Vitamin D The Sunshine Hormone Domenic Aiello, M.D., F.A.C.E.

Vitamin D Program The Basics Vitamin D Toxicity Vitamin D Deficiency Recommendations

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. Hormone A 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.

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 270-300 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 activity and 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 over the use of Vitamin D, the risk of hypercalcemia, kidney stones, ectopic calcifications and needless expense of over testing.

Does anyone have any epiphanies about this list? Sources of Vitamin D D2 – Plants (Mushrooms) Fortified Cereals Irradiated Yeast D3- Animal (ultraviolet radiation and skin) Deep Sea Fatty Fish Egg Yolk Liver Does anyone have any epiphanies about this list?

Toxicity = Hypercalcemia Vitamin D Toxicity Toxicity = Hypercalcemia This 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: Fluids Steroids Biphosphonates

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). Malabsorption Celiac Sprue Crohn’s Disease Pancreatic Insufficiency Cystic Fibrosis Cholestatic Liver Disease Gastrectomy Decreased 25-OH Activity Anticonvulsants. Biliary Cirrhosis ETOH Cirrhosis

Vitamin D Deficiency Binding Protein Deficiency – Nephrotic Syndrome Decreased 1-OH Activity Hypoparathyroidism Renal Failure (creatinine clearance < 35 ml/min) 1-OH deficiency (Vitamin D dependent Rickets Type 1). End-Organ Resistance Heredity Vitamin D Resistant Rickets Type 2.

Vitamin D Deficiency What to measure: 25-OH Vitamin D PTH Calcium and Albumin Alkaline phosphatase Urine calcium Special 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.1 You get maximal calcium absorption with a 25OH Vitamin D level of about 32 ng/ml.2 If the 25 OH Vitamin D level is < 12 ng/ml, think malabsorption. J Am Coll Nutr. 2007, 26(5): 462-470. 2. Am J Nutr. 2004, 80(6 supl) 1706S-1709S.

Vitamin D Deficiency Conditions resulting from Vitamin D Deficiency: 1. Secondary Hyperparathyroidism. 2. Rickets 3. Osteomalacia

Secondary Hyperparathyroidism Vitamin D Deficiency Secondary 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 normal calcium. The PTH is being made appropriately, to keep the serum calcium normal. It is 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 contributor to osteopenia/osteoporosis.

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.

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).

Vitamin D Dependant Rickets Type 1 Vitamin D Deficiency Vitamin D Dependant Rickets Type 1 This 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.

Very Rare (50 known Kindreds) Vitamin D Deficiency Hereditary 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.

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. Presentation Bone pain (long bones and joints) Proximal muscle weakness Pseudofractures Increased alkaline phosphatase and PTH +/- hypocalcemia

Causes of Osteomalacia Vitamin D Deficiency Causes of Osteomalacia Vitamin D Deficiency Hypophosphatasia Inhibitors of mineralization -> fluoride, aluminum, biphosphonates Phosphate Deficiency Antacids Vitamin D resistant rickets Fanconi’s Syndrome, Wilson’s Disease, Cystinosis, multiple myeloma Primary hyperparathyroidism Renal tubular acidosis Seconday hyperparathyroidism Osteogenic Osteomalacia

Vitamin D Deficiency Name available doses 1/2 life Calecalciderol (Vit D3) 200, 400, 600, 800, 1000, 2000, 5000 IU 3 weeks Ergocalciferol (Vit D2) 25,000, 50, 000 u Calcifediol (25 OH Vit D) 20 & 50 ugm. 2 weeks Dihydrotachysterol (DHT, 1 OH Vit D) 0.125, 0.2, 0.4 mg 4 days Calcitriol (1,25 OH Vit D) 0.25, 0.5 ugm PO & 1, 2 ugm IV 10-14 hours

Vitamin D Metabolism Up regulated by PTH, Down regulated By FGF23 (Fibroblast Growth Factor 23)

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!

Reading List LeFoith, D., MD, PhD, Endo and Metab Clinics of N Am, June 2010 (39)2: 243-479. “Dietary Reference Intakes for Calcium and Vitamin D”, Institute for Medicine, 11/30/2010. Thacher, T.D. & Clarke, B.L., Mayo Clin Proc. 2011 86(1): 50-60. Rosen, C.J., N Engl J Med, 2011 364:248-254.