Vitamin D testing: three important issues (letter)
British Journal of General Practice March 1, 2014 vol. 64 no. 620 124
Katy Gardner: GP and Clinical Lead for Vitamin D, Liverpool, UK. katyagardner at btinternet.com
Stephen Zhao: Rheumatology trainee Aintree University Hospital, Liverpool, UK.
In Liverpool we are auditing vitamin D testing and prescribing in primary care, following guidelines issued to GPs in early 2012 to encourage evidenced based testing and prescribing.1 Our data indicates that some GPs are testing in an increasingly non-targeted way. GPs in Liverpool ordered over £100 000 worth of vitamin D tests in 2012, over 10 times the amount spent in 2007. Though more people were identified as deficient, the proportion of deficient results identified decreased significantly. We feel guidance from NICE is needed for detection and treatment of vitamin D deficiency in primary care.
We also feel it is high time for universal vitamin D supplementation of pregnant and postnatal women and young children as recommended by Chief Medical Officers.2 With our increasingly diverse population in the UK we are very aware that currently some groups are missing out on prevention, and Healthy Start vitamin uptake is very low. In Liverpool we are rolling out universal supplementation out this spring. This should lead to a decrease in vitamin D deficiency, decrease in rickets and decrease in need for testing and high dose prescribing.
Thirdly and very importantly the authors wonder why the use of licensed preparations is so low in primary care. This is because there are no high-dose licensed preparations available for us to prescribe. I have been working with vitamin D deficient patients for the past 10 years. My experience, as well as that of GP colleagues up and down the country, is that compliance is a big problem with low dose preparations particularly in certain population groups at risk of deficiency.
Liverpool has a substantial Somali population with deficiency identified in around 80% of individuals.3 Our experience is that to ensure compliance with treatment in our Somali population we need to give a high loading dose of vitamin D over a short period of time. There is also no high-dose licensed liquid preparation for children. I note the authors appear to have had some connections with various pharmaceutical companies involved in vitamin D manufacture. It would be excellent to see some high dose preparations licensed for use in the UK.
- 1.↵ Gardner K (2012) Mersey Cluster — Guidance for Vitamin D Deficiency and Treatment Options. http://www.northmerseyammc.nhs.uk/Library/publications/North%20Mersey%20Guidance%20for%20Vitamin%20D%20Deficiency%20FINAL%20VERSION%20feb12.pdf (accessed 5 Feb 2014). PDF is attached at the bottom of this page and extracted below
- 2.↵ Vitamin D — advice on supplements for at risk groups (February, 2012) (Department of Health),
https://www.gov.uk/government/publications/vitamin-d-advice-on-supplements-for-at-risk-groups (accessed 5 Feb 2014).
- 3.↵ Bunn J, Gardner K, Vitlani K, et al. North West Public Health Conference (17 Sept 2013, Manchester), Vitamin D deficiency in Liverpool Somalis: a significant problem. abstract. Search Google Scholar
Leeds (UK) councillors worried about rickets Feb 2014
- The Lib Dem group on Leeds City Council wants funding for free vitamin supplements for children under four.
- The Lib Dems will propose an amendment which would see £430,000 of public health money spent on vitamins for children when the council budget is debated tomorrow.
See also VitaminDWiki
- Rickets in England – huge recent increase – Feb 2014
- Why the UK government ignores evidence for the benefits of Vitamin D - Nov 2013
- Presentation: pre and post natal vitamin D, with audience comments – Manchester UK Sept 2013
- National Osteoporosis Society of UK declares that 12 ng of vitamin D is enough – June 2013
- Vitamin D conference in England - April 23-25 2014
- Vitamin D – The Sunshine Vitamin Most Indoor Workers Are Lacking – Gillie May 2013
- Overview of Rickets and Vitamin D
Extract from Liverpool PDF
Mersey Cluster - Guidance for Vitamin D Deficiency and Treatment Options
Recent BMJ articles1,2 highlighted the problem of vitamin D deficiency in the UK population. There is an increasing body of evidence associating such deficiency with an increased risk of morbidity not only due to bone/muscle disorders but a variety of other conditions3. Prescribers may encounter patients whose clinical presentation is either principally due to vitamin D deficiency or is complicated by its presence. A recent letter was sent to all healthcare professionals from the Chief Medical Officer highlighting the risk of Vitamin D deficiency. +
Consensus suggests Vitamin D is mainly obtained by the action of UV rays on our skin. A US study4 suggests 5-15 minutes (longer for darker skin) daily sun exposure between 10am and 3pm from April to October would be sufficient to improve vitamin D status5. Dietary sources of Vitamin D include oily fish, egg yolk, fortified foods e.g. cereal and margarine6.
Please see national advice leaflet at:
http://www.dh.gov.uk/prod consum dh/groups/dh digitalassets/@dh/@en/documents/digitalas set/dh 132508.pdf
or Map of Medicines http://eng.mapofmedicine.com/evidence/map/index.html
There is a lack of consensus regarding the precise definition of vitamin D deficiency. Some authorities recommend treatment below 25nmol/L while others recommend 50nmol/L. The Liverpool criteria for deficiency (Total 25 (OH)D concentration) is <30 nmol/L and for insufficiency >30-50 nmol/L. This may vary across North Mersey.
The scope of this guidance is to review the treatment and prevention of Vitamin D deficiency, please see Appendix 1 for further information and advice regarding care of patients who fall outside the scope of this guidance including those with osteoporosis and eGFR <30 mL/minute/1.73m2
Please Note: Serum concentrations of 25(OH)D reported in either nanomoles per litre (nmol/L)
or nanograms per millilitre (ng/mL). 1ng/mL = 2.5nmol/L
Since 2010 clinical chemistry laboratories should be reporting results in nmol/L.
Who should be tested?
Routine testing of Vitamin D levels is NOT recommended.
Assessing the patient:
If patient is healthy with no risk factors and is symptom free - NO investigations are required. Offer lifestyle advice and consider over the counter preventative therapies.
If a patient presents with risks factors only - Offer lifestyle advice and consider long term preventative therapies
If a patient presents with risk factors and signs and symptoms - Vitamin D deficiency should be considered. Vitamin D levels should be measured ONLY if patients are symptomatic AND have other risk factors unless clinically appropriate.
Risk factors for vitamin D deficiency include:
• Black & ethnic minority patients with darker skin
• Elderly patients in residential care, housebound or institutionalised patients
• Older people aged 65 years and over
• Infants and young children under 5 years of age
• Intestinal malabsorption e.g. coeliac disease, crohns disease, gastrectomy, cholestatic liver disease
• Routine covering of face or body e.g. habitual sunscreen use factor 15 or above
• Vegan/vegetarian diet
• Liver or renal disease
• Medications including certain anticonvulsants, cholestyramine, colestipol, liquid paraffin, sucralfate, rifampicin, glucocorticoids, highly active antiretrovirals
• Obesity (BMI >30)
• All pregnant and breast feeding women, especially teenagers and young women
• Short interval pregnancies
• Patients with persistently low calcium, low phosphate or raised Alkaline Phosphatase
• Low vitamin D dietary intake
• Cystic fibrosis
• If one family member is Vitamin D deficient it is likely others in the family may also be deficient, unless that person has a specific medical condition
• Young children or infants can present with bony deformity (rickets), irritability, reluctance to weight bear, impaired growth and even neonatal tetany
• Older children may present with lethargy and general aches & pains e.g. growing pains7,8
• Adults often present with generalised musculoskeletal and or bone pain, muscle weakness and lethargy
Only test if both risk factors and symptoms are present or if clinically appropriate
If the patient has both risk factors and symptoms the following investigations should be carried out:
• Serum 25-hydroxyvitamin D (25(OH)D)
• Serum Calcium - to exclude hypercalcaemia and obtain baseline for monitoring. If low vitamin D confirmed and calcium result is raised or high-normal, check parathyroid hormone. Do not check parathyroid hormone routinely
• Alkaline Phosphatase and Phosphate
• Liver and renal function
• Full blood count (there may be coexisting anaemia if dietary factors are involved)
If there is a history of confirmed Vitamin D deficiency and anaemia ensure ongoing advice is provided to reduce associated risks.
Diagnosis and coding
NB If deficiency diagnosed use the Read code .C28 Vitamin D deficiency (for audit purposes)
All patients at risk of Vitamin D deficiency require ongoing lifestyle advice regarding sunlight exposure and diet. See Liverpool Patient leaflet for further information available at Map of Medicines http://eng.mapofmedicine.com/evidence/map/index.html or www.northmerseyammc.nhs.uk/
Table 2: Vitamin D treatment guidelines.
Exclude patients with hypercalcaemia or an eGFR <30mL/minute/1.73m2. See Appendix 1
Deficiency in adults:
<30nmol/L Or <12ng/mL
Deficiency: high dose treatment initially, then long term maintenance treatment required
If deficiency is diagnosed in pregnancy please follow guidelines of your local maternity services provider
Most UK Guidelines suggest a loading dose of 300,000IU colecalciferol is required to replenish Vitamin D concentration.
Various regimes can be considered to achieve this.
Check Vitamin D concentration
after 6 months to ensure
adequate replacement and/or
If >100nmol/L consider
If still deficient alter dose as
If sufficient no further
Due to compliance issues locally Liverpool are suggesting a loading dose is given by either:
Colecalciferol 20,000IU orally ONE daily for 15 days
Colecalciferol 20,000IU orally FIVE daily for 3 days
Colecalciferol 20,000 IU ONE orally once a month
Prescribers can prescribe from a selection of available products to give a total dose as recommended above. See Appendix 2 for further prescribing and product information
Alfacalcidol is not considered appropriate for community use in Vitamin D deficiency unless advised by specialists due to the risk of hypercalcaemia. See Appendix 3
Table 2: Vitamin D treatment guidelines.
Insufficiency in adults:
>30 to 50nmol/L Or
Maintenance treatment likely to be required
There is currently a lack of evidence on the functional outcomes of populations with insufficient vitamin D concentration to justify the treatment of all patients with insufficiency.
Assess patient holistically Consider prescribing if symptomatic & at risk / previously deficient/ unlikely to take supplements / breast feeding or considering pregnancy / wintertime
• Vitamin D equivalent to 800IU daily e.g. Vitamin D 400IU (10mcg) tablets. One tablet twice daily for life.
• A range of Vitamin D tablets are available to buy from community pharmacies, health food stores or via prescription. (See Appendix 2)
• Calcium and Vitamin D tablets e.g Calcichew D3 Forte and Adcal D3 are licensed preparations available on prescription and can be considered for maintenance treatment
Or where compliance may be an issue
• Colecalciferol 20,000IU one capsule per month available via prescription
Healthy or at risk adults
>50-75nmol/L Or > 20ng/mL
Can consider daily self treatment with over the counter purchased supplement of 400-800IU Vitamin D daily
Over the counter products contain amounts likely to prevent rickets/osteomalacia, but are unlikely to raise Vitamin D concentration to optimal in most people who are deficient.
NB prevention may be needed in older people / housebound / in institution
Prevention in children
COMA9 (Committee on Medical aspects of food) recommends:
All infants except those taking at least 500ml of infant formula have a total of 280-340iu Vitamin D daily for the first four years of life.
Fully breast fed infants: see prevention in pregnancy
At risk children supplemented up to the age of five years.
This can be achieved with Healthy Start vitamins.
Alternatives are Abidec and Dalivit drops (Vitamin A, B group, C and D) for children -available to buy or through GP
Healthy Start Children's Vitamin drops (Vitamin A 5000units, Vitamin D 2000units and ascorbic acid 150mg/ml)
Child 1 month - 5years: 5 drops daily (5 drops contain approximately 700units Vitamin A, 300units Vitamin D, 20mg Ascorbic Acid; BNF 62 page 627)
Healthy Start vitamins are usually available with vouchers through Children's Centres and many Health Centres. Only Healthy Start beneficiaries can access vouchers. However Healthy Start may be universally available in some parts of the Mersey Cluster.
See Appendix 4 for further information regarding this scheme or visit http://www.healthystart.nhs.uk/ or discuss with your health visitor / midwife
Table 2: Vitamin D treatment guidelines.
Prevention in Pregnancy and Breastfeeding
If deficiency is diagnosed in pregnancy please follow guidelines of local maternity services provider
COMA9 (Committee on Medical Aspects of food) recommends: All pregnant and lactating women have a total of 400iu Vitamin D/day
Pregnant women suspected of being vitamin D deficient should have their Vitamin D concentration measured.
NICE CG62 Antenatal care11 suggests that up to 1000IU daily is considered the maximum safe dose.
Ensure Vitamin D concentrations remain above 50nmol/L throughout the year
A recent letter was sent to all healthcare professionals from the Chief Medical officer (3/2/12) offering advice on Vitamin D supplements further information can be found via
All women should continue with Vitamin D supplementation throughout pregnancy and breastfeeding.
All women diagnosed with Vitamin D deficiency should continue treatment/maintenance whilst breast feeding.
If deficient check Vitamin D concentration at 6 months post delivery. Consider lifelong maintenance.
Advise all women about Healthy Start vitamins preconception and during pregnancy
If ineligible for Healthy Start advise 10 micrograms Vitamin D (400IU) daily -purchased over the counter. Vitamin supplements such as Pregnacare are available over the counter.
Siblings under five years old should have maintenance with Healthy Start Vitamins (or Abidec/Dalvit) see Appendix 4
NB: Women at risk (Black Minority Ethnic (BME)/darker skin) will be tested routinely by Liverpool Women's NHS Foundation Trust and treatment advised as necessary.
For advice re prevention and treatment of Vitamin D disorders in Children please refer to
separate Alder Hey Guidance
1. Sievenpiper J L, Mclntyre E A, Verrill M, Quinton R and Pearce SHS. Unrecognised severe Vitamin D deficiency. BMJ 2008; 336;1371-1374 doi:10.1136/bmj.39555.820394.BE
2. Pearce S, Cheetham D. Diagnosis and management of Vitamin D deficiency. BMJ 2010;340:65664 doi:101136/bmj/b5664
3. Holik FM. Vitamin D deficiency. NEJM 2007; 357; 1371-1374
4. Dietary Supplements. Vitamin D monograph. London: Pharmaceutical Press. Accessed via http://www.medicinescomplete.com on 16/06/10 and Holick M, Vitamin D. importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. American Journal of Clinical Nutrition 2004; 79: 362-371.
5. Cancer Research UK, National Osteoporosis Society, British Association of Dermatologists, Diabetes UK. Consensus Vitamin D position statement: 2010. Online: Available at http://www.nelm.nhs.uk/en/NeLM-Area/News/2010—December/17/Consensus-Vitamin-D-position-statement/
6. Dietary Supplements. Vitamin D monograph. London: Pharmaceutical Press. Accessed via http://www.medicinescomplete.com on 16/06/10
7. M Z Mughal, H Salama, T Greenaway, I Laing, E B Mawer. Florid rickets associated with prolonged breast feeding without vitamin D supplementation. BMJ 1999; 318 2 JANUARY 1999 www.bmj.com 3
8. Sharma S, Khan N, Khadri A, Julies P, Gnanasambandam S, Saroey S, Jacobs B, Beski S, Coren M, Alexander S .Vitamin D in pregnancy-time for action: a paediatric audit. BJOG 2009; 116 (12) 1678-1682 . Online: DOI: 10.1111/j.1471-0528.2009.02285
9. Committee on Medical Aspects (COMA) of Food and Nutrition Policy (DH 1991, 2004, 2002). Available at www.doh.gov.uk
10. NICE. NICE public health guidance 11: Improving the nutrition of pregnant and breastfeeding mothers and children in low-income households. NICE (2008) (updated July 2011) Available at www.nice.org.uk
11. NICE CG62 - Antenatal care www.nice.org.uk/CG62
12. East & South east England Specialist Pharmacy services - Vitamin d deficiency and insufficiency November 2011
13. Dietary Supplements. Vitamin D monograph. London: Pharmaceutical Press. Accessed via www.medicinescomplete.com on 16/06/10
Appendix 1 - Conditions outside the scope of this guidance
The following are outside the scope of this guideance. See condition related guidelines for further information. Referral to specialist may be appropriate.
• Renal disease1
• Secondary prevention post fractures
• Failure to respond to treatment after 3 months
• All children under 1 year
• Atypical biochemistry
• Atypical clinical manifestations or biochemistry
• Deficiency due to malabsorption
• Focal bone pain
• Liver disease
• Metastatic cancer
• Parathyroid disorders
• Renal stones
• Short stature and Skeletal deformity
• Unexplained deficiency
• Unexplained weight loss
*Renal Disease - eGFR less than 30mL/minute/1.73m2
NICE clinical guideline CG73 on chronic kidney disease, published in 2008, advises on which vitamin D preparations should be used and when, according to the stage of renal impairment.
NICE CG73 Chronic kidney disease. NICE Guideline. 2008. Available at http://www.nice.org.uk/nicemedia/live/12069/42117/42117.pdf
The information has been summarized in a NICE pathway see http://pathways.nice.org.uk/pathways/chronic-kidney-disease
See NICE Technology Appraisals TA160 and TA161 for further information re Osteoporosis www.nice.org.uk
Local osteoporosis guideline currently in development - http://www.northmerseyammc.nhs.uk/ Alternatively refer to your local Medicines Management Team for further advice
Appendix 2 - Prescribing Guidance
There are numerous issues surrounding Vitamin D products and availability and the Department of Health are aware of the need for a licensed product and are in discussion with the Medicines and Healthcare products Regulatory Agency (MHRA) and pharmaceutical industry.
Although licensed products should be used where available in some circumstances unlicensed or special products may be suitable following appropriate consideration of the increased risks and substantial costs of such medicines.12 For further information please see
• Pro D3 Colecalciferol 20,000IU capsules - This is not a licensed medicine as it is classed as a food/vitamin product. Capsules and liquid are available in various strengths ranging from 400IU to 30,000IU. This product is suitable for patients with nut allergies is gelatin free, suitable for vegetarians and halal diets. The 20,000IU capsules are available at a set price of £19.99 per 30 capsules and are not classed as a 'special' so there should be no price variation. Pro-D3 is available directly from the manufacturer, AAH and Phoenix wholesalers so there should not be any supply problems in primary care. Please prescribe on acute prescriptions. A liquid preparation and other strengths of Vitamin D are also available. Further information can be found at http://www.prod3.co.uk/ Nutritional supplements are generally subject to food safety labelling legislation and whilst this excludes them from a formal licensing process they may be considered a potentially useful option in some circumstances following consideration of the risks12.
• Dekristol 20,000IU capsules - Unlicensed special import from EU (price variable) specify "order from IDIS, Martindale or Pharmarama" on the prescription. Prescribe on acute prescriptions. Pack size available 50capsules. This product is licensed in Germany and manufactured by MIBE pharmaceuticals
NB Dekristol contains gelatin and is NOT suitable for nut allergies - for more information please see MHRA warning
• Fultium-D3 800IU capsules - Newly licensed product available. Contains peanut oil. 25 x 800IU caps equivalent to 1x 20,000IU. Not recommended for use in under 12years. Manufacturers licensed dose:
• Deficiency: 1-4caps daily (800-3200IU) for 12 weeks.
• Insuffiency / Maintenance / Prevention: 1-2caps (800-1600IU) daily.
• Ergocalciferol 300,000IU intra-muscular injection - once or twice a year (variable availability)
Alfacalcidol is not considered appropriate for community use in Vitamin D deficiency unless advised by Renal or Clinical Blood Sciences (Clinical Chemistry) Specialists due to risk of hypercalcaemia
A recent signal alert from the National Patient Safety Alerts (NPSA) highlights the risks associated with alfacalcidol prescribing
http://www.nrls.npsa.nhs.uk/resources/?entryid45=132827 Risks of hypercalcaemia
Alfacalcidol and excessive intake of products containing Vitamin D can lead to hypercalcaemia and its associated effects.
Symptoms of toxicity include:
• nausea & vomiting
• thirst and weakness
Toxicity can lead to:
• calcification of soft tissues and bone pain,
• cardiac arrhythmias,
• 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 indicated13
Patients receiving treatment with alfacalcidol should have plasma-calcium levels initially checked once or twice weekly as per product SPC when initiating treatment with alphacalcidol and whenever nausea and vomiting or other symptoms of toxicity occur during treatment. Once stabilised plasma calcium levels should be checked at intervals as per BNF 62.
Appendix 4 - Healthy Start Scheme
What is the Healthy Start Scheme?
The Healthy Start Scheme is a statutory scheme which started in 2006 and replaced the Welfare Food Scheme. The scheme aims to improve the health of pregnant women and families on benefits or low incomes. The scheme provides a nutritional safety net, encourages breastfeeding / healthy eating and is used as a public health tool.
How do you sign women / children up?
The application forms need to be signed by GPs, midwives, health visitors or other registered nurses. Health professionals are not required to check eligibility they just need to sign the application form. Any subsequent changes in personal circumstances must be reported by the beneficiary not the health professional.
The application forms (HS01) can be ordered via www.orderline.dh.gov.uk or by calling 0300 123 1002. The forms should be available in health and children centres.
N.B. Re-application for healthy start vitamins is required following the birth of child.
What are the beneficiaries entitled to?
Beneficiaries are sent vouchers that can be exchanged for cow's milk, fresh / frozen fruit, vegetables and infant formula.
Beneficiaries are also sent vitamin coupons which can be exchanged for vitamin supplements for pregnant women, new mothers and children up to 4 years. Women's tablets contain Vitamin C, D and folic acid and Children's drops contain Vitamin A, C and D.
N.B. Healthy Start Vitamins may be universally available in some parts of the Mersey Cluster Further information - www.healthystart.nhs.uk
Mersey Cluster Guidance Final version Updated February 20121
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Prepared by Liverpool Medicines Management Team, Dr Katy Gardner and Liverpool Vitamin D Group
Over the counter products - Patients can be directed to purchase over the counter products. A dose of 800IU per day should be recommended for maintenance and prevention regimes. Brands of Vitamin D tablets include:
• Solgar® (Vitamin D3 - Colecalciferol) vegetarian capsules available in various strengths (suitable for nut allergy sufferers),
• Pro D3 products available in a range of strengths from 400IU (10mcg) to 30,000IU,
• Boots and Holland & Barrett also offer a range of Vitamin D products.
Information correct as of 21st February 2012 - product availability and licensed indications change frequently, please contact
your Medicines Management Team if you have any queries
Mersey Cluster Guidance Final version Updated February 20121
Page 9 of 11
Prepared by Liverpool Medicines Management Team, Dr Katy Gardner and Liverpool Vitamin D Group