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A Review of Vitamin D in Pakistani Population.

Byline: Rabail Javed and Farkhanda Ghafoor

Abstract

Vitamin D is a secosteroid which has an important function in bone metabolism and immunomodulation. Decreased levels of vitamin D are associated with many critical diseases like cardiovascular, cancer, diabetes, tuberculosis and osteoporosis. Low vitamin D can cause obesity and restrict bone growth and bone health in children and adults. Despite being near to equator, Pakistani citizens suffer from low vitamin D levels making them prone to many diseases and there is no guidelines for the treatment of vitamin D deficiency in general and diseased population of Pakistan. This review highlights the prevalence of vitamin D in different disease as well as healthy groups of Pakistani citizens through literature search. Further it also reviewed the literature available on knowledge of clinicians about vitamin D deficiency and its affects.

Key words: Vitamin D, Pakistan, level, deficiency.

Introduction

Vitamin D is a hormone precursor involved in variant functions as calcium homeostasis, immune modulation, and anti-inflammatory process. Phytoplankton species (Emiliani huxleii) as old as 750 million years ago, were the source of vitamin D production catalyzed by UVB rays.1 Vitamin D insufficiency is a common finding worldwide. Levels vary in different areas depending on the demographic features, food fortifications, geographical locations, sun seeking behavior and seasons. It has been reported that a billion people globally have low serum vitamin D levels 2 but majority are asymptomatic, making, it clinically difficult to detect.

A large population of Pakistan is suffering from vitamin D insufficiency which may be occurring due to low intake of vitamin D rich food or less sun exposure or other co-morbids like cancer, diabetes, osteoporosis and cardiac problems. There is scarce data on vitamin D deficiency/ insufficiency and its consequences, on Pakistani population.

Vitamin D Physiology

Vitamin D is a secosteroid found in two major forms i.e. vitamin D2 and vitamin D3. Vitamin D2 is also known as Ergocalciferol which is present in plants, and a few fish, while vitamin D3 also known as Cholecalciferol, is synthesized in the skin when exposed to the sunlight. There are two ways to fulfill vitamin D3 requirements; one is through foods rich in vitamin D3 such as mushrooms and sea foods and the other is by exposing skin to the UV light.2 The time required to produce sufficient vitamin D3 from the skin depends on the strength of the UVB rays, the time spent in the sun and the amount of pigment present in the skin.2

Synthesis of Vitamin D3

The synthesis of vitamin D3 starts in keratinocytes and dermal fibroblasts. A precursor of vitamin D, 7-Dehydrocholesterol (7-DHC), is secreted on skin surface 3 and is converted by UVB radiations (290-315 nm) into pre-cholecalciferol (pre-D3). Pre-cholecalciferol forms cholecalciferol (D3) after undergoing thermal isomerazation. Cholecalciferol is absorbed in the skin and blood and is transported to the liver by a transporter a-2 globulin vitamin D-binding protein, VDBP. 4 In the liver, Cholecalciferol is converted into prohormone calcidol 25(OH) through an enzyme called vitamin D 25 hydroxylase.4 Calcidol is converted into calcitrol (1.25(OH)2D) in the kidneys. Plasma calcitrol is transferred to targeted organs by the help of vitamin D binding proteins (VDBP).3 Calcitrol is also synthesized by immune cells like monocytes and macrophages, where it acts as a cytokine.4 Calcitrol is a potent ligand of the vitamin D receptor and mediates the majority of physiological actions of vitamin D.4

Role of Vitamin D3

Vitamin D and osteoporosis is caused by decrease in bone mineral density due to low calcium and vitamin D3 in the body. Its prevalence is high in Pakistan. A study from Peshawar on 1000 post menopausal women reported osteoporosis in 55% aged between 45-54 years and this increased to 97% in those aged between 75-84 years.5 A previous survey reported 50% females from rural areas of Peshawar to be having low bone mineral density and low vitamin D3 status resulting in osteoporosis.6 Another study on rural women from Peshawar reported osteoporosis/osteopenia in 75.6% with possible causes being low dietary intake of vitamin D3 and lack of sun exposure due to covering their body by "burqas".7 A community based survey in Karachi on 305 premenopausal females aged above 18 years (mean age 31.978.0 years) showed vitamin D3 deficiency in 90.5%.8

Vitamin D3 supplementation prevents bone loss, but this supplementation needs to be supported with increased calcium intake otherwise only vitamin D3 does not affect bone density and improve fractures caused by osteoporosis.7

Vitamin D Status in Neonates and Children

Vitamin D deficiency in mothers results in serious health issues in off springs like improper skeletal and brain development, diabetes, asthma and schizophrenia.9 Its deficiency in childhood results in diseases like rickets, slow brain development and low immunity.9

In Pakistan, vitamin D deficiency is seen in all age groups. A study on 349 pregnant women from Karachi having mean age 28.523.4 reported vitamin D deficiency in 70% with their 203 neonates also vitamin D deficient. Within the group, 155 neonates had mothers who were vitamin D deficient.9 Another study from Karachi on 50 pregnant females reported 46% to be vitamin D deficient with 88% of their newborns also deficient in vitamin D. This study highlighted maternal vitamin D was significantly dependant on sun exposure (p less than 0.007) and diet (p less than 0.01).10

Breast fed infants can also suffer from vitamin D deficiency if their mothers are deficient in vitamin D. A study from Islamabad on 75 infants (4-12 months) reported 66.6% to be vitamin D deficient with 41% mothers also deficient.11 Rickets was reported in 85.3% breast fed children as compared to 40% formula fed based on x-rays, serum calcium, phosphorus and alkaline phosphatase levels.12

Vitamin D and Cancer

In Asian countries, the role of vitamin D in breast, colon and prostate cancer has been widely studied. A study from Shaukat Khanam Hospital, Lahore on breast cancer patients assessed the relation of vitamin D with grade and stage of tumor and found no significant relationship.13 Another study from Karachi in newly diagnosed leukemia patients (acute myeloid leukemia and acute lymphoblastic leukemia) aged 1-60 years, concluded that insufficiency of vitamin D was evident in majority of patients which was further reduced after remission when compared with untreated group.14

Vitamin D and Tuberculosis

Tuberculosis represents a major health issue in developing countries including Pakistan. Although there are various reasons of drug resistant tuberculosis and late sputum smear conversion.15 A study on 100 TB patients reported a significant difference between vitamin D levels and sputum smear conversion time (p less than 0.001).15

A randomized double blind multi centre placebo control trial on 259 smear positive patients aged [greater than or equal to]16 years concluded that high doses of vitamin D3 supplementation could lead to marked clinical and radiological recovery in TB patients along with immunity boosting in vitamin D deficient patients.16

Role of Vitamin D in Cardiac Diseases and Diabetes

Over 25-33% of all deaths in Pakistan are related to heart diseases or diabetes.17 A study from Lahore on non diabetic subjects (88) reported 98.5% to be vitamin D deficient and showed strong negative correlation between vitamin D3 level and LDL levels and a strong positive correlation between vitamin D3 level and HDL levels.17

Another case control study from Aga Khan University Karachi on adult diabetic patients showed significant association between vitamin D levels of diabetic and non diabetic patients. Almost 63% cases were vitamin D deficient while rest had insufficient levels. Direct association was seen between socioeconomic status and vitamin D levels.18

Vitamin D in General Population

Vitamin D levels in general asymptomatic population of Pakistan have also been studied extensively. A study from Islamabad on 737 people (mostly women=76.2%) showed 71.5% to be vitamin D deficient. Within gender, more females were deficient (56.2%) than males.19 Another study from Islamabad reported 82.8% prevalence of vitamin D deficiency and concluded inadequate sun exposure as the possible cause.20 A study from Karachi on healthy adults aged 16-62 years reported 77.7% females being vitamin D deficient with majority (76.6%) exposing only face and hands to sun for 1-2 hours.21 Another study in 30-80 years reported 57.7% to be vitamin D deficient with significant association between low vitamin D levels and glomerular filtration rate.22

A study from Karachi on 54 participants working indoor or outdoor areas reported 98% indoor participants to be vitamin D deficient/insufficient and showed a strong relation between sun exposure and vitamin D levels (p less than 0.01).23 A study from Sargodha showed vitamin D deficiency in 36% population irrespective of the gender but found significant difference in vitamin D levels of those working indoor and outdoor.24 A study from Lahore on healthy asymptomatic adults found 25% to be vitamin D deficient while 73.7% had insufficient levels. They attributed this to sedentary lifestyle, low sun exposure and low vitamin D intake 25 (Table-1).

Table 1: Frequency of serum vitamin D levels in various cities of Pakistan.

City###Sample Size###Mean Age###SD###Frequency of Serum Vitamin D Levels

###(n)###Years###Deficient###Cut Off###Insufficient###Cut Off###Sufficient###Cut Off

###(%)###(ng/ml)###(%)###(ng/ml)###(%)###(ng/ml)

Islamabad###737###36.3(15-75)###----###71.5###----###11.3###----###17.2###----

Islamabad###351###46.03(13-65)###16.8###82.8###less than 20###-----###20-30###17.2###>30

Karachi###300###48(30-80)###-----###57.7###less than 20###26.6###20-30###15.7###30

Karachi###244###33.62(16-62)###12.6###76.2###less than 20###14.8###20-30###9.0###30

Sargodha###100###36.8(14-58)###-----###36###less than 20###10###21-29###54###>30

Lahore###80###47.2(40-60)###6.3###25###less than 10###73.7###10-29###1.3###>30

Table 2: Prevalence of 25(OH) vitamin D3 in Pakistan.

Ref###Place and Study Site###Study###Method Used###Number Tested###Deficiency###Insufficiency###Sufficiency

###Year###less than 10ng/ml###10-29ng/ml###>30ng/ml

19###FGSH,Islamabad###2014###Information not###351###291###-------###60

###provided###both sexes

23###Clinics, Sargodha###2013###ILMA###100###36###10###54

###both sexes

10###Shifa Falahee,Shifa International###2013###Information not###75###56###9###10

###Hospital, Islamabad###provided###infants###infants###infants###infants

###75###71###2###2

###mothers###mothers###mothers###mothers

--###Hayatabad Medical Complex,###2013###CMIA###260###208###39###13

###Peshawar###females

18###Kulsum International Hospital,###2012###ECLIA###737###527###83###127

###Islamabad###both sexes

8###Liaquat National Hospital,###2012###ECLIA###349###243###106###------

###Karachi###mothers###mothers###------###146

###349###203

###neonates###neonates

13###University of Karachi, National###2012###CMIA###86 (Leukemia)###27###55###04

###Institute of Blood Disease and###both sexes

###Bone Marrow Transplantation,

###Department of pathology and

###Haem Oncology

16###University of Health Sciences,###2012###ELISA###88###86###02###------

###Lahore###both sexes

5###Khyber Teaching Hospital,###2011###ECLIA###107 (Post Meno)###-----###99###08

###Peshawar###females

7###Community, Karachi###2011###ECLIA###305 (Post Meno)###276###16###13

###females

21###Metropolis, Karachi###2011###RIA###300###173###80###47

###both sexes

12###Shaukat Khanam Memorial###2011###ELISA###180###86###4###-----

###Cancer Hospital, Lahore###females###breast cancer###breast cancer

###69###17###04

###control###controls###controls

24###Shaikh Zayed Medical Complex,###2010###ELISA###80###20###59###01

###Lahore###both sexes

15###Agha Khan University Hospital,###2010###ECLIA###250 (TB)###-----###250###-----

###Ojha Institute of Chest Diseases###both sexes

###and Dow University Hospital,

###Karachi

20###Hospitals, Karachi###2007###ECLIA###244###186###36###22

###both sexes

Vitamin D and Obesity

There is an increasing number of obese population in Pakistan which is attributable to unhealthy foods and sedentary lifestyle. Genetic variation in vitamin D receptor have been correlated with body mass measurements26 however, there is not much data on relation of vitamin D with obesity. In a genetic study on 100 subjects (50 obese, 50 non obese) between 18-45 years. vitamin D receptor, FOK 1 gene was mutated (ff=3) in 6% obese and was not mutated (ff=0) in any non obese person. Larger sample size was recommended to confirm this variation.26

Knowledge of Clinicians about Vitamin D and its Management

A survey on 400 practicing clinicians in Karachi showed only 62% knew the dietary sources for vitamin D, 85% for active form of vitamin D, 27% for conditions favorable for sunlight absorption and only 45% knew about importance of sun exposure for the production of vitamin D.

Signs and symptoms, risk factors and diseases leading to vitamin D deficiency were known to 66%, 82% and 83% clinicians, whereas 63% were not aware of importance of vitamin D in cellular processes (such as immune system, anti proliferation etc) other than bone and muscle. Only 35% and 52% had knowledge about how to manage and treat (non affording) patients with vitamin D deficiency respectively.27

Critical Analyses on Vitamin D Status

Vitamin D status is assessed by the measuring its storage form 25(OH) D which has a half life of 3 weeks rather than active form 1,25(OH) vitamin D which has a short half life of 6 hours.

It is unfortunate that most of the studies conducted in Pakistan published had no information regarding the time span between blood withdrawal and vitamin D test performance, questioning the variability in the results.

Vitamin D deficiency causing bone disease is linked with serum 25(OH) vitamin D levels of less than 10 ng/mL worldwide. 28 Most of the data from Pakistan has reported a deficiency of less than 20 ng/ml. Sub optimal levels (10-30ng/ml) of vitamin D are termed as vitamin D insufficiency. Defining vitamin D deficiency/ insufficiency on the basis of 25(OH) D levels is still a matter of debate. Optimal levels of vitamin D are [greater than or equal to] 30 ng/mL, however this cut off is applied regardless of age group and gender. Since every age has its own vitamin D requirement therefore, it is possible that optimal levels might differ. A large Pakistani population based study with age interval and gender is required to define the cut off levels for different age groups and diagnose deficient or insufficient individuals who have no evidence of disease.

Scientists describe worldwide that "Population reference ranges for vitamin D vary widely depending on ethnic background, age, geographic location and the sampling season.28 In northern latitude locations in particular, the level of vitamin D in 73% of the population is less than 20 ng/ml during winter season.29 Thus, it is also important to determine geographical, seasonal, age, gender variations in 25(OH) vitamin D levels before describing vitamin D cut off levels. The cut off used by researchers in Pakistani population is given in Table-2.

Conflict of interest: None declared.

References

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2. Mansoor S, Habib A, Ghani F, Fatmi Z, Badruddin S, Mansoor S, et al. Prevalence and significance of vitamin D deficiency and insufficiency among apparently healthy adults. Clin Biochem 2010; 43: 1431-5.

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Publication:Pakistan Journal of Medical Research
Article Type:Report
Geographic Code:9PAKI
Date:Jun 30, 2016
Words:3638
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