Vitamin D Deficiency in Adults
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Vitamin D Deficiency in Adults
Around 50% of the UK adult population have vitamin D insufficiency in winter and spring, whilst the
prevalence of vitamin D deficiency is 16%.1 This means that in Wandsworth alone there may be around
116,500 adults with vitamin D insufficiency at that time of year with over 37,000 of these who will be
deficient. Vitamin D is essential for good bone health and more recently insufficiency has been linked to
other health concerns. 2
*Nomenclature: The term vitamin D is used for a range of compounds. Vitamin D2 is known as
ergocalciferol. Vitamin D3 is known as cholecalciferol when referring to the analyte and colecalciferol
(the recommended International Nonproprietary Name (rINN)) when referring to the drug.*
What are the sources of vitamin D?
The main source of vitamin D for humans is ultraviolet B sunlight exposure. During summer two or three
exposures (of at least the face and arms without sunscreen and not behind glass) of 20 to 30 minutes
each week, which can be divided, between 10am and 3pm should provide adequate amounts of vitamin
D for most individuals.2 The elderly and those of non‐white ethnicity will have higher requirements. Due
to the latitude in the UK, from October to April sun exposure is not adequate for synthesis of vitamin D.
Oily fish such as herring, sardines, mackerel, salmon and tuna are the best dietary source of vitamin D.
Egg yolks, mushrooms and liver contain small amounts of vitamin D. Liver is also a rich source of vitamin
A, therefore consumption should be limited to once a week to avoid toxicity and avoided entirely in
pregnancy. There are also some foods such as margarines, cereals that are fortified with vitamin D
(check product labels).2,3,4
What is the recommended daily intake of vitamin D?
In the UK, a recommended dietary intake (RDI) has not been set for those leading a normal lifestyle
where they are exposed to solar radiation. For adults over 65 years or at risk (e.g. confined indoors,
extensively covered), and for pregnant or breastfeeding women the reference nutrient intake (RNI) is
400units (10mcg) per day5. The latter recommendation during pregnancy is endorsed by the
Department of Health (DoH).
*1mcg is equivalent to 40units. Units will be used throughout this document*
Based on current evidence however the consensus is that current governmental guidelines in all
countries are too low with respect to how much daily vitamin D is required to maintain bone health and
health in general, particularly in the absence of adequate sun exposure.2,3,4
How is vitamin D insufficiency and deficiency determined?
The most reliable way to determine vitamin D deficiency is by assay of serum 25‐hydroxyvitamin D
(25(OH)D) either by measuring 25 hydroxy vitamin D3 or total 25 hydroxy D2 and D3. 25(OH)D3 is a
metabolite of cholecalciferol (vitamin D3), as opposed to a metabolite of ergocalciferol (vitamin D2) or
total vitamin D. Either assay may used at local institutions. It is important to establish the assay used at
the laboratory where the requests are sent as this has implications assessing treatment response.
Prepared April 2010, updated August 2010, approved St George’s Hospital DTC and NHS Wandsworth CEMMaG October 2010
Sharon Wouda, GP Prescribing Advice Pharmacist, NHS Wandsworth
On behalf of a vitamin D working group between St George’s Hospital and NHS Wandsworth 1There is some consensus that vitamin D deficiency should be defined as 25(OH)D concentration of less
than 25 nmol/litre. 2,4 This is the level below which parathyroid hormone (PTH) starts to rise causing
increased bone turnover and hence the symptoms associated with osteomalacia.
Serum 25(OH)D Vitamin D status Manifestation Management
concentration
75 nmol/l Optimal Healthy None
When should vitamin D levels be measured?
Routine testing of vitamin D levels is not recommended given the large proportion of the population
who may have insufficient levels. Vitamin D deficiency should be considered and checked for only if:
1. A patient has one or more of the following clinical features: 2,5,6
• Insidious onset of widespread or localised bone pain and tenderness (especially lower
back and hip pain, but may include rib, thigh or foot pain)
• Proximal muscle weakness i.e. in quadriceps and glutei. This may cause difficulty rising
from a chair and/ or a waddling gait
• Swelling, tenderness and redness at pseudo‐fracture sites
• Fractures, typically femoral neck, scapula, pubic rami, ribs or vertebrae
• Non‐specific myalgia especially with a raised creatine kinase (CK)
• Myalgia on prescription of a statin
AND
2. The patient has one or more of the following risk factors: 2,5,6
• Black and ethnic minority patients with darker skin
• Elderly patients in residential care or housebound
• Intestinal malabsorption, for example coeliac disease, crohn’s disease, gastrectomy
• Routine covering of face or body, for example wearing a veil or habitual sunscreen use
• Vegan or vegetarian diet
• Liver or renal disease
• Medications including anticonvulsants, cholestyramine, rifampicin, glucocorticoids, anti‐
retrovirals
AND
3. Other causes for symptoms have been excluded, for example myeloma, rheumatoid arthritis,
polymyalgia rheumatica and hypothyroidism.
2It is worthwhile encouraging all patients with risk factors – even those not exhibiting symptoms – to
make lifestyle changes in order to achieve adequate amounts of vitamin D but it is not necessary to
measure their levels.
Pregnancy and breastfeeding are also risk factors for vitamin D deficiency however these two groups are
outside the scope of this document. Refer to relevant NICE and Royal College of Obstetricians and
Gynaecology guidelines, and the DoH ‘Healthy Start’ Program.
How should vitamin D status be assessed?
Assessment of vitamin D status should include 25(OH)D, serum calcium (to exclude hypercalcaemia and
provide a baseline for monitoring), parathyroid hormone (PTH) (to exclude primary
hyperparathyroidism), alkaline phosphatase (ALP) and phosphate. Renal function (to exclude renal
failure), liver function tests (to exclude hepatic failure), and full blood count (anaemia may be present if
there is malabsorption) are also recommended. The blood test for PTH is unstable therefore
phlebotomy needs to take place at the site where the assay is processed.
How should vitamin D deficiency be treated?
Colecalciferol (vitamin D3) is considered the preferred form of vitamin D for treatment. It has been
reported that colecalciferol raises vitamin D levels more effectively than ergocalciferol (vitamin D2), and
has a longer duration of action.7,8 This may be due to higher affinities of colecalciferol and its
metabolites for liver enzymes, plasma vitamin D binding protein, and vitamin D receptors.9
Whilst ergocalciferol is effective in treating vitamin D deficiency, the differences in potency suggest that
where possible colecalciferol should be used. Furthermore, considering some assays used in the local
area may only measure a metabolite of colecalciferol response to treatment may not be detected if
ergocalciferol is given.
Deficiency (25(OH)D less than 25nmol/L) will require high dose colecalciferol;
• First line: 60,000units (3 x 20,000unit capsule) colecalciferol orally once a week for 12 weeks.
• Second line: two intramuscular (IM) injections of 300,000units colecalciferol given 3 months apart
(use this option if malabsorption present or compliance is problematic).
• Third line: 150,000units (50mL of 3,000units/mL liquid or equivalent) colecalciferol once a day for 2
days (use oral liquid option only if capsules or injection are not suitable).
Insufficiency (25(OH)D 25 to 50nmol/L) should be treated with oral supplementation of 1,000 to
2,000units of colecalciferol taken daily for 12 weeks.
Maintenance therapy at a dose of 800 to 1,000units of colecalciferol daily may be required once
deficiency has been corrected for those patients who were severely deficient and are still considered to
be at risk. In some cases this may be lifelong therapy.
• First line: one tablet twice a day of a calcium carbonate 1.5g & colecalciferol 400units (10mcg)
combined preparation (essential for all institutionalised patients over 65 years).
• Second line: 1,000units colecalciferol taken orally once a day (only if patients have adequate dietary
calcium intake or are at risk of hypercalcaemia).
3As a fat soluble vitamin oral vitamin D products should be taken with food to improve absorption. Avoid
taking with orlistat as this reduces absorption.
Whilst on treatment patients should be advised of signs of hypercalcaemia; nausea, thirst and polyuria.4
Which vitamin D products are recommended?
The only licensed preparations of vitamin D alone in the UK contain ergocalciferol (vitamin D2);
10,000unit and 50,000unit tablet, and 300,000unit and 600,000unit injection. However as mentioned
above colecalciferol (vitamin D3) is the preferred treatment. Furthermore there have been ongoing
supply issues with ergocalciferol. Although there are no UK licensed medicinal products containing only
colecalciferol available to prescribe on the NHS, options are outlined below to meet the recommended
treatment. Despite some of the recommended options being unlicensed, clinical responsibility always
lies with the prescriber.
High dose colecalciferol (vitamin D3)
These will be required for deficiency and are only available on prescription.
A colecalciferol 20,000unit capsule (Dekristol; MIBE, Germany) is licensed in Europe. This is the most
appropriate option to provide 60,000units once a week orally for patients with deficiency. Caution in
patients with allergies and dietary restrictions as this product contains peanut oil, glycerol, gelatin and
soya.
OR
Where intramuscular administration is required, a colecalciferol 300,000unit injection (Vitamin D3;
Streuli, Switzerland) is licensed in Europe.
These preparations can be obtained through a company in the UK with a license to import, such as IDIS
(01932 824 000), Martindale Pharma (0800 137 627), Mawdsley Unlicensed (via Specials Laboratory
0800 028 4925 or Quantum Specials 0800 0439372), and Durbin (020 8869 6500). Most pharmacies or
pharmacy wholesalers will have an account with one of these companies. Ordering directly from the
importer is usually the most cost‐effective route of procurement with quotes obtained indicating a cost
of approximately £30 for a box of 50 capsules.
Colecalciferol preparations of various strengths are manufactured by commercial or hospital MHRA
licensed manufacturing units. ‘Specials’ products such as these are not commercially available and need
to be extemporaneously prepared. This can be costly as there is no price regulation. These liquid
preparations usually have a short shelf life therefore do not prescribe quantities of more than one
month’s supply without confirming a longer expiry.
It is usually more cost effective to order directly from the manufacturer, for example colecalciferol
300,000unit in 100mL liquid (30 day expiry after opening) from Martindale Pharma (0800 137 627) costs
£72 or colecalciferol 300,000units in 10ml solution (SGH formula, 7 day expiry) from St George’s Hospital
(020 8725 1768) costs £65.
Low strength colecalciferol (vitamin D3)
These products can be used for insufficiency or maintenance.
4Colecalciferol health food supplements (not licensed medicines) are available to prescribe or purchase
over‐the‐counter (OTC) from retail pharmacies and health food stores.
For patients not exempt from prescription charges these supplements are less expensive to purchase
OTC than to obtain on prescription. Where possible purchasing OTC should be encouraged. If purchasing
OTC is not an option, colecalciferol 1,000unit tablet or capsule should be prescribed. This prescription
can be dispensed either with an OTC supplement or a 1,000unit tablet licensed in Europe (Vigantolettin;
Merck Pharma, Germany).
Examples of colecalciferol supplements;
Product Strength and form Source Relevant excipients for any
dietary/allergy restrictions*
Sunvite Vitamin D3 400unit and 1000unit tablet Holland and Barrett Soya, gelatin (bovine origin)
Vitamin D 500unit capsule Boots Soya bean oil, gelatin, glycerin
Vitamin D 1000unit capsule Nature’s Remedy Rice bran oil, gelatin, glycerin
Vitamin D 1000unit tablet Nature’s Remedy Nil – suitable for vegetarians
BioLife Vitamin D 1000unit tablet Lifestyle Natural Health Nil – suitable for vegetarians
Vitamin D3 1000unit softgel Solgar Gelatin, glycerin
*Colecalciferol in supplements is derived from wool oil (lanolin); Products with soya are not suitable for those with nut allergies
Combined calcium and vitamin D preparations are licensed in the UK and available to prescribe on the
NHS. They are mostly commonly available with 5mcg or 10mcg (200 or 400units) of vitamin D in the
form of colecalciferol (vitamin D3) together with 1.25g or 1.5g of calcium carbonate. As UK licensed
products, these are the most appropriate option to use for maintenance depending on a patient’s
calcium level and dietary intake of calcium.
When is vitamin D supplementation not suitable?
Vitamin D is contraindicated in patients with hypercalcaemia or metastatic calcification.4 Relative
contraindications include primary hyperparathyroidism, renal stones and severe hypercalciuria.4
What monitoring should be done?
• In vitamin D deficiency 25(OH)D should be re‐checked 12 weeks after commencing high dose
replacement treatment in order to monitor response.
• It is not necessary to monitor 25(OH)D in vitamin D insufficiency where low dose treatment is
given.
• In patients with renal failure, serum calcium should be checked regularly for a few weeks after
starting treatment.
• Once vitamin D deficiency is corrected monitoring every 12 months may be advisable for
patients still considered at risk.
Who should be referred to secondary care?
• Patient with the above contra‐indications
• Patients with renal impairment (stage 4 Chronic Kidney Disease (CKD) or eGFR less than
30ml/minute)
• Primary hyperparathyroidism
• No response after 12 weeks of treatment
5Cost implications
It is estimated that at present 21,564 vitamin D assays are completed at St George’s Hospital per year. If
cases of vitamin D insufficiency and deficiency identified were treated according to these guidelines the
total cost would be £540,615. If we assume that 60% of all assays were done on Wandsworth patients
this estimates to £324,369. However, the prevalence of vitamin D insufficiency and deficiency is much
greater than the number currently identified. If all cases in Wandsworth were correctly identified and
treated the estimated cost would be £2,963,520.
Comparison of costs in Wandsworth between cases vitamin D deficiency and insufficiency currently
tested and treated against estimated costs if all cases were identified
Number in Estimated current Projected cost if all cases
Wandsworth cost/ year† identified††
Men (18+ years) 113,893
Vitamin D insufficiency (34%) 38,724
Vitamin D deficiency (16%) 18,223
Women (18+ years) 121,214
Vitamin D insufficiency (34%) 41,213
Vitamin D deficiency (16%) 19,394
Total (18+ years) 235,107
Vitamin D insufficiency (34%) 79,936 £72,493* £1,247,805*
Vitamin D deficiency (16%) 37,617 £251,876** £1,715,715**
*Based on £15.61 per Vitamin D assay. Assumes over the counter preparations used to treat Vitamin D
insufficiency
**Based on £15.61 per Vitamin D assay + estimated £30 per 12 week course high dose vitamin D
†Based on tests completed at St George’s Hospital between April‐May 2010, extrapolated to 12 months
and assumption that Wandsworth represents 60% of total assays done
††Based on estimated prevalence of vitamin D deficiency and insufficiency in Wandsworth
References:
1. Hypponen E, Power C. Hypovitaminosis D in British adults at age 45 y:nationwide cohort study of dietary and lifestyle predictors. Am
J Clin Nutr. 2007;85: 860‐8
2. Pearce SHS, Cheetham TD. Diagnosis and management of vitamin D. BMJ 2010; 340: 142‐147.
3. Norman AW, et al. The Workshop consensus for vitamin D nutritional guidelines. J Steroid Biochem Mol Biol 2007; 103: 204–5.
4. Primary vitamin D deficiency in adults. DTB 2006; 44: 25‐29.
5. DoH. Dietary reference values for food energy and nutrients for the United Kingdom: report of the panel on dietary reference values
of the committee on medical aspects of food policy. Report on health and social subjects 41. London: HMSO, 1991.
6. Holick MF. Vitamin D deficiency. NEJM 2007; 357: 266‐81.
7. Trang HM, et al. Evidence that vitamin D3 increases serum 25‐hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr
1998; 68: 854–8.
8. Armas LAG, et al. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004; 89: 5387–91.
9. Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 2006; 84: 694–7.
6Investigation and treatment of Vitamin D deficiency
Does the patient have ≥1 symptom of vitamin D deficiency?
• widespread bone pain or tenderness or myalgia
• proximal muscle weakness Vitamin D testing not
• tenderness over pseudofractures No required
• Insufficiency fractures
Yes
Does the patient have ≥1 risk factor for vitamin D deficiency?
• black or ethnic minority
• elderly and housebound
• habitual skin covering
• vegan/vegetarian
• liver/renal disease
• malabsorption
• anticonvulsants, cholestyramine, rifampicin or anti‐retrovirals
Vitamin D testing not
No
required at present.
Yes
First exclude other
Have other causes for symptoms been excluded? causes for symptoms.
No
Yes
Assessment of vitamin D status required: 25(OH)D, Ca2+, PTH, ALP, PO4. Also recommended: U+Es, LFTs, FBC
Do any of the following apply?
Refer to appropriate specialist in secondary
• Hypercalcaemia
Yes care.
• Metastatic calcification Depending on outcome vitamin D treatment
• Renal stones may still be required; of which the first
• Severe hypercalciuria treatment course should be prescribed and
• Stage 4 CKD or eGFR < 30ml/minute provided by secondary care before transferring
• Primary hyperparathyroidism patient with care plan back to primary care.
No
Treatment based on serum 25‐hydroxyvitamin D level
Deficiency 50nmol/L
Take 3 capsules once a week for 12 weeks Colecalciferol 1,000unit tablet: Lifestyle and dietary
2nd line: Colecalciferol 300,000unit IM injection: Take 1‐2 tablets daily for 12 advice
Give one immediately, repeat at 12 weeks weeks
3rd line: 300,000units in 100mL colecalciferol liquid:
Take 50mL once a day for 2 days
Refer to appropriate
Repeat levels at 12 weeks specialist in secondary
Has patient responded to treatment?
No
care
Yes
Monitor patient every 12 months
If patient considered still at risk give lifestyle advice or consider maintenance therapy
1st line: calcium carbonate 1.5g & colecalciferol 400unit (10mcg) chewable tablet: Take 1 tablet twice a day
2nd line: colecalciferol 1,000unit tablet: Take 1 tablet daily (only if patients have adequate dietary calcium intake
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