Intern Seminar： Vitamin D deficiency Presenter：Int. 許哲瑋 Supervisor：Dr. 林永傑 2016/10/03

Outline 02 Vitamin D insufficiency in Taiwan Biochemistry of Vitamin D Definition of Vitamin D insufficiency Disease associated with vitamin D deficiency / insufficiency Vitamin D supplement 02

03 Prevalence of Vitamin D deficiency in Taiwan Nutrition And Health Survey in Taiwan 台灣營養健康狀況變遷調查 03

60% population 3.5% population 04 Prevalence of Vitamin D deficiency in Taiwan Nutrition And Health Survey in Taiwan 台灣營養健康狀況變遷調查 60% population 3.5% population 04

05 Vitamin D insufficiency in Taiwan Biochemistry of Vitamin D Definition of Vitamin D insufficiency Disease associated with vitamin D deficiency / insufficiency Vitamin D supplement 05

Structure of Vitamin D 06 1 nmol/L = 400 ng/L = 0.4 ng/ml Cholecalciferol Ergocalciferol 384.64 g/mol 396.65 g/mol 1 nmol/L = 400 ng/L = 0.4 ng/ml 50 nmol/L = 20 ng/ml 06

Synthesis of Vitamin D 07 Dietary UVB 7-dehydrocholesterol Vitamin D3 Liver Calcidiol 25-OH Vitamin D Skin Gastrointestinal tract Kidney Vasculature 24,25-(OH)2 Vitamin D Calcitriol 1,25-(OH)2 Vitamin D Osteoblasts 07

Feedback system of Vitamin D 25-OH Vit D Negative Feedback PTH↑ Ca ↓ P↓ 1,25-(OH)2 Vit D 08

Functions of Vitamin D 09 Intestine Absorption of calcium and phosphate Kidney PTH↓ → Phosphate reasorption ↑ Bone Ca↑ P↑ → Bone mineralization↑ Vitamin D receptor element 3000 genes VDRE 09

Distribution of Vitamin D receptors https://www.ncbi.nlm.nih.gov/pubmed/23364265 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073895/ 10 Am J Physiol Cell Physiol. 2013 Jun 1;304(11)C1027-39.

11 Long half-life Storage Deficiency ? Large amount Measured Disease ? Dietary UVB 7-dehydrocholesterol Vitamin D3 Vitamin D2 Liver Long half-life Storage Calcidiol 25-OH Vitamin D Deficiency ? Large amount Measured Kidney 24,25-(OH)2 Vitamin D Calcitriol 1,25-(OH)2 Vitamin D Disease ? Bowel Kidney Bone VDRE 11

12 Vitamin D insufficiency in Taiwan Biochemistry of Vitamin D Definition of Vitamin D insufficiency Disease associated with vitamin D deficiency / insufficiency Vitamin D supplement 12

Definition of Vitamin D deficiency Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health For Bone health！ 13 Beyond skeletal system

Definition of Vitamin D deficiency Pediatrics Endocrine Kidney Adult https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979050/ 14 J Pediatr Pharmacol Ther 2013;18(4):277–291

15 Vitamin D insufficiency in Taiwan Biochemistry of Vitamin D Definition of Vitamin D insufficiency Disease associated with vitamin D deficiency / insufficiency Vitamin D supplement 15

Vit D Deficiency 16 Rickets Wound Diabetes Muscle Infection Cancer Osteomalacia Rickets Wound Diabetes Hypertension Vit D Deficiency Autoimmune Muscle Infection Cancer Obesity 16

17 Public Health Reviews, Vol. 32, No 1, 267-283

Rickets Deficient mineralization and architectural disruption at the growth plate Initially manifests at the distal forearm and knee Clinical presentation Deformity, valgus, varus Image: widening of the epiphyseal plate, disorganization Lab data: Alk-P↑, Ca, P, PTH, 25(OH)D, 1,25(OH)2D Classification Calcipenic: with/ without vitamin D deficiency Phosphopenic: renal phosphate wasting 18

19 cupping splaying widening fraying http://pediatrics.aappublications.org/content/pediatrics/122/2/398.full.pdf 19 PEDIATRICS Volume 122, Number 2, August 2008

Neonatal sepsis 20 Maternal Calcidiol↑ Neonatal Calcidiol↑ Journal of Perinatology (2015) 35, 39–45 Chin J Contemp Pediatr Vol.18 No.9 Sep. 2016 Maternal Calcidiol↑ Neonatal Calcidiol↑ http://www.cjcp.org/EN/abstract/abstract13977.shtml# 15 ng/mL , 20 ng/mL 20

Development delay 21 18 ng/ml 30 ng/ml Pediatrics March 2012, VOLUME 129 / ISSUE 3

Diabetes 22 Diabetes Care. 2013 May;36(5):1422-8. http://care.diabetesjournals.org/content/36/5/1422.long 22 Diabetes Care. 2013 May;36(5):1422-8.

Hypertension 23 15 ng/ml 30 ng/ml 32 ng/ml http://link.springer.com/article/10.1007%2Fs10654-013-9790-2 http://ajh.oxfordjournals.org/content/24/3/316 23 Eur J Epidemiol. 2013 Mar;28(3):205-21

Breast Cancer 24 27.0 ng/mL vs 19.8 ng/mL http://link.springer.com/article/10.1007%2Fs13277-013-0929-2#CR18 http://cebp.aacrjournals.org/content/19/9/2341.long 24 Tumour Biol. 2013 Dec;34(6):3509-17.

Leg ulcer 25 - 7 cm2 vs - 2.5 cm2 (p=0,0676) http://www.scielo.br/pdf/rcbc/v39n5/en_11.pdf 17,05 ng/ml vs 22,75 ng/ml (p=0,0182) 25 Rev. Col. Bras. Cir. 2012; 39(5): 401-407

Groups at Risk of Vitamin D Inadequacy Older adults People with limited sun exposure Fat malabsorption Obese Perinatal factors Maternal vitamin D deficiency Prematurity  Exclusive breast feeding 26

28 Vitamin D insufficiency in Taiwan Biochemistry of Vitamin D Definition of Vitamin D insufficiency Disease associated with vitamin D deficiency / insufficiency Vitamin D supplement 28

29 Recommendation of Vitamin D intake 1 micro gram = 40 IU 建議從新生兒開始每天給予400 IU口服維生素D 使用配方奶的兒童，如果每日進食少於1,000毫升加強維生素D的配方奶，需補充 維生素D 的其他來源，例如加強維生素D的食物，可計入400 IU的每日最低攝取量之中 29

30 Recommendation of Vitamin D intake 300 IU Nutrition And Health Survey in Taiwan 台灣營養健康狀況變遷調查 300 IU 30

Vitamin D in Food 31 100g D3 (μg) D3 (IU) 野生鮭魚 22 880 秋刀魚 19 760 吳郭魚 11 440 植物性奶油 10 400 鴨肉 3.1 120 豬肝 1.3 52 1 顆雞蛋黃 0.5 20 豬肉 0.1 4 31

Vitamin D supplement 30 IU/pack 200 IU/ml 32

= 2 IU/100 ml = 50 IU/100 ml 33

Sun Exposure 34 Season Cloud cover Time of day Skin melanin content UVB (290–320 nm) 600 cm2 (5% ), 3 min → 435 IU Season Cloud cover Time of day Total body surface, erythema → 10000 IU Skin melanin content http://www.altmedrev.com/publications/10/2/94.pdf http://ajcn.nutrition.org/content/69/5/842.full Sunscreen 34 Am J Clin Nutr 1999;69:842–56 Alternative Medicine Review ◆ Volume 10, Number 2 ◆ 2005

Take home message Preterm 400 IU 35

Thank you very much！