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27]

Review Article

How to treat Vitamin D deficiency in sun-drenched

India - guidelines
C. V. Harinarayan
Institute of Endocrinology, Diabetes, Thyroid and Osteoporosis Disorders, Sakra World Hospitals, Varathur Hobili, Marathahalli, Bangalore,
Karnataka State, India

Abstract Vitamin D plays an important role in calcium and mineral metabolism. It is astonishing to find vitamin
D deficiency in sun drenched country like India. This could probably due to modernisation of India-
mechanization, urbanization, change in life style, dress code and revision of vitamin D adequacy range. India
has the unique problem of twin nutrient deficiency- vitamin D and calcium. Low calcium in the diet coupled
with vitamin D deficiency has adverse consequences in the skeletal health. Any vitamin D schedule to treat/
supplement should be accompanied by adequate calcium in the diet/supplementation. There are many
international guide lines for vitamin D supplementation. This review aims at highlighting the vitamin D
supplementation schedule suitable in Indian context keeping in mind the cost and compliance. Studies in
south India using in vitro ampoule mode with 7-dehyrocholestrol has shown adequate formation of active
form of vitamin D from mid-day sun. Time of the day, latitude, and increased skin pigmentation all influence
the cutaneous production of vitamin D. Exposing 12%-18% of body surface area to unprotected sunlight for
30-45 mins is equivalent to taking 600-1000 IU of vitamin D which is the dose recommended by experts
for fortification of food. Vitamin D synthesized in the skin last twice as long. We as human can get Vitamin
D from abundant sunshine. There are various food fortification schedules suggested. The major source of
vitamin D for both children and adults is unprotected sun exposure. In the absence of sun exposure adequate
amount of vitamin D from dietary sources and supplementation is a must to satisfy body’s requirement. In
India, adequate amount of vitamin D should be accompanied by dietary/supplemental calcium to achieve
desired skeletal benefits.

Keywords: Calcium deficiency, India, Vitamin D deficiency

Address for correspondence: Dr. C. V. Harinarayan, Director, Institute of Endocrinology, Diabetes, Thyroid and Osteoporosis Disorders, Sarka World Hospital,
Bengaluru ‑ 560 103, Karnataka, India.
E‑mail: [email protected]

(See the editorial by Holick, on page 101-5, doi: 10.4103/JCSR.JCSR_3_19)

INTRODUCTION Sea was found to contain a large amount of ergosterol

(Vitamin D2 precursor). Vitamin D gained essential role
Vitamin D is one of the oldest hormones (>500 million years). (to maintain a rigid skeleton in calcium poor environment)
The Phytoplankton species that existed in the Sargasso in higher terrestrial animals to cope with higher gravity.

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DOI:
10.4103/JCSR.JCSR_1_19 How to cite this article: Harinarayan CV. How to treat Vitamin D deficiency
in sun-drenched India - guidelines. J Clin Sci Res 2018;7:131-40.

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Harinarayan: Vitamin D treatment guidelines - India

PHOTOBIOLOGY OF VITAMIN D retinoid X receptor (RXR) to form 1,25(OH) D‑RXR‑VDR

complex which further interacts with DNA sequences
The 7‑DHC‑7‑dehydrocholesterol (provitamin D 3‑in and Vitamin D‑responsive elements. The RR include the
lipid bilayer of the epidermis) is converted pre-vitamin opening of ion channels which occurs in few seconds
D 3 on exposure to sunlight ultraviolet B (UV‑B to as long as 10–60 min (e.g., intestinal absorption of
wavelengths 290–315 nm). [1] This pre-vitamin D 3 calcium‑transcaltachia), secretion of insulin by pancreatic
undergoes conformational changes in the lipid bilayer β‑cells, the opening of voltage‑gated Ca++ and Cl− channels
of the skin to convert into vitamin D3 (cholecalciferol) of osteoblasts, etc.).[3] While the non‑calcaemic benefits
at body temperature and is ejected from the plasma are becoming to be understood, calcaemia benefits are
membrane into extracellular space. The liver converts well established.
vitamin D3 into 25 hydroxy vitamin D3 (25[OH]D3).
While Vitamin D is the major storage form, 25(OH)D3 is VITAMIN D AND PEAK BONE MASS
the major circulating form of vitamin D. 1,25 di‑hydroxy
vitamin D3 is (1,25[OH]2D3) is synthesised by kidneys and The peak bone mass (bone density) at the end of the growth
other tissues. On excessive exposure to sunlight, previtamin period is attained with adequate vitamin D and calcium
D3 is converted to biologically inert products (lumisterol intake.[4‑6] An increase in dietary calcium intake during infancy,
and tachysterol). Vitamin D2 is derived from plant sources. childhood and adolescence favours bone mineral accrual. To
Most vitamin D2 comes from yeast and mushrooms attain bone growth potential, adequate nutrition and sufficient
exposed to sunlight and UV radiation. physical activity provide the necessary mechanical impetus.
Vitamin D and calcium status correlate with bone density.
Parathyroid hormone (PTH) converts 25(OH)D 3 to They have the potential to increase the peak bone mass and
1,25(OH)2D3 which helps in calcium absorption from effectively prevent osteoporosis at late age.
the gut. PTH is secreted when the serum calcium
FACTORS AFFECTING VITAMIN D SYNTHESIS
falls below the normal range, which resorbs the bone
to maintain the serum calcium to normal (secondary
The ability of the skin to synthesise vitamin D is affected
hyperparathyroidism [SHPT]). PTH also increases the
by: Environmental factors such as latitude, season, day and
tubular reabsorption of calcium in the kidneys and
night, time of the day, the solar zenith angle (SZA),
to increase the renal production of 1,25 di‑hydroxy
amount of cloud, ozone and aerosols, atmospheric
vitamin D3. Thus, the ‘Ca‑vitamin D‑PTH endocrine axis’
pollution, UV index and Personal factors such as, dress
is orchestrated by Vitamin D [Figure 1].[2]
code, skin pigmentation (Indians come under the skin
BIOLOGICAL FUNCTIONS category‑type V), age (reduced ability of skin capacity with
age), minimal erythemal dose (MED) and application of
1,25 dihydroxy vitamin D3 acts through genomes (genomic sun protection factor. The SZA becomes more oblique in
actions) and chemical messengers (Rapid winter and few UVB photons penetrate earth surface.[7,8]
responses‑RR) [Figure 2] genomic action take a few hours The SZA is also more oblique in the early morning and
to days. The Vitamin D receptor (VDR) interacts with afternoon which is why even in India very little if any

Figure 1: Calcium‑Vitamin D‑parathyroid hormone endocrine Figure 2: Vitamin D actions genomes and chemical messengers (rapid
axis (Copyright Permission‑Nutrition Foundation of India) responses) (Copyright Permission‑Nutrition Foundation of India)

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Harinarayan: Vitamin D treatment guidelines - India

vitamin D is produced in the skin before 10 a.m. and after Council of Medical Research (ICMR),[15] there is a high
3 p.m. prevalence of inadequate dietary calcium intake across rural,
urban and metro population. The average (mean ± standard
NORMAL RANGE OF 25 HYDROXY VITAMIN D deviation) dietary calcium intake in India is 560 ± 310 mg/
(VITAMIN D STATUS)
day in adults and 430 ± 180 mg/day in children.[11‑14] The
Serum 25‑hydroxyvitamin D (25[OH]D) level is the dietary calcium intake of rural, urban and metropolitan city
major circulating form providing vitamin D status of an subjects in India (mean ± standard error of mean) is 269 ± 2;
individual. Serum 25(OH)D levels (half‑life 3 weeks) reflect 308 ± 2.3; and 526 ± 8 mg/day, respectively (P < 0.001)
both cutaneous synthesis and absorption from the gut. which is lower than ICMR recommendations[15,16] [Table 1].
Biochemically, levels <20 ng/mL are defined as ‘deficiency’ The phytate content of the diet is high and is significantly
and levels of 25(OH)D >30 ng/mL (to convert ng/mL different in the rural, urban as well as the metropolitan city
to nmol/mL multiply by 2.5) are considered as ‘normal’. groups (P < 0.0001).[13,14,16,17] Phytates retard/prevent the
Levels between 20 and 30 ng/mL are defined as absorption of calcium from the gut.
‘insufficiency’.[9,10] CONSEQUENCES OF VITAMIN D AND CALCIUM
DEFICIENCY
MAGNITUDE OF VITAMIN D AND CALCIUM
DEFICIENCY IN INDIA
Vitamin D deficiency affects the calcium, phosphorous
Vitamin D and bone metabolism. With Vitamin D deficiency there
Vitamin D deficiency in a sun‑drenched tropical country is decreased efficiency of intestinal absorption of calcium
like India is surprising. About 85% of Indian population and phosphorous from the diet resulting in elevated PTH
are deficient in Vitamin D. It has been shown that the levels.[18‑21] The SHPT thus ensued, maintains the serum
25(OH)D levels inversely correlate with latitude (r = −0.48; calcium in the normal range, mobilising the calcium from
P  < 0.0001) from the various studies in the country.[8] the skeleton and increasing phosphate excretion from the
The 25(OH) D levels are relatively higher in south Indian kidneys. The PTH‑mediated osteoclastic activity weakens
subjects (in urban and rural Andhra Pradesh ~17 ng/mL the bone leading to decreased bone mineral density (BMD)
and ~19 ng/mL, respectively)[11] compared to that of north resulting in osteopenia and osteoporosis. The phosphaturia
Indians (urban northern India‑children 11.8 ± 7.2 ng/mL due to SPHT causes low normal or low‑serum phosphorus
and adolescents 13.84 ± 6.97 ng/mL).[12] Populations levels. The result is inadequate calcium phosphorous
studies from south India (Andhra Pradesh‑latitude 13.40° product causing mineralisation defect.
N and longitude 77.2° E) have shown that agricultural
labourers with their tarso (35% of body surface area) When there is dietary calcium deficiency (high phytate diet
exposed for >4 h a day have vitamin D deficiency (~24 ng/ worsens), there is SHPT with elevated 1,25(OH)2 D3 levels,
mL vs. 19 ng/mL as compared to urban dwellers).[13,14] which increase fractional absorption of calcium. When
unable to meet calcium demands, there is hypocalcaemia.
Dietary calcium intake The lower serum phosphate cuts associated with increased
Calcium and 1.25 dihydroxy vitamin D3 are closely linked levels of PTH is the cause for the mineralisation defect. This
in their action at the cellular level. Adequate dietary calcium mineralisation defect is known as osteomalacia and is often
is necessary for bone mineral accrual. Compared to the undetected. This causes decrease in BMD. In children when
recommended daily/dietary allowances (RDA) of the Indian there is little mineral in skeleton, this results in a variety of
skeletal deformities known as rickets. In adults (after fusion
Table 1: Daily recommended dietary allowances of of epiphysis), there is enough mineral in the skeleton to
calcium (mg/day) in India and USA prevent deformities. The complaints are often aches and
Category India[15] USA[17] pains in bones and muscles.[22‑24] In children, they may
Units mg/day mg/day
Infants (months)
present with difficulty in standing and walking. Elderly
Infants 0-6 500 500 may have frequent falls and increasing risk of fracture.[25,26]
Infants 6-12 500 750
Children boys and girls (years) FACTORS RESPONSIBLE FOR HIGH
1-9 600 700-1000 PREVALENCE OF VITAMIN D DEFICIENCY IN
10-15 800 1300
INDIA[27]
16-18 800 1300
Men 600 1000-1200
Women 600 1000-1200 Modernisation with prolonged indoor working hours,
Pregnant and lactating mothers 1200 1000-1300
sun‑shy nature of Indians, traditional clothing habits (‘burqa’
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Harinarayan: Vitamin D treatment guidelines - India

and ‘pardah’ further reduce skin exposure to sunlight in granulomatous disorders– tuberculosis; sarcoid; fungal
women), darker pigmentation, high atmospheric pollution, diseases– histoplasmosis, coccidiomycosis, some lymphomas
phytates in high‑fibre diet, low dietary calcium intake, and those on medications– anti‑seizure medications;
repeated, unplanned and unspaced pregnancies (decreased glucocorticoids; antifungals and cholestyramine.
maternal stores of vitamin D) are the factors responsible.
RECOMMENDED DIETARY ALLOWANCES OF
SOURCES OF VITAMIN D AND CALCIUM CALCIUM AND VITAMIN D FOR INDIANS

Sources of vitamin D: Sunlight‑UVB radiation, Cod The RDA of calcium (mg/day) (both genders) for
liver oil, salmon fish, Mackerel, Sardines, Tuna, Egg yolk, Infants 0–1 year 500, children 1–9 years 600; for children
Mushrooms (if exposed to sunlight or UV radiation). 10–18 years 800; for adults is 600; and for pregnant and
lactating women 1200 as per the revised guidelines of
Sources of calcium: [15] milk and milk products ICMR [Table 1].[15] The committee was of the view that
(120–210 mg/100 g edible portion)– buffalo’s and cow’s Vitamin D fortification and supplementation pertain
milk– curd; about 790–1370 mg/100 g edible portion to the population in developed countries where there is
in cheese, paneer, khoa, skimmed milk; Cereals and limited sunlight exposure. The committee felt that outdoor
Legumes (200–340 mg/100 g edible portion)‑Ragi, whole physical activity was not only a means of achieving adequate
bengal and horse gram, rajmah and soya bean; green leafy synthesis of Vitamin D but also helps in controlling
vegetables (500–800 mg/100 g edible portion)– Amaranth, overweight and obesity. The previous recommendation of
cauliflower greens, curry leaves, knol‑khol leaves; Nuts 400 IU/day for adults was retained.
and oil seeds‑coconut dry, almonds, hazelnuts, mustard,
sunflower  (130–490  mg/100  g edible portion), gingelly The RDA of calcium (mg/day) of USA[17] is‑Infants
and cumin seeds (1080–1450 mg/100 g edible portion). 0–1 year 500, children 1–9 years 800; 10–18 years 1200–
1300; adults (both genders) 800–1000; pregnant and
ASSESSMENT OF VITAMIN STATUS OF AN lactating mothers 1200–1300 [Table 1]. The Vitamin D
INDIVIDUAL
recommendation for the general population, of various
societies are given in Table 2.[17,27-31]
Serum 25OHD levels (half‑life 3 weeks), is an established
proxy of the vitamin D status of an individual. The CONCEPT AND BASIS OF VITAMIN D
concentrations of 25(OH)D in the serum reflect both SUPPLEMENTATION
absorption and cutaneous synthesis. The commercial
immunoassays quantify total 25(OH)D which includes SPHT occurs when the 25(OH)D levels are <20 ng/dl.
the exogenous and endogenous Vitamin D. Hence, the SPHT leashes the bone, conserves calcium from the
terminology ‘25(OH)D’ is preferred. Unfortunately, kidneys and converts 25(OH)D to 1,25(OH)2D and helps
most commercial kit assays cannot adequately measure in calcium absorption from gut to maintain serum calcium
25‑hydroxy vitamin D2. Now that India is fortifying food level to normal. Hence, vitamin D and calcium supplementation
with vitamin D2 this will be a major issue in the assessment therapy are to suppress SPHT and help in bone accretion. When
of Vitamin D status of an individual. Assessment of the vitamin D status is low only 10%–15% of dietary
active form 1,25(OH)2D3 (half‑life 4–6 h) is not used to calcium and 60% of phosphorous is absorbed. Vitamin D
estimate the vitamin D status of an individual except in sufficiency enhances the calcium absorption by 30%–40%
conditions such as acquired and inherited disorders of and phosphorous absorption by 80%.
vitamin D and phosphate metabolism.
PHARMACOLOGICAL PREPARATIONS OF
CANDIDATES FOR SCREENING VITAMIN D AND CALCIUM

Metabolic bone diseases– Rickets, osteomalacia, Cholecalciferol is the drug recommended for the general
osteoporosis, older adults with history of falls/or population, the population at risk and treatment of
non‑traumatic fractures; pregnant and lactating women; vitamin D deficiency. Vitamin D2 should also be included
Chronic hepatic and renal failure; Pancreatic diseases– cystic for pharmacological preparations since vegetarians
fibrosis, calcific pancreatitis; post‑whipple procedure; will not take vitamin D3. The blood level increase in
Disorders of gut– Inflammatory bowel diseases, 25‑hydroxy vitamin D depends on the baseline blood
Crohn’s disease, malabsorption syndromes, radiation level in response to Vitamin D. There is a robust increase
enteritis; post‑bariatric surgery; hyperparathyroidism; in 25‑hydroxy vitamin D levels with small amounts of
134 Journal of Clinical and Scientific Research | Volume 7 | Issue 3 | July-September 2018
 Table 2: Daily recommended dietary allowances of vitamin D‑of various societies and proposed guidelines
Age group Endocrine society IOM guide lines[17] Central Europe[29] SBEM[30] Indian Association of Proposed guidelines
guidelines[28] Paediatrics[31]
Daily UL, IU/day RDA, IU/day UL, IU/day Daily UL, IU/day RDA, At risk of RDA, UL, IU/day RDA, At risk of UL, IU/day
requirement, requirement, IU/day deficiency, IU/day IU/day deficiency,
IU/day IU/day IU/day IU/day
Infants (months)
0-6 400-1000 2000 400 1000 400 1000 400 400-1000 400 1000 400 1000 2000
6-12 400-1000 2000 400 1000 400-600 1000 400 400-1000 400 1000-1500 400 1000 2000
Children (years)
1-3 600-1000 4000 600 2500 600-100 2000 400 600-1000 600 3000 600 1000 4000
4-8 600-1000 4000 600 3000 600-100 2000 400 600-1000 600 3000 600 1000 4000
Males (years)
8-18 600-1000 4000 600 4000 600-100 4000 600 600-1000 600 3000 till 600 1000 4000
9 years,
4000
from 9 to
18 years
19-70 1500-2000 10,000 600 4000 800-2000 4000 600 1500-2000 ‑ ‑ 600 2000 10,000
>70 1500-2000 10,000 800 4000 800-2000 4000 800 1500-2000 ‑ ‑ 800 2000 10,000
Females (years)
8-18 600-1000 4000 600 4000 600-100 4000 600 600-1000 600 3000 till 600 1000 4000
9 years,
4000
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from 9 to
18 years
19-70 1500-2000 10,000 600 4000 800-2000 4000 600 1500-2000 ‑ ‑ 600 2000 10,000
Harinarayan: Vitamin D treatment guidelines - India

>70 1500-2000 10,000 800 4000 800-2000 4000 800 1500-2000 ‑ ‑ 800 2000 10,000
Pregnancy/
lactation (years)
19-50 1500-2000 10,000 600 4000 1500-2000 4000 600 1500-2000 ‑ ‑ 600 2000 10,000
Obese adult and 2-3 time the ‑ ‑ ‑ 1600-4000 1000 ‑ ‑ ‑ 2-3 time
elderly reference for the
age reference
for age
RDA=Recommended Daily/Dietary Allowance; IU/day=International units/day; UL=Tolerable upper intake level; SBEM=Brazilian Society of Endocrinology and Metabology; IOM=Institute of
Medicine

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Vitamin D when blood levels of 25‑hydroxy vitamin D concentrations consistently >30 ng/ml may require
are <20 ng/mL. Thereafter for every 100 IUs suggested 1500–2000 IU/day. Adults 70 years and above require
the blood levels of 25‑hydroxy vitamin D increase by 600–800 IU/day and at least 1500–2000 IU/day to raise
0.6–1 ng/mL.[28] the 25(OH) D levels >30 ng/ml consistently. In pregnancy
and lactation at least 600 IU/day of vitamin D is required.
Analogues such as 1α‑(OH)D3, 1α‑(OH)D2, 1,25(OH)2D3, 1500–2000 IU/day may be required to maintain blood
19‑nor‑1α,25(OH)2D2, 22‑oxa‑1α, 25(OH)2D3, 25(OH)2D3, levels of 25(OH)D above consistently 30 ng/mL. Night
should not be used to manage Vitamin D deficiency. They workers and dark‑skinned adults require 1000–2000 IU/day
are used in the chronic renal disease when associated with throughout the whole year. Obese individuals require
disorders of Vitamin D hydroxylation. 2–3 times the dose required for age‑matched peers
with normal body weight.[33] The tolerable upper intake
Calcium carbonate and citrate are the most common level (both genders) for infants 0–12 months is 2000 IU;
forms of calcium preparation. Calcium carbonate children 1–18 years 4000 IU; adults 19–70 years 10,000 IU;
is given immediately after a meal to ensure optimal and pregnancy and lactation 10,000 IU.
absorption (1250 mg of calcium carbonate gives 500 mg of
elemental calcium, which is the maximal dose of calcium VITAMIN D SUPPLEMENTATION BASED ON
given at a time). Calcium citrate can be taken without 25(OH)D CONCENTRATIONS
meals and is the supplement of choice in a patient with
achlorhydria and those taking proton pump blockers 25(OH)D levels 0–20 ng/mL
and histamine‑2 blockers. Calcium from calcium citrate The therapeutic dose of vitamin D should be supplemented
is slightly better absorbed than calcium from calcium and treatment carried out until the 25(OH)D concentrations
carbonate. Calcium carbonate is the least expensive and is of  >30 ng/mL is reached. The dose 0–1 year of age is
what often is recommended. It should be taken with a meal 2000 IU/day; 1–18 years 4000 IU/day; adults (19–70 years)
if at all possible. Studies by Recker have shown that calcium and elderly (>70 years) 10,000 IU/day. Alternatively, adults
carbonate is perfectly absorbed in achlorhydric patients as and elderly can be given 60,000 IU/weekly for 8 weeks
long as it is taken with a meal.[32] It is not absorbed on an to achieve 25(OH)D concentrations of  >30 ng/mL and
empty stomach if the calcium carbonate is in some type followed by maintenance dose for their respective age. In
of pill form.[32] Calcium gluconate and lactate are less patients with skeletal symptoms, it is necessary to assess and
concentrated form of calcium and are not practical for monitor a parameter of calcium and phosphate metabolism
supplementation in oral form. The upper tolerable (UL) (serum calcium, phosphorous, alkaline phosphatase, PTH
limit for calcium is 2500 mg/day. and calcium/creatinine ratio).

ABSORPTION OF VITAMIN D AND CALCIUM 25(OH)D levels 20–30 ng/mL

Verify if the patient was already on appropriate vitamin D
Vitamin D is absorbed into the lymphatic system through supplementation schedule the regularity of dose, intake,
chylomicrons. Vitamin D metabolite 1,25(OH)2D3 uses type of preparation and way of supply. If appropriate,
VDR to regulate intestinal calcium absorption. Four models increase the dose by 50% and reassess after 6 months.
of vitamin‑D‑regulated intestinal calcium absorption are If vitamin D was not supplemented previously, consider
proposed, namely, facilitated diffusion, vesicular trafficking, starting vitamin D intake as recommended for the general
transcaltachia and regulated paracellular transport. population.

RECOMMENDED DIETARY INTAKE OF VITAMIN 25 OH levels >30 ng/mL

D FOR PATIENTS AT RISK [TABLE 2][17,28-32] When the patient is on optimal vitamin D levels and on
supplementation, it is advisable to continue the previous
The candidate at risk for vitamin D deficiency is those management. In those not on supplementation to consider
mentioned under the section‑screening. In these individuals’ starting Vitamin D intake as recommended for the general
supplementation is to be implemented to maintain the population.
serum 25(OH)D concentration >30 ng/mL. For both
genders, the daily vitamin D requirements (IU/day) for STOSS THERAPY
infants and children 0–1 year require 400 IU; 1–18 years
600 IU. To raise the serum 25(OH)D concentrations “Stossen” (German) means to push. Stoss therapy involves
consistently >30 ng/ml may require 1000 IU/day. For pushing large doses of cholecalciferol to treat nutritional
age 19–70 years require 600 IU/day. To maintain serum rickets.[34] The basis of this therapeutic approach is that
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Harinarayan: Vitamin D treatment guidelines - India

adipose tissue and muscles efficiently store cholecalciferol benefits. In the Indian context, Vitamin D supplementation if not
after a single large dose. There is continued conversion accompanied by adequate calcium supplementation may not achieve
into active metabolite 1,25(OH)2D3 to heal rickets. In a desired skeletal benefits. Iron is not combined with calcium.
country like India, with limited resources, compliance
and cost are the major advantages of single‑dose MONITORING OF VITAMIN D TREATMENT
intramuscular stoss therapy over daily, weekly regimes
or oral stoss therapy. Cholecalciferol 600,000 IU deep Because of the cost of 25(OH)D estimation repeated
intramuscular (for >18 years age) would maintain serum estimation of 25(OH)D is not advised. However, repeat
levels adequately and supress PTH. The second dose estimations of 25(OH)D is undertaken in at‑risk patients
should not be repeated until the next 8 weeks. Stoss therapy when there is no desired response in patients treated with
should be followed by maintenance dose of vitamin D and metabolic bone diseases.[28] A serum calcium level of
adequate dietary calcium intake.[35] Calcitriol is not used for 10.5–11 mg/dL and above point to vitamin D toxicity.
stoss therapy. A baseline serum calcium helps in follow‑up. Fasting
urine calcium‑to‑creatinine ratio (calcium and creatinine
INDIAN EXPERIENCE measured as milligrams/dL in random urine specimens) of
0.25 and above is an indirect indicator of vitamin D excess.
In India, most supplementation schedules in adults
for correcting vitamin D deficiency have shown that DURATION OF THERAPY
with a dosage of cholecalciferol 60,000 IU/weekly for
8 weeks (with or without calcium supplementation) Once 25(OH)D concentrations of  >30 ng/mL is reached,
have achieved normal serum levels of 25(OH)D at the maintaining the serum levels along with adequate calcium
end 2 months.[36‑38] When the supplementation is not supplementation is important. Adequate 25(OH)D levels
followed by maintenance schedule the serum 25(OH)D will suppress SHPT. To calcify the osteoid formed due
levels drift back. Hence, they need to be followed up with to vitamin D deficiency adequate calcium is important. It
cholecalciferol 60,000 IU/once a month. has been shown from bone histomorphometric studies
that subjects with 25(OH)D levels <20 ng/dL have wide
In a study conducted in India, [38,39] vitamin D osteoid seams and may take anywhere from 10 to 15 years
supplementation (based on the Endocrine Society Clinical to mineralize (mineralization lag time) their bones.[40]
Practice Guidelines), even up to UL intake levels along Hence, maintaining adequate 25(OH)D levels >30 ng/mL
with elemental calcium of 1 g/day is safe and does not with adequate dietary calcium is imperative for skeletal
lead to hypercalcaemia. In another study conducted in health.
India, parental dose of 600,000 IU of cholecalciferol/
VITAMIN D TOXICITY
deep IM stat followed by maintenance cholecalciferol
therapy was compared with cholecalciferol 60,000 IU/ Serum concentrations of 25(OH) D >150 ng/mL
weekly for 8 weeks followed by maintenance cholecalciferol (375 nml/L) is considered as toxicity and levels up to
therapy. [39] Both groups received elemental calcium 100 ng/ml (250 nmol/L) are cited as safe for both children
throughout. Both groups achieved similar serum calcium, and adults.[41] Serum 25(OH)D concentrations are elevated
25 OH D levels and suppression of PTH.[39] Parenteral dose associated with hypercalcaemia or hypercalciuria and
of 600,000 IU of cholecalciferol/deep IM stat SHOULD suppressed PTH. Patients present with clinical features of
NOT be repeated until the 8th week. After 8 weeks, oral lethargy, vomiting, polyuria, polydipsia, altered sensorium,
cholecalciferol 60,000 IU/once a month can be given.[39] weight loss, nausea, constipation, renal dysfunction, renal
Loading doses of cholecalciferol (oral or parenteral) are calculi, muscle weakness, hypertension, neuropsychiatric
not reccomended in pregnant women unless the patient has disturbances, cardiac arrhythmias and ultimately death. It
symptomatic vitamin D deficiency (tetany or symptomatic is commonly due to overdosing by prescriptions or intake
hypocalcaemia). Daily requirement of cholecalciferol in by patient with high doses of vitamin D doses that exceed
pregnancy is 2000 IU/day. The UL limit of cholecalciferol suggested recommendations.
supplementation is 10,000 IU/day.
VITAMIN D HYPERSENSITIVITY
Thus, a simple supplemental dose without adequate loading
doses may not be sufficient to achieve therapeutic levels. The UL value is the highest value of vitamin D oral
Similarly, after a loading dose, if not sustained in the intake which is unlikely to produce risk of adverse
long term with supplemental dose may not give desired effects during growth and maturation, adulthood and
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Harinarayan: Vitamin D treatment guidelines - India

ageing. Two conditions to the exception of the rule correlation between the 25(OH)D levels and latitude (r =
are‑granulomatous diseases and genetic defect or absence −0.48; P < 0.0001). The 25(OH)D levels in South Indian
of 24‑hydroxylase (CYP24A1).[42] In granulomatous diseases subjects are relatively higher than in subjects in North India
like sarcoid, there is excess extrarenal 1‑alpha‑hydroxylase. clearly establishing the relationship between closeness to
This leads to excessive and uncontrolled production of the equator (smaller zenith angle) and natural Vitamin D
calcitriol (1,25[OH]2D3) resulting in low 25(OH)D levels. synthesis.[8]
In these conditions, the recommended target for serum
25(OH)D is 25 ng/mL. In another study,[48] authors assessed serum 25(OH)D and
bioavailable 25(OH)D in males with varying durations of
The active form of Vitamin D 1,25(OH)2D3 is formed sun‑exposure between indoor and outdoor environments
by 1‑alpha‑hydroxylase (CYP27B1). The levels of in Delhi (latitude 28.38° N and longitude 77.12° E)
25(OH)D and 1,25(OH)2D3 is regulated by cleavage reaction during August–September. They demonstrated that
of 24‑hydroxylase (CYP27A1). This enzyme catalyses 25(OH) outdoor workers with prolonged sun‑exposure were
D and 1,25(OH)2D3 to inert metabolites. Mutations of vitamin D‑sufficient, with higher serum bioavailable
CYP27A1 gene coding 24‑hydroxylase[43] or excessive synthesis 25(OH)D than the indoor workers during summer. Studies
1,25(OH)2D3 of resulting from the mutation of SLC34A1 from Pune (latitude 18.31° N and longitude 73.55° E)
gene coding sodium‑phosphate co‑transporter (NaPi‑IIA) in have shown that toddlers exposed to sunlight (playing
the kidney[44] can result in a risk of hypervitaminosis D even outside) for more than 30 min-a-day exposing more than
in prophylactive doses of Vitamin D. 40% of their body surface area have a normal Vitamin
SUNLIGHT AND VITAMIN D D status which was three times more compared with the
toddlers who were indoors for most part of the day.[49]
The most physiological relevant and efficient way Hence, the association between Sunlight exposure and
of acquiring vitamin D, in locations around the vitamin D synthesis is well established in South Asians.
equator (between latitudes 42° N and 42° S) is endogenous We as human can get vitamin D from abundant sunshine.
synthesis from the skin. A minimum of 30 min skin The position statement for vitamin D and health in adults
exposure (without sunscreen) of the arms and face to in Australia and New Zealand recommends a walk for 6-7
mid‑day sun will be sufficient for the day requirement. mins mid-morning or mid afternoon in summer and as
Vitamin D synthesised in the skin lasts twice as longer in the much bare skin exposed as feasible for 7-40 mins at noon
body compared to ingested/supplemented dose. Exposure in winter, for fair-skinned people on most days to maintain
of body in bathing suit (almost 100% of body surface area) adequate vitamin D levels in the body.[50]
to sunlight causes slight pinkness (1 MED) is equivalent to
ingesting approximately 20,000 IU of vitamin D orally.[45] FORTIFICATION OF FOODS
Applying the rule of nines Burns chart, exposure of both
forearms and face is equivalent to exposing 12% of body India has the unique burden of ‘twin nutrient
surface area. Exposure of 1 MED two to three times deficiency’–  vitamin D and calcium. Any public health
a week can meet the body’s requirement of Vitamin D measures which address the problem in isolation may
(Holick’s Rule). ‘1 Standard vitamin D Dose’  (SDD) is not have the desired skeletal benefits in the long term.
the time required to obtain recommended UV dose for Recently, in India, milk and cooking oil is being fortified
adequate vitamin D synthesis.[46] For Asians with skin with vitamin D. There are many reports[51‑56] and proposal
type V, 1 SDD at 11.5° N is 10–15 min, and at 29° N is for fortification process.
10–45 min at solar noon, with longer durations in winter.
Vitamin D synthesis can be reduced and force ‘Vitamin D India has 1.33 billion population with a rural‑urban
winter’ when there are clouds, aerosols and dense ozone.[47] distribution: 68.84% and 31.16%. There has been a spurt in
India is located at between 8.4° and 37.6°N. growth of population in Urban areas in the country, which
could be due to: migration, natural increase and inclusion
A study conducted from Tirupati (latitude 13.4° N and of new areas under ‘urban’ in the census. Majority of rural
longitude 77.2° E, south India) using ‘in vitro’ ampoule model population sell their produce (milk, vegetables, grains, etc.,)
with precursors of vitamin D (7‑dehydrocholesterol), when to the urban for their lively hood.[13,14] Only 35% of the
exposed to sunlight, converted to active Vitamin D best in Indian populations have access to regulated milk supply.
mid‑day sun (between 11 a.m. to 2 p.m).[8] From the various India ranks 97 among the 118 developed countries in
Indian studies in the literature, there is a strong inverse Global Hunger Index.
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Harinarayan: Vitamin D treatment guidelines - India

Any fortification measure should reach the population as a 2. Harinarayan CV. Multiple roles of Vitamin D. NFI Bull 2014;35:1‑8.
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~ / m e d i a / F i l e s / Re p o r t % 2 0 F i l e s / 2 0 1 0 /Dietary-
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