Medicines Q&As
Q&A 82.2
What dose of vitamin D should be prescribed for the treatment of vitamin D
deficiency?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 8th January 2013
Background
Vitamin D compounds are fat soluble sterols which are essential for the absorption and utilisation of
calcium and phosphorus (in the form of inorganic phosphate) in the body to maintain normal
calcification of the skeleton and bone mineralisation. (1, 2) Along with parathyroid hormone (PTH) and
calcitonin, the active form of vitamin D (25-OHD) regulates serum calcium concentration by altering
serum calcium and inorganic phosphate blood levels as needed. It maintains neuromuscular function
and various other cellular processes, including the immune system and insulin production. (1)
The recommended daily intake of vitamin D in the UK is around 400IU (10mcg) for an adult, 280IU
(7mcg) for children aged 6 months to 3 years and 340IU (8.5mcg) per day for infants under 6 months.
(3) The Scientific Advisory Committee on Nutrition is currently reviewing the dietary reference values
for vitamin D intake and is due to publish its report in 2014. (4)
Over 90% of the bodies vitamin D is produced from skin photosynthesis following ultraviolet B sunlight
exposure. In a fair skinned person, 20-30 minutes of sunlight exposure to the face and forearms at
midday generates about 2000 units of vitamin D. Two or 3 sunlight exposures per week are sufficient
to achieve vitamin D levels in the summer if individuals have adequate levels to begin with. However,
those with low vitamin D levels, pigmented skin and the elderly need increased exposure time or
frequency to get the same level of vitamin D synthesis. (3) Sun exposure should be avoided if
someone has a history of skin cancer, or conditions such as xeroderma pigmentosum or actinic
keratosis. (5)
The average adult daily diet in the UK provides only 3.7mcg of vitamin D for men and 2.8mcg for
women. Food sources which contain greater than 5mcg per portion of vitamin D include 2 teaspoons
cod liver oil, 70g sardines, 100g tinned salmon, pilchards or tuna, 110g of cooked mackerel or herring
and 130g cooked kipper. (1) Consumption of food sources alone, in the absence of skin synthesis, will
not provide optimal vitamin D status. (3)
Vitamin D deficiency develops when there is inadequate exposure to sunlight or a lack of vitamin D in
the diet and usually takes a long time to develop because of the slow release of the vitamin from body
stores. Between October and April, 90% of the UK lies above the latitude that permits exposure to the
ultraviolet B wavelengths necessary for vitamin D synthesis. Risk factors for reducing vitamin D levels
include – having a pigmented skin (e.g. black, Asian populations); routine use of sun protection factor
15 and above as this blocks 99% of vitamin D synthesis; infants who are exclusively breast fed;
multiple, short interval pregnancies; institutionalised, elderly or obese individuals; malabsorption or
short bowel syndrome; cholestatic liver disease; use of anticonvulsants, rifampicin, cholestyramine,
glucocorticoids or highly active antiretroviral treatment. (3)
Vitamin D deficiency is confirmed by the measurement of serum 25-OHD concentrations. A plasma
concentration of <25 nmol/L (<10ng/ml) for 25-OHD levels has been used as the lower limit of
adequacy of vitamin D status, although this has been questioned and higher thresholds proposed. (3,
6, 7) In America, vitamin D deficiency is defined as 25-OHD <50 nmol/L (<20ng/ml). (8) Experts have
suggested that a desirable 25-OHD concentration is ≥75 nmol/L (≥30ng/ml). (3, 6, 8)
Prolonged vitamin D deficiency in infants and children results in rickets. In adults, vitamin D deficiency
results in osteomalacia, the clinical symptoms of which include skeletal pain and muscle weakness
and pathological fractures. Less severe vitamin D deficiency (usually referred to as vitamin D
insufficiency) is often associated with secondary hyperparathyroidism and increased bone loss,
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
leading to high risk of fractures. Both vitamin D deficiency and insufficiency are becoming more
common in developed countries. (3, 9)
To treat deficiency, administration of vitamin D either orally or intramuscularly is required. Vitamin D is
available as either oral ergocalciferol (vitamin D2) or oral colecalciferol (vitamin D3) and intramuscular
(IM) ergocalciferol. (3, 10)
Answer
There is no UK guidance on what dose of vitamin D or regimen to use to treat deficiency. NICE are
developing public health guidance on implementing vitamin D guidance which is due to be published
in June 2014. (11) Consequently, a number of different regimens have been developed by primary
and secondary care NHS Trusts. (12) The primary aim for deficiency is to replenish vitamin D stores
then continue with a lower maintenance dose of vitamin D which may be lifelong. (3, 9) It has been
suggested that several vitamin D regimens are effective and total cumulative dose may be more
significant than frequency of dosing. (13)
A review of primary vitamin D deficiency in adults in 2006 stated those with confirmed primary vitamin
D deficiency needed a daily dose of oral vitamin D of 20mcg (800IU). With this dose, it would take at
least a year for bone to normalise. Higher doses may be needed to achieve adequate repletion. (9)
A review in 2006 looking at treatment for children with vitamin D deficiency highlighted clinical trials
which used daily oral doses (6000IU) and single oral or intramuscular high doses (150,000IU,
300,000IU and 600,000IU). (14) The BNF for Children gives clear guidance on use of oral or
intramuscular vitamin D therapy for treatment of nutritional vitamin D deficiency rickets and vitamin D
deficiency in intestinal malabsorption or in chronic liver disease – see table 1. (15)
A clinical review in the British Medical Journal in 2010 suggested different higher dose regimens for
the management of deficiency states in adults and children – see table 1. Daily doses of 10,000 IU or
weekly doses of 60,000 IU will restore body stores of vitamin D in 8-12 weeks. Large bolus doses are
equally effective as daily doses and may be preferred when compliance with long term therapy is
poor. If a child has vitamin D deficiency or insufficiency, it should be assumed that the mother and any
siblings are also affected, and should be treated. The review does not specify whether to use
ergocalciferol or colecalciferol, so states doses in international units (IU) for calciferol which can be
applied to either preparation. To convert doses in international units to micrograms, divide by 40. (3)
A study in 208 adult patients with mean serum 25-OHD levels of 20.5nmol/L at baseline, calculated a
formula for rapid correction of vitamin D deficiency using vitamin D3 doses of 25,000 IU/week. The
formula aimed to get patients back to a target level of 75nmol/L 25-OHD:
Vitamin D3 dose (IU) = 40 X (75 – serum 25-OHD) X body weight (kg).
The equation is based on data derived from subjects weighing 125kg or less. If doses greater than
25,000 IU/week are given or doses given more frequently, the pharmacokinetics of vitamin D3 might
be affected and require an adjusted dose calculation. (16)
The Endocrine Society in the USA produced a clinical practice guideline in 2011 for the evaluation,
treatment and prevention of vitamin D deficiency. The recommendations are set out in table 1 and are
based on consensus between experts because of the overall low quality of the evidence. The
guidelines suggest using vitamin D2 or D3. (8)
Vitamin D is administered as either D2 or D3 salts. Both D2, ergocalciferol and D3, colecalciferol are
physiologically inactive and have to be hydroxylated in the liver and kidneys to form active
compounds. (2) Colecalciferol and ergocalciferol are considered to have equal potency although
colecalciferol has been reported to raise serum vitamin D concentrations more effectively than
ergocalciferol due to higher affinities of colecalciferol and its metabolites for liver enzymes, plasma
vitamin D binding protein and vitamin D receptors. It has been suggested that this difference in
potency makes colecalciferol the drug of choice. (2, 3, 9)
Calciferols are available in a variety of preparations (3, 10, 17) –
 Multivitamin solutions and drops e.g. Dalavit and Abidec provide 400IU per 0.6ml, Healthy Start
vitamin drops provide 300 IU per 5 drops.
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As

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Ergocalciferol solution 3,000 IU/ml or 20,000IU/ml.
Over the counter colecalciferol tablets and capsules e.g. Solgar softgel capsules 200 IU, 400 IU,
600 IU, 1000 IU & 2200 IU; Solgar tablets 1000 IU and 5000 IU.
Ergocalciferol 10,000 IU or 50,000 IU tablets.
Colecalciferol 20,000 IU capsules.
Ergocalciferol 300,000 IU/ml IM injection.
Table 1 – Dose of calciferol for treatment of vitamin D deficiency (3, 8, 15)
Adults
UK vitamin D dose advice (3, 15)
(25-OHD <25 nmol/L (<10ng/ml))
10,000 IU daily for 8-12 weeks or
60,000 IU once weekly for 8-12 weeks
or
300,000 or 600,000 IU orally once or
twice only or
300,000 or 600,000 IU by IM injection
once or twice only
Adult
maintenance
therapy
1,000-2,000 IU daily or 10,000IU
weekly
Child
Over 1 year: 300,000 IU calciferol as a
one off single dose (Stoss regimen)
US vitamin D dose advice (8)
(25-OHD <50 nmol/L (<20ng/ml))
50,000 IU once weekly for 8 weeks or
6,000 IU daily for 8 weeks
Obese patients, patients with
malabsorption syndromes & patients on
medicines affecting vitamin D
metabolism need a higher dose: at
least 6,000-10,000 IU daily for 8 weeks
1,500-2,000 IU daily
3,000-6,000 IU daily for patients who
need a higher dose
Up to 18 yrs: 2,000 IU daily or 50,000
IU once weekly for 6 weeks
Nutritional vitamin-D deficiency rickets
1-6 months: 3,000 IU daily, adjusted as
necessary for 8-12 weeks
6 months-12 years: 6,000 IU daily,
adjusted as necessary for 8-12 weeks
12–18 years 10,000 IU daily, adjusted
as necessary for 8-12 weeks
Child
maintenance
therapy
Intestinal malabsorption or in chronic
liver disease
1-12 years: 10,000-25,000 IU daily,
adjusted as necessary
12-18 years: 10,000IU-40,000 IU daily,
adjusted as necessary
Under 6 months: 200-400IU daily
Over 6 months: 400-800IU daily
Up to 1 yr: 400-1,000 IU daily
1-18 yrs: 600-1,000 IU daily
A 12 month survey in south west Scotland in 2009/2010 assessed the extent to which patients with
vitamin D deficiency were being treated according to expert advice. The study showed that only about
60% of those diagnosed as deficient were prescribed vitamin D, and those who were treated
frequently received inadequate doses or inappropriate forms of therapy. The article concluded that
this is due to the lack of expert agreement on which to base firm recommendations and the lack of
availability of suitable preparations. (7)
There is wide variation in tolerance to vitamin D. At recommended supplemental or therapeutic doses
toxicity is unlikely. (1) The Food Standards Agency has suggested that using less than 20mcg (800
IU) of vitamin D daily is unlikely to cause any harm in the general population. (18) Research suggests
up to 250mcg (10,000 IU) can be taken daily by healthy people for up to 16 weeks without toxicity,
use beyond 6 months may result in toxicity. Infants and children are generally more susceptible than
adults to adverse effects. (1) In 2012, the European Food Safety Authority panel on dietetic products,
nutrition and allergy produced new guidance on tolerable upper intake levels for vitamin D
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
supplementation. The maximum safe dose (or no observed adverse effect level) is 11,000 IU/day or
275 mcg/day; adults (18 years or older) 4,000 IU/day or 100 mcg/day; children 11-17 years 4,000
IU/day or 100 mcg/day; children 1-10 years 2,000 IU/day or 50 mcg/day and infants less than 1 year
1,000 IU/day or 25 mcg/day. (19)
Vitamin D is the most likely of all vitamins to cause overt toxicity. Doses of 60,000 units daily can
cause hypercalcaemia, with muscle weakness, apathy, headache, anorexia, nausea and vomiting,
bone pain, ectopic calcification, proteinuria, hypertension and cardiac arrhythmias. (1, 2) Toxicity can
lead to calcification of soft tissues and include bone pain, cardiac arrhythmias, hypertension, kidney
damage (increased urinary frequency, decreased urinary concentration; nocturia, proteinuria),
psychosis (rarely) and weight loss. If toxicity is suspected, vitamin D must be withdrawn and serum
calcium and renal function checked urgently, since emergency inpatient care with rehydration is
usually indicated. (1)
Concomitant treatment with phenytoin, barbiturates and primodone can decrease vitamin D levels
because of metabolic changes. Colestyramine, colestipol, liquid paraffin and sucralfate may reduce
intestinal absorption of vitamin D. If hypercalcaemia occurs as a result of too much vitamin D, then the
effects of digoxin may be potentiated which may lead to cardiac arrhythmias. (1)
Summary
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
Rickets and osteomalacia are due to deficiency of vitamin D and are becoming increasingly
common in the UK.
The primary aim of treating deficiency is to replenish vitamin D stores with high oral doses over 612 weeks and then continue with a lower maintenance dose of vitamin D.
It has been suggested that several vitamin D regimens are effective and total cumulative dose
may be more significant than frequency of dosing.
There is currently no national guideline or recommendations regarding how much vitamin D to
prescribe for vitamin D deficiency in adults.
Limitations
This document does not cover the use of vitamin D for prophylaxis of deficiency or the use of vitamin
D supplementation in the management of vitamin D insufficiency. It does not focus on vitamin D
supplementation during pregnancy or breast feeding or give guidance for treating muslim, vegetarian,
or vegan patients, patients with renal impairment or patients being tube fed.
Disclaimer
 Medicines Q&As are intended for healthcare professionals and reflect UK practice.
 Each Q&A relates only to the clinical scenario described.
 Q&As are believed to accurately reflect the medical literature at the time of writing.
 The authors of Medicines Q&As are not responsible for the content of external websites and
links are made available solely to indicate their potential usefulness to users of NeLM. You must
use your judgement to determine the accuracy and relevance of the information they contain.
 See NeLM for full disclaimer.
References
1. Dietary Supplements. Vitamin D monograph. London: Pharmaceutical Press. Last revised
04/05/12. Accessed via http://www.medicinescomplete.com on 02/01/13.
2. Sweetman S (ed). Vitamin D substances. Martindale: The Complete Drug Reference (online)
London: Pharmaceutical Press. Date of revision of the text 05/12/11. Accessed 28/12/12 via
www.medicinescomplete.com.
3. Pearce SHS, Cheetham TD. Diagnosis and management of vitamin D deficiency. British Medical
Journal 2010; 340: 142-147.
4. Vitamin D Working Group. Scientific Advisory Committee on Nutrition. Accessed 03/01/13.
http://www.sacn.gov.uk/meetings/working_groups/vitamin/index.html
5. Anon. Skin cancer risks and causes. Cancer Research UK. Updated 1 June 2012. Accessed via
www.cancerresearch.org on 08/01/13.
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
6. Jackson AA (chair) Update on vitamin D: Position statement by the scientific advisory committee
on nutrition. Scientific Advisory committee on nutrition. London 2007. Accessed via
http://www.sacn.gov.uk/reports/position_statements/update_on_vitamin_d.html on 03/01/13.
7. Findlay M, Anderson J, et al. Treatment of vitamin D deficiency: divergence between clinical
practice and expert advice. Postgraduate Medical Journal 2012; 88 (1039): 255-60.
8. Holick MF, Binkley NC, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An
endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism
2011; 96 (7): 1911-1930.
9. Anon. Primary vitamin D deficiency in adults. Drug & Therapeutics Bulletin 2006; 44 (4): 25-9
10. Ryan R, editor. British National Formulary. London: British Medical Association and The Royal
Pharmaceutical Society of Great Britain; No. 64 September 2012. Accessed 28/12/12 via
http://www.bnf.org/bnf/
11. Implementing vitamin D guidance. NICE website. http://www.nice.org.uk/ Accessed 08/01/13
12. Rehman B, Rai V. Vitamin D deficiency and insufficiency in adults and paediatrics: a guideline
collation document for London and East & South-East England. London Medicines Information
Service, October 2012. Accessed 28/12/12 via http://www.nelm.nhs.uk
13. Osborn J; Germann A; St Anna L. Clinical inquiries. Which regimen treats vitamin D deficiency
most effectively? Journal of Family Practice 2011; 60 (11): 682-3.
14. Anon. Primary vitamin D deficiency in children. Drug & Therapeutics Bulletin 2006; 44 (2): 12-16.
15. Ryan R, editor. BNF for Children. London: British Medical Association, the Royal Pharmaceutical
Society of Great Britain, the Royal College of Paediatrics and Child Health, and the Neonatal and
Paediatric Pharmacists Group; December 2012. Accessed 03/01/13 via http://bnfc.org/bnfc/
16. van Groningen L, Opdenoordt S et al. Cholecalciferol loading dose guideline for vitamin D
deficient adults. European Journal of Endocrinology 2010; 162: 805-11.
17. Solgar website – http://www.solgar.co.uk. Accessed 08/01/13.
18. Expert Group on Vitamins and Minerals. Safe Upper Levels for Vitamins and Minerals. Vitamin D.
Food Standards Agency, May 2003 http://www.food.gov.uk/multimedia/pdfs/evm_d.pdf Accessed
08/01/13.
19. Scientific Opinion on the Tolerable Upper Intake Level of vitamin D. EFSA Journal 2012;10
(7):2813 [45 pp.]. http://www.efsa.europa.eu/en/efsajournal/doc/2813.pdf Accessed 28/12/12.
Quality Assurance
Prepared by
Katie Smith, East Anglia Medicines Information Service
Date Prepared
8 January 2013
Checked by
Sarah Cavanagh, East Anglia Medicines Information Service
Date of check
22 January 2013
Search strategy

Embase: [exp VITAMIN D/do [do=Drug Dose] AND exp VITAMIN D DEFICIENCY/dt [dt=Drug
Therapy]] AND exp PRACTICE GUIDELINE/; [Limit to: Human and English Language and
Publication Year 2010-Current

Medline: [exp VITAMIN D/ad [ad=Administration & Dosage] AND exp VITAMIN D
DEFICIENCY/dt [dt=Drug Therapy]] AND GUIDELINE/ OR PRACTICE GUIDELINE/; Limit to:
English Language and Humans and Publication Year 2010-Current

In-house database / resources including BNF online, BNF for Children online, Martindale, Dietary
Supplements, IDIS-web, Natural Medicines Comprehensive Database

Internet Search: NeLM, Cochrane Library, NHS Choices, Bandolier, PRODIGY, Cancer
Research UK
From the NHS Evidence website www.evidence.nhs.uk
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