2 Vitamin D Program The Basics Vitamin D Toxicity Vitamin D Deficiency Recommendations
3 Vitamin vs. Hormone Hormone Vitamin Any organic substance, found in minute amounts in the body, that acts as an essential co-factor or co-enzyme in an organic system. It is obtained from food sources and not produced in the body.HormoneA substance, peptide or steroid, that is produced by one tissue and conveyed by the bloodstream to another to affect physiologic activity, such as growth or metabolism.
4 Vitamin D-Discovered in 1921, from the irradiation of cod liver oil and found to treat rickets.-Produced in the skin, when exposed to ultraviolet radiation between nm.-It is essential to calcium and bone metabolism.-Over the last 20 years, it has been noted to be a modulator of other hormone activityand this has led to looking at cause and effects of Vitamin D in other systems.Unfortunately, like muddy waters, nothing is clear. Thus, concern exist about the overthe use of Vitamin D, the risk of hypercalcemia, kidney stones, ectopic calcifications andneedless expense of over testing.
6 Does anyone have any epiphanies about this list? Sources of Vitamin DD2 – Plants (Mushrooms)Fortified CerealsIrradiated YeastD3- Animal (ultraviolet radiation and skin)Deep Sea Fatty FishEgg YolkLiverDoes anyone have any epiphanies about this list?
7 Toxicity = Hypercalcemia Vitamin D ToxicityToxicity = HypercalcemiaThis is usually related to ingestion of Vitamin D.The ½ life of Vitamin D is 3 weeks, as apposed to calcitriol which is about 10 hours. So depending upon what was taken this can last some time.When not related to ingestion it is from increased 1-OH activity. Think granulomatous disease, e.g.. Sarcoidosis, TB or lymphoma.Treatment:FluidsSteroidsBiphosphonates
8 Vitamin D Deficiency Decrease Synthesis Age. Amount of pigment in the skin.Winter (actually there are only 2 weeks in mid-August, when UV radiation is optimal for skin production of Vitamin D).MalabsorptionCeliac SprueCrohn’s DiseasePancreatic InsufficiencyCystic FibrosisCholestatic Liver DiseaseGastrectomyDecreased 25-OH ActivityAnticonvulsants.Biliary CirrhosisETOH Cirrhosis
9 Vitamin D Deficiency Binding Protein Deficiency – Nephrotic Syndrome Decreased 1-OH ActivityHypoparathyroidismRenal Failure (creatinine clearance < 35 ml/min)1-OH deficiency (Vitamin D dependent Rickets Type 1).End-Organ ResistanceHeredity Vitamin D Resistant Rickets Type 2.
10 Vitamin D Deficiency What to measure: 25-OH Vitamin D PTH Calcium and AlbuminAlkaline phosphataseUrine calciumSpecial Considerations:There is a lot of variability from lab to lab and from kit to kit in 25OH Vit D measurements.During puberty, with adequate calcium replacement, a high normal PTH and a low normal Vitamin D level, you seem to maximize bone mass.1You get maximal calcium absorption with a 25OH Vitamin D level of about 32 ng/ml.2If the 25 OH Vitamin D level is < 12 ng/ml, think malabsorption.J Am Coll Nutr. 2007, 26(5):2. Am J Nutr. 2004, 80(6 supl) 1706S-1709S.
11 Vitamin D DeficiencyConditions resulting from Vitamin D Deficiency: 1. Secondary Hyperparathyroidism. 2. Rickets 3. Osteomalacia
12 Secondary Hyperparathyroidism Vitamin D DeficiencySecondary Hyperparathyroidism(In Endocrinology, primary refers to the organ of interest as the problem, secondary are things that cause that organ to malfunction and tertiary is the waste basket of what happens next.)In secondary Hyperparathyroidism, you have an elevated PTH in the face of a normalcalcium. The PTH is being made appropriately, to keep the serum calcium normal. Itis either related to decreased Ca++ intake, decrease GI absorption (Vit D Deficiency),or loss of Calcium in the urine. The overall effect, is a loss in bone mass.The goal for normal bone health/metabolism is a level of 30 ng/ml.This is the major form of Vitamin D Deficiency and a easily correctable contributorto osteopenia/osteoporosis.
13 Vitamin D Deficiency Rickets Presentation Hypocalcemia. Hypophosphatemia.Delayed closure of the Fontonelles.Craniotabes.Enlargement of costochondrial junction (rachitic rosary).Enlargement of wrist and bowing of the distal radius and ulna.Progressive lateral bowing of the femur and tibia.
14 Vitamin D Deficiency Nutritional Rickets The number 1 cause in the western world is prolonged breast feeding. You also need to consider all the GI causes of malabsorption, esp. sprue and cystic fibrosis.Treatment involves a) finding the cause and treating it, b) Vitamin D replacement (400 IU/day), and c) adequate calcium replacement (1000 mg/d).
15 Vitamin D Dependant Rickets Type 1 Vitamin D DeficiencyVitamin D Dependant Rickets Type 1This is a deficiency of 1-OH activity. Thus 25-OH vitamin D levels are normal, but the 1,25-OH levels are low. There are the x-ray findings of rickets, and a low calcium.Treatment is with Calcitriol. Treatment goal is to maintain a normal Calcium and phosphorous level, avoiding hypoparathyroidism or hypercalcemia. Dose is based on body weight and response. Usual dose is between 0.25 mcg to 1.0 mcg/day.
16 Very Rare (50 known Kindreds) Vitamin D DeficiencyHereditary Vitamin D Resistance Rickets (Type 2)Very Rare (50 known Kindreds)Cause – mutated vitamin D receptor causing resistance to action of the hormone.Treatment – try vitamin D, but it usually does not work. You are left with a combination of calcium supplementation/infusions.
17 Vitamin D Deficiency Osteomalacia A change in the character of the osteoid produced by the osteoblast during bone remodeling, resulting in a defect in calcification. As a result there is decreased bone strength and micro fractures.PresentationBone pain (long bones and joints)Proximal muscle weaknessPseudofracturesIncreased alkaline phosphatase and PTH+/- hypocalcemia
18 Causes of Osteomalacia Vitamin D DeficiencyCauses of OsteomalaciaVitamin D DeficiencyHypophosphatasiaInhibitors of mineralization -> fluoride, aluminum, biphosphonatesPhosphate DeficiencyAntacidsVitamin D resistant ricketsFanconi’s Syndrome, Wilson’s Disease, Cystinosis, multiple myelomaPrimary hyperparathyroidismRenal tubular acidosisSeconday hyperparathyroidismOsteogenic Osteomalacia
19 Vitamin D Deficiency Name available doses 1/2 life Calecalciderol (Vit D3)200, 400, 600, 800, 1000, 2000, 5000 IU3 weeksErgocalciferol (Vit D2)25,000, 50, 000 uCalcifediol (25 OH Vit D)20 & 50 ugm.2 weeksDihydrotachysterol (DHT, 1 OH Vit D)0.125, 0.2, 0.4 mg4 daysCalcitriol (1,25 OH Vit D)0.25, 0.5 ugm PO & 1, 2 ugm IV10-14 hours
21 Vitamin D Metabolism Up regulated by PTH, Down regulated By FGF23 (FibroblastGrowth Factor 23)
22 My Suggestions: Vitamin D is not a screening test. If you have clinical suspicion that there is a problem, based on the problem, you order a vitamin D level. Usually, this is a 25-OH Vitamin D. A 1,25-OH is a research tool. Clinically, it serves a purpose if you are taking 1,25-OH Vitamin D or if you are looking for a) cause of hypercalcemia or b) Type 1 Rickets.Unlike the Institute of Medicine, I subscribe to a minimal level of 30 ng/ml for bone health.Whatever you do, you need to follow it. (This is the biggest difference between me and the Institute of Medicine Recommendations.)Think in a circle, in-use-out.Try to avoid Voodoo!
24 Reading ListLeFoith, D., MD, PhD, Endo and Metab Clinics of N Am, June 2010 (39)2:“Dietary Reference Intakes for Calcium and Vitamin D”, Institute for Medicine, 11/30/2010.Thacher, T.D. & Clarke, B.L., Mayo Clin Proc (1):Rosen, C.J., N Engl J Med, :