Vitamin D Status Among Emirati Students

Vitamin D Status Among Emirati Students Avoidance of Sunlight Causing Vitamin D Deficiency Afrozul Haq, Ph.D. Pathology & Laboratory Medicine, SKMC, Abu Dhabi 2nd Biennial Pathology & Laboratory Medicine Update March 17,18, 2011

List of Publications & Abstracts During 2007 to 2011 1. Rajah J., Abdel-Wareth L. and Haq A. (2010). Failure of one alpha vitamin D (alphacalcidol) in treating nutritional rickets and biochemical response to ergocalciferol. J Steroid Biochem Mol Biol 121:273-276. 2. Rajah J., Haq, A. and Pettifor J. (2010) Vitamin D and calcium status in urban ambulatory children in the middle east. BMC Pediatrics(in press). 3. Al Anouti F., Thomas J., Abdel-Wareth L., Rajah J, Grant W. and Haq A. (2010). Vitamin D deficiency and sun avoidance among university students at Abu Dhabi, United Arab Emirates. DermatoEndocrinology (in press). 4. Haq A., Abdel-Wareth L. and Rajah J. (2009). Is there any correlation between 1,25(OH)2D and 25(OH)D in infants with rickets?. Bone, 45 Suppl.2: S102. 5. Rajah J., Haq A., Shalash A. and Du Plesis J. (2009). Diagnosis and prevention of vitamin D deficiency in childhood and a case report of an infant with prolonged QTc interval. Paediatrics. me 14: 71-73. 6. Haq A., Rajah J. and Abdel-Wareth L. (2009).Vitamin D: measurement, deficiency,and its health consequences. Middle East Lab.12(1): 6-10. 7. Rajah J., Jamal A., Amani S., Howard P. and Haq A. (2008). Nutritional rickets and Z scores for hight in the United Arab Emirates. To D or not to D. Pediatrics International (Japan) 50: 424-428. 8. Haq A., Rajah J. and Abdel-Wareth L. (2007). Routine HPLC analysis of vitamin D3 and D2. DIALOG (Germany) 2: 1-2. 9. Haq A. (2007) Measurement of Vitamin D by HPLC and its role in Health and Diseases: First Clin. Chem. Forum, Abu Dhabi, UAE,1: 4-5. 10. Al Anouti F., Thomas J., Ahmad B., Al Hasani S., Abdel-Wareth L., KhaliliAD. And Haq A. (2010) High prevalence of Vitamin D deficiency among young Emiratis in a sunny country. 28th Intl Symp Diabetes and Nutrition, Oslo, Norway. July1-4. 11. Haq, A. (2010) Vitamin D, metabolism, deficiency and cardiovascular disease. Pathology & Laboratory Medicine Update, UKAS-SKMC Conference, Abu Dhabi, UAE, March 20. 12. Rajah J., Haq A., Abdel-Wareth L. and Al Jubeh J. (2010). Biochemical differences in nutritional rickets at different ages. 26 th Intl. Pediatric Assoc. Cong. Johannesburg, South Africa, August 4-9. 13. Haq A., Abdel-Wareth L. and Rajah J.(2009) Failure of one alpha vitamin D (alphacalcidol) in treating nutritional rickets and biochemical response to ergocalciferol. 14 th Workshop on Vitamin D. Brugge, Belgium, October 4-8. 14. Rajah J, Al Jubeh J, Haq A, Shalash A and Parsons H. (2009). Osteopenia in mothers of rachitic infants: A new causal hypothesis for rickets. Bone, 45 Suppl. 2: S101. 15. Rajah J., Shalash A., Haq, A. and Plessis JD.(2007). Severe vitamin D deficiency induced cardiomyopathy. South African Critical Med Congress, Sun City, Gauteng, South Africa, August 14-17. 16. Haq A, Al Anouti F, Thomas J, Abdel-Wareth L and Rajah J.(2010) Avoidance of Sun Causing Vitamin D deficiency among Emirati students. 2 nd SEHA Research Conference, Abu Dhabi, December 12-13. 17. Al Anouti F., Thomas J., Abdel-Wareth L., Grant BG and Haq A. (2011).The impact of life style and dietary habits on vitamin D status among young Emiratis.1 st WHO Regional Nutritional Conference, Doha(Qatar),.. 18. Haq A., Al Anouti F, Thomas J, Abdel-Wareth L and Rajah J. (2010). Avoidance of sunlight causing vitamin D deficiency among Emirati students. 2 nd SEHA Annual Research Conference, Abu Dhabi(UAE), December 12-13. 19. Al-Anouti, F.,Thomas, J., Al Hasani, S., Abdelwareth, L, Haq A.,(2010). Sun, Sea, Sand and Sadness: Exploring the Links between Vitamin D deficiency and depressive illness in the United Arab Emirates.The British Psychology Society Meeting, Manchester,UK, December1-3.

WHY IS AN OLD VITAMIN SUDDENLY IN THE NEWS? Vitamin D and its metabolites have many actions in the body not just those required to prevent rickets and osteomalacia. These newly discovered actions include cancer prevention and treatment; regulation of hormone secretion; increased resistance to infections; protection against autoimmune diseases; prolonged survival of transplanted organs. These newly discovered actions require vitamin D levels greater that those found in most people.

Vitamin D & UVBR 10,000 IU of vit D generates in 15-20 minutes exposure. Longer exposure does not induce more vit D because UVB also degrades vit D, preventing too much of it from building up in the skin

All studies, in virtually all nations, irrespective of latitude, show that the majority of the world s population has inadequate vitamin D status

Types & Sources of Vitamin D Vitamin D2 (Ergocalciferol) Ergo sterol from plants/mushrooms/yeast leads to the formation of Vitamin D2 (calciferol). Biologically inert Conversion (OH) in the liver and then in kidneys produces active form. D2 is less potent than vitamin D3 Vitamin D3 (Cholecalciferol) Naturally occurring form in humans, formed by the action of ultraviolet light (UVB) on Vitamin D precursors in the skin (7-DHC). Lanolin is often used as a raw material for producing vitamin D3. Present in fish(salmon), other sea food. Biologically inert Conversion(OH) in the liver and then in kidneys produces active form. MW: 396 MW: 384 Lanolin Mushrooms Asclepius A. Haq, 2010

1% 3% 6% SUN

Vitamin D Endocrine, Autocrine / Paracrine Systems Vitamin D3 Vitamin D3 & D2 25(OH)D Prostate, skin, lung, breast, colon, macrophages, monocytes, other cells & tissues 1,25(OH)2D 1,25(OH)2D Calcium homeostasis, muscle health, bone health, neurodevelopment Immunomodulation, gene transcription, cardiovascular health, & cancer prevention Haq A et al. (2009) Middle East Laboratory, 12:6-10.

Vitamin D activaton, mechanism of action and biological response

WHY DOES VITAMIN D AFFECT SO MANY BIOLOGIC PROCESSES? Vitamin D controls (directly or indirectly) more than 3000 genes that regulate calcium and bone metabolism, modulate innate immunity, control cell growth and maturation, regulate the production of insulin and renin, induce apoptosis and inhibit angiogenesis. Many tissues are able to make their own 1,25(OH)2D.

Vitamin D Shortage When vitamin D is in short supply, the various tissues and cells of our bodies cannot make enough calcitriol to open up their DNA libraries adequately Their functioning is thus impaired

Vitamin D Deficiency in the Gulf Countries A study in Kuwait revealed that VTD deficiency was common in veiled Kuwaiti women El-Hajj Fuleihan GE et. al. J.Clin.Endocrinol.Metab.200 6,91:405-412 A study conducted on 433 school girls, revealed that VTD deficiency was highly prevalent (81%) among adolescent females. A study showed that VTD deficiency is common in women of child-bearing age (33 subjects) in Arab communities residing in the UAE

The D-lemma: To Screen or Not to Screen for 25(OH)D Concentrations? With the recognition of widespread vitamin D deficiency/insufficiency in children and adults, there is no need to measure everybody's blood 25(OH)D. It would be much more cost-effective to implement a vitamin D supplementation program for all children and adults until there is higher fortification of vitamin D in foods and drinks Michael F. Holick, Clinical Chemistry, 56:729-731(2010)

Causes and Consequences of Vitamin D Deficiency Holick MF, Nat Rev Endocrinol 7: 73-75 (2011)

Three Ways to Obtain Vitamin D Sun exposure obtaining 10 to 15 minutes per day, with 40% of the skin exposed without sunscreen, can help prevent vitamin D deficiency Consuming vitamin D rich foods also can help to maintain the beneficial (75 nm) to optimal levels (90 to150 nm) of 25-hydroxyvitamin D in the blood Vitamin D supplementation with vitamin D3 (Cholecalciferol) or D2 (get blood levels of 25(OH)D tested first)

Vitamin D Reference Ranges 25(OH)D (nmol/l) Vitamin D status < 25 Severe Deficiency 25 75 Insufficiency 75 200 Sufficiency > 250 Toxicity HPLC Lab at SKMC 2010

Updated Vitamin D Status Serum 25(OH)D Vitamin D Clinical/Biochemical (nmol/l) Status Alterations < 25 25 49 50 74 Severely Deficient Deficient Insufficient Rickets, osteomalacia, myopathy, calcium malabsorption, severe hyperparathyroidism, impaired immune and cardiac function. Reduced bone mineral density, impaired muscle function, low intestinal calcium absorption rate, elevated PTH. Low bodily stores of 25(OH)D, elevated PTH 75-374 > 375 Sufficient Toxic No disturbances of D-dependent functions Soft tissue calcification, hypercalcemia Zittermann A et al. Current Opin Clin Nutr & Metabolic Care 2009,12: 634 639

The Upper Limit of Possible 25(OH)D is 150-200 nmol/l 250 25(OH)D (nm mol/l) 200 150 100 50 150 160 200 0 HI/WI Farmers Outdoor Workers savannah Am J Clin Nutr 80,1645-1649, 2004; J Clin Endocrinol Metab 87,4952-4956,2002

Research Project Small Scale Study (Target: ZU male/female students) & Larger population based study (Target: Adult Emirati population residing in Abu Dhabi) Objectives and rationale of the study Assess the Prevalence of Vitamin D deficiency among the target population (274/ZU students and 500/general population) Evaluate the influence of sun avoidance attitude, diet and life style/depression (psychosocial factors) on Vitamin D status 2nd Biennial Pathology & Laboratory Medicine Update March 17,18, 2011

Methodology Vitamin D blood testing by HPLC (modified method) Sun Avoidance Inventory/Sun Academic Initiative (SAI) to assess attitude towards sun avoidance in the context of Vitamin D deficiency BDI (Beck Depression Inventory) FFQ (Food Consumption and Diet)

Requirements for 25(OH)D Assays Choose an assay that measures both 25(OH)D2 and 25(OH)D3 If using an assay that separates 25(OH)D2 and 25(OH)D3 (i.e. HPLC or LC/MS-MS) indicate the sum of the 2 compounds (25(OH)D2+25(OH)D3) as the main results in your results sheet. Participate to an external quality control scheme that provides materials with a documented commutability with human sera (e.g. the CAP or the UK based DEQAS) An internal quality control program has to be carried out in every laboratory by using different levels samples and valuable criteria for rejecting or accepting the analytical run Do not use population-based reference values (i.e. the concentrations of an apparently healthy population) in addition to a recommended range for 25(OH)D. We recommend serum as the sample of choice. Express results in nmol/l

Vitamin D Status in the UAE 80 70 274 UAE STUDENTS FROM ZAYED UNIVERSITY 68 % of St tudents 60 50 40 30 20 26 <25 25-49 50-75 >75 10 0 5 1 <25 25-49 50-75 >75 Vitamin D (nmol/l)

Table 1: Baseline characteristics of male and female students that participated in the study Characteristics Males (n = 70) Females (n = 208) t-test 95% Confidence Interval of the Difference Age (years) 21.0 ± 4.6 20.8 ± 4.0 0.211 BMI (kg/m 2 ) 23.7 ± 4.2 23.2 ± 5.0 0.057 25 (OH)D(nmol/L) 27.3 ± 15.7 24.2 ± 14.9 0.0025* SAI score 34.6 ± 7.0 39.4 ± 7.4 0.000* FFQ score 17.4 ± 5.8 12.5 ± 4.9 0.064 * Differences are significant; p<0.05. All values are shown as mean ± SD.BMI,body mass index; SAI, sun avoidance inventory; FFQ, food frequency questionnaire.

Table 2: Baseline characteristics of female students in summer and winter Characteristics Females (summer) (n = 138) Females(winter) (n = 70) t-test 95% Confidence Interval of the Difference Age (years) 21.1 ± 4.6 20.3 ± 1.9 0.106 BMI (kg/m 2 ) 22.6 ± 4.6 24.4 ± 5.6 0.30 25 (OH)D(nmol/L) 20.9 ± 14.9 31.3 ± 12.3 0.0005* SAI score 41.4 ± 7.4 35.1 ± 5.4 0.000* FFQ score 13.2 ± 5.4 11.0 ± 3.2 0.003 * Differences are significant; p<0.05. All values are shown as mean ± SD., BMI, body mass index; SAI, sun avoidance inventory; FFQ, food frequency questionnaire.

Effect of Sun Avoidance on Vitamin D Levels

Correlation Between Vitamin D, SAI, BDI & BMI Vitamin D SAI Total BDI-Total Body Mass Index Vitamin D 1-0.327** -0.311** 0.030 Significance-1 tailed 0.000 0.000 0.332 n 212 208 211 209 SAI Total -0.327** 1 0.178** 0.099 Significance-1-tailed 000 0.005 0.078 n 208 208 207 205 BDI Total -0.311** 0.178** 1-0.005 Significance-1 tailed 000 0.005 0.471 n 211 207 211 208 BMI 0.030 0.099-0.005 1 Significance-1 tailed 0.332 0.078 0.471 n 209 205 208 209 ** Correlation is significant at the 0.01 level (1-tailed), Pearson Correlation, Significance (1-tailed)

Results Significant negative correlation between vitamin D status and SAI Significant negative correlation between vitamin D status and BDI Significant positive correlation between BDI and SAI X No correlation between vitamin D and FFQ X No correlation between vitamin D and BMI

Conclusions Documents the true picture of Vitamin D deficiency among University students in the UAE Guide future intervention studies which would aim at implementing awareness programs to educate people about the beneficial role of Vitamin D (implications from SAI results) Vitamin D deficiency and insufficiency can be both corrected/treated and prevented safely through supplementation, fortification and UVB Encourage policy makers to implement a policy in the UAE regarding the need for fortification of drinks and some food items with Vitamin D

I recommend: Recommendation: 400-1000 IU/day for infants 1000-1500 IU/day for Children 1-10 years 1500-2000 IU/day for teenagers and adults Michael F. Holick, Clinical Chemistry, 56:729-731(2010)

Treatment Recommendations For Vitamin D Deficiency 1Tab VitaminD3 50,000 IU/ month

Serum 25(O OH)D (nmol/l) 110 Vitamin D 3 100,000 IU 100 90 80 70 Serum 25(OH H)D (nmol/l) 110 100 90 80 70 by mouth one time 60 60 0 20 0 40 20 6040 60 80 80100 100 120 120 Time (days) Time (days) Ilahi M. et al 2008, Am J Clin Nutr 87:688

Is Vitamin D Toxic.?.. Excessive exposure to sunlight does not lead to overproduction of vitamin D. Supplemental vitamin D in certain clinical settings may have toxicity. Symptoms are largely hypercalcaemia, high blood pressure, headache, fatigue, loss of appetite, excessive thrust and polyurea, severe itching, vomiting, diarrhoea, constipation, kidney damage, joints and muscle pain.

1217 Clinical Trials Related to Vitamin D on Jan 20, 2011 Bone 84 Calcium 51 Osteoporosis 51 Kidney 44 Renal 28 Postmenopausal 25 Hyperparathyroidism 20 Prostate 19 Obese 19 Breast Cancer 16 Fracture 15 Diabetes 12 HIV 10 Elderly 9 Tuberculosis 9 Chronic Obstructive Pulmonary Disease 7 Colon 6 Multiple Sclerosis 5 Blood Pressure 5 Muscle 5 Cystic Fibrosis 5 Hip 5 Rheumatoid Arthritis 5 Lung 4 Psoriasis 4 Lupus 4 Crohn's 4 Knee 3 Heart 9 Rickets 7 http://clinicaltrials.gov/

Outstanding Questions 1. What is the optimal level of vitamin D suppl. and or level of D in the blood to achieve maximal benefits?. 2. Is vitamin D suppl. given orally is equally effective to D produced endogenously in the skin?. 3. Do low concentrations of D predispose people to malignancy or inflammatory disease?.

Acknowledgements Dr. Fatme Al Anouti Dr. Laila Abdel-Wareth Dr. Jaishen Rajah Mr. Nafiz Nimer

afhaq@skmc.ae