1. Effect of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Levels in Children with Chronic Disease Primary investigators: Tania Vander Meulen, MEd, Dietetic Intern Josee Beauchamp, MSc,RD Krista Wadden, RD

2. Outline Acknowledgements Introduction Current Literature Objectives Methodology Results Conclusions Questions

3. Acknowledgements A special thanks to the following who have contributed to my research project: Beauchamp, J. RD, MSc.; Research advisor Wadden, K. RD; Research advisor Gariepy, L. Ph.D. Candidate; Statistitian Murphy, J. RD; Research Mentor Khouzam, B.DtP, MAP; Research Coordinator Kennedy, C. RD; Peer Reviewer

4. Introduction 40-70% of children with IBD and CF are vitamin D deficient and have low [25(OH)D] (1,2,3) due to: malabsorption impaired hydroxylation of vitamin D altered concentration or activity of 25-hydroxylase enzyme low albumin levels lack of adequate sunlight increased use of sunscreen steroid therapy 1.Stephenson A. American Journal of Clinical Nutrition 2007 2. Pappa HM. Pediatrics 2006 3. Udall JN. American Journal of Clinical Nutrition 2002

5. Current Literature-25(OH)D The most accurate way to test vitamin D status is [25(OH)D]. 25(OH)D reflects dietary intake: For every 40 IU/day, 25(OH)D increases by 0.70nmol/L (4,6) or 1-2 nmol/L (7). 25(OH)D reflects subcutaneous synthesis: Vitamin D derived from sunlight exposure can account for 80% of vitamin D levels (23) How much vitamin D is needed to raise [25(OH)D] above 80nmol/L? Some studies have shown 200-800 IU inadequate in children with IBD and CF (1,4,6,7,14) Some researchers suggest 1000-1300IU may be needed (1,6) 4. Aris RMJournal of Clinical Endocrinology and Metabolism 2004 6. Heany RP. American Journal of Clinical Nutrition 2004 7. Cranney A. University of Ottawa Evidence-based Practice Center 2007 23. Rayner RJ. Proceedings of the Nutrition Society 1992; 51: 245-50.

6. Current Literature-BMD Children with IBD or CF have a 40% greater risk of developing a bone fracture than healthy counterpart (15) Although [25(OH)D] is often used as a marker of bone health, many researchers have not found a positive correlation between [25(OH)D] and BMD (16,18,19). BMD lower in IBD subjects compared to healthy subjects, despite normal 25(OH)D levels. (21) 16% of children and young adults with CD (n= 112) had vitamin D deficiency but no association was found between low vitamin D intake and BMD. (22) 16.Boyle MP. American Journal of Respiratory and Critical Care Medicine 2005 18. Grey V. American Journal of Pediatric Gastroenterology 2000

7. Current Literature-Seasonal Influence [25(OH)D] often higher in summer due to greater sun exposure 49nmol/L difference between late summer and late winter in 30 healthy men (24) Lower winter concentrations in adult CD patients (25) 33.4% lower [25(OH)D] during the winter months in pediatric IBD subjects (2) 19. O’Sullivan M. Best Practice & Clinical Gastroenterology 2006 21. Sentongo TA. American Journal of Clinical Nutrition 2002 22. Paganeli M. Journal of Pediatric Gastroenterology 2005 24. Barger-Lux J. The Journal of Clinical Endocrinology & Metabolism 2002 25. McCarthy D. Alimentary Pharmacology & Therapeutics 2005

8. Objectives Primary Objective: Determine if a daily increase of vitamin D coming from food and/or supplementation for a period of at least six months would increase [25(OH)D] by 10nmol/L in children with CD, UC, IC and CF that had a [25(OH)D] below 80nmol/L. Secondary Objectives: 1) Compare the success of vitamin D supplementation in raising [25(OH)D] above 10nmol/L in CD, UC, IC and CF individually. 2) Determine if there was a correlation between 25(OH)D and Z-score lumbar BMD.

9. Methodology 209 IBD and 14 CF subjects aged 4-18, were assessed for Vitamin D intake (via food frequency/supplement questionnaire) and [25(OH)D] at baseline and again at 6-8 months Subjects with [25(OH)D] <80nmol/L were encouraged to increase vitamin D by 400 IU via food and/or supplementation. 50 subjects were eliminated due to: Decreased vitamin D intake [25(OH)D] taken at more than 1.5 months of vitamin D assessment Presence of additional disease (diabetes, sclerosing cholangitis, celiac disease) Failure to complete second assessment

10. Methodology Of the 173 IBD subjects remaining: 104 CD 50 UC 5 IC 14 CF Demographic data collected: age, DOB, date of diagnosis, diagnosis, gender Other data collected: sed rate, C-protein, albumin, steroid use, season of assessment (spring vs winter)

11. Methodology Bone mineral data collected in 80 subjects via DEXA: lumbar z-score, total body z-score, bone age Statistical analysis was performed using SPSS software: Paired t-tests used to compare vitamin D intake and [25(OH)D] at baseline and six to eight months, as well as mean values of [25(OH)D] between season (winter vs summer). Standard pearson correlations used to correlate [25(OH)D], Z-score lumbar BMD and Z-score total body BMD. Significance was set at p<0.05 for all analysis

12. Results Figure 1. Change in vitamin D intake at baseline and 6-8 months Change in Vitamin D Intake * * * * = p<0.05

13. Results Figure 2. Change in [25(OH)D] at baseline and 6-8 months. Change in [25(OH)D] * * * * = p<0.05

14. Results All: A significant increase of 329 IU (+- S.E. 28.4) vitamin D/d raised [25(OH)D] by 14.5 nmol/L (+- S.E. 2.18) within 7.2 months. CD: A significant increase of 347 IU/d (+-S.E. 32.2) raised [25(OH)D] by 13.4 nmol/L (+-S.E. 2.92) UC: A significant increase of 314 IU/d (+-S.E. 62.2) raised [25(OH)D] by 18.1 nmol/L (+-S.E. 4.1) IC & CF: No significant change in vitamin D or [25(OH)D]

15. Results Relationship between [25(OH)D] and BMD Pearson correlation revealed no significant relationship between [25(OH)D] and z-score lumbar BMD (p=0.84), or [25(OH)D] and z- score total body BMD (p=0.82).

16. Results Table 2. Increase in [25(OH)D] according to season Baseline 6-8 Months Difference_ Season Subjects (N) Mean Mean Mean S.E. Winter 23 57.1 68.5 11.4 4.6*** Summer 15 59.7 78.3 18.3 8.5*** S.E. = standard error ***p<0.05 To get a true reflection of vitamin D intake alone on [25(OH)D], we eliminated seasonal effect by eliminating those subjects who had both vitamin D assessments in different seasons. [25(OH)D] According to Season

17. Conclusions An increase of 329 IU vitamin D did significantly increase [25(OH)D] by 14.5 nmol/L within 7.2 months. Despite increase, most subjects still remained below 80nmol/L. The current recommendation of 400 IU vitamin D is inadequate to normalize serum [25(OH)D] in IBD and CF populations Vitamin D intake may need to be greater than 1000 IU to raise [25(OH)D] over 80nmol/L.

18. Questions