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Vit D: Discussion

- Discussion:
    - see: abnormalities associated with vitamin D.
    - primary function of vitamin D is to maintain skeletal calcium homeostasis;
          - promotes gut absorption of calcium (and absorption of phosphorous);
          - promotes bone absorption;
          - important for maintaining adequate quantities of Ca & Phos for bone formation thru its effects on the kidney & gut;
          - in addition, it may have a direct effect on bone formation;
    - proper functioning of the vitamin D system is necessary for PTH to maintain plasma calcium effectively, although drops in plasma
                    Ca occur only with severe Vit D depletion;
          - it appears that only minute amounts of Vit D are necessary for PTH to carry out its actions on the bone and kidney;
  - biosynthesis:
          - provitamin D2 (ergocalciferol from certain plants and animal fat) and 7-dehydroxycholesterol (endogenous) to form cholecalciferol (vit D3);
          - provitamin D3 (7-dehydroxycholesterol synthesized in  liver & stored in skin);
          - in the skin, the provitamin is converted to the active form of cholecalciferol thru the activity of ultraviolet irradiation;
          - hepatic hydroxylation to 25-OH vit D3;
          - renal hydroxylation to 1,25 di OH D3;
                 - in proximal renal tubule: conversion to 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, or 25,26-dihydroxyvitamin D);
                 - 1,25-dihydroxyvitamin D:
                       - is the most active of these metabolites;
                       - this hydroxylation is controled (increased) by PTH
                 - 24,25-dihydroxyvitamin D is the least active metabolite;

    - concentration of 25-hydroxyvitamin D should remain between 20 - 32 ng per milliliter to avoid problems;
    - reference:
           - Review Article: Vitamin D Deficiency

- Vit D Deficiency:
    - see: abnormalities associated with vitamin D.
    - primary effect of lack of Vit D is decrease in miceralization of newly formed bone matrix (osteoid);
    - rate of bone formation is decreased;
    - net result is less total bone & marked change in quality of bone;
    - osteomalacia:
           - disease processes characterized by defective mineralizaiton caused by any problem resulting in inadequate amounts of Vit D or
                     low plasma PO4;
           - in osteomalacia defective mineralizaiton results in relative increase in amount of osteoid (unmineralized bone matrix) in bone;
    - persons who do not receive adequate daily sunlight exposure, such as those confined to home or nursing facility, may be at special
           risk for vitamin D deficiency;
    - rickets:
           - in skeletally immature individuals, mineralization in the growth plates is also affected;
           - osteomalacia in this setting is called rickets;
           - in rickets, impaired mineralization of cartilage in zone of calcification arrests enchondral ossification & prevents formation of
                     primary spongiosa;
    - osteoporosis (see osteoporosis)
           - in healthy young adults recommended daily allowance for Vit D is 400 U/day;
           - w/ osteoporosis, supplementation with calcium and at least 800 U daily of vitamin D is treatment of choice;
           - among elderly patients with hip fractures, 10 to 20 percent have impaired bone mineralization because of vitamin D deficiency;
           - reference: Early intervention for postmenopausal osteoporosis. Scheiber LB. J Musculoskel Med. 1999:276.

- Vitamin Sub Types:
          - provitamin D2:
                   - (ergocalciferol from certain plants and animal fat) and 7-dehydroxycholesterol (endogenous) to form cholecalciferol (vit D3);
                   - activity of D2 is short acting and may drop off after 3 days.
                   - ref: Vitamin D2 is much less effective than vitamin D3 in humans.
          - provitamin D3:
                   - (7-dehydroxycholesterol synthesized in  liver & stored in skin);
                   - this is the form that humans synthesize from sunlight (and is at least 3 times more potent than provitamin D2)
                   - supplementation with D3 may last up to 3 weeks;
                   - can be made from sheep's wool and fish oil;
                   - dietary sources of vitamin D3:
                           - cod liver oil (3.5 oz): 8500 international units
                           - raw herring, 3.5 oz: 900 international units
                           - salmon, 3.5 oz: 600 international units
                           - multivitamin: 400 international units
                           - milk, 1 cup: 100 international units
                   - reference:
                           - Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults.
          - l,25-Vitamin D3:
                   - note that this form of vitamin D, is chiefly indicated for patients with renal failure who cannot synthesis vitamin D3 to more active 1,25 Vit D3 hormone;      
                   - unlike the standard Vit D3 whose dose is measured in international units, the 1,25 form is measured in micrograms;

 - Vit D Toxicity:
    - high doses of vitamin D may be toxic;
    - toxicity has occurred at levels as low as 2,000 to 5,000 IU / day;
    - it is not recommended that anyone consume more than 600 to 800 IU/day without a doctor's recommendation.

- Immunology Considerations:
    - vitamin D3 may promote antimicrobial peptides, cathelicidins;

    - references:
          - Scientists Find Why 'Sunshine' Vitamin D Is Crucial
          - The antibiotic vitamin: deficiency in vitamin D may predispose people to infection 
          - Vitamin D Deficiency Study Raises New Questions About Disease And Supplements 
          - Vitamin D: its role and uses in immunology 
          - Vitamin D deficiency in patients with osteoarthritis undergoing total hip replacement: a cause for concern?
          - Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.
          - Vitamin D regulation of cathelicidin in the skin: toward a renaissance of vitamin D in dermatology?    
          - Vitamin D3 Provides Skin With Protection From Harmful Microbes
          - Multiple health concerns surface as winter, vitamin D deficiences arrive
          - Vitamin D, Miracle Drug: Is It Science, or Just Talk
          - WELL; Vitamin D, Miracle Drug: Is It Science, or Just Talk? 
          - Prevalence of Vitamin D Insufficiency in African American Children with Forearm Fractures: A Preliminary Study

Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: the Tasmanian older adult cohort study.

Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial.

A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study

Vitamin D Sufficiency Screening in Preoperative Pediatric Orthopaedic Patients

The Effects of Vitamin D Deficiency in Athletes

Vitamin D Profile in National Football League Players

Bioavailability of Vitamin D and Its Metabolites in Black and White Adults