circulating vitamin d levels
DESCRIPTION
Circulating Vitamin D Levels. Beth Zubal, MS, AOCNP, FNP-BC. D History…. 1822 – Sniadecki: Clinical observation of urban children with ↑rickets compared to rural children By 1900 , 80% of Boston children had rickets (pollution) 1930s , food fortified with Vitamin D, - PowerPoint PPT PresentationTRANSCRIPT
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Circulating Vitamin D Levels
Beth Zubal, MS, AOCNP, FNP-BC
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D History…• 1822 – Sniadecki: Clinical observation of urban children
with ↑rickets compared to rural children
• By 1900, 80% of Boston children had rickets (pollution)
• 1930s, food fortified with Vitamin D,Schlitz Brewery (Milwaukee, WI) introduced beer fortified with Vitamin D
• 1980, Coppertone developed UVA/UVB sunscreen
Holick MF. VITAMIN D AND HEALTH IN THE 21ST CENTURY: BONE AND BEYOND. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Amer J Clin Nutr, Vol. 80, No. 6, 1678S-1688S, December 2004.
Sniadecki J. Jerdrzej Sniadecki (1768–1838) on the cure of rickets (1840); cited in Mozolowski W. Nature 1939;143:121–4.
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20,000 IU of Vitamin D < 30 min of sunlight
=200 glasses of milk or 50 standard multivitamins (400IU/tab) in one sitting
Cannell, JJ, Hollis BW, Zasloff M et al. Diagnosis and treatment of Vitamin D deficiency. Expert Opin Pharmacother (2008) 9(1), 107-118.
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Selected Food Sources of Vitamin D
FoodIUs per serving*
Percent DV**
Cod liver oil, 1 tablespoon 1,360 340
Salmon, cooked, 3.5 ounces 360 90
Mackerel, cooked, 3.5 ounces 345 90
Tuna fish, canned in oil, 3 ounces 200 50
Sardines, canned in oil, drained, 1.75 ounces 250 70
Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup 98 25
Margarine, fortified, 1 tablespoon 60 15
Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75-1 cup (more heavily fortified cereals might provide more of the DV)
40 10
Egg, 1 whole (vitamin D is found in yolk) 20 6
Liver, beef, cooked, 3.5 ounces 15 4
Cheese, Swiss, 1 ounce 12 4
*IUs = International Units**DV = Daily ValueTable from Office of Dietary Supplements: NIH. Retrieved January 15, 2009 http://ods.od.nih.gov/factsheets/vitamind.asp
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Circulation
Vitamin D enters circulation through
• Skin (D to D3) (Endogenous)
• Diet (D3) (Exogenous)
• Supplements Vit D2 - ergocalciferol
D3 - cholecalciferol
• Prescription – Calcitriol (synthetic analog)
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D Conversion:
• Liver converts to inactive 25 (OH)D (=calcitriol) by cytochrome P450
• Kidney = “gets it going” 25(OH)D physiologically active to 1,25(OH)D most potent form of Vit D
• Parathyroid – stimulates synthesis
1,25(OH)D maintains calcium level
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Intestine↑ absorption dietary Ca++
Kidney(active D=calcitriol)
Parathyroid
Liver (inactive D)
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Parathyroid Hormone
• During hypocalcemia, responsible for:
– Mobilizing bone calcium
– Increasing reabsorption of calcium by kidneys
– Intestinal absorption of calcium
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Definitions
• Normal level of 25-Hydroxy Vitamin D:– > 30 ng/ml
• Insufficiency:– 21 – 29 ng/ml
• Deficiency:– < 20 ng/ml
From: Holick (2008) Nutrition Reviews, Vol 66 (Suppl 2), S182-S194
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Levels Associated with Disorders
• Prevention of rickets and osteomalacia– 15 ng/ml
• Supression of parathyroid hormone– 20 – 30 ng/ml
• Optimal intestinal absorption of calcium– 34 ng/ml
• Neuromuscular function/performance– 38 ng/ml
Cannell, Hollis, Zasloff, & Heaney. (2008). Expert Opin. Pharmacother. 9(1): 107-118.
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Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health
ng/mL**nmol/L**
Health status
<11 <27.5 Associated with vitamin D deficiency and rickets in infants and young children
<10-15 <25-37.5
Generally considered inadequate for bone and overall health in healthy individuals
≥30 ≥75 Proposed by some as desirable for overall health and disease prevention, although a recent government-sponsored expert panel concluded that insufficient data are available to support these higher levels
Consistently >200
Consistently >500
Considered potentially toxic, leading to hypercalcemia and hyperphosphatemia, although human data are limited. In an animal model, concentrations ≤400 ng/mL (≤1,000 nmol/L) demonstrated no toxicity
* Serum concentrations of 25(OH)D are reported in both nanograms per milliliter (ng/mL) and nanomoles per liter (nmol/L).** 1 ng/mL = 2.5 nmol/L.Table from Office of Dietary Supplements: NIH. Retrieved January 15, 2009 http://ods.od.nih.gov/factsheets/vitamind.asp
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Dosing Recommendations for Deficiency
• Insufficiency– 800 – 1,000 IU of D³ daily– Brings level to 30ng/ml in 3 months
• Deficiency– Initial dose: 50,000 IU of D² or D³ po weekly for 6 – 8 weeks – Subsequent dose: 800 – 1,000 IU of D³ daily
• Malabsorptive States– Doses from 10,000 – 50,000 IU daily may be needed
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Covered Diagnoses
• Hypocalcemia
• Persistent, nonspecific musculoskeletal pain
• Fatigue
• Those on anticonvulsant therapy
• Suspected toxicity
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Factors Contributing to Decreased Levels
• Living in a northern latitude- > 35º• Melanin content in skin• Age: Elderly • Obesity• Use of sunscreen• Clothing coverage• Breast fed infants
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Vitamin D Deficiency in the Elderly
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Symptoms Associated with Vitamin D Deficiency
• Muscle weakness• Myalgia• Bone pain• Nausea• Hypocalcemia• Hyperparathyroidism• Osteopenia• Fractures
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Frequency of Testing
• At risk patients– Check twice a year, once in early spring to
determine lowest level and again in late summer for peak level.
• Those started on treatment– Three months after therapy initiated
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Drug Interactions with Vitamin D
• Steroids• Anti-convulsants: phenytion• Bile acid sequestrants: Questran• Thiazide diuretics given to patients with
hypoparathyroid on D2 may cause hypercalcemia
• Mineral oil effects absorption
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Laboratory Tests for Vitamin D
• 25-Hydroxy Vitamin D
• 1,25-Dihydroxy Vitamin D
• Vitamin D panel: includes 25-Hydroxy and 1,25-Dihyroxy levels
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Functions of Vitamin D
• Promotes calcium absorption from gut• Maintain adequate calcium and phosphate
concentrations• Modulates neuromuscular and immune
function• Reduces inflammation• Has a role in cell proliferation, differentiation,
and apoptosis
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Consequences of Vitamin D Deficiency
• Skeletal– Osteoporosis– Osteomalacia and bone pain– Muscle weakness
• Nonskeletal– Chronic disease: autoimmune diseases,
osteoarthritis, diabetes– Cancer– Tuberculosis– Cardiovascular disease
Holick, M. N Engl J Med, 2007;357:266-281; Wicherts et al. J Clin Endocrinol Metb. 2007;92:2058-2065. ; van Loden et al. Semin Oncol. 2008;35(6):643-651.
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PharmacogenomicsNearly 200 human genes contain vitamin D
receptors (1)
(brain, pancreas, heart, GI tract, immune system, prostate, bones)
Binding of VDR by calcitriol leads to multiple cellular effects: apoptosis, angiogenesis and potential of metastasis (2)
1. Carlberg C. Current understanding of the function of the nuclear vitamin D receptor In response to its natural and synthetic ligands. Recent Results Cancer Res. 2003; 164: 29-42.
2. Ng K, Meyerhardt, JA, Wu K, et. al. Higher pre-diagnosis plasma levels of serum 25-hydroxy-vitamin D (25[OH]D) after a diagnosis of colorectal cancer may significantly improve overall survival. J Clin Oncol 26(18), 2984-2991, 2008.
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Fok1 polymorphism
• Vitamin D receptor (VDR) important role in Vitamin D pathway• May be greater in European women
• Steroid family of nuclear receptors
• More than 80% of breast cancers are VDR +
Tang C, Chen N, Wu M, et al. Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility. Breast Cancer Res Treat. Published online: 06 January 2009: DOI 10.1007/s10549-008-0262-4.
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Breast Cancer
94% more likely to develop metastases and 73% more likely to die than women with normal levels of vitamin D at diagnosis
Goodwin P. Frequency of vitamin D (Vit D) deficiency at breast cancer (BC) diagnosis and association with risk of distant recurrence and death in a prospective cohort study of T1-3, N0-1, M0 BC. American Society of Clinical Oncology Annual Meeting: Abstract 511. 2008.
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Balance of Calcium
Vitamin D balance is crucial for proper calcium utilization including:
calcium absorptionbone growthosteoclast/osteoblast activity
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Bone Loss and Breast Cancer
• Treatment with Aromatase Inhibitors (AIs)
• Chemotherapy causing ovarian failure
• Radiotherapy
Hadji P, Body JJ, Aapro MS, et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Onc 2008 Aug; 19(8): 1407-16. Epub 2008 Apr 29.
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Vitamin D deficiency-incidence and response to oral supplementation
among various gastrointestinal malignancies
Gilmore C, James J, Zubal B, Thomas D, Tan B
Washington University School of Medicine
Siteman Cancer Center
St. Louis, MO
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Treatment
Pts with 25-OH Vitamin D level < 20-Vitamin D 50,000u q week x12
Pts with 25-OH Vitamin D level 21-50-Vitamin D 50,000u q week x8
Serum 25-OH re-checked after 8-12 weeks of therapy and if still <50 ng/ml continued on therapy according to above guideline
Goal to get 25-OH vitamin D level to 50 ng/ml and then maintain with 1000 to 2000u q day
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Gilmore C, James J, Zubal B et al. Vitamin D deficiency-incidence and response to oral supplementation among various gastrointestinal malignancies. 2009 GI ASCO. Abstract No: 329.
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Conclusions
• Vitamin D Deficiency is common among patients with GI malignancies.
• Vitamin D levels should routinely be evaluated for patients with GI malignancies.
• Oral supplementation decreases the rate of ‘any’ vitamin D deficiency from 81% to 61%, and of ‘severe to moderate’ deficiency from 58% to 17%.
• Prospective studies on the impact of vitamin D deficiency and supplementation on various clinical outcomes among patients with GI cancers would improve supportive care management of these patients.
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Who should undergo serum testing?
or
Should we be asking,
Who should not?
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