Khan, Aysha Habib

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eCommons@AKUDepartment of Pathology and Laboratory Medicine Medical College, PakistanDecember 2018Seven decades of vitamin D research in Pakistan :Too little, too much or just right!Aysha Habib KhanAga Khan University, aysha.habib@aku.eduFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiolPart of the Pathology CommonsRecommended CitationKhan, A. H. (2018). Seven decades of vitamin D research in Pakistan : Too little, too much or just right!. Journal of Pakistan MedicalAssociation, 68(12), 1742-1743.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/1164Pakistan has one of the highest reported incidence ofvitamin D deficiency (VDD) in studies conductedworldwide and within Pakistan. Data mining of vitaminD (VD) testing and small scale community studies fromour center in the last decade indicates that VDD inPakistan is not limited to gender, age group or province1,2 .Significant correlates of bone health in communitydwelling females in Karachi are serum 25-hydroxyvitamin D (25OHD) levels, duration of sun exposure, andwearing veil while determinants of VD levels wereidentified to be age, town of residence and housingstructure. High and low-income localities of both urbanand rural environments are identified at risk of VDD. 3,4.Secondary hyperparathyroidism (sHPT), high boneturnover and other parathyroid hormone relateddisorders are identified.5. GC genotype of R990G SNP ofcalcium sensitive receptor (CaSR) was found to beassociated with higher iPTH levels and lower calciumlevels.6Replenishing and maintaining D stores and optimum25OHD levels to achieve peak bone mass is a challenge.While VD is required for intestinal absorption ofcalcium, no change in calcium absorption was foundbefore and after VD correction using calcium assurrogate, suggesting the possibility that maximumvitamin D-dependent calcium absorption is achieved inour subjects at a lower 25OHD status, with higher meanparathyroid hormone levels and normal1, 25 dihydroxyvitamin D levels.7 Association of low levels of VD with health or diseasehas been emphasized a lot over the last decade, whileimpact of high VD levels has not been studied.Hypervitaminosis D and toxicity is rare and results afterprolonged ingestion of large VD doses or use ofoverzealous VD supplementation with mega dosepreparations and can give rise to hypercalcaemia andhypercalciuria.  Higher mortality rates have been reported at both thelower and upper ends of the 25OHD spectrum. In thiscontext a study in 24,000 adults admitted for acute careby Amrein et al has performed analysis of theassociation between 25OHD levels measured in the yearpreceding hospital admission with all-cause mortalityafter hospitalization. After adjustment for multipleconfounders, significantly increased risk for all-cause90-day mortality was identified in patients with 25OHDlevel <30 ng/mL or >60 ng/mL, measured beforehospitalization, compared to patients with levelsbetween 30 and 60 ng/mL8. A U-shaped optimal25OHDrange has been proposed for VD. However, it is debatedthat the reports recommending U-shaped distributionare not representative of findings for disease outcomeand are due either to statistical fluctuations associatedwith low numbers of cases or confounding factors notconsidered9.A review of VD results reported from our laboratoryshows increase trend in the results of VD withhypervitaminosis and toxicity (unpublished data). Thisis also evident in children under 1 year of age.Inaddition, a recently published study identified 27% ofpatients admitted to a tertiary care hospital withhypercalcaemia had VD toxicity.10,11Variable practice pattern in treating VD deficiencycontinue to exist in Pakistan. With the two mostcommonly available VD preparations in Pakistan, wehave shown that single dose of 600,000 IU or 200,000 IUof VD given per oral or intramuscular achieved optimalVD levels in 70% of the subjects after two months ofintervention. We have previously demonstratedimportant implications of dose difference andadministration routes in our subjects12,13. But due toabsence of clear guidelines for the replacementstrategies of VD in deficient states, there is inadvertentuse of higher doses of VD in patients usually byrepeated injectable mega doses of cholecalciferolresulting in hypervitaminosis D and toxicity. In thestudy by Qamar et al, 27% of the patients withhypercalcaemia were identified to be due to vitamin Dtoxicity where multiple injections of high doseJ Pak Med Assoc1742EDITORIALSeven Decades of Vitamin D research in Pakistan: Too little, too much or justright!Aysha Habib Khan Department of Pathologist and Laboratory Medicine, Aga Khan UniversityHospital,Karachi.Correspondence: Email: aysha.habib@aku.edupreparations were given to these patients and in manyit was Vitamin D3 600,000IU injection given weekly for6-8 weeks.13Life style measures including dietary interventions,education and awareness of pharmacist, physicians,nutritionists, patients and general public is the wayforward. The road to bone health and life-longproductivity can be achieved through amultidisciplinary approach. There is a need to performmeaningful research to develop local guidelinesconsidering our life style risk factors and availableinformation.Keywords & abbreviation:Vitamin D (VD) Vitamin Ddeficiency (VDD), Hypervitaminosis D, Vitamin Dtoxicity.Disclaimer: None to declared.Conflict of Interest: None to declared.Funding Source: None to declared.References1. Hassan S, Muzammil SM, Jafri L, Khan AH. An audit of clinicallaboratory data of 25 [OH]D at Aga Khan University as reflectingvitamin D Deficiency in Pakistan. J Pak Med Assoc 2015; 65: 1247-50.2. Iqbal R, Jafri L, Khan AH. Illuminating the Dark Side- Vitamin D inDifferent Localities of Karachi. J Coll Physician Surg Pak 2013; 23:604-6. 3. Dar FJ, Iqbal R, Ghani F, Siddiqui I, Khan AH. Bone health status ofPre-menopausal healthy adult females in Pakistani females. ArchOsteoporos 2012; 7: 93-9. 4. Khan AH, Naureen G, Iqbal R, Dar FJ. Assessing the Effect ofDietary Calcium Intake and 25 OHD Status on Bone Turnover inWomen in Pakistan. Arch Osteoporos 2013; 8: 151.  5. Majid H, Khan AH, Riaz M, Karimi H, Talati J. Identifyingparathyroid hormone disorders and their phenotypes through abone health screening panel: It’s not a simple vitamin DDeficiency.  Endocr Pract 2016;22: 814-21. 6. Majid H, Khan AH, Moatter T. R990G Polymorphism Of CalciumSensing Receptor Gene Is Associated With High ParathyroidHormone Levels In Subjects With Vitamin D Deficiency: A Cross-Sectional Study. BioMed Res Int 2015; 2015: 407159 7. Khan AH, Rohra DK, Saghir SA, Udani SK, Wood RJ, Jabbar A. Nochange in calcium absorption in adult Pakistani population beforeand after Vitamin D administration using strontium as surrogate.Osteoporos Int 2013; 24: 1057–62.8. Amrein K, Quraishi SA, Litonjua AA, Gibbons FK, Pieber TR,Camargo CA Jr, et al. Evidence for a U-Shaped Relationshipbetween Prehospital Vitamin D Status and Mortality: A CohortStudy. J Clin Endocrinal Metab 2014; 99: 1461–99. Grant WB. Critique of the U-shaped serum 25-hydroxyvitamin Dlevel-disease response relation. Dermatoendocrinol 2009; 1: 289-9310. Khan AH, Majid H, Iqbal R. Shifting of Vitamin D Deficiency toHypervitaminosis and Toxicity. J Coll Physicians Surg Pak 2014; 24:53611. Khan MN, Masood MQ, Siddiqui MA, Naz S, Islam N. Vitamin Dtoxicity and other non-malignant causes of hypercalcemia: Aretrospective study at a Tertiary care hospital in Pakistan. J AyubMed Coll Abbottabad 2017; 29: 436-4012. Khan AH, Rohra DK, Saghir SA, Udani SK, Wood R, Jabbar A.Response of a single 'mega intramuscular dose' of vitamin D onserum 25OHD and parathyroid hormone levels. J Coll PhysicianSurg Pak 2012; 22: 207-12.13. Masood MQ, Khan A, Awan S, Dar F, Naz S, Naureen G, et al.Comparison of Vitamin D Replacement Strategies with High doseIntramuscular or Oral Cholecalciferol: A Prospective InterventionStudy. Endocr Pract 2015; 21: 1125-33Vol. 68, No. 12, December 2018Seven Decades of Vitamn D research in Pakistan:Too little, too much or just right ! 1743

Seven decades of vitamin D research in Pakistan : Too little, too much or just right!

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Seven decades of vitamin D research in Pakistan : Too little, too much or just right!

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