Vitamin D Status Among Emirati Students“Avoidance of Sunlight Causing Vitamin D Deficiency”

Afrozul Haq, Ph.D. Afrozul Haq, Ph.D. Afrozul Haq, Ph.D. Afrozul Haq, Ph.D. Pathology & Laboratory Medicine,Pathology & Laboratory Medicine,

SKMC, Abu DhabiSKMC, Abu Dhabi

2nd Biennial Pathology & Laboratory Medicine Update March 17,18, 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

List of Publications & Abstracts During 2007 to 2011

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.

26th 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. 14th 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. 2nd 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.1st 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. 2nd 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.

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

WHY IS AN OLD “VITAMIN” SUDDENLY

IN THE NEWS?

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 haspopulation hasinadequate vitamin D status

� 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

MW: 396

Types & Sources of Vitamin D

Asclepius

Mushrooms

� 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: 384

Lanolin

A. Haq, 2010

6%3%1%

SUN

Vitamin D3

Vitamin D3 & D2

25(OH)D Prostate,skin, lung, breast,

colon, macrophages,monocytes , other cells

& tissues

Vitamin D Endocrine, Autocrine / ParacrineSystems

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.

�When vitamin D is in short supply, the various tissues and cells of our bodies cannot make enough calcitriolto open up their DNA libraries adequately

Vitamin D Shortage

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

A study

showed that El-Hajj Fuleihan GE et. al.

J.Clin.Endocrinol.Metab.200

A study conducted

on 433 school

girls, revealed that

VTD deficiency

was highly

prevalent (81%)

among adolescent

females .

showed that

VTD deficiency

is common in

women of

child-bearing

age (33

subjects) in

Arab

communities

residing in the

UAE

J.Clin.Endocrinol.Metab.200

6,91:405-412

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)

� 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

Three Ways to Obtain Vitamin D

to maintain the beneficial (75 nM) to optimallevels (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

HPLC Lab at SKMC 2010

75 – 200 Sufficiency

> 250 Toxicity

Updated Vitamin D Status

Serum 25(OH)D Vitamin D Clinical/Biochemical (nmol/L) Status Alterations

� < 25 Severely Severely Deficient Deficient Rickets, osteomalacia, myopathy, calcium malabsorption, severe hyperparathyroidism, impaired immune and cardiac function.

� 25 – 49 Deficient Deficient Reduced bone mineral density, impaired muscle function, low intestinal calcium absorption rate, elevated PTH.

Zittermann A et al. Current Opin Clin Nutr & Metabolic Care 2009,12: 634–639

muscle function, low intestinal calcium absorption rate, elevated PTH.

� 50 – 74 Insufficient Insufficient Low bodily stores of 25(OH)D, elevated PTH

� 75 - 374 SufficientSufficient No disturbances of D-dependent functions

� > 375 Toxic Toxic Soft tissue calcification, hypercalcemia

150160

200

150

200

250

25

(OH

)D (

nm

ol/

L)

The Upper Limit of Possible 25(OH)D is

150 - 200 nmol/L

0

50

100

HI/WI Farmers Outdoor

Workers

25

(OH

)D (

nm

ol/

L)Am J Clin Nutr 80,1645-1649, 2004;

J Clin Endocrinol Metab 87,4952- 4956,2002

savannah

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

2nd Biennial Pathology & Laboratory Medicine UpdateMarch 17,18, 2011

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

Methodology

�Vitamin D blood testing by HPLC (modified method)

�Sun Avoidance Inventory/Sun Academic Initiative (SAI) to assess attitude towards sun avoidance in (SAI) to assess attitude towards sun avoidance in the context of Vitamin D deficiency

�BDI (Beck Depression Inventory)

� FFQ (Food Consumption and Diet)

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)

Requirements for 25(OH)D Assays

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

68

50

60

70

80

of S

tud

en

ts

<25

25-49

274 UAE STUDENTS FROM ZAYED UNIVERSITY

26

51

0

10

20

30

40

<25 25-49 50-75 >75

% o

f S

tud

en

ts

Vitamin D (nmol/L)

25-49

50-75

>75

Table 1: Baseline characteristics of male and

female students that participated in the study

CharacteristicsMales

(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

* Differences are significant; p<0.05. All values are shown as mean ± SD.BMI,bodymass index; SAI, sun avoidance inventory; FFQ, food frequency questionnaire.

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

Table 2: Baseline characteristics of

female students in summer and winter

CharacteristicsFemales

(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, bodymass index; SAI, sun avoidance inventory; FFQ, food frequency questionnaire.

Effect of Sun Avoidance on Vitamin D

Levels

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

Correlation Between Vitamin D,

SAI, BDI & BMI

Significance-1-tailed 000 0.005 0.078

n 208 208 207 205

BDI Total -0.311** 0.178** 1 -0.005Significance-1 tailed

000 0.005 0.471

n 211 207 211 208

BMI 0.030 0.099 -0.005 1Significance-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 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)SAI results)

� Vitamin D deficiency and insufficiency can be bothcorrected/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

Recommendation:

I recommend:

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 1Tab VitaminD3 VitaminD3 50,000 IU50,000 IU/ / monthmonth

Seru

m 2

5(O

H)D

(nm

ol/

L)

90

100

110

Seru

m 2

5(O

H)D

(nm

ol/

L)

90

100

110� Vitamin D 3

� 100,000 IU � by mouth� one time

Time (days)

0 20 40 60 80 100 120

Seru

m 2

5(O

H)D

(nm

ol/

L)

60

70

80

Time (days)

0 20 40 60 80 100 120

Seru

m 2

5(O

H)D

(nm

ol/

L)

60

70

80

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 � 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.

Bone 84Calcium 51Osteoporosis 51Kidney 44Renal 28Postmenopausal 25Hyperparathyroidism 20

Chronic Obstructive Pulmonary Disease 7Colon 6Multiple Sclerosis 5Blood Pressure 5Muscle 5Cystic Fibrosis 5Hip 5

1217 Clinical Trials Related to Vitamin D

on Jan 20, 2011

http://clinicaltrials.gov/

Hyperparathyroidism 20Prostate 19Obese 19Breast Cancer 16Fracture 15Diabetes 12HIV 10Elderly 9Tuberculosis 9

Hip 5Rheumatoid Arthritis 5Lung 4Psoriasis 4Lupus 4Crohn's 4Knee 3Heart 9Rickets 7

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 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� Dr. Jaishen Rajah�Mr. Nafiz Nimer

afhaq@skmc.ae