Vitamin DThe Sunshine Hormone

Domenic Aiello, M.D., F.A.C.E.

Vitamin D Program1.The Basics2.Vitamin D Toxicity

3.Vitamin D Deficiency

4.Recommendations

Vitamin vs. 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.

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 andneedless expense of over testing.

Sources of Vitamin DD2 – Plants (Mushrooms)

Fortified CerealsIrradiated Yeast

D3- Animal (ultraviolet radiation and skin)Deep Sea Fatty FishEgg YolkLiver

Does anyone have any epiphanies about this list?

Vitamin D ToxicityToxicity = Hypercalcemia

i. This is usually related to ingestion of Vitamin D. ii. 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.

iii. When not related to ingestion it is from increased 1-OH activity. Think granulomatous disease, e.g.. Sarcoidosis, TB or lymphoma.

Treatment:iv. Fluidsv. Steroids vi. Biphosphonates

Vitamin D Deficiency1. 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).2. Malabsorption

Celiac Sprue Crohn’s Disease Pancreatic Insufficiency Cystic Fibrosis Cholestatic Liver Disease Gastrectomy

3. Decreased 25-OH Activity Anticonvulsants. Biliary Cirrhosis ETOH Cirrhosis

Vitamin D Deficiency

4. Binding Protein Deficiency – Nephrotic Syndrome5. Decreased 1-OH Activity

Hypoparathyroidism Renal Failure (creatinine clearance < 35 ml/min) 1-OH deficiency (Vitamin D dependent Rickets Type 1).

6. End-Organ Resistance Heredity Vitamin D Resistant Rickets Type 2.

Vitamin D Deficiency

1. 25-OH Vitamin D2. PTH3. Calcium and Albumin4. Alkaline phosphatase5. Urine calcium

What to measure:

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.

1. 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. Rickets3. Osteomalacia

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 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.

Vitamin D Deficiency

RicketsPresentation 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 DeficiencyVitamin 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.

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 DeficiencyOsteomalacia

• 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

Vitamin D DeficiencyCauses of Osteomalacia

1. Vitamin D Deficiency2. Hypophosphatasia3. Inhibitors of mineralization -> fluoride, aluminum, biphosphonates4. Phosphate Deficiency

1. Antacids2. Vitamin D resistant rickets3. Fanconi’s Syndrome, Wilson’s Disease, Cystinosis, multiple myeloma4. Primary hyperparathyroidism5. Renal tubular acidosis6. Seconday hyperparathyroidism7. Osteogenic Osteomalacia

Vitamin D Deficiency

Name available doses 1/2 lifeCalecalciderol (Vit D3)

200, 400, 600, 800, 1000, 2000, 5000 IU 3 weeks

Ergocalciferol (Vit D2) 25,000, 50, 000 u 3 weeks

Calcifediol (25 OH Vit D) 20 & 50 ugm. 2 weeksDihydrotachysterol (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 regulatedBy FGF23 (FibroblastGrowth Factor 23)

My Suggestions:

1. Vitamin D is not a screening test. 2. 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.

3. Unlike the Institute of Medicine, I subscribe to a minimal level of 30 ng/ml for bone health.

4. Whatever you do, you need to follow it. (This is the biggest difference between me and the Institute of Medicine Recommendations.)

5. Think in a circle, in-use-out. 6. 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.