Nutrition: Vitamin D
What is the active form of D3 that is metabolized in the LV? Describe how the liver converts D3 to this active form.
* Active form is: 25-OH D3 (25-hydroxy vitamin D3). Aka: calcidiol Metabolism: *Absorbed through the small intestine as cholecalciferol (AKA D3) *Synthesized in the LV to 25-hydroxy vitamin D3 by the enzyme 25-hydroxylase * Requires Mg as a co-factor *Most is released into the blood bound to DBP *Main circulating form of vitamin D
How is Vit D stored?
* Cholecalciferol is stored in the skin and adipose tissue *25-OH D3 (convereted/circulating form) stored in the blood and muscle
What form of Vit D accurately reflects vit. D status from food and sunlight?
25-OH D3 (25-hydroxy vitamin D3)
What is the half life of 1,25 di-hydroxy vitamin D3 vs 25-hydroxy vitamin D3?
4-6 hours (cholecalciferol) vs 10 days to 3 weeks (calcidiol)
What is the tolerable UL for Vit D?
4000 IU But that may be overly conservative. 10,000 IU has been proposed based on risk assessment. All documented cases of toxicity have been with >40,000 IU/d D2 may be more toxic than D3
How does Vit D interact with Vit K?
Osteocalcin & matrix Gla protein synthesis are stimulated by 1,25-(OH)2 D3 ***Matrix gla protein (MGP) is a protein found in numerous body tissues that requires vitamin K for its optimum function.
What are the clinical indications for Vit D?
Osteoporosis Psoriasis Cancer Influenza Diabetes
What is cholecalciferol?
The inactive form of Vit D3 (sometimes called calciol). Whereas, calcitriol is the active form of D3
What role does Vit D play with BP?
Vitamin D down regulates production of renin & angiotensin which will lower blood pressure. renin & angiotensin are both enzymes that regulate blood pressure and fluid balance.
What is the name of 25-hydroxy vitamin D3?
calcidiol
What are the newest (2010) adequate intake levels for Vit D?
New RDA (Nov 30, 2010) Infants 0-12 months should get Vit D. 10 µg (400 IU) The rest of the RDAs are still low. Cdn Cancer Society says: "We're recommending 1,000 IUs daily because the current evidence suggests this amount will help reduce cancer risk with the least potential for harm"
How does Vit D interact with Mg?
Required for the conversion to the active form
With respect to Ca homeostasis, what effect does it have when calcitriol binds to bone cells?
In HYPOcalcemic conditions PTH & calcitriol: It stimulate the production & maturation of osteoclasts, mobilizing Ca & P from bone (resorption) In HYPERcalcemic conditions calctonin & calcitriol: It promote mineralization of Ca & P in the bone
How is Vit D excreted?
In feces (>70%) & urine
Who is at increased risk of deficiency for Vit D?
Insufficient sun exposure: Those who wear head coverings/live in a city where there are lots of tall buildings. Critically ill Elderly Adolescents (not outside enough, and don't eat well) Exclusively breastfed infants Obesity (adipose tissue will sequester more Vit D) Fat malabsorption History of GI surgery Parathyroid disorders Liver disease Kidney disease Strict vegans
How is Vit D obtained via the skin transported?
* Diffuses into blood * Picked up by DBP for transport *Travels primarily to the liver but can be picked up by other tissues, especially muscle and adipose tissues
What are the symptoms of Vit D toxicity?
* Hypercalcemia & hypercalciuria: W/ increased Ca levels, there can be an inappropriate deposition of Ca in the tissues. * Hyperphosphatemia *Anorexia, constipation, nausea & vomiting *Muscle weakness *Hypertension & cardiac arrhythmias b/c of Ca deposits in the vascular system *Calcification of soft tissues *Renal dysfunction: polyuria, polydipsia, nephrolithiasis & renal failure *Mental confusion (caused by hypercalcemia) *Death *****Really important to check someone's Ca levels when you are dosing Vit D at high doses.
What happens when 1,25-(OH)₂ D3, Ca, and phosphorus levels are high?
*1,25-(OH)2 D3 is converted into 1,24,25-(OH)₃ D3 *25-(OH) D3 is converted into 24,25-(OH)₂ D3 ***24,25-(OH)₂ D3 is also increased in periods of adequate vitamin D status and calcium homeostasis???
How is Vit D absorbed?
*By passive diffusion *Primarily in the distal small intestine. However, the rate is fastest in the duodenum *Animals excrete Vit D on the skin and on the fur. (As a result, we can get Vit D from sheeps wool.) Note: When animals were grooming, they would orally absorb Vit D which is how we've evolved to absorb it from animals.
Clacitriol is required for the differentiation of what cells? (3)
*Premyeloid WBCs & stem cells into active immune cells like macrophages & monocytes *Stem cell monocytes in bone marrow to mature osteoclasts *Skin epidermal cells
Why is it really important to check someone's Ca levels when you are dosing Vit D at high doses???
...
What are the deficiency symptoms in adults for Vit D?
1. Adults are more at risk for osteomalacia: *Bone mineralization defects *This is secondary to changes in calcium and phosphate absorption and excretion * Less calcium is absorbed. *This stimulates PTH secretion which, in turn, promotes bone resorption and increased urinary phosphate excretion *Bone matrix is preserved but remineralization is impaired *This results in bone pain and softening of the bones. Consequences include: Muscle weakness, low back pain, diffuse aches & pains, hyperesthesia, fatigue, & head sweating.
What are the deficiency syndromes/symptoms in children for Vit D?
1. Children mostly at risk for rickets. Bone mineralization defects include: *Epiphyseal cartilage continues to grow without replacement by bone matrix & minerals *Wrists, ankles & knees enlarge *Legs bow & knees knock as walking begins *Spine becomes curved *Pelvic & thoracic deformities occur 2. There can also be: *Dental abnormalities *Growth retardation *Muscle weakness *Seizures
The mount of vitamin D produced in the skin depends on what?
1. Season 2. Latitude 3. Time of day 4. Degree of pigmentation: The lighter the skin, the 5. Age: The older you are, the less efficient your circulatory system is, so maybe your skin isn't as well perfused. AND/OR As we age, liver and kidney function are run down so not producing as much. AND/OR Older people are not outside as often.
How is Vit D digested?
Dietary vitamin D in association with dietary fats is packaged into micelles with the aid of bile salts
With respect to Ca homeostasis, what effect does it have when calcitriol binds to intestinal cells?
Leads to enhanced intestinal Ca & P absorption
Excessive sun exposure (is/is not) associated with risk of vitamin D toxicity.
is not
What role does Vit D play with the Role in pancreatic β -cell function? ??? Is it beta cells?
Higher calcidiol (25-OH D3) levels are associated with decreased insulin secretion and increased insulin sensitivity Involved in neuromuscular function
How is Vit D contribute to Ca homeostasis?
Hypoclacemia stimulates secretion of PTH PTH stimulates 1-hydrolase activity in the kidney which converts 25-OH D3 to calcitriol Calcitriol binds to: intestinal, kidney, and bone cells. Regulated by Negative Feedback loop whereby increasing serum Ca and calcitriol levels inhibit PTH secretion
What role does Vit D play with the immune system modulation?
Inadequate vitamin D levels are linked with autoimmune conditions like rheumatoid arthritis, Crohn's disease, multiple sclerosis, and type I diabetes mellitus It effects the immune system. For example, cytokine production, lymphocyte and macrophage activity, monocyte maturation, and the production of certain antimicrobial peptides are all mediated by vitamin D
How does Vit D interact with iron?
Iron deficiency may decrease vitamin D absorption
How does Vit D interact with Ca & P?
Vitamin D increases their intestinal absorption Vitamin D promotes their deposition into bone Vitamin D regulates their serum levels
What are the different preparations of Vit D?
*Ergocalciferol (D2): (By prescription) 50,000 IU/pill, usually given once a week for 8 weeks * Cholecalciferol (D3)
Calcitriol inhibits the proliferation of:
*Fibroblasts, keratinocytes, & lymphocytes *Abnormal intestinal, lymphatic, mammary, & skeletal cells. It down regulates cancer cell growth in some tissues & is able to induce apoptosis if needed. *Low vitamin D levels are associated with increased risk of developing & dying of several cancers.
How is dietary vit D transported?
*It's incorporated into chylomicrons within the enterocytes for transport *Chylomicron remnants deliver the vit D to liver
Where are Vit D receptors found?
*On many, many cells (eg. Intestine, bone, kidney, cardiac, pancreatic b-cells, brain, skin, hematopoietic and immune cells. *This shows that Vit D is incredibly imp in many systems in our body. Not just for Ca regulation. There is a preferential use for 1-hydrolase use of Vit D. When it is used up, then the body will convert to active forms of Vit D in all these other parts of the body.
How do we get Vit D?
1. Synthesize it in skin - from sunlight. If we have adequate sun exposure, we don't need it from our diet. 2. Animal sources: Saltwater fish, especially fish liver, meat (liver & beef) & egg yolks BUT We can also get Ergocalciferol (Vit D2) AKA: pre-vit D from plant sources: mushrooms (trace amounts), dairy, & fortified foods (milk & margarine). Most fortification uses the D₂ form.
As a general rule ~1000 IU of vitamin D is produced in _______ minutes of sun exposure between _______ am to _____pm during the spring, summer & fall in fair skinned middle-aged people.
5-15 10am - 3pm
Describe the process of ultraviolet synthesis of Vit D.
7-dehydrocholesterol (aka provitamin D3) *Synthesized in the sebaceous glands of skin from cholesterol *Secreted onto skin's surface & reabsorbed into epidermis & dermis *Absorbs photons produce precalciferol (pre-vit D3) *These unstable bonds rearrange in 2-3 days at body temperature resulting in vitamin D3 *Vitamin D3 diffuses from the skin into the blood *It's transported in blood by vit D binding protein (DBP) known as transcalciferin
What is the active form of D3 that is metabolized in the kidney? Describe how the kidney converts D3 to this active form.
Active form: 1,25-(OH)2 D3 (1,25 di-hydroxy vitamin D3) AKA: colecalciferol Metabolism: *Absorbed through the small intestine as cholecalciferol (AKA D3) *Converted in kidney tubules to 1,25 di-hydroxy vitamin D3 by the enzyme 1-hydroxylase *Functions as a steroid hormone *Transported in blood via DBP *Binds to vitamin D receptors on target tissues
How is the enzyme 1,25 hydroxylase regulated?
It's INCREASED by: *Low 1,25-(OH)2 D3 concentrations *Parathyroid hormone (when Ca levels are low) *Low plasma Ca concentrations *Low phosphorus intake DECREASED by: *High 1,25-(OH)₂ D3 concentrations *High phosphorus intake
What is the therapeutic dosage of Vit D?
It's controversial. It depends on: Age Fat mass Sun exposure Skin pigmentation Risk of certain diseases 800 IU/d shown to be more effective than 400 IU/d at preventing fractures in elderly *Typical dosage: 1000-2000 IU/d Up to 10,000 IU/d (and higher) *Monitor serum 25-(OH) D3 levels & serum calcium levels with high doses
What is the mechanism of action with Vit D?
It's not fully understood, however, there are 2 primary proposed mechanisms: 1. Functions as a steroid hormone: Activation of signal transduction pathways linked to cell membrane VDRs 2. Promotes genomic actions: Interacts with nuclear vitamin D receptors influencing gene transcription
What co-factor is required to convert D3 (cholecalciferol) to 25-OH D3 (calcidiol) in the LV?
Mg
What is the best way to assess Vit D status?
Plasma concentration of 25-OH D3 are more reliable than serum vitamin D levels.
With respect to Ca homeostasis, what effect does it have when calcitriol binds to kidney cells?
With PTH stimulates Ca reabsorption in the distal renal tubules. The main role of PTH is to act to increase the concentration of Ca in the blood.
