Micronutrients: Vitamin D

Explain D2 and D3 Digestion.

Neither require digestion

How are deficiencies of vitamin D typically treated?

Supplements: one 50,000IU dosage given once per week for 8 weeks is sufficient, with follow up of 1,000/week for several months.

Food sources of D?

Small number of foods of animal origin: liver, fatty fish, cheeses, shittake mushroom.

Form of D in supplements? What is the other form called? How do they vary in the body?

D3; daily value is 400 IU 1 ug = 40 IU of D 1 IU = 0.025 ug of D D2; Found in plant foods.

Explain the relationship between calcitriol, PTH and (FGF) 23.

Calcitriol is the active form of D3, which is synthesized primarily in the kidney when stimulated by PTH. FGF is synthesized by osteoclasts and osteoblasts and inhbits Calcitriol synthesis.

What foods are typically fortified with D3 and in what amounts?

Orange juice, cereal and milk. Milk and orange juice may be fortified with 2.5 µg (100 IU) of vitamin D3/cup.

Calcitriol and Blood Glucose regulation

Plays a role in B-cell function in pancreas for insulin section. Positive correlation of insulin sensitivity and D status

What are the target tissues of calcitriol?

Intestine, bone, kidney, cardiac muscle, pancreas, brain, skin, hematopoietic and immune system tissues.

Discuss effect of Calcitriol and muscle function

Myopathy correlates with low Vit D. Supplementation improves it. Genomic activity: increases transcription for Calcium ATPase pumps (Ca transporters) Nongenomic: D binds second message systems to promote Ca release from intracellular stores. Same mechanism enhances myogenesis, cell proliferation, differentiation and apoptosis.

Is vitamin D in foods stable?

Yes. Not prone to loss in cooking storing or processing.

Describe the cutaneous production of vitamin D.

7-dehydrocholesterol (aka provitamin D3) Synthesized in the sebaceous glands of skin from cholesterol Absorbs photons and produces precholecalciferol (pre-vit D3) These unstable bonds rearrange in 2-3 days at body temperature resulting in vitamin D3 (25 OH D3)

Explain transport of both sunshine D and dietary D

60% of D from skin binds w DBP transporter and 40% of D from diet transports in the form of chylomicrons

How does Calcitriol impact the immune system?

Activated T- and B-cells express VDRs, as do antigen-presenting dendritic cells, monocytes, macrophages, and cytotoxic T-cells. Many of these cells also produce calcitriol. Vitamin D enhances antibody synthesis from activated B-cells and phagocytosis by macrophages . D also regulates the expression and production of several cytokines and produces antimicrobial peptides.

Discuss D's roles in blood pressure, heart disease, autoimmune conditions, blood glucose control

BP: lowers by downregulating Renin gene CVD: Low D associated with increased CVD Autoimmune: Low D associated. 2,000IU =+ve results perhaps by affect on immunity

Explain absorption of dietary D2/D3

Both forms are absorbed via micelle with fat and bile via passive diffusion. Most rapid in the duodenum an jejunum, BUT most is absorbed in the distal small intestine. Forms chylomicrons

How does Calcitriol affect phosphorous homeostasis?

Calcitriol will increase the levels of alkaline phosphatase and increase phosphatase absorption at the brush border. Calicitriol will modulate the #of carriers needed for phosphorous absorption at the jejunum and ileum brush border.

WHat conditions are associated with impaired absorption of D?

GI/fat malabsorption problems Disorders affecting the parathyroid, liver or kidney . People w kidney disease can't synthesize calcitriol into blood People on anticonvulsant drug therapy may develop an impaired response to vitamin D and exhitibt problems with calcium metabolism.

What are manifestations of vitamin D toxicity?

Levels greater than 375 nmol/L (150ng/mL) are associated with possible toxicity. UL is 2000 IU/day 10,000IU/day for several months= hypercalcemia and associated calcification of soft tissues such as the kidney, heart, lung, etc. Can be fatal.

How does Calcitriol affect cell differentiation, proliferation and growth:

Local presence of calcitriol within the tissues regulates these. W/ Calcitriol, WBCs and stem cells differentiate into macrophages and monocytes. Calcitriol can stimulate epidermal cell differentiation but also prevent it. Can also inhibit proliferation of abnormal intestinal/lymphatic/skeletal cells Calcitriol can down regulate cancer cell growth & induce apoptosis. Low D associated with increased death risk with breast, prostate, colon, ovarian and non-Hodgkins lymphoma.

Describe the non-genomic and genomic actions of calcitriol in serum calcium homeostasis

Low calcium triggers PTH which stimulates conversion of inactive D3 to Calcitriol, which will increase calcium absorption. In intestines: Genomic: Calcitriol is transported into enterocyte nucleus, interacting with VDR to regulate specific genes encoding for proteins involved in calcium absorption in the duodenum and jejunum. Nongenomic: Calcitriol binds with MARRS In kidneys: Genomic: Targets renal cell nucleus to make D28K and TRVP5 which binds and reabsorbs Ca. In bone: With high PTH and Calcitriol, Calcitriol will, via osteoblast nucleus, express RANKL, a cytokine. RANK will stimulate osteoclasts to mature. Osteoclasts will release Ca and phosphorus from bone.

What concentration of serum 25-OH D is thought to be sufficient to maintain health?

Measuring 25-OH D: Concentrations less than 50 nmol/L (10-12 ng/mL) = deficiency. Concentrations in the range of 50 to 72 nmol/L (20-29 ng/mL) constitute vitamin D insufficiency. Serum 25-OH D concentrations in excess of about 75 or 80 to 100 nmol/L (30 or 32-40 ng/ mL) are thought to be needed for bone health

Does Calcitriol affect a decrease in serum Ca?

Not directly. However, it does indirectly by decreasing the gene transcription for PTH.

How does vitamin D storage vary in individuals of normal weight vs. obese individuals

Obese store more in adipose tissue and thus need larger doses of the vitamin if serum is low.

How does PTH regulate vitamin D distribution?

PTH stimulates the conversion of 25 OH D to 1, 25 OH2 D in the kidneys.

How is vitamin D status assessed?

Plasma 25-OHD (calcidiol) if often used as an index of status. 15/ng/mL or <37nmol/L is subclincial deficiency and suggest Deficiency Newer findings suggest: <32ng/mL is deeficient 80nm/mL associated with plateau in PTH. OPtimal serum suggested as 30-60ng/mL or 80-120 nmol/L Toxicity is when 375 nmol/L

What form of vitamin D might be best absorbed in someone with intestinal disease? Hint: It related to how the different forms of vitamin D are transported.

Precholecalciferol and cholecalciferol via the skin have higher binding affinity with DBP.

Write up a summary (in the form of a client "prescription") for obtaining adequate levels of vitamin D.

Sunshine 3 x a week, midday (10a-3pm) for 5-15 minutes, depending on skin color. Season, year, and latitude all affect this. Eat foods rich in vitamin D, such as fish liver oil, fatty fish, eggs, and fortified foods such as OJ, cereals, and milk. Consider supplementing with D3 at 2,000IU/day esp in winter.

What is the main form of vitamin D in the body?

The largest pool of vitamin D takes the form of 25-OH-D3 bound to DBP in the blood, after being hydroxylated in the liver.