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Nutrients 2014, 6, 729-775; doi:10.3390/nu6020729
nutrients
ISSN 2072-6643
www.mdpi.com/journal/nutrients
Special Report
Vitamin D Deficiency in India: Prevalence, Causalities
and Interventions
Ritu G 1 and Ajay Gupta 1,2,*
1 Charak Foundation, P.O. Box 3547, Cerritos, CA 90703, USA
2 Rockwell Medical Inc., 30142 S. Wixom Road, Wixom, MI 48393, USA
* Author to whom correspondence should be addressed; E-Mail: agupta@rockwellmed.com;
Tel.: +1-562-809-8899; Fax: +1-702-974-1001.
Received: 16 November 2013; in revised form: 28 January 2014 / Accepted: 28 January 2014 /
Published: 21 February 2014
Abstract: Vitamin D deficiency prevails in epidemic proportions all over the Indian
subcontinent, with a prevalence of 70%–100% in the general population. In India, widely
consumed food items such as dairy products are rarely fortified with vitamin D. Indian
socioreligious and cultural practices do not facilitate adequate sun exposure, thereby
negating potential benefits of plentiful sunshine. Consequently, subclinical vitamin D
deficiency is highly prevalent in both urban and rural settings, and across all
socioeconomic and geographic strata. Vitamin D deficiency is likely to play an important
role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes,
cancer and infections such as tuberculosis in India. Fortification of staple foods with
vitamin D is the most viable population based strategy to achieve vitamin D sufficiency.
Unfortunately, even in advanced countries like USA and Canada, food fortification
strategies with vitamin D have been only partially effective and have largely failed to attain
vitamin D sufficiency. This article reviews the status of vitamin D nutrition in the Indian
subcontinent and also the underlying causes for this epidemic. Implementation of
population based educational and interventional strategies to combat this scourge require
recognition of vitamin D deficiency as a public health problem by the governing bodies so
that healthcare funds can be allocated appropriately.
Keywords: vitamin D; vitamin D deficiency; 25-hydroxyvitamin D; India; Indian
subcontinent; healthy individuals; fortification strategies; supplementation; sun exposure;
osteoporosis; fractures
OPEN ACCESS
Nutrients 2014, 6 730
1. Introduction
Vitamin D deficiency is pandemic, yet it is the most under-diagnosed and under-treated nutritional
deficiency in the world [1–3]. Vitamin D deficiency is widespread in individuals irrespective of their
age, gender, race and geography. Vitamin D is photosynthesized in the skin on exposure to UVB rays.
Sun exposure alone ought to suffice for vitamin D sufficiency. However, vitamin D deficiency is
widely prevalent despite plentiful sunshine even in tropical countries like India.
Vitamin D deficiency has a bearing not only on skeletal but also on extraskeletal diseases. Owing
to its multifarious implications on health, the epidemic of vitamin D deficiency in India is likely
to significantly contribute to the enormous burden on the healthcare system of India. Cultural and
social taboos often dictate lifestyle patterns such as clothing—that may limit sun exposure and
vegetarianism—which certainly limits vitamin D rich dietary options. Most Indians are vegetarians.
The socioeconomically backward people constitute a large percentage of the population in India. The
underprivileged generally suffer from overall poor nutrition. Vitamin D rich dietary sources are limited
and unaffordable to most Indians. Vitamin D supplements are available, but most Indians are not
aware that they need additional vitamin D. Additionally, the cost of these supplements is essentially
prohibitive to the majority. Fortification of staple foods with vitamin D may prove to be a more viable
solution towards attaining vitamin D sufficiency in India.
There are scores of research papers in the literature reporting poor vitamin D status from all over
India and some from other countries of the Indian subcontinent too. These research papers have been
included in this review. Many of these studies measured serum 25-hydroxyvitamin D levels in
ostensibly healthy subjects. Biochemical evidences of suboptimal bone health are elevated alkaline
phosphatase (ALP) and elevated PTH levels (secondary hyperparathyroidism or SHPT). These were
often reported in research papers, especially with respect to their correlation with vitamin D status.
However, the most accurate and convincing measure of bone mineral density (BMD) is DEXA (Dual
Energy X-ray Absorptiometry). Research articles reporting BMD, as measured by DEXA, in the
context of vitamin D status of ostensibly healthy individuals, are few. BMD data, as they correlated
with the vitamin D status in ostensibly healthy Indians is compiled. A few articles also reported results
of interventions studies such as vitamin D supplementation and vitamin D fortified foods.
The aim of the paper is to impress upon the practicing physicians in India about the gravity of the
vitamin D deficiency problem throughout India, so that they may take necessary caution and care in
the diagnosis and treatment of vitamin D deficiency. Additionally, this article may also serve to make
the case to the Health ministry, and the Food and Nutrition Board in India for population based
strategy of fortification of staple foods with vitamin D. This paper provides a comprehensive picture of
the vitamin D status of ostensibly healthy Indians, countrywide. The most reliable marker of vitamin D
status is the serum concentration of 25(OH)D. In the publications, investigators reported their data on
25(OH)D levels either as nM (nanomoles per liter) or ng/mL. To simplify information and for the ease
of comparison, in this review all the data on 25(OH)D levels are presented in a single concentration
unit for serum 25(OH)D levels—ng/mL. Most investigators have used different cut-off levels to define
vitamin D deficiency, insufficiency and sufficiency levels. While some may have done so due to
preference perhaps, other investigators defined their own cut-off levels as determined by the linear
regression between 25(OH)D levels and PTH levels. Therefore, to further facilitate comparison, in this
Nutrients 2014, 6 731
review vitamin D deficiency is defined as 25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and
sufficiency as ≥30 ng/mL. The data compiled here are also stratified by geographic locale of the study
subjects, to press home the fact that vitamin D deficiency is widespread throughout the nation,
irrespective of diverse dietary and social practices. For instance, despite fish being a staple diet in
Bengal (eastern India) vitamin D nutrition is no better than in other regions. Geographical stratification
of data also indicates regions of the country from where more data is needed. The effectiveness or
failure of vitamin D supplementation and food fortification in restoring vitamin D levels and bone
health have been reviewed, while making the case that vitamin D deficiency needs to be recognized as
a public health problem. This review also discusses the need and feasibility of fortification of staple
foods with vitamin D in India. Steps to be taken by the policymakers in India are also mentioned.
Data, when available, from other countries of the Indian subcontinent are also compiled and presented
for comparison.
2. Vitamin D Metabolism
Vitamin D can be synthesized in sufficient amounts by most vertebrates on adequate exposure of
the skin to sunlight (UVB rays). It is critical that most vertebrates obtain a sufficient amount of vitamin
D either from their diet or from adequate exposure of the skin to sunlight. The term “vitamin D” refers
to compounds vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Vitamin D3 is produced in
the skin on exposure to sunlight. Vitamin D3 is derived from 7-dehydrocholesterol by ultraviolet
irradiation of the skin. Vitamin D3 is also found in animal food sources e.g., fatty fish (e.g., salmon,
mackerel and tuna) cod liver oil, milk, etc. Vitamin D2 is found in vegetal sources like sun-exposed
yeast and mushrooms. Notably, most dietary sources are not sufficiently rich in their vitamin D content.
Vitamin D (both forms D3 or D2) is a prohormone which requires two hydroxylations to finally
attain its biologically active form—1,25(OH)2D. The first hydroxylation occurs in the liver, at position
C25 to form 25-hydroxyvitamin D, also known as 25(OH)D or calcidiol. 25(OH)D is the major
circulating form of vitamin D. The second hydroxylation occurs at position C1α to form 1,25(OH)2D,
also known as calcitriol. 1,25(OH)2D is produced primarily but not exclusively in the kidneys.
1,25(OH)2D is released in blood, where it binds to vitamin D binding protein (DBP) and reaches its
target tissues to exert its endocrine functions through the vitamin D receptor (VDR). 1,25(OH)2D is
also produced in several extrarenal tissues for its paracrine and autocrine functions. Most cells in the
body have VDR. Many cell types can also produce 1,25(OH)2D. 1,25(OH)2D is capable of regulating a
wide variety of genes that have important functions in regulating cell growth and differentiation.
3. Vitamin D and Skeletal Health
Rickets, osteomalacia and osteoporosis are widely prevalent all over the world. The most well
recognized function of 1,25(OH)2D involves regulation of calcium and phosphorus balance for bone
mineralization and remodeling. Without adequate levels of 1,25(OH)2D in the bloodstream, dietary
calcium cannot be absorbed. Low calcium levels lead to an increase in serum PTH concentration,
which leads to increased tubular reclamation of calcium in kidneys and resorption from the skeleton at
the cost of lowering bone density. In the long term this leads to weakened and brittle bones that break
easily. Approximately 40%–60% of total skeletal mass at maturity is accumulated during childhood
Nutrients 2014, 6 732
and adolescence. Rickets results from inadequate mineralization of growing bone. Thus it is a
childhood disease and it is manifested as bone deformities, bone pain and weakness. Biochemical
abnormalities consistently include hypophosphatemia, elevated alkaline phophatase levels and serum
25(OH)D levels are usually below 5 ng/mL. Chronic vitamin D deficiency in adults results in osteomalacia,
osteoporosis, muscle weakness and increased risk of falls [4–11]. Epidemiological support for skeketal
benefits of vitamin D is well known [5,6,12–14].
4. Vitamin D: Extraskeletal Effects
Biochemical studies have implicated vitamin D deficiency in many chronic diseases including,
but not limited to, infectious diseases, autoimmune diseases, cardiovascular diseases, diabetes and
cancer. Numerous epidemiological publications support the extraskeletal benefits of vitamin D and
they cannot be ignored even though majority of these are association studies or small randomized
controlled trials. Nevertheless, stronger evidence is required with the aid of more robust and reliable
statistical methods such as randomized controlled trials (RCTs). These RCTs should be well-designed,
well-executed and conducted worldwide to generate dependable and incontrovertible data, in order to
assess the benefits of vitamin D supplementation not only as a preventive measure but also as adjuvant
therapies [12,15,16].
4.1. Immunity
As early as in the 19th century, cod liver oil (a rich source of vitamin D) was used for treating
tuberculosis (TB). Skin exposure to sunlight was an effective therapy for treating Mycobacterium
infections of the skin. In 1903, Finsen received the Nobel Prize for demonstrating that Lupus vulgaris,
the epidermal form of TB, could be cured using light from an electric arc lamp. In early 1900s,
growing awareness of benefits of sun exposure pertaining treatment of infectious diseases led to the
development of sanatoriums in “sun-rich areas”. These sanatoriums enabled regimented sun exposure,
diet and exercise. These sanatoriums primarily hosted TB patients [17]. Recent studies have linked
vitamin D deficiency with increased risk of developing TB [18,19], otitis media [20], upper respiratory
tract infections [21] and influenza [22].
4.2. Cardiovascular Health
Cardiovascular diseases (CVDs), including heart failure and coronary artery disease are a major
cause of morbidity and mortality worldwide. There is accumulating epidemiological evidence from
observational studies suggesting that CVDs are associated with vitamin D deficiency [23,24]. Increased
risk of hypertension was associated with living at higher latitudes [25]. 25(OH)D level
< 21 ng/mL was associated with increased risk of hypertension, diabetes, obesity and high triglyceride
levels—all associated with increased cardiovascular mortality [26]. Various studies have reported
reduced 25(OH)D concentrations in patients with previous and prevalent cardiovascular or cerebrovascular
diseases [15,27].
Nutrients 2014, 6 733
4.3. Type 1 Diabetes
Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic β cells, which eventually
leads to insulin-dependent diabetes. Higher rates of incidence of T1D were observed at higher latitudes
worldwide [28,29]. Epidemiological association of vitamin D intake and reduced risk of T1D was also
seen [30]. A meta-analysis of observational studies showed a 30% reduction in risk of T1D in children
receiving vitamin D supplements [31].
4.4. Type 2 Diabetes
Type 2 diabetes (T2D) is marked by insulin resistance (IR). In IR insulin is adequately or
overproduced by pancreatic β cells, but is ineffectively utilized by the target cells of adipose, hepatic
and skeletal muscles tissues. As a response to hyperglycemia, β cells further increase insulin
production leading to hyperinsulinemia, which is often indicative of a pre-(T2D) stage. Hyperinsulinemia
is associated with hypertension, obesity, dyslipidemia, and glucose intolerance [32]. These conditions
are collectively known as “metabolic syndrome” [33]. A meta-analysis of observational studies showed
inverse relation of 25(OH)D levels and calcium status with insulin resistance and hyperglycemia. In this
meta-analysis, supplementation with both the nutrients combined showed benefit in optimizing glucose
levels [34].
4.5. Cancer
Adults living at higher latitudes are more likely to develop and die of colorectal cancer [35,36], prostate
cancer [37], ovarian cancer [38], breast cancer [39], lung cancer [40] and esophageal cancer [41].
Retrospective and prospective epidemiologic studies showed that when 25(OH)D levels were <20 ng/mL
there was a 30%–50% increased risk of developing and dying of colorectal, prostate, breast, pancreatic,
and esophageal cancer [36,39,42–45].
5. Serum 25(OH)D Levels as Indicative of Vitamin D Deficiency, Insufficiency or Sufficiency
Maintenance of adequate levels of serum 25(OH)D is essential to sustain the claimed pleiotropic
effects, whether skeletal (classical) or extra-skeletal (non-classical). The threshold levels of serum
25(OH)D required to optimize its effects may not be the same in the various target organs. Based on
classical skeletal effects, vitamin D deficiency is defined as serum levels of 25(OH)D < 20 ng/mL
(50 nmol/L) with consequent and consistent elevation of PTH and reduction in intestinal calcium
absorption. Vitamin D insufficiency is defined as serum 25(OH)D levels in the range of 20–29 ng/mL.
At serum 25(OH)D levels of 30 ng/mL intestinal calcium absorption reaches its peak, and PTH levels
continue to fall until this level of 25(OH)D is attained. Thus, vitamin D sufficiency is defined as serum
levels of 25(OH)D 30–32 ng/mL. A desirable and safe range of serum 25(OH)D levels would be
30–100 ng/mL. This range would be sufficient for most known effects of vitamin D and also significantly
lower to obviate concerns pertaining vitamin D toxicity.
Nutrients 2014, 6 734
6. Vitamin D Supplements and Efficacy Concerns
Commercially, vitamin D2 is manufactured by ultraviolet irradiation of ergosterol from yeast.
Vitamin D3 is produced by the ultraviolet irradiation of 7-dehydrocholesterol from lanolin. Both forms
of vitamin D are available as vitamin D supplements. Several other forms of vitamin D supplements
are also available. 1,25(OH)2D is indicated specifically for patients with renal diseases and 25(OH)D is
useful when hepatic hydroxylation of vitamin D is impaired.
Whether D2 or D3, is more efficacious in raising and sustaining serum 25(OH)D levels, remains
controversial. Several studies have proved equivalence between the two forms [46–49]. However,
other studies reported that D3 is more effective than D2 in achieving and maintaining higher serum
25(OH)D levels [50–53]. Nevertheless, on a long term basis either form may be used, bearing in mind
the long half-life (2–3 weeks) of 25(OH)D in circulation.
7. Testing Vitamin D Status
Plasma 25(OH)D or calcidiol (a summation of D3 and D2 forms) is the most reliable marker of
vitamin D status. Immunoassays such as radioimmunoassay (RIA), enzyme linked immunosorbant
assay (ELISA), chemiluminescence immunoassay and protein binding assays are used in routine
testing of 25(OH)D in clinical laboratories. LCTMS (liquid chromatography tandem mass
spectrometry) is the widely accepted reference method for 25(OH)D measurement. However, LCTMS
is tedious, expensive and time consuming and therefore seldom used commercially.
Since vitamin D undernutrition is largely silent and subclincal, the indication for testing remains
controversial. At present 25(OH)D test is the “most ordered test” in the USA. A similar trend has just
begun in the upper socioeconomic stratum in India too. This clearly shows increasing awareness
pertaining widespread prevalence of vitamin D deficiency among Indian clinicians. A 25(OH)D test
using antibody based technologies in India costs an individual approximately INR 1500, which is
unaffordable for most Indians. Surely, vitamin D status needs to be improved in most individuals in
India and not just the privileged or a select few. However, testing every individual’s vitamin D levels,
in a population with such a high prevalence of vitamin D deficiency is not economically and
practically feasible. Furthermore, whether subclinical vitamin D deficiency in otherwise healthy
individuals should be treated or not, and to what target level of serum 25(OH)D remains controversial.
It will be more cost-effective to implement aggressive nationwide vitamin D supplementation and food
fortification programs for the benefit of all ostensibly healthy individuals.
8. Vitamin D Status of Ostensibly Healthy Indians
Countrywide studies (Table 1) have reported vitamin D deficiency in as high as 70%–100% of
ostensibly healthy individuals. High prevalence of vitamin D deficiency was reported from northern to
southern and western to eastern India, in ostensibly healthy children, adolescents, young adults and
those ≥50 years old. All over India, vitamin D deficiency was highly prevalent in pregnant women and
lactating mothers. Vitamin D status of these mothers correlated well with their neonates and their
exclusively breastfed infants. Subjects from rural and urban areas presented a similar picture.
Relatively, fish are a rich source of vitamin D. The residents of Bengal (eastern India) eat more fish
Nutrients 2014, 6 735
compared to the rest of the Indians. Surprisingly, their vitamin D status appears to be just as poor as in
the rest of the country [54]. Similarly, even healthy young soldiers with sufficient intake of calcium,
adequate sun exposure and regular exercise regimen were found to be vitamin D deficient [55,56],
as were young sportswomen [57]. Among resident doctors from Mumbai (western India) [58] and also
doctors from eastern India [54], most were vitamin D deficient. Vitamin D deficiency was also
observed in most of 2119 healthcare professionals studied from all over India [59]. Evidently,
countrywide prevalence of vitamin D deficiency is undeniable.
9. Correlation of Vitamin D Status with Bone Health of Ostensibly Healthy Adolescents and
Adults in India
Among otherwise healthy adolescents and adults studied, along with low serum 25(OH)D levels, a
significant number of subjects also revealed other biochemical and clinical manifestations of vitamin
D deficiency. Biochemical evidences of suboptimal bone health are: elevated alkaline phosphatase, a
surrogate marker for increased bone turnover, and elevated PTH levels (secondary
hyperparathyroidism or SHPT). ALP and PTH were often reported in research papers, especially with
respect to their correlation with vitamin D status. However, the most accurate and convincing evidence
of bone density is DEXA. Only research articles reporting BMD, as measured by DEXA, in the
context of vitamin D status of ostensibly healthy individuals are included in this section (Table 2).
Vitamin D intervention studies that measured resultant BMD outcomes are discussed later in section
15 of this review.
Most studies did not show any correlation of BMD with vitamin D status. Notably, among
90 adults, who were 20–30 year-old soldiers from Indian paramilitary forces, with adequate nutrition,
sun exposure and physical exercise, BMD was lower when compared to Caucasians. Among men,
osteopenia was noted in 50% at the lumbar spine, 35% at the hip, and 50% at the forearm.
Additionally, 10% of men had osteoporosis of the lumbar spine. Among women, osteopenia was noted
in 32% at the lumbar spine, 14% at the hip and 21% at the forearm. The authors speculated that the
effect of childhood malnutrition may have contributed to lower peak bone mass accumulation in these
subjects [56]. BMD studies emphatically underline the need for adequate nutrition, sun exposure and
physical exercise from the very beginning of one’s life, to attain peak bone mass, and later to maintain
it. Indubitably, vitamin D status in India is grim and needs to be reckoned with.
10. Vitamin D Sufficiency via Sun Exposure Is Not a Tenable Solution for Most Indians
Vitamin D deficiency is a major health concern in India, notwithstanding the brightly shining sun.
The “adequacy of exposure to sunlight of an individual’s bare skin” required to photosynthesize
vitamin D is grossly ill understood. Darker skin has high melanin content which acts as a natural
sunscreen. Therefore, darker skin produces a significantly lesser amount of vitamin D when compared
with the individuals with fairer skin, such as Caucasians [60–62]. Thus, for Indian skin tone, minimum
“direct sun exposure” required daily is more than 45 min to bare face, arms and legs to sun’s UV rays
(wavelength 290–310 nm). With the exception of those who perforce need to work outdoors in the sun,
most Indians do not get adequate sun exposure to produce sufficient amounts of vitamin D
endogenously. Indian social and or religious norms related to public modesty dictate that most parts of
Nutrients 2014, 6 736
an individual’s body, irrespective of gender, be covered. The not so D-lightful price of urbanization —in
big cities a majority of people live in very high population density areas. They perforce live in
overcrowded tenements, which are closely packed and 3–4 stories high. Consequently, direct sunlight
does not reach inside most parts of the dwellings, thereby disallowing any sun exposure to an
individual in the privacy of one’s home. Additionally, lack of space offers limited options for outdoor
activities. Atmospheric pollution of metropolitan India also factors in with respect to vitamin D status [63].
Use of sunscreen creams and umbrellas do not help either. The extreme discomfort of the scorching
heat associated with most sunny days of Indian summer and (not to mention) the undying desire of
most Indians to attain a fairer skin complexion instantly extinguish any desire for sun exposure, and a
person’s primary focus is on finding ways to avoid the sun, at all costs. In the blazing heat of India
these two concerns score very high and the quest for vitamin D sufficiency takes a backseat, always.
Therefore, in the Indian scenario, vitamin D sufficiency cannot be attained by depending on adequate
sun exposure.
11. Nutritional Factors Attributing to High Prevalence of Vitamin D Deficiency in India
Vitamin D sufficiency by dietary intake is the only tenable solution for Indians. However, this
solution itself has a barrage of problems.
• Most dietary sources of vitamin D have very low vitamin D content. Most of the food items rich
in vitamin D are of animal origin. Most Indians are vegetarians. Commonly, a dietary source of
vitamin D for vegetarians is milk, provided milk has been fortified with vitamin D. Milk is rarely
fortified with vitamin D in India. The vitamin D content of unfortified milk is very low
(2 IU/100 mL). Additionally, milk and milk products are unaffordable to the socioeconomically
underprivileged. Another concern in India is the rampant dilution and/or adulteration of milk and
milk products.
• Low calcium in Indian diet: Low dietary intake of calcium in conjunction with vitamin D
insufficiency is associated with secondary hyperparathyroidism (SHPT). SHPT is further
exacerbated by induced destruction of 25(OH)D and 1,25(OH)2D by 24 hydroxylase [64].
24 hydroxylase is the key enzyme of vitamin D catabolism and is regulated by 1,25(OH)2D, PTH
and FGF23 (Fibroblast Growth Factor 23) levels. FGF23 is a phosphate regulator. High serum
phosphate levels increase production of FGF23 in bone osteocytes via the action of 1,25(OH)2D.
Subsequently, FGF23 reduces renal phosphate resorption, indirectly suppresses intestinal
phosphate absorption and also suppresses PTH and 1,25(OH)2D synthesis. Overproduction of
FGF23 can result in increased morbidity associated with vitamin D deficiency [65]. This
regulatory mechanism may explain the low 25(OH)D levels in rural subjects on a high phytate
and/or low calcium diet, despite plentiful sun exposure. Most studies reported calcium intake
much lower than the RDA (Recommended Daily Allowance) defined by the Indian Council of
Medical Research (ICMR). Only two studies reported adequate calcium intake. In both these
publications the study subjects were paramilitary soldiers [55,56]. ICMR’s RDA for calcium
intake in India is lower than that of the western world.
• Calcium balance is a function of intake and excretion [66,67]. Even though the Indian diet is
low in calcium content, it also has a lower protein content and therefore low endogenous
Nutrients 2014, 6 737
acid production, which may reduce urinary calcium loss. Therefore, the amount of dietary
calcium required to maintain calcium balance may be lower than for those in the Occident. The
protein-induced alterations in calcium homeostasis (and possibly in bone mass) have been
attributed to increments in endogenous acid production and net acid excretion due to the
oxidation of the constituent sulfur containing amino acids. On the other hand, the high salt
content of Indian diet is likely to increase urinary calcium excretion. A direct relation between
high sodium intake and lower bone mass has been reported [68].
• Intake of caffeine from tea and coffee is very high in India. Most Indians consume milk as part
of their tea or coffee. The proportion of milk is very low in these drinks. Thus calcium intake
through these beverages is low. Vitamin D is stable during cooking. It is stable up to 200 °C.
However, thermal stability of vitamin D is an inverse function of both temperature and time.
In India, milk is boiled for several minutes before consumption. Before the same lot of milk is
consumed in entirety, it is subjected to two-three rounds of boiling. In India most of the times,
beverages like tea and coffee are boiled for several minutes to get the right flavor. This boiling
may reduce the content of any vitamin D that there may have been left after boiling of the milk
itself. Therefore, these beverages may not contribute significantly to either calcium or vitamin D
intake in Indians. Vitamin D is a fairly robust vitamin. The preceding statements about its
thermal degradation have been made as precautionary stance to not overstate the thermal
robustness of this micronutrient. Additionally, studies have reported association of high caffeine
intake with increased risk of low bone mineral density, osteoporosis, and osteoporotic fractures
in middle-aged women. This situation is exacerbated in women with low calcium intake,
especially in lean subjects [69].
• High prevalence of lactose intolerance in India is a major deterrent pertaining milk consumption,
further lowering intake of calcium and vitamin D in these individuals. Ethnic and geographic
variations of lactose intolerance were observed, with a higher prevalence in southern (Dravidian
descent) and eastern India compared to northern India (Aryan descent) [70–73].
• Indian diet has high phytate content. Phytate is the principal storage form of phosphorus in many
plant tissues, especially the bran portion of grains and other seeds. Phytate is indigestible to
humans. Phytates chelate micronutrients such as calcium and iron, and thus reduce intestinal
absorption of these nutrients. Benefits of sun exposure in rural subjects owing to an agrarian life
were seen by significantly higher 25(OH)D levels [74]. However, possibly owing to high phytate
content in diet, these levels were still insufficient in most individuals. Possibly, high phytate
content in the diet of soldiers in northern India may have contributed to their vitamin D
insufficiency, despite adequate sun exposure, nutrition and physical exercise [56].
• Notably, nearly all studies pertaining vitamin D status in healthy subjects reported a high
phytate/calcium intake ratio. What Indians may require is a higher intake of calcium in their diet
to lower the phytate/calcium intake ratio. Dietary habits in India have changed significantly. Many
people remove a substantial proportion of bran from whole wheat flour before kneading to
improve texture and fluffiness of chapatis (unleavened flat bread). Consumption of white bread
is also very high. Most people prefer processed, split and polished pulses to whole seeds due to
the ease of shorter time required for cooking and the consequent lowered expense of cooking
Nutrients 2014, 6 738
fuel. Consumption of instant (or not) noodles and burgers also is on the rise across all
socio-economic strata, with the exception of the impecunious.
• High phytate in Indian diet especially among the socio-economically lower classes stems from
the elementary and immediate need of sufficiency of the calorific need. Cereals and legumes are
more affordable and easily available than vegetables, milk and other dairy products. Besides,
they are sources of protein for the vegetarians. Many cereals are also sources of calcium,
however due to chelation by phytates its bioavailability is limited.
• In the scenario of inadequate calcium intake, vitamin D insufficiency and high phytate content in
diet, environmental pollutants such as fluoride add insult to injury. Toxins like fluoride affect
bone metabolism severely in the conjunction with inadequate calcium intake, especially in
children [75,76].
• Cooking practices in India: Indians in general adhere to traditional cooking styles and practices,
irrespective of their migration to any part of the world. In tropical climate perishable food items
putrefy quickly. Notably, in India there is no perceptible government regulation on the hygiene
and microbial quality control of fresh produce that reaches from the producer to the
end-consumer. Consumption of uncooked fresh produce, especially vegetables, milk, etc., is
generally considered ill-advised. As in the rest of the world, in India too, slow cooking is widely
practiced. This culinary practice, however, is ill-advised bearing in mind the thermal instability
of many vitamins. As mentioned earlier vitamin D is degraded at temperatures above 200 °C. Its
thermal stability is inversely related to temperature and time. Cooking gas flame reaches
temperature above 1900 °C and coal stove heat reaches 300–700 °C. Water boils at 100 °C.
Baking is done mostly above 175 °C but the temperature in the food does not reach such high
temperatures, therefore stability of vitamin D during baking is well within acceptable
range [77]. Pertaining shallow and deep-frying of food, most cooking fats and oils have smoke
points above 180 °C. Shallow and deep frying of foods is very popular in India. When foods are
fried, vitamin D in the food comes out into the cooking medium and is thermally degraded [78].
Pressure cooking temperatures vary depending on the pressure withstood by the cooker used and
may range from 100 °C to 120 °C. Short-time (as short as possible) pressure cooking is
definitely advisable to retain at least some of the thermally more stable essential nutrients in
cooked food, including vitamin D.
• Protein malnutrition and poor overall nutrition resulting from poverty: Perforce, in the sordid
context of poverty, focus on a balanced diet is always on the back burner. It is very convenient to
attribute dietary patterns or cooking traditions, than face a reality as grim as poverty. Factually,
balanced diet is only an occasional treat to the impecunious. An old adage, “When a poor man
eats chicken, one of them is sick”, says it all.
• Publications indicating wide prevalence of vitamin D deficiency in healthy Indians have studied
subjects mostly from lower and upper middle classes. Individuals below poverty line were not
represented well in these studies. Hence, poor nutrition observed in these studies may also stem
from lack of awareness of the features, benefits and necessity of balanced nutrition.
Nutrients 2014, 6 739
Table 1. Vitamin D status of ostensibly healthy Indians. All 25(OH)D values have been shown in ng/mL. To convert from nM to ng/mL,
nM values were divided by (2.5). Vitamin D deficiency is defined as 25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and sufficiency as
≥30 ng/mL; ‡ Information available from the abstract of the article. Age of the subjects is in mean age (SD) years, unless otherwise indicated.
Locale Study Subjects
25(OH)D
(ng/mL)
Mean (SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Northern India
Kashmir
(34.3° N)
Total N = 92 Adults, age 28.15 (4.9) years. - 83 - - Zargar
2007 [79]
N = 64 M 15.06 (12.0) 76.6 - -
N = 28 F 5.51 (4.42) 94.4 - -
N = 50 Urban subjects 11.26 (9.65) 85.7 - -
N = 42 Rural subjects 12.84 (12.39) 80 - -
N = 17
N = 23
N = 15
N = 23
N = 14
Occupation:
Rural/farmer, 17 M/0 F
Government employee, 20 M/3 F
Household, 0 M/15 F
Medical professional, 16 M/7 F
Student 11 M/3 F
-
-
-
-
-
70.6
69.6
100
91.3
85.3
-
-
-
-
-
-
-
-
-
-
Punjab
(31.1° N) &
Haryana
(29° N)
Total N = 90 Adults, paramilitary soldiers. Adequate diet, sun exposure
and physical exercise.
- - - - Tandon
2003 [56]
N = 40 M, in winter, age 22.7 (2.8) years. 18.4 (5.3) - - -
N = 50 F, in summer, age 23.4 (3.1) years. 25.3 (7.4) - - -
Chandigarh
(30.7° N
Total N = 329 Young urban adults, age 18–25 years, at the end of
summer
52.9 (33.7) - - 72.5% ‡ Ramakrishnan
2011 [80]
N = 237 Subjects from the same cohort at the end of winter 31.8 (21.1) - - 50.7%
Nutrients 2014, 6 740
Table 1. Cont.
Locale Study Subjects
25(OH)D
(ng/mL)
Mean (SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Delhi
(28.3° N)
N = 31 Urban adults, M, age 25 (5) years, soldiers, winter 18.87 (4.69) - - - Goswami
2000 [55]
N = 15 Urban adults, 10 M + 5 F, age 43 (16) years, depigmented
persons, winter
7.28 (4.49) - - -
N = 19 Urban adults, 11 M + 8 F, age 23 (5) years, physicians and
nurses, winter
3.19 (1.39) - - -
N = 19 Urban adults, 11 M + 8 F, age 24 (4) years, physicians and
nurses, summer
7.17 (3.19) - - -
N = 29 Urban adult F/mothers, age 23 (5) years, low income,
summer
8.76 (4.29) - - -
N = 29 Newborns of the mothers studied, 16 M + 13 F, summer 6.68 (1.99) - - -
Agota
village
(29° N)
80 km from
Delhi
Total N = 57 Rural Adults 14.56 (9) 68.5 - - Goswami
2008 [81]
N = 32 M, rural, age 42.8 (16.6) years 17.68 (9.76) - - -
N = 25 F, rural, age 43.4 (12.6) years 10.76 (6.86) - - -
Delhi
(28.3° N)
Total N = 186 Young adults F, age 18.6 (1.3) years 12.96 (9.84) - - - Marwaha
2011 [57]
N = 90 Sports-girls from colleges 21.2 (7.57) - - -
N = 96 College girls 5.16 (3.08) 100 0 0
Delhi
(28.3° N)
Total N = 642 Urban adults, middle income group 7 (4.08) - - - Goswami
2009 [82]
N = 244 Adult M, age 31.4 (13.4) years 7.2 (3.64) - - -
N = 398 Adult F, age 35.1 (13.4) years 6.88 (4.36) - - -
Delhi
(28.3° N)
Total N = 105 Urban adults, middle income group, age 43.3 (9.7) years 9.8 (6.0) 94.3 - - Vupputuri
2006 [83]
N = 51 M, indoor workers 10.8 (6.8) - - -
N = 54 F, housewives 8.8 (4.9) - - -
Delhi
(28.3° N)
Total N = 404 Adolescents, F, urban, age 12.3 (3.4) years 12.74 (6.17) 90.8 - - Puri
2008 [84]
N = 193 Low income level 13.84 (6.97) 89.6 - -
N = 211 Higher income level 11.75 (5.07) 91.9 - -
Nutrients 2014, 6 741
Table 1. Cont.
Locale Study Subjects
25(OH)D
(ng/mL)
Mean (SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Delhi
(28.3° N)
Total N = 5137 Adolescents, urban, school children, age 10–18 years 11.8 (7.2) - - - Marwaha
2005 [85]
N = 3089 Lower income level, 1079 M, 2010 F 10.4 (0.4) 92.6 - -
N = 2048 Higher income level, 968 M, 1080 F 13.7 (0.4) 84.9 - -
Delhi
(28.3° N)
Total N = 664 Urban adolescent F, school girls, age 12.8 (2.7) years 11.4 (5.8) - - - Marwaha
2007 [86]
N = 369 Lower income level, age 12.8 (2.7) years 11.1 (5.2) - - -
N = 295 Higher income level, age 12.7 (2.6) years 11.8 (6.4) - - -
Delhi
(28.3° N)
Total N = 1346 Urban adults ≥50 years, 643 M, 703 F, age 58 (9.5)years
(range 50–84 years)
9.79 (7.61) 91.2 6.8 2 Marwaha
2011 [87]
N = 995 Age group 50–65 years 9.72 (7.75) 91.3 6.9 1.8
N = 351 Age group >65 years 9.99 (7.2) 91.2 6.6 2.2
Delhi
(28.3° N)
N = 1346 Adults, ≥50 years, age 58 (9.5) years, 48% M, 52% F 9.8 (7.6) 91.3 6.8 1.9 Garg
2013 [88]
N = 1829 Adolescents, 45% M, 55% F, age 13.3 (2.5) years 8.3 (5.2) 96.9 2.6 0.5
Delhi
(28.3°N)
N = 521 Pregnant women, lower-middle income level,
age 24.6 (2.8) years
9.28 (4.88) 96.3 - - Marwaha
2011 [89]
N = 342 Lactating mothers, from the above group 6–8 weeks
postpartum.
7.84 (3.32) 99.7 - -
N = 342 Exclusively breastfed Infants 8.92 (4.2) 98.8 - -
Delhi
(28.3° N)
N = 180 Lactating mothers 10.88 (5.8) - - - ‡ Seth
2009 [90]
N = 180 Exclusively breastfed infants, 2–24 weeks old 11.56 (8.3) - - -
Delhi
(28.3° N)
N = 26 Infants, urban, age 16 ± 4.1 months, 15 M/11 F, low
income families, high air pollution area
12.4 (7) - - - Agarwal
2002 [63]
N = 31 Infants, urban, 15.9 (3.8) months, 15 M/16 F, low income
families, low air pollution area
27.1 (7) - - -
Nutrients 2014, 6 742
Table 1. Cont.
Locale Study Subjects
25(OH)D
(ng/mL) Mean
(SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Delhi
(28.3° N)
Urban slum children, age 9–30 months Tiwari
2004 [91]
N = 47 Sundernagari area, winter 38.52 (10.28) - - -
N = 49 Rajiv Colony area, winter 9.5 (10.8) - - -
N = 48 Rajiv Colony area, summer 7.12 (8.96) - - -
N = 52 Gurgaon area, summer 7.68 (8.08) - - -
Delhi
(28.3° N)
N = 60 Lactating mothers 25.0 (2.0) years 9.06 (4.78) 98.3 - - Mehrotra
2010 [92]
N = 60 Breastfed infants, 3.0 (0.14) months 9.03 (4.63) 100 0 0
Delhi
(28.3° N)
N = 98 Lactating mothers 23.1 (3.3) years Median
9.8 (5.0–13.8)
- - - Jain
2011 [93]
N = 98 Breastfed infants, 58.2% M, age 13.6 (2.2)weeks Median
10.1 (2.5–17.1)
- - -
Delhi
(28.3° N)
N = 220 Infants, low birth-weight, at birth Median
6.5 (4.0–54.5)
93 - - Agarwal
2012 [94]
N = 127 Infants, low birth-weight, at 3 months Median
11.1 (4.0–78.0)
72.4 - -
N = 116 Infants, normal birth-weight, at birth Median
5.8 (4.0–26.6)
94.8 - -
N = 77 Infants, normal birth-weight, at 3 months Median
8.2 (4–29.7)
83.1 - -
N = 216 Mothers of low birth-weight infants, at term Median 5.6
(4.0–38.3)
93.5 4.2 2.3
N = 116 Mothers of normal birth-weight infants at term Median
5.8 (4.0–21.1)
96.6 1.7 1.7
Delhi
(28.3° N)
N = 97 Urban, lactating mothers, low income level 9.85 (6.28) - - - Agarwal
2010 [95]
N = 97 Exclusively breastfed infants, age 10 weeks 12.59 ( 8.37) - - -
Nutrients 2014, 6 743
Table 1. Cont.
Locale Study Subjects
25(OH)D
(ng/mL)
Mean (SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Lucknow,
26.8° N
N = 92 Urban adults, 67 F, 25 M, age 34.2 (6.7) years,
hospital staff
12.3 (10.9) 78.3 - - Arya
2004 [96]
Lucknow
(26.8° N)
Total N = 207 Pregnant women before labor, low and middle income
group, age 24.0 (4.1) years.
14 (9.3) - - - Sachan
2005 [97]
N = 140 Urban F 14.0 (9.5) - - -
N = 67 Rural F 14.1 (8.9) - - -
N = 207 Neonates/cord blood 8.4 (5.7) 95.7 - -
Barabanki
32 km from
Lucknow
(27° N)
N = 139 Rural pregnant women, age 26.7 (4.1) years 15.12 (7.92) 74 - - Sahu
2009 [98]
N = 121 Rural F adolescents, age 14.3 (2.7) years. 13.32 (6.4) 88.6 - -
N = 28 sisters of 34 boys, age 14.4 (2.7) years, in winter 12.52 (5.4) - - -
N = 34 brothers of 28 girls, age 14 (3) years, in winter 27 (11.6) - - -
N = 260 Rural (pregnant women + girls) in summer 22.2 (7.92) - - -
N = 260 Rural (pregnant women + girls) in winter 10.92 (4.92) - - -
Varanasi
(25.3° N)
N = 200 Adults, M, ≥50 years, age 62.61 (7.64) years 18.96 (10.23) 58 28.5 13.5 Agarwal
2013 [99]
Southern India
Tirupati
(13.4° N)
Total N = 316 - 69.3 - - Harinarayan
2004 [74]
N = 191 Rural adults, age 44 (1.03) years 21 (0.46) 58.6 - -
N = 125 Urban adults, age 45.5 (0.95) years 13.52 (0.59) 85.6 - -
Tirupati
(13.4° N)
Total N = 1285 21% M, 79% F - - - - Harinarayan
2008 [100]
N = 205 Rural adults, age 43 years. 53% M, 47% F M 23.73 (0.8)
F19 (0.89)
M 44
F 70
M 39.5
F 29
M 16.5
F 1
N = 941 Urban adults, age 46 years. 14% M, 86% F
Hospital staff & relatives
M 18.54 (0.8)
F 15.5 (0.3)
M 62
F 75
M 26
F 19
M 12
F 6
N = 70 Rural children, age 13 years. 48% M, 52% F M 17 (1.3)
F 19 (1.59)
M 76.5
F 72.2
M 14.7
F 13.9
M 8.8
F 13.9
N = 69 Urban children, age 13 years. 43% M, 57% F M 15.57(1.2)
F 18.5 (1.66)
M 81.5
F 62.9
M 14.8
F 25.7
M 3.7
F 11.4
Nutrients 2014, 6 744
Table 1. Cont.
Locale Study Subjects
25(OH)D
(ng/mL)
Mean (SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Tirupati
(13.4° N)
N = 164 Rural postmenopausal women, age 54 (8) years. 14.6 (7) 82 - - Harinarayan
2005 [101]
Tirupati
(13.4° N)
N = 150 Semi-urban postmenopausal women, age 60.1 (5.0) years 20.85 (8.63) 50 - - Paul
2008 [102]
Tirupati
(13.4° N)
Total N = 191 Semi-urban women - - - - Harinarayan
2011 [103]
N = 55 Reproductive F age 37.42 (0.72) years 15.70 (1.38) 76.3 16.4 7.3
N = 136 Postmenopausal F, age 53.29 (0.72) years. 17.70 (0.94) 66.9 22.8 10.3
Mysore
(12.3° N)
N = 559 Pregnant women at the 30th week of pregnancy,
age 24 years.
Median 15.12
(9.6–23.4)
66.5 - - Farrant
2009 [104]
Eastern India
Kolkata
(22.5° N)
N = 40 Doctors, 39 M, 1 F, age 52.22 (10.91) years. 13.02 (4.77) 92.5 5 2.5 Baidya
2012 [54]
Western India
Mumbai
(18.9° N)
N = 42 Pregnant women 37th week of pregnancy,
age 20–35 years, middle income group
22.99 (10.93) - - - Bhalala
2007 [105]
N = 42 Cord blood/neonates 19.36 (9.57) - - -
N = 35 Infants, 3 months old, exclusively breastfed 18.19 (9.74) - - -
Mumbai
(18.9° N)
Total N = 214 Urban adults, 81% M, 19% F, age 26–30 years. - 87.5 - - Multani
2010 [58]
N = 174 M, Resident doctors 12.80 (7.94) 85 - -
N = 40 F, Resident doctors 10.94 (4.54) 97.5 - -
Mumbai
(18.9° N)
Total N = 1137 Young urban adults, age 30.38 (3.55) years 17.4 (9.1) - - 7.2 Shivane
2011 [106]
N = 558 M 18.9 (8.9) - - 9.7
N = 579 F 15.8 (9.1) - - 4.8
Nutrients 2014, 6 745
Table 1. Cont.
Locale Study Subjects
25(OH)D
(ng/mL)
Mean (SD)
Vitamin D Status
Reference
% deficient % insufficient % sufficient
Pune
(18.5° N)
N = 110 Slum toddlers, age 2.6 (0.7) years - - - - Ekbote
2010 [107]
N = 50 25 M, 25 F, outdoors (daily sun exposure of 15–60 min or
more)
45.24 (31.88) - - -
N = 60 31 M, 29 F, indoors 3.84 (10.64) - - -
Pune
(18.5° N)
N = 71 Urban children, 36 M, 35 F, age 2.8 (0.6) years, all income
groups
11.94 (12.61) - - - Ekbote
2011 [108]
Pune
(18.5° N)
N = 50 Adolescent girls, low income group, age 14.7 (0.10) years Median 9.36
(5.4–12.76)
- - - Khadilkar
2010 [109]
Pune
(18.5° N)
Women: housewives, working women, retired - - - - Kadam
2010 [110]
N = 80 Premenopausal F, age 45.6 (4.8) years 9.68 (4.56) - - -
N = 92 Postmenopausal F, age 54.0 (7.1) years. 10.76 (6.8) - - -
Pune
(18.5° N)
Total N = 214 Premenarchal school girls, low income group 24.6 (10.4) 34.2 - - Kadam
2011 [111]
N = 134 Age 8–9 years 24.36 (10.32) - - -
N = 80 Age 10–12 years 25.12 (10.64) - - -
All over India
18 cities
spread all
over India
N = 2119 Adults, medical and paramedical personnel, 72% M, 28%
F, age 42.71 (6.8) years.
14.35 (10.62) 79 15 6 Beloyartseva
2012 [59]
No significant differences were found either between men and women, or northern and southern India.
Nutrients 2014, 6 746
Table 2. Vitamin D status and its correlation with bone mineral density (BMD) in ostensibly healthy Indians. For additional details of vitamin
D status, see Table 1. All 25(OH)D values have been shown in ng/mL. To convert from nM to ng/mL, nM values were divided by (2.5).
Vitamin D deficiency is defined as 25(OH)D < 20 ng/mL. DEXA is Dual Energy X-ray Absorptiometry. Age of the subjects is in mean
age (SD) years, unless otherwise indicated.
Locale Study Subjects BMD Measured by DEXA as Mean (SD) gm/cm2 Reference
Vitamin D status correlated positively with BMD:
Varanasi
(25.3° N)
N = 200 Adults, M, ≥50 years,
age 62.61 (7.64) years,
58% subjects were
vitamin D deficient.
At right femoral neck, 42% subjects had osteopenia and 8.5% had osteoporosis. At trochanter of right
femur, 37% had osteopenia and 7.5% had osteoporosis. At right hip 41% subjects had osteopenia and
7% had osteoporosis.
Mean T scores of the subjects (right femur): Neck = −0.92 (1.22), Trochanter = −0.59 (1.41) and
Total hip = −0.55 (1.37). T score = (subject’s BMD-young adult mean BMD)/(1 SD of adult
mean BMD) or normal BMD.
Agarwal
2013 [99]
25(OH) D level > 22 ng/mL normal mean BMD at femur neck, trochanter, and total hip
25(OH)D < 10 ng/mL osteoporosis at femur neck and trochanter
25(OH) > 15 ng/mL osteopenia at femur neck and total hip
25(OH) > 16 ng/mL osteopenia at trochanter
Vitamin D status correlated positively with BMD, but not at all the sites studied:
Lucknow,
26.8° N
N = 92 Urban adults, M 25, F 67,
78.3% subjects were vitamin
D deficient.
BMD of the spine, femur (neck, trochanter, inter-trochanter and Wards’ triangle regions) and forearm
(distal, mid and ultradistal regions) was lower compared with Caucasians. 25(OH)D levels correlated
with BMD at the femoral neck (r = 0.46, p = 0.037) and Ward’s triangle only. (r = 0.50, p = 0.020)
Arya
2004 [96]
Delhi
(28.3° N)
Total
N = 105
Urban adults, 51 M and 54 F,
age 43.3 (9.7) years. 94.3%
subjects were vitamin D
deficient.
25(OH)D levels correlated with BMD at hip, but not at lumbar spine or forearm. Vupputuri
2006 [83]
N = 41 25(OH)D > 9.0 ng/mL BMD at the hip = 0.893 (0.114) was higher than of those at 25(OH)D ≤ 9.0 ng/mL (p = 0.001)
N = 64 25(OH)D ≤ 9.0 ng/mL BMD at the hip = 0.839 (0.112)
Nutrients 2014, 6 747
Table 2. Cont.
Locale Study Subjects BMD Measured by DEXA as Mean (SD) gm/cm2 Reference
Vitamin D status did not correlate with BMD:
Punjab
(31.1° N)
&
Haryana
(29° N)
N = 42 Adults, age 20–30 years,
20 M, 22 F, paramilitary
soldiers. Adequate diet, sun
exposure and physical
exercise.
Individual BMD data with peak bone mass in white Caucasians revealed that among Indian men,
osteopenia was noted in 50% at the lumbar spine, 35% at the hip and 50% at the forearm. 10% of men
had osteoporosis of the lumbar spine. Among women, osteopenia was noted in 32% at the lumbar spine,
14% at the hip and 21% at the forearm. In men, mean BMD was significantly lower when compared to
Caucasians at the lumbar spine only. Indian men = 0.947 (0.086) vs. Caucasian controls = 1.091 (0.110),
p = 0.0004.
Tandon
2003 [56]
Delhi
(28.3° N)
N = 664 Urban adolescent F, school
girls, age 12.8 (2.7) years.
Lower income level N = 369
and Higher income level
N = 295.
The upper income level girls were significantly taller and weighed more. They also had higher BMD in
distal forearm and calcanium.BMD forearm (g/cm2): lower income level 0.337 (0.070) and upper
income level 0.366 (0.075). BMD calcaneum (g/cm2): lower income level 0.407 (0.073) and upper
income level 0.464 (0.093).
Marwaha
2007 [86]
Delhi
(28.3° N)
N = 5137 Urban adolescents and
school children, age 10–18
years. 92.6% children from
lower income level (N =
3089) and 84.9% children
from upper income level (N
= 2048) were vitamin D
deficient.
BMD was evaluated in 555 children. Children in the lower income level group had significantly lower
BMD values at the forearm than did those in the upper income level group. Only BMD of age group
(10–12) years is mentioned in this review. Boys, lower income level = 0.313 (0.044), (N = 27); boys,
upper income level = 0.387 (0.146), (N = 24); girls, lower income level = 0.297 (0.048), (N = 70) and
girls upper income level = 0.345 (0.054), (N = 39).
Marwaha
2005 [85]
Delhi
(28.3° N)
N = 1600 Urban adults (M 49.5%,
F 50.5%), age > 50 years.
91.2% subjects were
vitamin D deficient.
35.1% subjects (M 24.6% and F 42.5%) had osteoporosis and
49.5% (M 54.3%, F 44.9%) had osteopenia.
Marwaha
2011 [112]
Delhi
(28.3° N)
Total
N = 186
Young urban college women,
age 18.6 (1.3) years. 96 were
college girls (control group)
and 90 were sportswomen.
With the exception of femur neck, higher BMD was noted in sportswomen by 5, 13.1, 10.3,
and 9.2% in total body, total hip, forearm and lumbar spine and 33% radius, respectively.
Marwaha
2011 [57]
Nutrients 2014, 6 748
Table 2. Cont.
Locale Study Subjects BMD Measured by DEXA as Mean (SD) gm/cm2 Reference
Tirupati
(13.4° N)
Total
N = 149
Semi-urban women. 82.5%
out of 40 premenopausal
and 67.8% out of 109
postmenopausal women were
vitamin D deficient.
Comparatively, postmenopausal women had lower BMD in forearm, hip and lumbar spine. Osteoporosis
was seen at hip (15% and 28%), forearm (0% and 11%), lumbar spine
antero-posterior (6% and 22%) and lumbar spine lateral (0% and 23%) among premenopausal and
postmenopausal, respectively.
Harinarayan
2011 [103]
Tirupati
(13.4° N)
N = 150 Semi-urban postmenopausal
women, age 60.1 (5) years.
50% women were vitamin D
deficient.
Osteoporosis was noted at lumbar spine in 48% women, at femoral neck in 16.7% women
BMD: lumbar spine (LS) = 0.798 ± 0.142, femoral neck = 0.675 ± 0.108
Paul
2008 [102]
N = 74 25(OH)D (>20 ng/mL) BMD: lumbar spine = 0.816 (no SD), femoral neck = 0.694 (no SD)
N = 59 25(OH)D (10–20 ng/mL) BMD: lumbar spine = 0.780 (no SD), femoral neck = 0.657 (no SD)
N = 14 25(OH)D (5–10 ng/mL) BMD: lumbar spine = 0.733 (0.151), femoral neck = 0.649 (0.102)
Mumbai
(18.9° N)
N = 214 Resident doctors M 81.3%,
F 18.7%, age 26–30 years.
87.5% subjects were vitamin
D deficient.
59.7% men and 67.5% women had osteopenia. 18.39% men and 12.5% women had osteoporosis. Multani
2010 [58]
Pune
(18.5° N)
N = 50 Adolescent girls, low income
group, age 14.7 (0.10) years.
Pune girls had lower bone area and bone mineral content, (i.e., shorter and lighter girls) compared to UK
South Asian and UK Caucasian girls.
Khadilkar
2010 [109]
Pune
(18.5° N)
N = 172 Semi-urban women.
Premenopausal N = 80,
and postmenopausal N = 92.
Comparatively, postmenopausal women had lower BMD in femoral neck, total hip and lumbar spine.
Prevalence of osteoporosis at lumbar spine was observed in 25.8% of postmenopausal women and 7.6%
of pre-menopausal women. Prevalence of osteopenia was observed in 48.4% of post-menopausal and
44.3% of premenopausal women.
Kadam
2010 [110]
Nutrients 2014, 6 749
12. Genetic and Epigenetic Factors Affecting Vitamin D Status
Genetic factors leading to vitamin D deficiency in Indians, due to their effect on expression of
genes that modulate vitamin D metabolism may not be ruled out. Genetic factors such as
polymorphisms in 7 dehydroxylase reductase, DBP, 1 alpha hydroxylase, VDR, 25 hydroxylase,
24 hydroxylase have been studied. However, a clear association between these polymorphisms and
vitamin D status is yet to be established [113–115]. Epigenetic factors too may be important in this
context. Epigenetic factors pertain to heritable changes in the gene expression, while the DNA sequence
is unchanged. These are several possibilities—post-translational modifications of histones—methylation,
acetylation and phosphorylation, and also aberrant expression of microRNAs. Interaction between
genetic and environmental factors, modulated by epigenetic factors has been reported. 1α hydroxylase
and 24 hydroxylase have been shown to be epigenetically controlled. Information regarding
association between genetic and/or epigenetic factors and vitamin D status is inconclusive and
warrants further study [116].
13. Population Based Approaches to Improve Vitamin D Status in India: Supplementation,
Food Fortification and Educational Programs
There is protracted debate ongoing on issues pertaining optimal levels of intake of vitamin D,
preferred form of vitamin D for human use and extraskeletal benefits of vitamin D. However, one
thing is clear—Indians need more vitamin D. Vitamin D can be obtained from three sources: sun
exposure (limitations of which has been discussed earlier), vitamin D supplements and vitamin D
fortified foods. There is urgent need to prioritize development of national level programs to make
available, quality-regulated and affordable vitamin D supplements and vitamin D fortified foods to the
Indian populace. Very importantly, the government needs to implement measures to educate the Indian
populace about the current status of vitamin D in India and also the modes to attain vitamin D sufficiency.
14. Vitamin D Supplements Available in India
Information was collected from 10 pharmacists, from an upper middleclass locality of Delhi.
Supplements commonly available are—D3 (cholecalciferol), 1,25(OH)2D3 and 1 alpha hydroxy
vitamin D3 (alfacalcidol). Some formulations have calcium too. Multivitamin formulations are also
available and contain about 400 IU of D3. None of the pharmacists had heard of D2 supplements. D3
supplement of 60,000 IU is the highest selling one and is available in powder form in sachets or as
oil-based capsules. Recommended dose on the label is once per week. The sachets indicate that half a
sachet per week may also be taken. According to some pharmacists, many clinicians recommended
1 sachet daily for 10 days, followed by 1 sachet/week for 5–6 weeks to 1 sachet/week forever. The
other vitamin D supplements mentioned here are present in lower doses (0.25 µg or 500 IU) and daily
intake (1–4 times/day) may be recommended by the clinicians. Calcium supplementation is generally
recommended with vitamin D intake.
The cost of a single dose of 60,000 IU of vitamin D3 is about INR 30. Intake of 60,000 IU of
vitamin D3 per week may be advisable for a short duration, for patients with severe vitamin D
deficiency, but a regular weekly dose may be lead to toxicity problems. A lower dose of vitamin D not
Nutrients 2014, 6 750
exceeding the limit of 4000 IU per day would be advisable for otherwise healthy individuals. This will
also reduce the cost of the supplement and become more affordable to the common people of India.
Purchase of most drugs in India does not require a prescription. Additionally, more often than not
pharmacists (commonly called “Chemists” in India) often claim to have all the information needed to
prescribe medicines. Other than for acute health problems most socioeconomically backward people
go directly to the pharmacist, more often than not, in order to save consultation fee of a licensed
clinician. Pharmacists boldly recommended and sell medications to patients and often recommend a
longer duration of medications to boost their sales. It is not uncommon for active vitamin D analogs
such as calcitriol or 1-alpha D to be wrongfully prescribed by physicians and pharmacists in lieu of
nutritional vitamin D supplements, thus putting unsuspecting patients at grave risk of hypercalcemia
and if taken long-term possibly vascular calcification and kidney stones. In this context, it is very
important that the along with the clinicians, pharmacists also be educated about toxicity issued related
with vitamin D.
15. Vitamin D Supplementation Studies in Ostensibly Healthy Indians
Vitamin D supplementation studies in ostensibly healthy were compiled (Table 3). Supplementation
resulted in significant improvement in vitamin D status, but a large proportion of the population had
still did not attain sufficiency. The following study is noteworthy. In India, physicians often prescribe
D3 60,000 IU per week for 8 weeks for vitamin D deficiency. Twenty two healthy Indians with
subnormal serum 25(OH)D levels were supplemented with oral D3 60,000 IU/week and calcium
1 gm/day for 8 weeks. At 8 weeks the mean 25(OH)D levels increased from 10.16 (3.96) ng/mL to
22.4 (6.8) ng/mL and serum PTH normalized in all. Twenty two of the 23 subjects had 25(OH)D levels
> 20 ng/mL. At the end of 12 months however, all the subjects were vitamin D deficient, once again.
To sustain optimal 25(OH)D levels vitamin D supplementation would need to be ongoing after the
initial loading [117].
Some supplementation studies, in ostensibly healthy adolescents and adult subjects, resulted in
improved bone health. These are tabulated separately (Table 4).
More frequent and lower doses, not exceeding 4000 IU/day of vitamin D supplementation may be
better for maintenance of serum 25(OH)D level. Most of the studies from India mention vitamin D
status in terms serum 25(OH)D levels as below or above 20 ng/mL (or 50 nmol/L). However, one must
not lose sight of the fact that the aim of all interventions in terms of vitamin D status should be
≥ 30 ng/mL or above to derive both skeletal and extraskeletal benefits of this D-lightful nutrient [118],
but with a precautionary stance to not exceed 100 ng/mL.
16. Vitamin D Fortification in USA and Canada
Despite predominantly non-vegetarian dietary pattern, approximately 60% of the intake of vitamin
D from food comes from fortified foods in USA [119] and Canada [120]. In USA, vitamin D
fortification of foods is voluntary, but it is strictly regulated pertaining categories of foods, functional
use and level of use, thus limiting over-fortification. Vitamin D fortified milk has been available in
USA since the 1930s. Vitamin D is added to most milk sold in the United States, although it is not
added to all milk products like cheese and ice cream. Some manufacturers also add it to cereal, soy
Nutrients 2014, 6 751
milk, rice milk, and orange juice, usually along with calcium. In USA either form, D2 or D3, may be
used for fortification, but commonly D3 is used. In Canada, the law mandates fortification of milk,
milk alternatives and margarine. Similar to USA, for other permitted foods, vitamin D fortification D
is voluntary, but fortification level is limited [121].
17. Need for Vitamin D Fortified Food Products in India
Vitamin D sufficiency via sun exposure is untenable for most Indians, as discussed earlier. Vitamin D
(relatively) rich dietary sources are unaffordable and mostly limited, especially for vegetarians. Most
Indians are vegetarians. Vitamin D supplements are unaffordable and not feasible as a population
based approach. Fortification of widely consumed staple foods with vitamin D is the only viable
solution towards attaining vitamin D deficiency in India. Unlike supplementation strategies,
fortification of food with vitamin D poses a negligible risk of toxicity.
18. Feasibility of Fortification of Foods with Vitamin D in India
Food fortification is a much more economically viable approach compared to vitamin D
supplementation. While the cost of fortified food items will be more than unfortified foods, it will be
lower than supplementation.
1. Adaptability to fortified food by the consumers is much better than to supplementation. Food
fortification requires relatively less change in food habits and preferences, leading to better
efficacy of fortification programs, lowered cost to the consumer and a larger profit to the food
manufacturers. Clearly a win-win partnership for all.
2. Food fortification may be a better choice compared to supplementation strategies, especially
when targeting those who need it the most—women (including non-pregnant, pregnant and
lactating), infants, children (especially girls, who are sidelined, more often than not, in India) and
senior citizens.
3. Use of staple foods such as chapati flour, rice, etc., for fortification may have certain advantages
over other fortification matrices. Indian government offers cereals, chapati flour, rice, lentils,
etc., at subsidized rates to the socioeconomically underprivileged citizens. Additionally, cost of
these products is generally tightly regulated by the government. Thus, no large fluctuations are
observed in the cost of these food items in the open market also. This will ensure continued
consumption of these foods fortified with vitamin D, by those who avail of them and result in
better and sustained economical feasibility of the fortification programs in the long run.
4. Two vitamin D fortification studies in ostensibly healthy subjects were reported in the literature
(see Table 5). Underprivileged toddlers, fed with fortified laddoos, resulted in significant
increase in serum calcium and vitamin D levels and also in total body less head (TBLH) bone
mineral content (BMC) [122]. The cost of fortified laddoo was INR 20 per laddoo, which may
be prohibitive in itself. More cost effective food items could be fortified with vitamin D.
In another study, 776 subjects (boys and girls) were given fortified milk, which resulted in
significant improvement in their vitamin D status [123]. These results support the strategy of
fortification of foods in India for redressing malnutrition problems in India.
Nutrients 2014, 6 752
Table 3. Vitamin D supplementation studies in ostensibly healthy Indians. All 25(OH)D values have been shown in ng/mL. To convert from
nM to ng/mL, nM values were divided by (2.5). Vitamin D deficiency is defined as 25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and
sufficiency as ≥30 ng/mL. ‡ Information available from the abstract of the article. D3 is cholecalciferol. Calcium amount mentioned is of
elemental calcium. Age of the subjects is in mean age (SD) years, unless otherwise indicated.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD)
25(OH)D
Mean (SD)
25(OH)D
Mean (SD) % Deficient
Barabanki, 32 km
from Lucknow
(27° N)
Total N = 84, Rural pregnant women, low income
group, all received 1 gm calcium/day
Median 12.92
(9.12–20.04) - - -
Sahu
2009 [124]
N = 14, Control group Median 10.32
(7.56–12.28) - Median 9.52
(6.88–13.04) -
N = 35, Group A, 60,000 IU D3 in
the 5th gestational month
Median 13.26
(9.04–19.08) - Median 12.36
(9.92–19.24) -
N = 35, Group B, 120,000 IU D3 in the 5th and 7th
gestational month
Median 16.04
(10.76–23.36) - Median 21.36
(16.46–35.02) -
Lucknow
(26.8° N)
Pregnant women and neonates. Women age
26.7 (4.0) years, low and middle income group.
All were prescribed 1 gm calcium/day
- - - -
Kalra
2012 [125]
N = 48, Control group - Median 15.68
(8.48–29.36) -
N = 33, Neonates of control group - - Median 7.4
(4.04–11.88) -
N = 48, Group A, 60,000 IU D3 in 2nd trimester Median 12.68
(5.8–18.28) - Median 10.48
(7.08–23.08) -
N = 31, Neonates of group A - - Median 11.28
(6.04–17.2) -
N = 48, Group B, 120,000 IU D3 in 2nd and
3rd trimester
Median 12.8
(5.8–18.28) - Median 23.48
(15.36–35.76) 38
N = 28, Neonates of group B - - Median 9.64
(4.88–17.56) -
Nutrients 2014, 6 753
Table 3. Cont.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD) % Deficient 25(OH)D
Mean (SD) % Deficient
Delhi (28.3° N) Low birth weight term infants,
from all income groups. - - - -
Kumar
2011 [126]
N = 237, Control group - - 14.4 (10.2) 73.4
N = 216, Study group, started at 7 days after birth,
1400 IU D3 (dissolved in breast milk) per week, given
for 6 months
- - 22.0 (9.0) 43.5
Delhi (28.3° N) Low birth weight term infants, from all
income groups. - - - -
Trilok-Kumar
2012 [127]
N = 187, Control group - - 15.1 (10.5) 72.19
N = 164, Study group, started at 7 days after birth,
1400 IU D3 (dissolved in breast milk) per week, given
for 6 months
- - 22.8 (8.9) 37.8
Delhi (28.3° N) Urban adolescent schoolgirls - 93.7 - - Marwaha
2010 [128]
N = 60, low income group, age 12 (2.8) years,
60,000 IU D3/2 months, for 1 year 12.48 (0.67) 98 21.2 (1.22) 38
N = 64, low income group, age 11.4 (3) years,
60,000 IU D3/month, for 1 year 13.17 (0.54) 97 23.73 (1.05) 28
N = 81, high income group, age 11.6 (2.7) years, 60,000
IU D3/2 months, for 1 year 11.65 (0.61) 94 15.3 (0.85) 80
N = 85, high income group, age 11.7 (2.8) years, 60,000
IU D3/month, for 1 year 12.32 (0.55) 88 19.97 (0.80) 57
Nutrients 2014, 6 754
Table 3. Cont.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD) % Deficient 25(OH)D
Mean (SD) % Deficient
Delhi (28.3° N) Total N = 482, Adolescents, after 60,000 IU D3/week, as
per each group. All subjects in all groups received 600
IU D3/day for 12 weeks
- - - -
‡ Garg
2013 [129]
Group A, 60,000IU D3/week for 4 weeks - - - -
Group B, 60,000IU D3/week for 6 weeks - - 27.0 (6.6) -
Group C, 60,000IU D3/week for 8 weeks - - 28.0 (8.7) -
Delhi (28.3° N) N = 172, Urban young women, nursing students, age
21.7 (4.4) years 9.3 (3.37) - - - Goswami
2012 [130]
N = 43, Group A, double placebo 8.6 (3.26) - 7.7 (3.64) -
N = 43, Group B, 1 gm calcium/day 9.9 (3.24) - 8.1 (2.92) -
N = 43, Group C, 60,000 IU D3/week for
8 weeks, followed by 60,000 IU D3 twice/month for
4 months
9.2 (3.40) - 29.9 (8.35) -
N = 43, Group D, 1 gm calcium/day. Also
60,000 IU D3/week for 8 weeks, followed by
60,000 IU D3 twice/month for 4 months
9.5 (3.47) - 27.0 (9.54) -
Nutrients 2014, 6 755
Table 3. Cont.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD) % Deficient 25(OH)D
Mean (SD) % Deficient
Delhi (28.3° N) Urban adults, medical students,
age 31.5 (5) years - 100 - -
Gupta
2010 [131]
N = 20, Control group, 11 M, 9 F, double placebo 8.44 (3.76) - 11.88 (6.0) -
N = 20, Study group, 13 M, 7 F, received
1 gm calcium/day for months and 60,000 IU D3/week
for 8 weeks and then once per month for 4 months
10.16 (3.96) - 22.4 (6.8) -
Delhi (28.3° N) N = 23, Urban adults, age F 33.9 (13.1) years,
age M 34 (17) years. 60,000 IU D3/week for 8 weeks.
1 gm calcium was given daily for 8 weeks. Subjects
measured at 8 weeks.
5.4 (1.2) 100 32.96 (8.29) 4.3
Goswami
2008 [117]
The subjects were measured again at 12 months. 9.88 (4.6) 100
Delhi (28.3° N) Urban postmenopausal women, age 54.8 (6.7) years.
All subjects in all groups received calcium 1 gm/day for
3 months.
- 83.7% - -
Agarwal
2013 [132]
N = 21, Control group A 12.99 (6.74) - 8.0 (5.28) 95.3
N = 25, Group B, 500 IU/day D3 for 3 months 12.92 (8.20) - 13.34 (9.52) 84.0
N = 18, Group C, 1000 IU/day D3 for 3 months 14.38 (11.07) - 23.71 (11.71) 33.33
Nutrients 2014, 6 756
Table 4. Vitamin D supplementation studies reporting improved bone health post-intervention, in ostensibly healthy Indians (adolescents and
adults). All 25(OH)D values have been shown in ng/mL. To convert from nM to ng/mL, nM values were divided by (2.5). Vitamin D
deficiency is defined as 25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and sufficiency as ≥30 ng/mL. D3 is cholecalciferol and D2 is
ergocalciferol. Calcium amount mentioned is of elemental calcium. Age of the subjects is in mean age (SD) years, unless otherwise indicated.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD)
25(OH)D
Mean (SD) Bone Health Status
Pune
(18.5°N)
Urban, postmenarchal schoolgirls, age 14–15 years,
low income group. All the girls were shorter and
lighter compared to Indian norms.
- - -
Khadilkar
2010 [133]
N = 24, Control group: placebo and 250 mg
calcium/day for 1 year.
Median 8.32
(5.08–12.16)
Median 11.24
(6.68–13.6)
Mean increase in 25(OH)D was 19%, mean decrease in
PTH was 9%. BMD showed no change.
N = 25, Study group: 300,000 IU D2 once every
3 months and 250 mg calcium/day for 1 year.
Study group was divided into sub groups: (1) girls who
had menarche within 2 years and (2) girls who had
menarche for over 2 years, at the start of the study.
Median 9.8
(5.08–13.28)
Median 30.08
(25.68–34.2)
Overall, 25(OH)D increased by 68% and PTH decreased
by 27%. No significant changes were observed in
subgroup (2). However, in subgroup (1) total bone
mineral content (TB BMC) and total bone area (TB BA)
increased and lumbar spine BMC was higher.
Pune
(18.5°N)
Urban, premenarchal schoolgirls, age 9.8 (1) years. All
the girls were shorter and lighter compared to Indian
norms. All subjects received 300,000 IU D3 once every
3 months, for 1 year.
65.7%
vitamin D
deficient
-
TB BMC, TB BA, TB BMD, TB LBM (lean body mass)
and TB fat% increased significantly in all three groups
over baseline. There was no significant difference
between the results of study groups (Ca) and (Ca + MZ).
Khadilkar
2012 [134]
N = 69, Control group, two placebos. 23.08 (10.68) - Total body BMC increased by 17.6%,
N = 70, Study group (Ca), 500 mg calcium
6 days/week, for 1 year. 24.76 (10.36) - Total body BMC increased by 22.3%.
N = 71, Study group (Ca + MZ), 500 mg calcium and
multivitamin + zinc (Becosule-Z®) 1 tablet
6 days/week, for 1 year.
26.36 (10.92) - Total body BMC increased by 20.8%.
Nutrients 2014, 6 757
Table 5. Vitamin D food fortification studies in ostensibly healthy Indians. All 25(OH)D values have been shown in ng/mL. To convert from
nM to ng/mL, nM values were divided by (2.5). Vitamin D deficiency is defined as 25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and
sufficiency as ≥30 ng/mL. Age of the subjects is in mean age (SD) years.
Locale Study Subjects and Fortification Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD) % Deficient % Sufficient 25(OH)D
Mean (SD) % Deficient % Sufficient
Delhi
(28.3° N)
Northern
India
Total N = 713, Urban school children and
adolescents, age 11.74 (1.05) years, 300 M, 413 F.
All were given unfortified milk for 12 weeks and
then divided into 3 groups.
11.69 (5.36) 92.3 0.7 20.44 (9.88) - -
Khadgawat
2013 [123]
N = 237, Control group: Unfortified milk
200 mL/day for 12 weeks, 102 M, 135 F 11.74 (5.23) 93.6 - 10.83 (5.24) 94.0
N = 243, Study Group A, fortified milk, 600 IU
D3/200 mL/day for 12 weeks, 97 M, 146 F 11.42 (5.24) 95.0 1.23 22.87 (6.75) 30.0 12.34
N = 233, Study Group B, fortified milk, 1000IU
D3/200 mL/day for 12 weeks, 101 M, 132 F 11.94 (5.62) 87.9 0.42 27.67 (8.47) 18.9 36.05
Pune
(18.5° N)
Western
India
Total N = 58, Urban children, low income group, age 2.7 (0.52) years. While both groups received D3 fortified laddoos. Control group received
only 156 mg of calcium, as opposed to 405 mg of calcium to the study group.
Ekbote
2011 [122]
N = 28, Control Group, 1 fortified laddoo *, 156 mg
of calcium, 5 times/week for a year. Also given, 1
laddoo with 30,000 IU D3/month for 1 year.
7.56 (10.8) 84 - 23.24(4.76) - -
N = 30, Study Group, 1 fortified laddoo, 405 mg of
calcium, 5 times/week for a year. Also given,
1 laddoo with 30,000 IU D3/month for 1 year.
10.0 (10.84) 83 - 25.75 (9.56) - -
* A laddoo is an Indian cereal-legume snack, spherical, about 4 cm in diameter and weight 50 g. The ingredients for unfortified laddoos, were ragi (Eleusine coracana)
and whole dried Bengal gram (Cicer arietinum) 7.5 g each, sesame seeds (Sesamum indicum) and poppy seeds (Papaner somniferum) 5 g each, 5 g of clarified butter
(Ghee) and 15 gm of refined palm sugar.
Nutrients 2014, 6 758
19. Food Items Which Could Be Fortified with Vitamin D in India
1. Milk: The whole array of different grades of milk available could be fortified—whole milk,
toned, double toned and skim milk.
2. Milk curd and yogurt.
3. Infant formulas.
4. Butter, ghee (clarified butter) and oils, to use as spreads or to spike already cooked food.
5. Soy milk, soy curd (tofu), orange juice and mango juice may be fortified to cater to the needs of
the lactose intolerant individuals and those who are allergic to milk proteins. Processed cheese
also has very low lactose content and is rich in calcium and may be fortified for the benefit of the
lactose intolerant. Due to high prevalence of dyslipidemia, metabolic syndrome and
cardiovascular diseases in India, these fortified items will also offer healthier choices to the
general population.
6. Widely consumed and affordable staple food items such as chapati flour, maida (all purpose
wheat flour, used to make bread and other bakery products), rice and rice flour may be suitable
vehicles for fortification strategies in the Indian scenario.
20. Foods Fortified with Vitamin D Available in the Indian Market
Vitamin D fortified milk from Amul® (an Indian dairy cooperative, located in Anand, Gujarat,
India) is the only fortified milk product found in the general market. It is 4.5% fat, homogenized milk
fortified with calcium 150 mg, vitamin A 75 μg and vitamin D 0.5 μg (20 IU), etc., per 100 mL. The
expiry date of this milk is 120 days if the carton is unopened. Incidentally, with a 10% or more loss per
month at 4 °C, there is not much vitamin D left by 120 days. It may be hoped that storage temperatures
are always adhered to. But in India this is a remote possibility due to economical and technical
limitations. In a brief survey, most retailers reported that the Amul® milk cartons supplied to them
were generally one month past expiry date already at the time of delivery and that the demand for this
product was very low. Cost per liter is INR 48 (as on 12 January 2013) as opposed to the cost of
unfortified milk (INR 30).
Kellogg’s breakfast cereals fortified with vitamin D along with other micronutrients are also
available. However, the exorbitant prices of these products are essentially prohibitive for consumption
by the common people of India.
21. Estimated Burden of Bone Diseases on Indian Healthcare System
There is no “national body” instituted by the government of India, to study and document the
prevalence of bone diseases in India. The following figures pertaining bone health were perforce taken
from research articles. In India, bone diseases such as rickets, osteomalacia and osteoporosis have
been [67,135–137] and still are widely prevalent and formidable problems of our nation. As per 2001
Census Report about 163 million people were above the age of 50 years. This figure will be much
bigger from the 2011 Census Report and may exceed 200 million. About 15%–20% of persons above
the age of 50 years would be developing osteoporosis [136]. As presented in this review, BMD studies
of ostensibly healthy Indians show that a significant proportion of younger Indians too are suffering
Nutrients 2014, 6 759
from this silent disease. As the early signs of osteoporosis are diagnosed with accuracy, BMD data will
add to these already astounding figures. Some staggering figures and estimates pertaining rickets,
osteomalacia and osteoporosis are mentioned in some reviews [136,137].
Vitamin D status in India is grim not only in the lower and but also in the upper socioeconomic
classes. For the sake of simplicity and argument, let us consider only the skeletal benefits of vitamin D.
Vitamin D sufficiency in women of reproductive age would at the very least result in —improved
women’s health, improved outcome of childbirth and birth of infants who may have a better chance of
a healthy existence from the beginning of their lives. Vitamin D sufficiency in growing children would
mean allowing for their full growth potential—physically, mentally and psychologically. In children,
rickets translates into life-long deformity, osteomalacia—a painful and subpar existence. Osteoporosis
is a silent disease tethered to a constant threat of fractures to the unbeknownst afflicted. In elderly
patients, especially hip fractures result in the end of an independent existence. Notably, most people in
India do not have health insurance. Hospitalization of patients with hip fractures is much longer than
for those being treated for cancers. For those who cannot afford hospitalization for treatment, it is a
long, agonizing and often an unending wait for resurrection. This fact indicates the heavy load on the
healthcare system and the economy of the nation due to bone diseases alone.
22. Government’s Intervention Required
Vitamin D sufficiency status may not be treated as a “feel good status” for the affluent who can
afford medical expenses and expensive vitamin D supplements. Vitamin D is prevalent across all
socioeconomic strata. It is imperative that policymakers understand the gravity of the situation
pertaining vitamin D status and as a consequence—the untold burden on the healthcare system in
India. The information presented in this article ought to persuade policymakers to take substantive
measures towards attaining vitamin D sufficiency. Actions needed to be taken by the government of
India are as follows:
1 Revision of RDA (Recommended Daily Allowance) values for vitamin D and calcium intake, by
ICMR (Indian Council of Medical Research) is imperative.
2 Educational Programs: Vitamin D deficiency is the world’s most under-diagnosed and
under-treated disease. There is great need for awareness of its implications among physicians
and the general public at large. Adequate investment of money, time and effort is required to
develop, launch and sustain public awareness programs.
2.1 The curricula of medical colleges need to be updated pertaining vitamin D status of the
Indian populace. Inclusion of pertinent and updated information pertaining vitamin D, and
its skeletal and extraskeletal benefits is required.
2.2 Making bone and mineral health a priority: All healthcare facilities, including all primary
health care facilities should institute awareness programs to educate the physicians and the
local residents about the need for vitamin D sufficiency.
2.3 Active participation of social organizations is required. Social workers and school teachers
need to be duly informed and educated, so they can spread the word about necessity for
vitamin D sufficiency and the ways to achieve it.
Nutrients 2014, 6 760
2.4 Aggressive government sponsored mass media programs, with the aid of tele-media and
print media are required to educate the masses about the grim vitamin D deficiency status
in India. The masses should be educated on the benefits of a combination of sun exposure,
vitamin D fortified food items, supplements and regular physical exercise.
2.5 A need for sufficient calcium intake along with vitamin D must be stressed at all times.
3 Vitamin D supplements: Affordable, good quality and readily available vitamin D supplements
for the masses are needed. Vitamin D supplements should be made available at all primary care
health centers to pregnant women and lactating women.
4 Fortification of foods with vitamin D: First and foremost possibility thinking is required. Indian
government has successfully launched food-fortification programs before. The most visible
result to the public eye being—iodized salt. Fortification of food with vitamin D is doable.
Political and administration’s will and support should be available from the development stage
of the fortification program and equally importantly sustained.
4.1 Involvement of the food industry by encouraging private enterprises operating at the
national and local level is required. Support in terms of technical expertise pertaining
production of fortified food items, availability of standardized vitamin D formulation(s)
and information on the marketing potential of the fortified items should be made available.
4.2 Effective legislation to ensure good quality and regulated vitamin D fortified foods at
minimal cost to the end consumer is required. That said, both the administration and
legislature should very importantly be facilitative and not be restrictive or punitive to those
who are striving towards attaining better bone and mineral health of the masses.
5 School going children could benefit from the following:
5.1 Educators should emphatically teach the need for vitamin D sufficiency and benefits
of a healthy lifestyle. Inclusion of the benefits of vitamin D in the ken of the kids may
perchance spread this information to their (unaware) kin too.
5.2 Mandatory distribution of vitamin D fortified foods at midday meals in schools.
5.3 Daily physical exercise should be made compulsory in schools.
6 Affordable and widely accessible testing facilities for vitamin D levels should be made available
to individuals who are at high risk of clinical vitamin D deficiency.
7 Reliable and sensitive technology such as DEXA should be made available at minimal cost for
screening bone mineral density in individuals at high risk, with easy accessibility, throughout India.
8 Last, but not the least, government should extend support to research groups, so that the impact
of supplementation programs and fortification strategies in actual practice may be studied and
monitored and more efficacious ways developed. Continued research and epidemiological
studies are required, to clearly state the enormity of the vitamin D deficiency status and its
implications on general health of Indians, countrywide. Vitamin D status from western, eastern,
northeastern India and the Himalayan regions and are still either few or lacking. Also, the very
poor and the marginalized citizens have not been included in such studies.
Nutrients 2014, 6 761
23. A Lagniappe for the Readers: Other Countries of the Indian Subcontinent Present a Similar
Scenario Pertaining Vitamin D Status
Other countries of the Indian subcontinent: Pakistan, Bangladesh, Nepal, Sri Lanka, Myanmar and
Bhutan share the same geographic locale and socioeconomic culture with India. Data were compiled
from these countries too. Vitamin D deficiency is highly prevalent in these countries (Table 6). One
report was available from Pakistan pertaining bone health of ostensibly healthy subjects. In a cohort of
140 rural postmenopausal women from Khazana (34.7° N) and Nahaqi (34.2° N), age 52(SD 2) years,
42% had osteopenia and 28% had osteoporosis. 25(OH)D levels correlated with BMD [138].
No reports were available from other countries of the Indian subcontinent pertaining vitamin D status
and its correlation with BMD. One supplementation study from Bangladesh showed significant
improvement in the vitamin D status (Table 7). One supplementation study from Pakistan showed
significant improvement in the vitamin D status and improved bone health (Table 8). No food
fortification studies were available from any of these countries. From the available data, it is clear that
vitamin D scenario in these countries is similar to that in India. The data from other countries of the
Indian subcontinent also show that though India may be economically more advanced that some of its
neighbors, the vitamin D scenario is similar all over the subcontinent.
24. Conclusions
Widespread prevalence of vitamin D deficiency in India is undeniable. Factually, sun exposure is an
untenable solution, for most individuals in India, towards attaining vitamin D sufficiency. Low
calcium intake in conjunction with vitamin D deficiency makes matters worse. The need for
improvement in vitamin status of the Indian population is both important and urgent. The Indian
government needs to take substantive measures in this direction. Revision of RDA for calcium and
vitamin D is required. Better facilities and technologies should be made available countrywide to
enable timely diagnosis of clinical manifestations of vitamin D deficiency in individuals who need
attention by the clinicians. Population-based programs at the national level must be developed to
increase awareness of the problem at hand, to provide affordable vitamin D supplements and also to
provide vitamin D fortified foods to the Indian populace at large. Research in this field needs
continued support to provide a comprehensive picture of the ongoing vitamin D problem and also to
study and monitor the effect(s) of a partnership between the government, healthcare system, industry
and consumers, aimed at improving the vitamin D status in India.
Nutrients 2014, 6 762
Table 6. Vitamin D status of ostensibly healthy subjects from other countries of the Indian subcontinent. All 25(OH)D values have been
shown in ng/mL. To convert from nM to ng/mL, nM values were divided by (2.5). Vitamin D deficiency is defined as 25(OH)D < 20 ng/mL,
insufficiency as 20–29 ng/mL and sufficiency as ≥30 ng/mL. Age of the subjects is in mean age (SD) years, unless otherwise indicated.
Locale Study Subjects
25(OH)D (ng/mL)
Mean (SD)
Vitamin D Status
Reference
%
Deficient
%
Insufficient
%
Sufficient
PAKISTAN
Lahore (31.5° N)
& Rawalpindi
(33.6° N)
N = 92 Adults, median age 29 (11–75) years,
rural & urban.
Median 29.7
(3.0–63.1)
- - - Rashid
1983 [139]
N = 48 M 33.0 (11.0) - - -
N = 44 F 27.0 (11.3) - - -
Karachi
(24.8° N)
Total N = 123 Urban adults, age 32.7 (8.7) years, hospital staff 16.44 (3.84) 69.9 21.1 8.9 Mansoor
2010 [140]
N = 53 F 14.88 (9.2) - - -
N = 70 M 17.64 (3.88) - - -
Karachi
(24.8° N) N = 305
Urban adults, F, low, middle and high income
groups equally represented,
age 31.97 (8.00) years
8.70 (8.64) 90.5 5.2 4.3 Khan
2012 [141]
Karachi
(24.8° N) N = 50 Pregnant women, age 28.16 (4.4) years, low and
middle income group
24.1 (11.70) 46 32 22 Karim
2011 [142]
N = 50 Cord blood/neonates 20.4 (10.99) - - -
Karachi
(24.8° N) N = 75 Pregnant women at term, age 26 (6.5) years, low
income group
Preterm 16.89 (7.83)
Term 13.19 (6.74) 72 17 11
Hossain
2011 [143]
N = 75 Cord blood/neonates Preterm 21.91 (9.73)
Term 15.81 (9.56) 72 17 11
Karachi
(24.8° N)
N = 62 Exclusively breastfed Infants 13.83 (10.62) - - - Atiq
1998 [144]
N = 62 Mothers 12.8 (8.98) - - -
N = 37
High income
Breastfed infants, age 6 weeks–11 months 8.98 (6.56) - - -
Mothers, housewives, mostly indoors 10.6 (9.64) - - -
N = 25
Low income
Breastfed infants, age 6 weeks–11 months 20.93 (15.7) - - -
Mothers, working 15.90 (6.03) - - -
Nutrients 2014, 6 763
Table 6. Cont.
Locale Study Subjects 25(OH)D (ng/mL)
Mean (SD)
Vitamin D Status
Reference
%
Deficient
%
Insufficient
%
Sufficient
BANGLADESH
Dhaka
(23.7° N) N = 99 Adults, F, low income level, age 16–40 years,
88% housewives
Median 14.68
(range 10–48) - - -
Islam
2002 [145]
N = 90 Adults, F, high income level, age 16–40 years,
76% housewives
Median 17.4
(range 10–48) - - -
Dhaka
(23.7° N) N = 36 Adults, F, high income level, age 22.3 (1.9) years,
unveiled 12.12 (9.04) - - - Islam
2006 [146]
N = 30 Adults, F, medium income level, age 47.7 ( 9.4)
years, veiled/purdah 12.4 (4.4) - - -
Dhaka
(23.7° N) N = 200 Adults, F, urban factory workers, low income
group, age 22.6 (3.7) years 14.68 (4.48) 88.5 - - Islam
2008 [147]
Sylhet
(24.9° N) N = 29 Infants, age 71 (32) days, 25 M, 4 F, rural, low
income group 14.68 (6.84) - - - Roth
2010 [148]
Matlab
(23.3° N) N = 98 Cord blood, neonates of rural women/mothers,
age 25.8 (5.9) years
Median
23·8 (18·6–30·8) - - -
Doi
2011 [149]
Dhaka (23.7°N) N = 76 Pregnant women, 20 weeks of gestation,
age 21.55 (4) years 24.86 (1.02) - - 34.21 Ullah
2013 [150]
NEPAL
Sarlahi
(26.5° N) N = 1163 Rural F, pregnant, age 23.6 ± 6.0 years,
gestational age 10.9 (4.6) week. 20.44 (9.85) - - - Jiang
2005 [151]
SRI LANKA
Kandy
(7.2° N)
N = 85 Adults, M, age 47.0 (8.3) years. 25.2 (9.12) 34·1 - -
Meyer
2008 [152]
N = 111 Adults, F, age 46.4 (7.8) years. 18.96 (6.32) 58·6 - -
Galle (6.2° N) N = 122 Preschool children, M, age 45.93 (9.8) months 34.8 (13.4) - - - Hettiarachchi
2012 [153]
N = 126 Preschool children, F, age 46.56 (8.5) months 32.62 (14.8) - - -
No pertinent reports were available from Myanmar and Bhutan.
Nutrients 2014, 6 764
Table 7. Vitamin D supplementation studies in ostensibly healthy subjects from other countries of the Indian subcontinent. All 25(OH)D
values have been shown in ng/mL. To convert from nM to ng/mL, nM values were divided by (2.5). Vitamin D deficiency is defined as
25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and sufficiency as ≥30 ng/mL. D3 is cholecalciferol.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD) % Deficient 25(OH)D
Mean (SD) % Deficient
PAKISTAN One report is included in Table 8
BANGLADESH
Dhaka
(23.7° N)
Pregnant women, age 22.4 (SD 3.5) years, 26–29 weeks of gestation, - - - -
Roth
2013 [154]
N = 80, Control group, placebo 17.6 (8.36) 66.25 15.36 (7.24) 79.3
N = 67, Cord blood/neonates of control group - - 15.6 (7.48) 80.5
N = 80, Study group, received 35,000 IU D3/week until delivery 18.16 (7.36) 62.5 53.76 (12.28) 0
N = 65, Cord blood/neonates of study group - - 41.12 (11.44) 4.6
No pertinent reports with information required were found from Nepal, Sri Lanka, Myanmar and Bhutan.
Table 8. Vitamin D supplementation studies reporting improved bone health post-intervention, in ostensibly healthy subjects from other
countries of the Indian subcontinent: All 25(OH)D values have been shown in ng/mL. To convert from nM to ng/mL, nM values were divided
by (2.5). Vitamin D deficiency is defined as 25(OH)D < 20 ng/mL, insufficiency as 20–29 ng/mL and sufficiency as ≥30 ng/mL. D3 is
cholecalciferol. Calcium amount mentioned is that of elemental calcium.
Locale Study Subjects and Supplementation Protocols
Vitamin D Status
Reference
Before After
25(OH)D
Mean (SD)
25(OH)D
Mean (SD) Bone Health Status
PAKISTAN
Lahore
(31.5° N)
N = 53, premenopausal women, age 41.3 (SD 8.2)
years. All subjects had anterior tibial tenderness (ATT).
Subjects received a total of 1,800,000 IU intramuscular
D3, in 3 doses of 600,000 IU each, on alternate days.
All subjects received 1.2 gm calcium/day for 3 months.
12.1 (17.5)
81.1% were vitamin D
deficient
51.9 (no SD)
Significant improvement in ATT was observed.
88.7% women attained vitamin D sufficiency
and 92.4% had normalization of PTH levels.
Change in ATT correlated with change in PTH,
but did not correlate with 25(OH)D levels.
Ali
2013 [155]
No pertinent reports with information required were available from Bangladesh, Nepal, Sri Lanka, Myanmar and Bhutan.
Nutrients 2014, 6 765
Conflicts of Interest
The authors declare no conflict of interest.
References
1. Van Schoor, N.M.; Lips, P. Worldwide Vitamin D Status. Best Pract. Res. Clin. Endocrinol.
Metab. 2011, 25, 671–680.
2. Mithal, A.; Wahl, D.A.; Bonjour, J.P.; Burckhardt, P.; Dawson-Hughes, B.; Eisman, J.A.;
El-Hajj Fuleihan, G.; Josse, R.G.; Lips, P.; Morales-Torres, J.; et al. Global vitamin D status and
determinants of hypovitaminosis D. Osteoporos Int. 2009, 20, 1807–1820.
3. Van der Meer, I.M.; Middelkoop, B.J.; Boeke, A.J.; Lips, P. Prevalence of vitamin D deficiency
among Turkish, Moroccan, Indian and sub-Sahara African populations in Europe and their
countries of origin: An overview. Osteoporos. Int. 2011, 22, 1009–1021.
4. Hazell, T.J.; DeGuire, J.R.; Weiler, H.A. Vitamin D: An overview of its role in skeletal muscle
physiology in children and adolescents. Nutr. Rev. 2012, 70, 520–533.
5. Holick, M.F. The role of vitamin D for bone health and fracture prevention. Curr. Osteoporos.
Rep. 2006, 4, 96–102.
6. Lips, P.; van Schoor, N.M. The effect of vitamin D on bone and osteoporosis. Best Pract. Res.
Clin. Endocrinol. Metab. 2011, 25, 585–591.
7. Janssen, H.C.; Samson, M.M.; Verhaar, H.J. Vitamin D deficiency, muscle function, and falls in
elderly people. Am. J. Clin. Nutr. 2002, 75, 611–615.
8. Bischoff, H.A.; Stahelin, H.B.; Urscheler, N.; Ehrsam, R.; Vonthein, R.; Perrig-Chiello, P.;
Tyndall, A.; Theiler, R. Muscle strength in the elderly: Its relation to vitamin D metabolites.
Arch. Phys. Med. Rehabil. 1999, 80, 54–58.
9. Bischoff-Ferrari, H.A.; Dawson-Hughes, B.; Willett, W.C.; Staehelin, H.B.; Bazemore, M.G.;
Zee, R.Y.; Wong, J.B. Effect of Vitamin D on falls: A meta-analysis. JAMA 2004, 291,
1999–2006.
10. Bischoff-Ferrari, H.A.; Dietrich, T.; Orav, E.J.; Dawson-Hughes, B. Positive association between
25-hydroxy vitamin D levels and bone mineral density: A population-based study of younger and
older adults. Am. J. Med. 2004, 116, 634–639.
11. Bischoff-Ferrari, H.A.; Zhang, Y.; Kiel, D.P.; Felson, D.T. Positive association between serum
25-hydroxyvitamin D level and bone density in osteoarthritis. Arthritis Rheum. 2005, 53,
821–826.
12. Thacher, T.D.; Clarke, B.L. Vitamin D insufficiency. Mayo Clin. Proc. 2011, 86, 50–60.
13. Murad, M.H.; Elamin, K.B.; Abu Elnour, N.O.; Elamin, M.B.; Alkatib, A.A.; Fatourechi, M.M.;
Almandoz, J.P.; Mullan, R.J.; Lane, M.A.; Liu, H.; et al. Clinical review: The effect of vitamin D
on falls: A systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2011, 96,
2997–3006.
14. Lips, P. Worldwide status of vitamin D nutrition. J. Steroid Biochem. Mol. Biol. 2010, 121,
297–300.
Nutrients 2014, 6 766
15. Pilz, S.; Tomaschitz, A.; Marz, W.; Drechsler, C.; Ritz, E.; Zittermann, A.; Cavalier, E.;
Pieber, T.R.; Lappe, J.M.; Grant, W.B.; et al. Vitamin D, cardiovascular disease and mortality.
Clin. Endocrinol. 2011, 75, 575–584.
16. Haines, S.T.; Park, S.K. Vitamin D supplementation: What’s known, what to do, and what’s
needed. Pharmacotherapy 2012, 32, 354–382.
17. Sisodia, R.S.; Jain, D.K.; Agarwal, S.S.; Gupta, A. TB control in India—Efforts, challenges and
priorities. J. Indian Med. Assoc. 2011, 109, 921–924, 928.
18. Nnoaham, K.E.; Clarke, A. Low serum vitamin D levels and tuberculosis: A systematic review
and meta-analysis. Int. J. Epidemiol. 2008, 37, 113–119.
19. Martineau, A.R. Old wine in new bottles: Vitamin D in the treatment and prevention of
tuberculosis. Proc. Nutr. Soc. 2012, 71, 84–89.
20. Linday, L.A.; Shindledecker, R.D.; Dolitsky, J.N.; Chen, T.C.; Holick, M.F. Plasma
25-hydroxyvitamin D levels in young children undergoing placement of tympanostomy tubes.
Ann. Otol. Rhinol. Laryngol. 2008, 117, 740–744.
21. Ginde, A.A.; Mansbach, J.M.; Camargo, C.A., Jr. Association between serum
25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and
Nutrition Examination Survey. Arch. Intern. Med. 2009, 169, 384–390.
22. Cannell, J.J.; Vieth, R.; Umhau, J.C.; Holick, M.F.; Grant, W.B.; Madronich, S.; Garland, C.F.;
Giovannucci, E. Epidemic influenza and vitamin D. Epidemiol. Infect. 2006, 134, 1129–1140.
23. Wang, T.J.; Pencina, M.J.; Booth, S.L.; Jacques, P.F.; Ingelsson, E.; Lanier, K.; Benjamin, E.J.;
D’Agostino, R.B.; Wolf, M.; Vasan, R.S. Vitamin D deficiency and risk of cardiovascular
disease. Circulation 2008, 117, 503–511.
24. Ginde, A.A.; Scragg, R.; Schwartz, R.S.; Camargo, C.A., Jr. Prospective study of serum
25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older
U.S. adults. J. Am. Geriatr. Soc. 2009, 57, 1595–1603.
25. Rostand, S.G. Ultraviolet light may contribute to geographic and racial blood pressure
differences. Hypertension 1997, 30, 150–156.
26. Martins, D.; Wolf, M.; Pan, D.; Zadshir, A.; Tareen, N.; Thadhani, R.; Felsenfeld, A.; Levine, B.;
Mehrotra, R.; Norris, K. Prevalence of cardiovascular risk factors and the serum levels of
25-hydroxyvitamin D in the United States: Data from the Third National Health and Nutrition
Examination Survey. Arch. Intern. Med. 2007, 167, 1159–1165.
27. Brewer, L.C.; Michos, E.D.; Reis, J.P. Vitamin D in atherosclerosis, vascular disease, and
endothelial function. Curr. Drug Targets 2011, 12, 54–60.
28. Karvonen, M.; Viik-Kajander, M.; Moltchanova, E.; Libman, I.; LaPorte, R.; Tuomilehto, J.
Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group.
Diabetes Care 2000, 23, 1516–1526.
29. Mohr, S.B.; Garland, C.F.; Gorham, E.D.; Garland, F.C. The association between ultraviolet B
irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide.
Diabetologia 2008, 51, 1391–1398.
30. Hypponen, E.; Laara, E.; Reunanen, A.; Jarvelin, M.R.; Virtanen, S.M. Intake of vitamin D and
risk of type 1 diabetes: A birth-cohort study. Lancet 2001, 358, 1500–1503.
Nutrients 2014, 6 767
31. Zipitis, C.S.; Akobeng, A.K. Vitamin D supplementation in early childhood and risk of type 1
diabetes: A systematic review and meta-analysis. Arch. Dis. Child. 2008, 93, 512–517.
32. Modan, M.; Halkin, H.; Almog, S.; Lusky, A.; Eshkol, A.; Shefi, M.; Shitrit, A.; Fuchs, Z.
Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J. Clin. Investig.
1985, 75, 809–817.
33. Dankner, R.; Chetrit, A.; Shanik, M.H.; Raz, I.; Roth, J. Basal-state hyperinsulinemia in healthy
normoglycemic adults is predictive of type 2 diabetes over a 24-year follow-up: A preliminary
report. Diabetes Care 2009, 32, 1464–1466.
34. Pittas, A.G.; Lau, J.; Hu, F.B.; Dawson-Hughes, B. The role of vitamin D and calcium in type 2
diabetes. A systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2007, 92,
2017–2029.
35. Garland, C.F.; Garland, F.C.; Gorham, E.D. Can colon cancer incidence and death rates be
reduced with calcium and vitamin D? Am. J. Clin. Nutr. 1991, 54, 193S–201S.
36. Gorham, E.D.; Garland, C.F.; Garland, F.C.; Grant, W.B.; Mohr, S.B.; Lipkin, M.;
Newmark, H.L.; Giovannucci, E.; Wei, M.; Holick, M.F. Optimal vitamin D status for colorectal
cancer prevention: A quantitative meta analysis. Am. J. Prev. Med. 2007, 32, 210–216.
37. Hanchette, C.L.; Schwartz, G.G. Geographic patterns of prostate cancer mortality. Evidence for a
protective effect of ultraviolet radiation. Cancer 1992, 70, 2861–2869.
38. Bischoff-Ferrari, H.A.; Giovannucci, E.; Willett, W.C.; Dietrich, T.; Dawson-Hughes, B.
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health
outcomes. Am. J. Clin. Nutr. 2006, 84, 18–28.
39. Bertone-Johnson, E.R.; Chen, W.Y.; Holick, M.F.; Hollis, B.W.; Colditz, G.A.; Willett, W.C.;
Hankinson, S.E. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast
cancer. Cancer Epidemiol. Biomark. Prev. 2005, 14, 1991–1997.
40. Moan, J.; Porojnicu, A.C.; Dahlback, A.; Setlow, R.B. Addressing the health benefits and risks,
involving vitamin D or skin cancer, of increased sun exposure. Proc. Natl. Acad. Sci. USA 2008,
105, 668–673.
41. Grant, W.B. Lower vitamin-D production from solar ultraviolet-B irradiance may explain some
differences in cancer survival rates. J. Natl. Med. Assoc. 2006, 98, 357–364.
42. Garland, C.F.; Gorham, E.D.; Mohr, S.B.; Grant, W.B.; Giovannucci, E.L.; Lipkin, M.;
Newmark, H.; Holick, M.F.; Garland, F.C. Vitamin D and prevention of breast cancer: Pooled
analysis. J. Steroid Biochem. Mol. Biol. 2007, 103, 708–711.
43. Ahonen, M.H.; Tenkanen, L.; Teppo, L.; Hakama, M.; Tuohimaa, P. Prostate cancer risk and
prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000, 11,
847–852.
44. Giovannucci, E.; Liu, Y.; Rimm, E.B.; Hollis, B.W.; Fuchs, C.S.; Stampfer, M.J.; Willett, W.C.
Prospective study of predictors of vitamin D status and cancer incidence and mortality in men.
J. Natl. Cancer Inst. 2006, 98, 451–459.
45. Lee, J.E.; Li, H.; Chan, A.T.; Hollis, B.W.; Lee, I.M.; Stampfer, M.J.; Wu, K.; Giovannucci, E.;
Ma, J. Circulating levels of vitamin D and colon and rectal cancer: The Physicians’ Health Study
and a meta-analysis of prospective studies. Cancer Prev. Res. 2011, 4, 735–743.
Nutrients 2014, 6 768
46. Holick, M.F.; Biancuzzo, R.M.; Chen, T.C.; Klein, E.K.; Young, A.; Bibuld, D.; Reitz, R.;
Salameh, W.; Ameri, A.; Tannenbaum, A.D. Vitamin D2 is as effective as vitamin D3 in
maintaining circulating concentrations of 25-hydroxyvitamin D. J. Clin. Endocrinol. Metab.
2008, 93, 677–681.
47. Biancuzzo, R.M.; Clarke, N.; Reitz, R.E.; Travison, T.G.; Holick, M.F. Serum concentrations of
1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin
D3 supplementation. J. Clin. Endocrinol. Metab. 2013, 98, 973–979.
48. Thacher, T.D.; Obadofin, M.O.; O’Brien, K.O.; Abrams, S.A. The effect of vitamin D2 and
vitamin D3 on intestinal calcium absorption in Nigerian children with rickets. J. Clin.
Endocrinol. Metab. 2009, 94, 3314–3321.
49. Thacher, T.D.; Fischer, P.R.; Obadofin, M.O.; Levine, M.A.; Singh, R.J.; Pettifor, J.M.
Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets. J. Bone
Miner. Res. 2010, 25, 1988–1995.
50. Armas, L.A.; Hollis, B.W.; Heaney, R.P. Vitamin D2 is much less effective than vitamin D3 in
humans. J. Clin. Endocrinol. Metab. 2004, 89, 5387–5391.
51. Trang, H.M.; Cole, D.E.; Rubin, L.A.; Pierratos, A.; Siu, S.; Vieth, R. Evidence that vitamin D3
increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am. J. Clin. Nutr.
1998, 68, 854–858.
52. Heaney, R.P.; Recker, R.R.; Grote, J.; Horst, R.L.; Armas, L.A. Vitamin D(3) is more potent
than vitamin D(2) in humans. J. Clin. Endocrinol. Metab. 2011, 96, E447–E452.
53. Houghton, L.A.; Vieth, R. The case against ergocalciferol (vitamin D2) as a vitamin supplement.
Am. J. Clin. Nutr. 2006, 84, 694–697.
54. Baidya, A.; Chowdhury, S.; Mukhopadhyay, S.; Ghosh, S. Profile of vitamin D in a cohort of
physicians and diabetologists in Kolkata. Indian J. Endocrinol. Metab. 2012, 16, S416–S417.
55. Goswami, R.; Gupta, N.; Goswami, D.; Marwaha, R.K.; Tandon, N.; Kochupillai, N. Prevalence
and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am. J.
Clin. Nutr. 2000, 72, 472–475.
56. Tandon, N.; Marwaha, R.K.; 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.
57. Marwaha, R.K.; Puri, S.; Tandon, N.; Dhir, S.; Agarwal, N.; Bhadra, K.; Saini, N. Effects of
sports training & nutrition on bone mineral density in young Indian healthy females. Indian J.
Med. Res. 2011, 134, 307–313.
58. Multani, S.K.; Sarathi, V.; Shivane, V.; Bandgar, T.R.; Menon, P.S.; Shah, N.S. Study of bone
mineral density in resident doctors working at a teaching hospital. J. Postgrad. Med. 2010, 56,
65–70.
59. Beloyartseva, M.; Mithal, A.; Kaur, P.; Kalra, S.; Baruah, M.P.; Mukhopadhyay, S.; Bantwal, G.;
Bandgar, T.R. Widespread vitamin D deficiency among Indian health care professionals. Arch.
Osteoporos. 2012, 7, 187–192.
60. Lo, C.W.; Paris, P.W.; Holick, M.F. Indian and Pakistani immigrants have the same capacity as
Caucasians to produce vitamin D in response to ultraviolet irradiation. Am. J. Clin. Nutr. 1986,
44, 683–685.
Nutrients 2014, 6 769
61. Clemens, T.L.; Adams, J.S.; Henderson, S.L.; Holick, M.F. Increased skin pigment reduces the
capacity of skin to synthesise vitamin D3. Lancet 1982, 1, 74–76.
62. Matsuoka, L.Y.; Wortsman, J.; Haddad, J.G.; Kolm, P.; Hollis, B.W. Racial pigmentation and the
cutaneous synthesis of vitamin D. Arch. Dermatol. 1991, 127, 536–538.
63. Agarwal, K.S.; Mughal, M.Z.; Upadhyay, P.; Berry, J.L.; Mawer, E.B.; Puliyel, J.M. The impact
of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India. Arch. Dis.
Child. 2002, 87, 111–113.
64. Jones, G.; Prosser, D.E.; Kaufmann, M.; Jones, G.; Prosser, D.E.; Kaufmann, M.
25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of
vitamin D. Arch. Biochem. Biophys. 2012, 523, 9–18.
65. Liao, E. FGF23 associated bone diseases. Front. Med. 2013, 7, 65–80.
66. Weaver, C.M.; Proulx, W.R.; Heaney, R. Choices for achieving adequate dietary calcium with a
vegetarian diet. Am. J. Clin. Nutr. 1999, 70, 543S–548S.
67. Gupta, A. Osteoporosis in India—The nutritional hypothesis. Natl. Med. J. India 1996, 9,
268–274.
68. Caudarella, R.; Vescini, F.; Rizzoli, E.; Francucci, C.M. Salt intake, hypertension, and
osteoporosis. J. Endocrinol. Investig. 2009, 32, 15–20.
69. Beaudoin, M.S.; Graham, T.E. Methylxanthines and human health: Epidemiological and
experimental evidence. Handb. Exp. Pharmacol. 2011, 200, 509–548.
70. Tandon, R.K.; Joshi, Y.K.; Singh, D.S.; Narendranathan, M.; Balakrishnan, V.; Lal, K. Lactose
intolerance in North and South Indians. Am. J. Clin. Nutr. 1981, 34, 943–946.
71. Babu, J.; Kumar, S.; Babu, P.; Prasad, J.H.; Ghoshal, U.C. Frequency of lactose malabsorption
among healthy southern and northern Indian populations by genetic analysis and lactose
hydrogen breath and tolerance tests. Am. J. Clin. Nutr. 2010, 91, 140–146.
72. Gallego Romero, I.; Basu Mallick, C.; Liebert, A.; Crivellaro, F.; Chaubey, G.; Itan, Y.;
Metspalu, M.; Eaaswarkhanth, M.; Pitchappan, R.; Villems, R.; et al. Herders of Indian and
European cattle share their predominant allele for lactase persistence. Mol. Biol. Evol. 2012, 29,
249–260.
73. Hollox, E.J.; Poulter, M.; Zvarik, M.; Ferak, V.; Krause, A.; Jenkins, T.; Saha, N.; Kozlov, A.I.;
Swallow, D.M. Lactase haplotype diversity in the Old World. Am. J. Hum. Genet. 2001, 68,
160–172.
74. Harinarayan, C.V.; Ramalakshmi, T.; Venkataprasad, U. High prevalence of low dietary calcium
and low vitamin D status in healthy south Indians. Asia Pac. J. Clin. Nutr. 2004, 13, 359–364.
75. Harinarayan, C.V.; Kochupillai, N.; Madhu, S.V.; Gupta, N.; Meunier, P.J. Fluorotoxic
metabolic bone disease: An osteo-renal syndrome caused by excess fluoride ingestion in the
tropics. Bone 2006, 39, 907–914.
76. Khandare, A.L.; Harikumar, R.; Sivakumar, B. Severe bone deformities in young children from
vitamin D deficiency and fluorosis in Bihar-India. Calcif. Tissue Int. 2005, 76, 412–418.
77. Natri, A.M.; Salo, P.; Vikstedt, T.; Palssa, A.; Huttunen, M.; Karkkainen, M.U.; Salovaara, H.;
Piironen, V.; Jakobsen, J.; Lamberg-Allardt, C.J. Bread fortified with cholecalciferol increases
the serum 25-hydroxyvitamin D concentration in women as effectively as a cholecalciferol
supplement. J. Nutr. 2006, 136, 123–127.
Nutrients 2014, 6 770
78. Lu, Z.; Chen, T.C.; Zhang, A.; Persons, K.S.; Kohn, N.; Berkowitz, R.; Martinello, S.;
Holick, M.F. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate
to satisfy the dietary requirement for vitamin D? J. Steroid Biochem. Mol. Biol. 2007, 103,
642–644.
79. Zargar, A.H.; Ahmad, S.; Masoodi, S.R.; Wani, A.I.; Bashir, M.I.; Laway, B.A.; Shah, Z.A.
Vitamin D status in apparently healthy adults in Kashmir Valley of Indian subcontinent.
Postgrad. Med. J. 2007, 83, 713–716.
80. Ramakrishnan, S.; Bhansali, A.; Bhadada, S.K.; Sharma, R.; Walia, R.; Ravikiran, M.;
Shanmugasundar, G.; Ravikumar, P. Vitamin D status and its seasonal variability in healthy
young adults in an Asian Indian urban population. Endocr. Pract. 2011, 17, 185–191.
81. 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, 755–757.
82. Goswami, R.; Marwaha, R.K.; Gupta, N.; Tandon, N.; Sreenivas, V.; Tomar, N.; Ray, D.;
Kanwar, R.; Agarwal, R. Prevalence of vitamin D deficiency and its relationship with thyroid
autoimmunity in Asian Indians: A community-based survey. Br. J. Nutr. 2009, 102, 382–386.
83. Vupputuri, M.R.; Goswami, R.; Gupta, N.; Ray, D.; Tandon, N.; Kumar, N. Prevalence and
functional significance of 25-hydroxyvitamin D deficiency and vitamin D receptor gene
polymorphisms in Asian Indians. Am. J. Clin. Nutr. 2006, 83, 1411–1419.
84. Puri, S.; Marwaha, R.K.; Agarwal, N.; Tandon, N.; Agarwal, R.; Grewal, K.; Reddy, D.H.;
Singh, S. Vitamin D status of apparently healthy schoolgirls from two different socioeconomic
strata in Delhi: Relation to nutrition and lifestyle. Br. J. Nutr. 2008, 99, 876–882.
85. Marwaha, R.K.; Tandon, N.; Reddy, D.R.; Aggarwal, R.; Singh, R.; Sawhney, R.C.; Saluja, B.;
Ganie, M.A.; Singh, S. Vitamin D and bone mineral density status of healthy schoolchildren in
northern India. Am. J. Clin. Nutr. 2005, 82, 477–482.
86. Marwaha, R.K.; Tandon, N.; Reddy, D.H.; Mani, K.; Puri, S.; Aggarwal, N.; Grewal, K.;
Singh, S. Peripheral bone mineral density and its predictors in healthy school girls from two
different socioeconomic groups in Delhi. Osteoporos. Int. 2007, 18, 375–383.
87. Marwaha, R.K.; Tandon, N.; Garg, M.K.; Kanwar, R.; Narang, A.; Sastry, A.; Saberwal, A.;
Bandra, K. Vitamin D status in healthy Indians aged 50 years and above. J. Assoc. Physicians
India 2011, 59, 706–709.
88. Garg, M.K.; Tandon, N.; Marwaha, R.K.; Menon, A.S.; Mahalle, N. The relationship between
serum 25-hydroxy vitamin D, parathormone and bone mineral density in Indian population. Clin.
Endocrinol. 2013, 80, 41–46.
89. Marwaha, R.K.; Tandon, N.; Chopra, S.; Agarwal, N.; Garg, M.K.; Sharma, B.; Kanwar, R.S.;
Bhadra, K.; Singh, S.; Mani, K.; et al. Vitamin D status in pregnant Indian women across
trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D
levels. Br. J. Nutr. 2011, 106, 1383–1389.
90. Seth, A.; Marwaha, R.K.; Singla, B.; Aneja, S.; Mehrotra, P.; Sastry, A.; Khurana, M.L.;
Mani, K.; Sharma, B.; Tandon, N. Vitamin D nutritional status of exclusively breast fed infants
and their mothers. J. Pediatr. Endocrinol. Metab. 2009, 22, 241–246.
Nutrients 2014, 6 771
91. Tiwari, L.; Puliyel, J.M. Vitamin D level in slum children of Delhi. Indian Pediatr. 2004, 41,
1076–1077.
92. Mehrotra, P.; Marwaha, R.K.; Aneja, S.; Seth, A.; Singla, B.M.; Ashraf, G.; Sharma, B.;
Sastry, A.; Tandon, N. Hypovitaminosis d and hypocalcemic seizures in infancy. Indian Pediatr.
2010, 47, 581–586.
93. Jain, V.; Gupta, N.; Kalaivani, M.; Jain, A.; Sinha, A.; Agarwal, R. Vitamin D deficiency in
healthy breastfed term infants at 3 months & their mothers in India: Seasonal variation &
determinants. Indian J. Med. Res. 2011, 133, 267–273.
94. Agarwal, R.; Virmani, D.; Jaipal, M.L.; Gupta, S.; Gupta, N.; Sankar, M.J.; Bhatia, S.; Agarwal, A.;
Devgan, V.; Deorari, A.; et al. Vitamin D status of low birth weight infants in Delhi:
A comparative study. J. Trop. Pediatr. 2012, 58, 446–450.
95. Agarwal, N.; Faridi, M.M.; Aggarwal, A.; Singh, O. Vitamin D Status of term exclusively
breastfed infants and their mothers from India. Acta Paediatr. 2010, 99, 1671–1674.
96. Arya, V.; Bhambri, R.; Godbole, M.M.; Mithal, A. Vitamin D status and its relationship with
bone mineral density in healthy Asian Indians. Osteoporos. Int. 2004, 15, 56–61.
97. Sachan, A.; Gupta, R.; Das, V.; Agarwal, A.; Awasthi, P.K.; Bhatia, V. High prevalence of
vitamin D deficiency among pregnant women and their newborns in northern India. Am. J. Clin.
Nutr. 2005, 81, 1060–1064.
98. Sahu, M.; Bhatia, V.; Aggarwal, A.; Rawat, V.; Saxena, P.; Pandey, A.; Das, V. Vitamin D
deficiency in rural girls and pregnant women despite abundant sunshine in northern India.
Clin. Endocrinol. 2009, 70, 680–684.
99. Agrawal, N.K.; Sharma, B. Prevalence of osteoporosis in otherwise healthy Indian males aged
50 years and above. Arch. Osteoporos. 2013, 8, 116.
100. Harinarayan, C.V.; Ramalakshmi, T.; Prasad, U.V.; Sudhakar, D. Vitamin D status in Andhra
Pradesh: A population based study. Indian J. Med. Res. 2008, 127, 211–218.
101. Harinarayan, C.V. Prevalence of vitamin D insufficiency in postmenopausal south Indian
women. Osteoporos. Int. 2005, 16, 397–402.
102. Paul, T.V.; Thomas, N.; Seshadri, M.S.; Oommen, R.; Jose, A.; Mahendri, N.V. Prevalence of
osteoporosis in ambulatory postmenopausal women from a semiurban region in Southern India:
Relationship to calcium nutrition and vitamin D status. Endocr. Pract. 2008, 14, 665–671.
103. Harinarayan, C.V.; Sachan, A.; Reddy, P.A.; Satish, K.M.; Prasad, U.V.; Srivani, P. Vitamin D
status and bone mineral density in women of reproductive and postmenopausal age groups: A
cross-sectional study from south India. J. Assoc. Physicians India 2011, 59, 698–704.
104. Farrant, H.J.; Krishnaveni, G.V.; Hill, J.C.; Boucher, B.J.; Fisher, D.J.; Noonan, K.; Osmond, C.;
Veena, S.R.; Fall, C.H. Vitamin D insufficiency is common in Indian mothers but is not
associated with gestational diabetes or variation in newborn size. Eur. J. Clin. Nutr. 2009, 63,
646–652.
105. Bhalala, U.; Desai, M.; Parekh, P.; Mokal, R.; Chheda, B. Subclinical hypovitaminosis D among
exclusively breastfed young infants. Indian Pediatr. 2007, 44, 897–901.
106. Shivane, V.K.; Sarathi, V.; Bandgar, T.; Menon, P.; Shah, N.S. High prevalence of
hypovitaminosis D in young healthy adults from the western part of India. Postgrad. Med. J.
2011, 87, 514–518.
Nutrients 2014, 6 772
107. Ekbote, V.H.; Khadilkar, A.V.; Mughal, M.Z.; Hanumante, N.; Sanwalka, N.; Khadilkar, V.V.;
Chiplonkar, S.A.; Kant, S.; Ganacharya, R. Sunlight exposure and development of rickets in
Indian toddlers. Indian J. Pediatr. 2010, 77, 61–65.
108. Ekbote, V.H.; Khadilkar, A.V.; Chiplonkar, S.A.; Khadilkar, V.V. Determinants of bone mineral
content and bone area in Indian preschool children. J. Bone Miner. Metab. 2011, 29, 334–341.
109. Khadilkar, A.; Crabtree, N.J.; Ward, K.A.; Khadilkar, V.; Shaw, N.J.; Mughal, M.Z. Bone status
of adolescent girls in Pune (India) compared to age-matched South Asian and white Caucasian
girls in the UK. Osteoporos. Int. 2010, 21, 1155–1160.
110. Kadam, N.; Chiplonkar, S.; Khadilkar, A.; Divate, U.; Khadilkar, V. Low bone mass in urban
Indian women above 40 years of age: Prevalence and risk factors. Gynecol. Endocrinol. 2010,
26, 909–917.
111. Kadam, N.S.; Chiplonkar, S.A.; Khadilkar, A.V.; Fischer, P.R.; Hanumante, N.M.;
Khadilkar, V.V. Modifiable factors associated with low bone mineral content in underprivileged
premenarchal Indian girls. J. Pediatr. Endocrinol. Metab. 2011, 24, 975–981.
112. Marwaha, R.K.; Tandon, N.; Garg, M.K.; Kanwar, R.; Narang, A.; Sastry, A.; Saberwal, A.;
Bhadra, K.; Mithal, A. Bone health in healthy Indian population aged 50 years and above.
Osteoporos. Int. 2011, 22, 2829–2836.
113. Wang, T.J.; Zhang, F.; Richards, J.B.; Kestenbaum, B.; van Meurs, J.B.; Berry, D.; Kiel, D.P.;
Streeten, E.A.; Ohlsson, C.; Koller, D.L.; et al. Common genetic determinants of vitamin D
insufficiency: A genome-wide association study. Lancet 2010, 376, 180–188.
114. McCullough, M.L.; Bostick, R.M.; Mayo, T.L. Vitamin D gene pathway polymorphisms and risk
of colorectal, breast, and prostate cancer. Annu. Rev. Nutr. 2009, 29, 111–132.
115. McGrath, J.J.; Saha, S.; Burne, T.H.; Eyles, D.W. A systematic review of the association
between common single nucleotide polymorphisms and 25-hydroxyvitamin D concentrations.
J. Steroid Biochem. Mol. Biol. 2010, 121, 471–477.
116. Hossein-nezhad, A.; Holick, M.F. Optimize dietary intake of vitamin D: An epigenetic
perspective. Curr. Opin. Clin. Nutr. Metab. Care 2012, 15, 567–579.
117. 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,
526–529.
118. Vieth, R. Why the minimum desirable serum 25-hydroxyvitamin D level should be 75 nmol/L
(30 ng/mL). Best Pract. Res. Clin. Endocrinol. Metab. 2011, 25, 681–691.
119. Fulgoni, V.L., III; Keast, D.R.; Bailey, R.L.; Dwyer, J. Foods, fortificants, and supplements:
Where do Americans get their nutrients? J. Nutr. 2011, 141, 1847–1854.
120. Langlois, K.; Greene-Finestone, L.; Little, J.; Hidiroglou, N.; Whiting, S. Vitamin D status of
Canadians as measured in the 2007 to 2009 Canadian Health Measures Survey. Health Rep.
2010, 21, 47–55.
121. Calvo, M.S.; Whiting, S.J. Survey of current vitamin D food fortification practices in the United
States and Canada. J. Steroid Biochem. Mol. Biol. 2013, 136, 211–213.
Nutrients 2014, 6 773
122. Ekbote, V.H.; Khadilkar, A.V.; Chiplonkar, S.A.; Hanumante, N.M.; Khadilkar, V.V.;
Mughal, M.Z. A pilot randomized controlled trial of oral calcium and vitamin D supplementation
using fortified laddoos in underprivileged Indian toddlers. Eur. J. Clin. Nutr. 2011, 65, 440–446.
123. Khadgawat, R.; Marwaha, R.K.; Garg, M.K.; Ramot, R.; Oberoi, A.K.; Sreenivas, V.;
Gahlot, M.; Mehan, N.; Mathur, P.; Gupta, N. Impact of vitamin D fortified milk
supplementation on vitamin D status of healthy school children aged 10–14 years. Osteoporos.
Int. 2013, 24, 2335–2343.
124. Sahu, M.; Das, V.; Aggarwal, A.; Rawat, V.; Saxena, P.; Bhatia, V. Vitamin D replacement in
pregnant women in rural north India: A pilot study. Eur. J. Clin. Nutr. 2009, 63, 1157–1159.
125. Kalra, P.; Das, V.; Agarwal, A.; Kumar, M.; Ramesh, V.; Bhatia, E.; Gupta, S.; Singh, S.;
Saxena, P.; Bhatia, V. Effect of vitamin D supplementation during pregnancy on neonatal
mineral homeostasis and anthropometry of the newborn and infant. Br. J. Nutr. 2012, 108,
1052–1058.
126. Kumar, G.T.; Sachdev, H.S.; Chellani, H.; Rehman, A.M.; Singh, V.; Arora, H.; Filteau, S.
Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight
term infants in India up to age 6 months: Randomised controlled trial. BMJ 2011, 342, d2975.
127. Trilok-Kumar, G.; Arora, H.; Rajput, M.; Chellani, H.; Singh, V.; Raynes, J.; Arya, S.;
Aggarwal, S.; Srivastava, N.; Sachdev, H.P.; et al. Effect of vitamin D supplementation of low
birth weight term Indian infants from birth on cytokine production at 6 months. Eur. J. Clin.
Nutr. 2012, 66, 746–750.
128. Marwaha, R.K.; Tandon, N.; Agarwal, N.; Puri, S.; Agarwal, R.; Singh, S.; Mani, K. Impact of
two regimens of vitamin D supplementation on calcium - vitamin D - PTH axis of schoolgirls of
Delhi. Indian Pediatr. 2010, 47, 761–769.
129. Garg, M.K.; Marwaha, R.K.; Khadgawat, R.; Ramot, R.; Obroi, A.K.; Mehan, N.; Gupta, N.;
Madan, R. 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. Pediatr.
Endocrinol. Metab. 2013, 26, 515–523.
130. Goswami, R.; Vatsa, M.; Sreenivas, V.; Singh, U.; Gupta, N.; Lakshmy, R.; Aggarwal, S.;
Ganapathy, A.; Joshi, P.; Bhatia, H. Skeletal muscle strength in young Asian Indian females after
vitamin D and calcium supplementation: A double-blind randomized controlled clinical trial.
J. Clin. Endocrinol. Metab. 2012, 97, 4709–4716.
131. Gupta, R.; Sharma, U.; Gupta, N.; Kalaivani, M.; Singh, U.; Guleria, R.; Jagannathan, N.R.;
Goswami, R. Effect of cholecalciferol and calcium supplementation on muscle strength
and energy metabolism in vitamin D-deficient Asian Indians: A randomized, controlled trial.
Clin. Endocrinol. 2010, 73, 445–451.
132. Agarwal, N.; Mithal, A.; Dhingra, V.; Kaur, P.; Godbole, M.M.; Shukla, M. Effect of two
different doses of oral cholecalciferol supplementation on serum 25-hydroxy-vitamin D levels in
healthy Indian postmenopausal women: A randomized controlled trial. Indian J. Endocrinol.
Metab. 2013, 17, 883–889.
133. Khadilkar, A.V.; Sayyad, M.G.; Sanwalka, N.J.; Bhandari, D.R.; Naik, S.; Khadilkar, V.V.;
Mughal, M.Z. Vitamin D supplementation and bone mass accrual in underprivileged adolescent
Indian girls. Asia Pac. J. Clin. Nutr. 2010, 19, 465–472.
Nutrients 2014, 6 774
134. Khadilkar, A.; Kadam, N.; Chiplonkar, S.; Fischer, P.R.; Khadilkar, V. School-based
calcium-vitamin D with micronutrient supplementation enhances bone mass in underprivileged
Indian premenarchal girls. Bone 2012, 51, 1–7.
135. Nordin, B.E. International patterns of osteoporosis. Clin. Orthop. Relat. Res. 1966, 45, 17–30.
136. Malhotra, N.; Mithal, A. Osteoporosis in Indians. Indian J. Med. Res. 2008, 127, 263–268.
137. SP, S.T.; Teotia, M. Nutritional bone disease in Indian population. Indian J. Med. Res. 2008,
127, 219–228.
138. Lowe, N.M.; Ellahi, B.; Bano, Q.; Bangash, S.A.; Mitra, S.R.; Zaman, M. Dietary calcium
intake, vitamin D status, and bone health in postmenopausal women in rural Pakistan. J. Health
Popul. Nutr. 2011, 29, 465–470.
139. Rashid, A.; Mohammed, T.; Stephens, W.P.; Warrington, S.; Berry, J.L.; Mawer, E.B. Vitamin D
state of Asians living in Pakistan. Br. Med. J. 1983, 286, 182–184.
140. Mansoor, S.; Habib, A.; Ghani, F.; Fatmi, Z.; Badruddin, S.; Mansoor, S.; Siddiqui, I.;
Jabbar, A. Prevalence and significance of vitamin D deficiency and insufficiency among
apparently healthy adults. Clin. Biochem. 2010, 43, 1431–1435.
141. Khan, A.H.; Iqbal, R.; Naureen, G.; Dar, F.J.; Ahmed, F.N. Prevalence of vitamin D deficiency
and its correlates: Results of a community-based study conducted in Karachi, Pakistan.
Arch. Osteoporos. 2012, 7, 275–282.
142. Karim, S.A.; Nusrat, U.; Aziz, S. Vitamin D deficiency in pregnant women and their newborns
as seen at a tertiary-care center in Karachi, Pakistan. Int. J. Gynaecol. Obstet. 2011, 112, 59–62.
143. Hossain, N.; Khanani, R.; Hussain-Kanani, F.; Shah, T.; Arif, S.; Pal, L. High prevalence of
vitamin D deficiency in Pakistani mothers and their newborns. Int. J. Gynaecol. Obstet. 2011,
112, 229–233.
144. Atiq, M.; Suria, A.; Nizami, S.Q.; Ahmed, I. Vitamin D status of breastfed Pakistani infants.
Acta Paediatr. 1998, 87, 737–740.
145. Islam, M.Z.; Lamberg-Allardt, C.; Karkkainen, M.; Outila, T.; Salamatullah, Q.; Shamim, A.A.
D deficiency: A concern in premenopausal Bangladeshi women of two socio-economic groups in
rural and urban region. Eur. J. Clin. Nutr. 2002, 56, 51–56.
146. Islam, M.Z.; Akhtaruzzaman, M.; Lamberg-Allardt, C. Hypovitaminosis D is common in both
veiled and nonveiled Bangladeshi women. Asia Pac. J. Clin. Nutr. 2006, 15, 81–87.
147. Islam, M.Z.; Shamim, A.A.; Kemi, V.; Nevanlinna, A.; Akhtaruzzaman, M.; Laaksonen, M.;
Jehan, A.H.; Jahan, K.; Khan, H.U.; Lamberg-Allardt, C. Vitamin D deficiency and low bone
status in adult female garment factory workers in Bangladesh. Br. J. Nutr. 2008, 99, 1322–1329.
148. Roth, D.E.; Shah, M.R.; Black, R.E.; Baqui, A.H. Vitamin D status of infants in northeastern
rural Bangladesh: Preliminary observations and a review of potential determinants. J. Health
Popul. Nutr. 2010, 28, 458–469.
149. Doi, M.; Rekha, R.S.; Ahmed, S.; Okada, M.; Roy, A.K.; El Arifeen, S.; Ekstrom, E.C.;
Raqib, R.; Wagatsuma, Y. Association between calcium in cord blood and newborn size in
Bangladesh. Br. J. Nutr. 2011, 106, 1398–1407.
150. Ullah, M.I.; Koch, C.A.; Tamanna, S.; Rouf, S.; Shamsuddin, L. Vitamin D deficiency and the
risk of preeclampsia and eclampsia in Bangladesh. Horm. Metab. Res. 2013, 45, 682–687.
Nutrients 2014, 6 775
151. Jiang, T.; Christian, P.; Khatry, S.K.; Wu, L.; West, K.P., Jr. Micronutrient deficiencies in early
pregnancy are common, concurrent, and vary by season among rural Nepali pregnant women.
J. Nutr. 2005, 135, 1106–1112.
152. Meyer, H.E.; Holvik, K.; Lofthus, C.M.; Tennakoon, S.U. Vitamin D status in Sri Lankans living
in Sri Lanka and Norway. Br. J. Nutr. 2008, 99, 941–944.
153. Hettiarachchi, M.; Liyanage, C. Coexisting micronutrient deficiencies among Sri Lankan
pre-school children: A community-based study. Matern. Child Nutr. 2012, 8, 259–266.
154. Roth, D.E.; Al Mahmud, A.; Raqib, R.; Akhtar, E.; Perumal, N.; Pezzack, B.; Baqui, A.H.,
Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3
supplementation in Bangladesh: The AViDD trial. Nutr. J. 2013, 12, 47.
155. Ali, B.; Butt, A.; Fatima, A.; McDonnell, M.E.; Masud, F. Tibial tenderness identifies secondary
hyperparathyroidism responding to high-dose vitamin d in pakistani women. Endocr. Pract.
2013, 19, 596–601.
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