Vitamin D Supplements in The Indian Market

Download as pdf or txt
Download as pdf or txt
You are on page 1of 15

Vitamin D supplements in the Indian Market

Y. Lhamo, Preeta Kaur Chugh* and C. D. Tripathi

Department of Pharmacology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New
Delhi-110 029, India

*Corresponding Author:
Preeta Kaur Chugh
Department of Pharmacology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New
Delhi-110 029, India
E-mail: [email protected]

Date of Submission 15 December 2014

Date of Revision 22 November 2015

Date of Acceptance 07 February 2016

Indian J Pharm Sci 2016;78(1):41-47


This is an open access article distributed under the terms of the Creative Commons
Attribution?NonCommercial?ShareAlike 3.0 License, which allows others to remix, tweak, and build
upon the work non?commercially, as long as the author is credited and the new creations are licensed
under the identical terms.

DOI: 10.4103/0250-474X.180248

Abstract
It is now known that vitamin D deficiency is a worldwide health problem. In our country, as food
fortification is lacking, supplementation with pharmaceutical preparations is the only means of treatment
of vitamin D deficiency. We aimed to study the composition and availability of various vitamin D
preparations in the Indian market, data about which was collected from annual drug compendium. The
preparations were assessed for total number, different formulations, constituents and amount of each
constituent present in the formulation. Vitamin D3 is available in the form of cholecalciferol, alfacalcidiol
and calcitriol as single ingredient products and in combination with calcium and other micronutrients.
Most of the supplements contain calcitriol (46.5%) or alfacalcidiol (43%) as tablets (51.1%) and capsules
(35.2%). Cholecalciferol, the preferred form for prophylaxis and treatment of vitamin D deficient states,
constitutes only 10% of the available market preparations. High market sales of calcium supplements
containing calcitriol indicate increasing intake of calcitriol rather than cholecalciferol; which could
predispose to toxicity. There is a need for marketing and rational prescribing of the appropriate vitamin D
supplement in ostensibly healthy Indian population. Implementation of population-based education and
intervention programmes with enforcement of strict regulations could generate awareness and curb
unsupervised intake of vitamin D containing dietary supplements. This health challenge mandates

1
effective nutritional policies, fortification and supplementation programmes and partnership between
government, healthcare and industry to safeguard the health of Indian population at large.

Keywords
Vitamin D, India, vitamin, supplement, nutrition, health

It has been widely accepted that vitamin D deficiency (VDD) is a global health problem that impacts not
only musculoskeletal health but also varied acute and chronic diseases [1]. Low vitamin D has been
associated with an increased risk of diabetes mellitus, cardiovascular disease, certain cancers, cognitive
decline, autoimmune disorders and pregnancy complications [2]. It has been estimated that 20 to 80% of
US, Canadian and European men and women are vitamin D deficient [1,3,4]. In Middle East and Asia,
VDD is highly prevalent in both children and adults [1,2,5]. Even in India, numerous studies across
various regions of the country indicate that approximately 70-90% of apparently healthy population is
vitamin D deficient [6-9]. Low vitamin D status is prevalent irrespective of age, sex, profession,
rural/urban settings or regional distribution [10,11] (Table 1).

Mean 25(OH) D
Study population Number of Age mean serum levels (ng/ml)
participants (SD) State (SD) References

Young adults

Adults 50 28.15 (4.9) Kashmir 11.26 (9.65) Zargaret al. [8]


years

Adults 90 22?23 Punjab and 18.4 (4.3) Tandonet al.


years Haryana [12]

Urban adults 31 25 (5) Delhi 18.87 (4.69) Goswamiet al.


years [13]

Young adults 186 18.6 (13) Delhi 12.96 (9.84) Marwahaet al.
years [14]

Urban adults 642 31.4 (13.4) Delhi 7 (4.08) Goswamiet al.


years [15]

Rural adults 57 42–43 Delhi 14.56 (9) Goswamiet al.


years [7]

Urban adults 125 45.5 (0.95) Tirupathi 13.52 (0.59) Harinarayanet


years al. [16]

Urban adults 214 26–30 Mumbai 12.80 (7.94) Multaniet al.


years [17]

Infants and

2
Mean 25(OH) D
Study population Number of Age mean serum levels (ng/ml)
participants (SD) State (SD) References

children

Exclusively 97 10 weeks Delhi 12.59 ( 8.37) Agarwal et al.


breastfed infants [18]

Breastfed infants 60 3.0 (0.14) Delhi 9.03 (4.63) Mehrotraet al.


months [19]

Infants 127 3 months Delhi 6.5 (4.0) Agarwal et al.


[20]

Infants, urban area 26 16±4.1 Delhi 12.4 (7) Agarwal et al.


months [11]

Adolescent girls 50 14.7 (0.10) Pune 9.36 Khadilkaret al.


years [21]

Adolescents 3089 10–18 Delhi 10.4 (0.4) Marwahaet al.


years [22]

Pregnant and
lactating women

Lactating mothers 342 24.6 (2.8) Delhi 7.84 (3.32) Marwahaet al.
years [23]

Lactating mothers 180 Delhi 10.88 (5.8) Seth et al. [24]

Pregnant women 207 24.0 (4.1) Lucknow 14.00 (9.3) Sachanet al. [25]
years

Pregnant women 42 20–35 Mumbai 22.99 (10.93) Bhallaet al. [26]


years

Pregnant women 559 24 years Mysore 15.12 (9.6) Farrantet al. [27]

Pregnant women 521 24.6 (2.8) Delhi 9.28 (4.88) Marwahaet al.
years [14]
SD: Standard deviation, 25(OH) D: 25?hydroxy Vitamin D
Table 1: Vitamin D Serum Levels In Different Population Groups Across India

The major source of vitamin D is exposure to sunlight. It has been presumed that Indians are vitamin D
sufficient due to adequate sunshine throughout the year [6]. However, reduced cutaneous synthesis of
vitamin D could be attributed to limited UV exposure owing to increased skin pigmentation, topical
application of sunscreen, certain socio cultural practices and urban life style [6]. Secondary sources

3
include dietary intake of foods naturally rich in vitamin D such as salmon, cod liver oil, sun dried
mushrooms or vitamin D fortified foods [2,28]. In our country, availability, acceptability and cost of these
dietary products limits their widespread use by the general population. This complex interplay between
lack of adequate sun exposure, deficient intake and effective food fortification strategies makes Asian
Indian population particularly susceptible to vitamin D insufficiency/deficiency. Thus, vitamin D
supplementation in the form of pharmaceutical preparations is one of the most effective ways to prevent
and treat VDD in high-risk groups [29]. We, therefore undertook a study to ascertain that availability and
composition of various pharmaceutical preparations of vitamin D in the Indian market.

Materials and Methods


This study was conducted to determine the number and composition of the various vitamin D
pharmaceutical preparations. Data for the study was collected from an annual Drug Compendium
entitled The Drug Today 2013 (October–December 2013 issue) and product labels. The preparations
were assessed for total number, different formulations, constituents and amount of each constituent
present in the formulation.

Results
Analysis of various vitamin D preparations

A total of 258 vitamin D formulations are available in the Indian market. Vitamin D is commonly available
in two forms: Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Only two preparations contain
vitamin D2 (ergocalciferol). More than 99.9% of the preparations contain vitamin D3 in the form of
alfacalcidiol (25 hydroxycholecalciferol), calcitriol (1,25 dihydroxycholecalciferol) or cholecalciferol
(inactive vitamin D). Most of the preparations contain calcitriol (n=120, 46.5%) or alfacacidiol (n=111;
43.02%). Approximately 10% of preparations contain cholecalciferol (n=27, 10.5%) (fig. 1, Tables
2 and 3).

4
Fig. 1: Various vitamin D preparations available in Indian market. All the available cholecalciferol
preparations (CC) (10.5%) contain only vitamin D3. 39 % of calcitriol preparations contain vitamin D3 in
combination with minerals /vitamins (C-MV) and 7.5% contain vitamin D3 alone (C). 23.22% of
alfacalcidiol preparations contain vitamin D3 in combination with minerals /vitamins (A-MV) and 19.8%
contain vitamin D3 alone (A)

Alfacalcidiol (25 Calcitriol (1,25


hydroxy dihydroxy Cholecalciferol Total
cholecalciferol) cholecalciferol) (inactive Vitamin D)

Total number of 111 (43.02) 120 (46.5) 27 (10.5) 258


preparations (%)* (100)*

Number of 22 (19.8) 9 (7.5) 27 (100) 58


preparations that (22.4)*
contain only

Vitamin D3 (%)**

5
Alfacalcidiol (25 Calcitriol (1,25
hydroxy dihydroxy Cholecalciferol Total
cholecalciferol) cholecalciferol) (inactive Vitamin D)

Number of preparation 85 (76.5) 26 (21.6) 0 111


that contain Vitamin (43)*
D3 in

combination with
calcium (%)**

Number of 10 (9.0) 87 (72.5) 0 97


preparations that (37.6)*
contain Vitamin D3

in combination with
zinc (%)**

Number of constituents 1–14 1–12 1 1–14


(range)

Number of 68 (61.2) 60 (50) 4 (14.8) 132


preparations available (51.1)*
as tablets (%)**

Number of 35 (31.5) 53 (44.1) 3 (11.1) 91


preparations available (35.2)*
as capsules (%)**

Number of 0 2 (1.6) 4 (14.8) 6 (2.3)*


preparations available
as injectable (%)

Number of 0 0 17 (62.9) 17
preparations available (6.5)*
as sachets (%)

*: Percentage of the total number of vitamin D preparations; **: percentage of the total
number of that particular vitamin D preparation
Table 2: Vitamin D3 Preparations Available In The Market

Amount
Vitamin D of
Brand biochemical Formulation Vitamin Available
name Company form D as Cost (INR)

Rocaitrol Abott Healthcare Cholecalciferol Capsules 0.25 µg 10 175.4/17.5*


Pvt. Ltd. capsules

6
Amount
Vitamin D of
Brand biochemical Formulation Vitamin Available
name Company form D as Cost (INR)

Calosto Abott Healthcare Calcitriol Capsules 0.25 µg 15 198.36/13.22*


Pvt. Ltd. capsules

Alpha Cadila Alfacalcidiol Capsules 0.25 µg 10 48.87/4.8*


calcirol Pharmaceutical Ltd. capsules

Alfarich Cipla Ltd. Alfacalcidiol Capsules 0.25 µg 10 54.30/5.4*


capsules

Alfado GlaxoSmithKline Alfacalcidiol Capsules 0.25 µg 10 54.30/5.4*


Pharmaceuticals capsules
Ltd.

Alfa D3 GlaxoSmithKline Alfacalcidiol Capsules 0.5 µg 10 268/26.8*


Pharmaceuticals capsules
Ltd.

Rocaltrol Sun Pharmaceutical Calcitriol Capsules 0.25 µg 10 123/12.3*


Industries Ltd. capsules

Alphadol Panacea Biotec Ltd. Alfacalcidiol Capsules 0.25 µg 10 169/16.9*


capsules

Vitanova Zuventus Cholecalciferol Capsules 60,000 IU 10 250/25*


SG Healthcare Ltd. capsules

Quente Stanley Healthcare Cholecalciferol Capsules 60,000 IU 4 capsules 86.25/21.5*


D3

Minroset Win Medicare Ltd. Alfacalcidiol Capsules 0.25 µg 10 56.8/5.6*


capsules

Calcit SG ZudusCadila Alfacalcidiol Tablets 0.25 µg 10 tablets 94.40/9.4#


Healthcare Ltd.

Vitalcal Genesis Biotec Inc. Cholecalciferol Tablets 60,000 IU 4 tablets 96.00/24#

Hira D3 Hiral Lab Ltd. Cholecalciferol Tablets 60,000 IU 4 tablets 80/20#

Calcit SG ZudusCadila Alfacalcidiol Tablets 0.25 µg 10 tablets 94.40/9.4#

Arachitol Solvay Pharma Cholecalciferol Injection 600,000 1 injection 34


India Pvt. Ltd. IU (2 ml)

Fovit D3 Forgo Cholecalciferol Injection 600,000 1 injection 21.90


Pharmaceuticals (P) IU (1 ml)

7
Amount
Vitamin D of
Brand biochemical Formulation Vitamin Available
name Company form D as Cost (INR)

Ltd.

D3 UP Abott Healthcare Cholecalciferol Granules 60,000 IU 1 sachet 21


Pvt Ltd.

Caldikind Mankind Cholecalciferol Granules 60,000 IU 1 sachet 21


Pharmaceutical Pvt.
Ltd.

Calotec Lupin Laboratories Cholecalciferol Powder 60,000 IU 1g 29


D3 Ltd.

Sorvate Glenmark Calcitriol Ointment 0.0003% 20 g 175

Rosical Sun Pharma Calcitriol Ointment 3 µg 15 g 213


INR: Indian national rupees, *: cost per capsule; #: cost per tablet
Table 3: Commonly Available Vitamin D Branded Preparations In The Market

Different formulations of vitamin D

The most common formulation for oral administration is in the form of tablets (n=132, 51.1%) and
capsules (n=91, 35.2%). Though alfacalcidiol and calcitriol are commonly available as tablets and
capsules; cholecalciferol is in the form of granules in sachets (n=17, 62.9%). Other dosage forms
include syrups and softgel capsules. Though oral administration in the form of drops is commonly
recommended for infants and children, adolescents and adults are usually prescribed tablets, capsules
or granules for supplementation. While all cholecalciferol preparations are available as a single
constituent; more than 75% of alfacalcidiol preparations also contain calcium (n=85, 76.5%). Majority of
calcitriol preparations are combined with zinc or zinc sulphate (n=87, 72.5%). Vitamin D preparations
also contain various other minerals/vitamins such as magnesium, cupric, boron, methylcobalamin,
vitamin E, vitamin K, vitamin C, pyridoxine, folic acid, beta-carotene, glutamic acid, manganese, omega
3 and docosapentaenoic acid. Tablets and capsules contain 10 IU (0.25 µg) -10000 IU (25 mg) of
vitamin D and are usually administered on a daily basis. Sachets of cholecalciferol containing granules
of vitamin D amount to 60,000 IU of vitamin D are administered weekly. Vitamin D2 (doxercalciferol)
preparation is available in tablet form (two formulations) containing 20 IU (0.5 µg) and 100 IU (2.5 µg)
respectively (Table 3).

Cost analysis

Cost analysis reveals that tablets/capsules of alfacalcidiol (equivalent to 10 IU of vitamin D) and calcitriol
(0.25 µg) commonly costs Indian National Rupees (INR) 5.5 and INR 7, respectively (Table 4).

8
Whereas, cholecalciferol granules (equivalent to 60,000 IU) costs INR 20. The common treatment
regime for VDD is 60000 IU weekly for eight weeks, which costs approximately INR 160. Furthermore,
vitamin D given monthly as maintenance therapy for a year would cost INR 240.

Alfacalcidiol Calcitriol

(0.25 µg) 10 IU (0.25 µg) 10 IU Cholecalciferol (60,000 IU)

Average cost 4.3 5.15 10.10

Modal 5.5 7 20

Cost range of 0.75–7.5 (10 IU) 3–13.5 (10 IU) 4.9 (5000 IU)

tablets (strength)

Cost range of 3–22.6 (10 IU) 4–12.9 (10 IU) 5.9 (1000 IU)

capsules (strength)

Cost of granules 16 (60,000 IU) NA 0.73–23.23

(strength) (60,000 IU)


NA: Not available
Table 4: The cost (in Indian national rupees) Of various dosage forms of vitamin D3 Preparations

Discussion
Vitamin D deficient state has become one of the most prevalent and underdiagnosed medical conditions
in the world [1,30]. Recent evidence suggests that lack of adequate sun exposure is the most important
factor for this global pandemic as very few foods naturally contain vitamin D (wild caught salmon and UV
exposed mushrooms) [2]. Analysis in children and adults indicate that dietary sources are grossly
inadequate in providing the Recommended Dietary Allowances (RDA) for vitamin D. In our population,
cutaneous production of vitamin D is further limited by increased melanin content of skin or sun
avoidance by use of sunscreens, extensive clothing cover due to sociocultural practices or staying
indoors for most of the day [6]. Deficient vitamin D status can be corrected either by vitamin D
fortification (addition of micronutrients to processed foods) or supplementation (the provision of relatively
large doses of micronutrients, usually in form of pills, capsules or syrup). Vitamin D fortification is an
effective and passive way to increase vitamin D intake in both general population and vulnerable groups
[31-33]. However, it mandates political commitment and involvement of various ministries (health,
agriculture and social welfare) to develop nationwide strategies for a better vitamin D status in the
population. In our country, where vitamin D fortification initiative is lacking, supplementation is the only
alternative [34].

In our analysis, we found that multiple supplements of vitamin D are available. The two common forms
are vitamin D3 (alfacalcidiol, cholecalciferol and calcitriol) and vitamin D2 (ergocalciferol). Evidence

9
suggests that cholecalciferol is superior to ergocalciferol in terms of potency, elevating and sustaining 25
(OH) D concentrations and maintaining the storage form of vitamin D [35,36]. In our analysis, we were
not able to ascertain the cause of lack of availability of vitamin D2 preparations in the Indian market.
Majority of preparations available in the market contain vitamin D3 (99.9%). About half of the
preparations (46.5%) contain calcitriol in the form of tablets or capsules of 0.25 mcg. Calcitriol has a
rapid onset of action with short half-life of 6 h. It is most useful in chronic kidney disease and type I and
type II vitamin D deficient rickets (VDDR) with decreased synthesis of calcitriol. Though calcitriol is the
most commonly available form, it is not the preferred agent for treatment of nutritional deficiency or stoss
therapy (single large oral/ intramuscular therapy). It is associated with a high incidence of hypercalcemia
and requires serum calcium monitoring. Furthermore, when calcitriol is used as a supplement, 25(OH) D
levels do not indicate clinical vitamin D status. Calcitriol does not build up stores and is an expensive
preparation [37]. Around 43% of the preparations contained alfacalcidiol (25 dihydroxy cholecalciferol). It
is most commonly available as tablets or capsules of 10 IU, usually in combination with calcium (76.5%
of alfacalcidiol preparations). Alfacalcidiol has a rapid onset of action with a half life of 2-3 weeks. It does
not require hepatic 25-hydroxylation, and is therefore most useful in patients with liver disease.
Approximately 10% of vitamin D3 preparations are available as cholecalciferol. It is the inactive,
unhydroxylated form of vitamin D3, synthesized in skin from 7 dehydrocholesterol. It has a slow onset of
action with a half-life of 12-30 days. Thus, it is the preferred form for prophylaxis or treatment of vitamin
D deficient states [37].

Vitamin D can be administered daily, weekly, monthly, or every 4 months to sustain an adequate serum
25 (OH) D concentrations [38-40]. A high bolus dose of vitamin D (up to 300,000 IU) can be used initially
in persons with extreme VDD. Repeated boluses of high-dose vitamin D at 6- to 12-month intervals have
been used in a nursing home setting, but a steady-state serum 25(OH) D concentration is likely to be
maintained by more frequent, lower doses of vitamin D. An effective strategy to treat vitamin D deficient
state in children and adults is to administer 50,000 IU of vitamin D3 once a week for 6-8 weeks
respectively [41,42]. To prevent recurrence, administration of 600 to 1000 IU/day is effective [43]. In our
country, most market preparations contain 60, 000 IU, and are usually recommended for 6 to 8 weeks
for obtaining adequate serum 25 (OH) D concentrations. A monthly maintenance therapy is usually
required and should be continued for over one year [44]. Another study suggested that a single high
dose of 120,000-180,000 IU of oral cholecalciferol was adequate to elevate 25(OH) D out of the
deficiency range. However, maintenance dose is required for sustaining the desired concentration of
25(OH) D [44,45]. Our analysis suggests that this treatment regime would initially cost approx. INR 160
and a maintenance therapy for a year would cost INR 240. However, the treatment costs are usually
higher as calcium supplements are coadministered with vitamin D therapy. Vitamin D supplementation

Vitamin D supplementation varies with the RDA, tolerable upper levels in different age groups and in
certain circumstances [46]. The Institute of Medicine (IOM), USA guidelines suggest a vitamin D
sufficient level of 20 ng/ml to optimize bone health [47]. In contrast, US Endocrine Society recommends
that serum 25 (OH) D levels of 30 ng/ml (vitamin D sufficiency) should be attained for children and
adults to optimize the probability of good health and avoid other risk associated with vitamin D deficient

10
status (Table 5). Furthermore, it is now acknowledged that previously recommended vitamin D intake of
200 IU/day in the American recommended intakes or 400 IU/day in the WHO report are grossly
inadequate [46]. Thus, RDA of 600-800 IU is recommended to maintain adequate levels of vitamin D
[46]. In our country, Indian Council of Medical Research (ICMR) recommends a daily supplement of 400
IU/day of vitamin D for Indians under situations of minimal exposure to sunlight [34]. However, in light of
recent evidence, there is a need to update these guidelines regarding vitamin D intake and
supplementation in adults, vulnerable population and susceptible groups [48-50]. It is now recognized
that vitamin D is not as toxic as once thought to be. IOM recommends that up to 4,000 IUs of vitamin
D/day is safe for most children and adults. Studies in various populations have shown that adults can
tolerate 10,000 IU of vitamin D/day for at least five months without altering their serum calcium or urinary
calcium output [50]. However, in rare cases, vitamin D toxicity can cause hypercalcemia,
hyperphosphatemia, nephrocalcinosis, and soft tissue calcification, thus contributing to high risk of
mortality [51].

US IOM classification* [30] US Endocrine Society classification [3]

Severe deficiency: <5 Deficiency: <20

Deficiency: <15 Insufficiency: 21–29

Sufficiency: >20 Sufficiency: >30

Risk of toxicity: >50 Toxicity: >150


Values are given in ng/ml, IOM: institute of medicine
Table 5: Vitamin D status in relation to 25?Hydroxy vitamin D levels

Studies indicate general and widespread use of dietary supplements across populations [52,53]. Though
these supplements often are used with the intention of attaining health benefits by preventing chronic
diseases, cumulative effects of widespread supplement use, together with food fortification, have raised
concern regarding exceeding upper recommended levels and, thus, long-term safety [53]. In case of
vitamin D, unsupervised intake of alfacalcidiol and calcitriol, which are not recommended for vitamin D
deficient states, could result in adverse effects/toxicity [54]. Thus, it is recommended that supplements
should only be used with strong medically based cause, such as symptomatic nutrient deficiency
disease [53]. ‘Blanket prescription’ of these supplements in all patients for prolonged use should be
stopped. Physicians need to evaluate the patient’s dietary nutrient consumption, intake of any other
multivitamin supplement, potential interactions and prescribe them only on an individual basis.

Widespread VDD in the Indian population is a cause for grave concern. Adequate measures are
imperative to prevent VDD at the outset. There is a need for educating the masses about sensible sun
exposure for vitamin D synthesis and dietary intake of vitamin D rich foods. Fortification of commonly
available foods could prevent vitamin D insufficiency in our large population. There is an urgent need to
prioritize development of national level programs to provide regulated vitamin D fortified foods at
affordable prices for Indian population at large. As far as vitamin D supplements are concerned, their

11
easy availability and chronic self-administration mandates awareness on the part of the consumer,
pharmacist, chemists, physicians and regulatory bodies to prevent misuse and serious harm. As evident
by high market sales, high intake of calcitriol in the form of dietary calcium supplement in the general
population could result in serious hypercalcemia, calcium stones and metastatic calcification. The
prescribing physicians need to be aware of this potential risk and should prescribe supplements only on
an individual basis for requisite duration. These supplements should be adequately labeled indicating
the amount of each constituent with special instructions/precautions/warnings, if any. Stringent
regulations are required to keep a check on their marketing and availability. Adequate legal actions are
required for pharmaceutical companies/ drug firms not adhering to regulatory provisions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References
1. Hossein-nezhad A, Holick MF. Vitamin D for health: A global perspective. Mayo ClinProc
2013;88:720-55.
2. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-8.
3. Ganji V, Zhang X, Tangpricha V. Serum 25-hydroxyvitamin D concentrations and prevalence
estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. J Nutr
2012;142:498-507.
4. Greene-Finestone LS, Berger C, de Groh M, Hanley DA, Hidiroglou N, Sarafin K, et al. 25-
Hydroxyvitamin D in Canadian adults: Biological, environmental, and behavioral correlates.
OsteoporosInt 2011;22:1389-99.
5. Fields J, Trivedi NJ, Horton E, Mechanick JI. Vitamin D in the Persian Gulf: Integrative physiology
and socioeconomic factors. CurrOsteoporos Rep 2011;9:243-50.
6. Gupta A, Gupta R. Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients
2014;6:729-75.
7. Goswami R, Kochupillai N, Gupta N, Goswami D, Singh N, Dudha A. Presence of 25(OH) D
deficiency in a rural North Indian village despite abundant sunshine. J Assoc Physicians India
2008;56:755-7.
8. Zargar AH, Ahmad S, Masoodi SR, Wani AI, Bashir MI, Laway BA, et al. Vitamin D status in
apparently healthy adults in Kashmir Valleyof Indian subcontinent. Postgrad Med J 2007;83:713-6.
9. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, et al. High
prevalence of low dietary calcium, high phytate consumption, and Vitamin D deficiency in healthy
South Indians. Am J ClinNutr 2007;85:1062-7.

12
10. Garg MK, Marwaha RK, Khadgawat R, Ramot R, Obroi AK,Mehan N, et al. Efficacy of Vitamin D
loading doses on serum 25-hydroxy Vitamin D levels in school going adolescents: An open label
non-randomized prospective trial. J PediatrEndocrinolMetab 2013;26:515-23.
11. Agarwal KS, Mughal MZ, Upadhyay P, Berry JL, Mawer EB,
12. Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in
healthy young Indian adults with optimal Vitamin D availability. Natl Med J India 2003;16:298-302.
13. Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N,
14. Marwaha RK, Tandon N, Garg MK, Kanwar R, Narang A, Sastry A, et al. Vitamin D status in
healthy Indians aged 50 years and above. J Assoc Physicians India 2011;59:706-9.
15. Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N, et al. Prevalence of
Vitamin D deficiency and its relationship withthyroid autoimmunity in Asian Indians: A community-
based survey. Br J Nutr 2009;102:382-6.
16. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh:
A population based study. Indian J Med Res 2008;127:211-8.
17. Multani SK, Sarathi V, Shivane V, Bandgar TR, Menon PS, Shah NS. Study of bone mineral
density in resident doctors working at a teaching hospital. J Postgrad Med 2010;56:65-70.
18. Agarwal N, Faridi MM, Aggarwal A, Singh O. Vitamin D Status of term exclusively breastfed
infants and their mothers from India. ActaPaediatr 2010;99:1671-4.
19. Mehrotra P, Marwaha RK, Aneja S, Seth A, Singla BM, Ashraf G, et al. Hypovitaminosis d and
hypocalcemic seizures in infancy. IndianPediatr 2010;47:581-6.
20. Agarwal R, Virmani D, Jaipal ML, Gupta S, Gupta N, Sankar MJ, et al. Vitamin D status of low
birth weight infants in Delhi: Acomparative study. J Trop Pediatr 2012;58:446-50.
21. Khadilkar A, Crabtree NJ, Ward KA, Khadilkar V, Shaw NJ,
22. Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney RC, et al. Vitamin D and
bone mineral density status of healthy schoolchildren in northern India. Am J ClinNutr
2005;82:477-82.
23. Marwaha RK, Tandon N, Chopra S, Agarwal N, Garg MK, Sharma B, et al. Vitamin D status in
pregnant Indian women across trimestersand different seasons and its correlation with neonatal
serum 25-hydroxyvitamin D levels. Br J Nutr 2011;106:1383-9.
24. Seth A, Marwaha RK, Singla B, Aneja S, Mehrotra P, Sastry A, et al. Vitamin D nutritional status
of exclusively breast fed infants and their mothers. J PediatrEndocrinolMetab 2009;22:241-6.
25. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High prevalence of Vitamin D
deficiency among pregnant women and their newborns in northern India. Am J ClinNutr
2005;81:1060-4.
26. Bhalala U, Desai M, Parekh P, Mokal R, Chheda B. Subclinical hypovitaminosis D among
exclusively breastfed young infants. Indian Pediatr 2007;44:897-901.
27. Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, et al.Vitamin D
insufficiency is common in Indian mothers but is not associated with gestational diabetes or
variation in newborn size. Eur J ClinNutr 2009;63:646-52.

13
28. Biancuzzo RM, Young A, Bibuld D, Cai MH, Winter MR, Klein EK, et al. Fortification of orange juice
with Vitamin D2 or Vitamin D3 isas effective as an oral supplement in maintaining Vitamin D status in
adults. Am J ClinNutr 2010;91:1621-6.
29. Vieth R, Carter G. Difficulties with Vitamin D nutrition research: Objective targets of adequacy, and
assays for 25-hydroxyvitamin D. Eur J ClinNutr 2001;55:221-2.
30. Ben-Shoshan M. Vitamin D deficiency/insufficiency and challenges in developing global Vitamin D
fortification and supplementation policy in adults. Int J VitamNutr Res 2012;82:237-59.
31. Babu US, Calvo MS. Modern India and the Vitamin D dilemma: Evidence for the need of a national
food fortification program.Mol Nutr Food Res 2010;54:1134-47.
32. Allen L, de Benoist B, Dary O, Hurrel R, editors. Guidelines on food fortification with micronutrients.
In: Food and Agricultural Organization of the United Nations. Geneva: World Health Organization;
2009. Available from: http://www.who.int/nutrition/publications/ micronutrients/9241594012/en/. [Last
accessed on 2014 Jul 14].
33. Calvo MS, Whiting SJ. Public health strategies to overcome barriers to optimal Vitamin D status in
populations with special needs. J Nutr 2006;136:1135-9.
34. A Report of the Expert Group of the Indian Council of Medical Research. Jamai-Osmania PO,
Hyderabad: National Institute of Nutrition, Indian Council of Medical Research, Nutrient
Requirements and Recommended Dietary Allowances for Indians; 2009. Available from:
http://www.pfndai.com/Draft_RDA-2010.pdf. [Last accessed on 2014 Jul 12].
35. Biancuzzo RM, Clarke N, Reitz RE, Travison TG, Holick MF. Serum concentrations of 1,25-
dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to Vitamin D2 and Vitamin D3
supplementation. J ClinEndocrinolMetab 2013;98:973-9.
36. Park SY, Murphy SP, Wilkens LR, Yamamoto JF, Kolonel LN. Allowing for variations in multivitamin
supplement composition improves nutrient intake estimates for epidemiologic studies. J Nutr
2006;136:1359-64.
37. Malluche HH, Monier-Faugere MC, Koszewski NJ. Use and indication of Vitamin D and Vitamin D
analogues in patients with renal bone disease. Nephrol Dial Transplant 2002;17Suppl 10:6-9.
38. Demetriou ET, Travison TG, Holick MF. Treatment with 50,000 IU Vitamin D2 every other week and
effect on serum 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, and total 25-hydroxyvitamin D in a
clinical setting.EndocrPract 2012;18:399-402.
39. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose
oral Vitamin D and falls and fractures in older women: A randomized controlled trial. JAMA
2010;303:1815-22.
40. Heikinheimo RJ, Inkovaara JA, Harju EJ, Haavisto MV, Kaarela RH, Kataja JM, et al. Annual
injection of Vitamin D and fractures of aged bones. Calcif Tissue Int 1992;51:105-10.
41. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral Vitamin D3 (cholecalciferol) supplementation
on fractures and mortality in men and women living in the community: Randomised double blind
controlled trial. BMJ 2003;326:469.
42. Gordon CM, Williams AL, Feldman HA, May J, Sinclair L, Vasquez A, et al. Treatment of
hypovitaminosis D in infants and toddlers. J ClinEndocrinolMetab 2008;93:2716-21.

14
43. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Guidelines
for preventing and treating Vitamin D deficiency and insufficiency revisited. J ClinEndocrinolMetab
2012;97:1153-8.
44. Goswami R, Gupta N, Ray D, Singh N, Tomar N. Pattern of 25-hydroxy vitamin D response at short
(2 month) and long (1 year) interval after 8 weeks of oral supplementation with cholecalciferol in
Asian Indians with chronic hypovitaminosis D. Br J Nutr 2008;100:526-9.
45. Pietras SM, Obayan BK, Cai MH, Holick MF. Vitamin D2 treatment for Vitamin D deficiency and
insufficiency for up to 6 years. Arch Intern Med 2009;169:1806-8.
46. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on
dietary reference intakes for calcium and Vitamin D from the Institute of Medicine: What clinicians
need to know. J ClinEndocrinolMetab 2011;96:53-8.
47. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation,
treatment, and prevention of Vitamin D deficiency: An Endocrine Society clinical practice guideline. J
ClinEndocrinolMetab 2011;96:1911-30.
48. Marwaha RK, Tandon N, Agarwal N, Puri S, Agarwal R, Singh S, et al. Impact of two regimens of
Vitamin D supplementation oncalcium – Vitamin D-PTH axis of schoolgirls of Delhi. Indian Pediatr
2010;47:761-9.
49. Haga HJ, Schmedes A, Naderi Y, Moreno AM, Peen E. Severe deficiency of 25-hydroxyvitamin D3
(25-OH-D3) is associated with high disease activity of rheumatoid arthritis. ClinRheumatol
2013;32:629-33.
50. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-
hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J ClinNutr
2003;77:204-10.
51. Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brothers Medical
Publisher; 2014. p. 335-46.
52. Mileva-Peceva R, Zafirova-Ivanovska B, Milev M, Bogdanovska A,
53. Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr. Dietary supplements and mortality rate in
older women: The Iowa Women’s Health Study. Arch Intern Med 2011;171:1625-33.
54. Chugh PK, Lhamo Y. An assessment of vitamin supplements in the Indian market. Indian J Pharm
Sci 2012;74:469-73.

15

You might also like