosphate

• ↓ inhibited by higher concentration of 1,25-(OH)2-D, FGF23 hormone, and high serum phosphate

how is 1,25-(OH)2-D transported?

Loosely bound to vitamin-D-binding protein (facilitates tissue uptake). It has a short half-life.

what are 1,25-(OH)2-D’s target tissues?

bone, intestine, kidney, and also heart, muscle, pancreas, and central nervous system

what are other metabolites of vitamin D?

• 1,24,25-(OH)3 D via 24-hydroxylase

• 24R,25-(OH)2 D via 24-hydroxylase

• Calcitroic acid

what is the major excretory product of vitamin D and how is vitamin D excreted?

• Calcitroic acid is the major excretory product

• Conjugation and excretion via the bile (happens in liver)

what are the metabolic functions of vitamin D?

1. genomic action - regulation of gene expression, e.g., calcium homeostasis

2. non-genomic action - activation of signal transduction pathways, physiological responses

vitamin D is involved in the regulation of > __ genes, including:

• regulation of > 200 genes, including:

  • Calbindin, Ca-channel transporter, Ca2+-ATPase, osteocalcin (all of which are proteins that are important for absorption of calcium in the intestine)

what does calcitriol do in terms of gene expression and how does it do it?

it enhances gene expression by binding to vitamin D receptor (VDR) at the VDR/RXR complex, triggering the vitamin D response element to enhance gene expression

what are some effects of vitamin D genomic action on cells?

• Increased expression of proteins needed to maintain calcium homeostasis

• Promotes differentiation of white blood cells, intestinal epithelial cells and osteoclasts

• Reduces cell proliferation of fibroblasts and keratinocytes

what is the non-genomic action of vitamin D?

Activation of signal transduction pathways via VDR or MARRS protein on cell membranes, leading to physiological responses.

What physiological processes may non-genomic actions of vitamin D affect?

Calcium absorption

• Regulation of calcium channels in muscle

• Maintenance of blood calcium homeostasis

what happens when blood calcium level is low?

Stimulates parathyroid hormone (PTH) release

• PTH increases 1,25-(OH)₂-D synthesis in the kidney

• Leads to:

  1. Increased kidney calcium reabsorption

  2. Increased intestinal absorption of calcium and phosphorus

  3. Increased bone resorption of calcium and phosphorus
     NET RESULT: Increased blood calcium

what are the nutrient-nutrient interactions with vitamin D?

1. calcium and phosphorus

2. dietary lipids (FAs)

3. vitamin A

4. vitamin A, E, and K

what is the nutrient-nutrient interaction with vitamin D and calcium & phosphorus?

Absorption and serum levels of calcium and phosphorus regulated by vitamin D

what is the nutrient-nutrient interaction of vitamin D with dietary lipids?

improve absorption of vitamin D

what is the nutrient-nutrient interaction of vitamin D with vitamin A

Gene expression control requires calcitriol and retinoic acid for vitamin D response element to exert its function

what is the nutrient-nutrient interaction of vitamin D with vitamins A, E, and K?

Vitamin D may compete for incorporation into micelles

What is the status biomarker for vitamin D?

Most commonly used indicator: plasma/serum 25-(OH)-D concentration

• strong correlation with dietary vitamin D intake

What does vitamin D deficiency cause in infants and children?

rickets which is a disorder of failed bone mineralization, defective mineralization of cartilage in the epiphyseal growth plate, and bowing of legs with weight-bearing

What does vitamin D deficiency cause in adults?

• Osteomalacia

• Osteoporosis

what is osteomalacia?

impaired bone remineralization (“softening” of bones), and prolonged elevation of blood PTH

Why does vitamin D deficiency cause osteomalacia?

bc causes decrease in Ca absorption and decrease serum Ca → decrease Ca for bone mineralization. Also causes a decrease in phosphorus absorption. As bone turnover occurs, the bone matrix is preserved while bone mineralization is impaired

what is osteoporosis?

reduced total bone mass (density)

what are the risk factors for developing osteoporosis?

• Non-modifiable

  • estrogen deficiency

  • ethnicity

  • family history

• Potentially modifiable

  • Vitamin D deficiency

  • Excess alcohol

  • Smoking

  • Malnutrition, incl. calcium, phosphorus, magnesium

  • Physical inactivity

what are the potential causes of vitamin D deficiency?

• Insufficient exposure to sunlight with inadequate intake

  • Limited time outside, use of sun protection (clothing, sunscreen), higher latitudes

• Fat malabsorption and inadequate endogenous synthesis

what are the populations at risk for vitamin D deficiency?

1. Older adults: typically have lower intake and lower synthesis

2. Human milk fed infants: human milk low in vitamin D, infants most protected from sun exposure

what are symptoms of vitamin D excess?

• Hypercalcemia

• Calcification of soft tissues

• Impaired renal function