Guidance on Vitamin D Deficiency/Insufficiency November 2011 (updated February 2012)

Transcription

1 Guidance on Vitamin D Deficiency/Insufficiency vember 2011 (updated February 2012) This guidance aims to provide general advice for clinicians in a community setting including areas where clinical uncertainty remains. Background Information Awareness of Vitamin D deficiency in the UK population has increased substantially in recent years and there have been numerous articles published on the subject. There are different opinions regarding the ideal levels of vitamin D and the potential consequences of deficiency and insufficiency. Vitamin D includes ergocalciferol (calciferol, vitamin D2) and colecalciferol (vitamin D3). The BNF states the forms of colecalciferol and ergocalciferol should be considered bioequivalent and interchangeable. The availability of licensed vitamin D products is limited and unlicensed products have variable (and often substantial) costs. There are no national guidelines or recommendations on who to screen and how and when to treat vitamin D deficiency/insufficiency. The evidence-base is not completely defined in relation to best management of vitamin D deficiency states and the monitoring required following treatment. Population screening of Vitamin D levels is not currently recommended. Guidance is needed on how patients with possible suboptimal vitamin D status should be investigated and managed. Vitamin D deficiency 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. 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. Evidence suggesting that vitamin D might protect against non-bone health outcomes (e.g. cancer, heart disease, diabetes, multiple sclerosis) is insufficient, conflicting or inconclusive. More randomised trials are needed. Current data is insufficient to clarify relationships between intake, biochemical status and chronic illness outcome. Vitamin D levels Opinions on the ideal level of vitamin D and optimal serum concentrations vary. For the purpose of this guideline the following definitions for vitamin D status measured by total serum 25-hydroxyvitamin D (25-OHD) will be used although it should be noted that these definitions originate from different populations to those in the UK and may not be directly applicable to our climate: o Vitamin D levels <25 nmol/l probably indicate vitamin D deficiency. o Vitamin D levels nmol/l probably indicates vitamin D insufficiency. o Vitamin D levels between 50 nmol/l and 75 nmol/l probably indicate suboptimal levels. o Vitamin D levels between 75 nmol/l and approximately 220 nmol/l probably indicate normal vitamin D status. Individual laboratory assays may vary in their definitions of thresholds for deficiency and insufficiency. However, the above definitions are those which have been agreed locally and will be used as intervention thresholds. Vitamin D status may be reported separately as 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3. The two values should added together to obtain the total serum 25-hydroxyvitamin D (25-OHD). All patients, where appropriate, should receive lifestyle advice to help to meet their vitamin D requirements (see Advice section page 5). Risk Factors for reduced Vitamin D levels Groups at high risk of vitamin D deficiency include: pregnant and breastfeeding women (including multiple, short interval pregnancies) young children (under the age of 5, particularly infants who are exclusively breast fed) Page 1 of 9

2 older people (65 years and over) darker-skinned people low sun exposure (those who avoid the sun, wear whole-body coverings, live in institutions or are housebound, skin conditions e.g. skin cancer, habitual sunscreen use) obese individuals malabsorption or other dietary problems vegetarian or fish free diet severe liver disease chronic kidney disease and nephrotic syndrome certain medicines e.g. use of anticonvulsants (e.g. carbamazipine, phenobarbital, phenytoin, primidone), rifampicin, cholestyramine, glucocorticoids, highly active antiretroviral treatment. Investigation and Treatment of Vitamin D deficiency and insufficiency For guidance on investigation and treatment of vitamin D deficiency and insufficiency: in adults - refer to the flowchart on page 3 in children - refer to the flowchart on page 4 Further Considerations The regimes recommended in the flowchart have taken into account potential costs and availability (see product availability tables on page 7-8). Loading/treatment dose Currently there are no suitable licensed medicinal products containing just colecalciferol, available in the UK. This is an important determinant for clinicians to note when considering product selection for the treatment of vitamin D deficiency. There is a licensed ergocalciferol injection but there are often availability issues with this. As with all unlicensed specials, all clinical and legal responsibility lies with the prescriber rather than the manufacturer (unless it can be proven that the product was faulty). Informed consent should always be obtained from patients before prescribing in these circumstances. Maintenance Treatment All patients, where appropriate, should receive lifestyle advice to help to meet their vitamin D requirements (see Advice section page 5). Patients requiring ongoing oral maintenance treatment should be encouraged to take over the counter (OTC) vitamin D supplements (a variety of preparations are available to buy commercially; refer to page 8) unless Adcal D3 or Calceos is indicated (see flowchart page 3 and pages 6 & 7). Patients should be advised if there are any restrictions to the type of vitamin D preparation they should take (e.g. vegan, allergy or calcium restrictions). Safety Considerations High doses of vitamin D can be toxic (resulting in hypercalcaemia and renal failure). This is most likely to occur if high doses (used as initial treatment loading doses) are taken over a prolonged period of time, or if alfacalcidol or calcitriol are given in error. Vitamin D treatment doses are contraindicated in patients with hypercalcaemia or metastatic calcification, or where there may be significant interactions with other medications. Supplements of vitamin D containing vitamin A should not be taken in pregnancy as excessive vitamin A doses are associated with foetal CNS malformations. Alfacalcidol & calcitrol should only be used in patients who cannot activate vitamin D and should therefore not be used for the routine treatment of primary vitamin D deficiency/insufficiency, as they carry a higher risk of toxicity and require long-term monitoring. There is a small risk of hypercalcaemia developing in the presence of undiagnosed sarcoidosis or primary hyperparathyroidism in patients taking vitamin D. Some products may contain peanut (arachis) oil, sunflower oil or soya oil. Allergy to these may lead to severe allergic reactions including anaphylaxis. Healthcare professionals should check for allergies before prescribing or when recommending supplements. Patients should also be advised to raise allergies at the point of dispensing or purchase to ensure the content of the product is safe to take. Current status of the product ingredients should be obtained from the manufacturer as formulation may change. Refer to UKMI document on suitable products for patients with peanut or soya allergies in references section on page 9. Page 2 of 9

3 Investigation and treatment of Vitamin D deficiency / insufficiency in adults Does the patient have 1 CLINICAL or BIOCHEMICAL FEATURE of vitamin D deficiency? widespread bone pain or tenderness or myalgia proximal muscle weakness tenderness over pseudo fractures Insufficiency fractures low serum calcium or high ALP Does the patient have 1 RISK FACTOR for vitamin D deficiency? elderly and housebound pregnancy & breast feeding darker skinned people low sun exposure (e.g. habitual skin covering, housebound, skin conditions) vegan/vegetarian liver/renal disease malabsorption anticonvulsants, glucocoticoids, cholestyramine, rifampicin or anti-retrovirals obesity Known disorder of calcium metabolism Have other causes for symptoms been excluded? Vitamin D testing not required at this stage + Give advice Exclude other causes of symptoms then restart pathway Carry out tests for suspected vitamin D deficiency: 25-OHD, Ca 2+, ALP, PO 4, also U+Es, LFTs, FBC. PTH is elevated in vitamin D deficient states but routine measurement not indicated. Do any of the following apply? focal bone pain skeletal deformity malabsorption renal stones chronic renal disease, severe liver disease, lymphoma, metastatic cancer, parathyroid disorders, sarcoidosis, TB Atypical biochemistry (e.g. low vit D and hypercalcaemia) Pregnancy or breastfeeding Refer to appropriate secondary care specialist(s). If patient referred and treatment is necessary then 1st treatment course initiated by secondary care. Patient should only be transferred back to primary care with a treatment plan. Assess need for treatment based on total serum 25-OHD level 25-OHD < 25nmol/L 25-OHD 25-49nmol/L 25-OHD 50-75nmol/L Loading/ Treatment dose required (*) 1st line: Colecalciferol 20,000 IU capsule: 5 capsules a day for 3 days (total dose of 300,000 IU). 2nd line: Colecalciferol 20,000 IU capsule: 3 capsules (60,000 IU) weekly for 8-12 weeks. 3rd line: Colecalciferol 300,000 IU IM injection: single dose where oral therapy cannot be tolerated or concordance is poor. 4th Line: Ergocalciferol 300,000 IU IM injection: single dose where oral therapy cannot be tolerated or concordance is poor and colecalciferol injection is unavailable. Maintenance of IU/day (*) (Doses of up to 2000 IU may be required) OTC high strength vitamin D preparation providing 800-2,000 IU/day + advice OR Consider Adcal D3-2 daily (containing 400 IU colecalciferol per tablet) for 65 and over due to evidence of reduced fall and fracture risk + advice Routine monitoring of 25-OHD not necessary Calcium levels may need to be checked 3-6 monthly in patients on doses higher than 1,000 IU/Day advice See Monitoring below - Check Ca & Vitamin D levels after 8-12 weeks Has patient responded to treatment? - Consider non-compliance Repeat loading dose Has patient responded to treatment? Refer to appropriate specialist in secondary care MAINTENANCE Once 25-OHD levels are optimal give lifestyle advice and advise on maintenance treatment. See Maintenance box above. MONITORING Check serum calcium levels 4 weekly and 25-OHD levels 8-12 weekly for patients on high (treatment) dose of vitamin D. * Check for allergies (some products may contain peanut (arachis) oil, sunflower oil or soya oil. Alfacalcidol & calcitrol should only be used in patients who cannot activate vitamin D and should therefore not be used for the routine treatment of primary vitamin D deficiency/insufficiency, as they carry a higher risk of toxicity and require long-term monitoring. Patients should be advised of the symptoms of hypercalcaemia (nausea, abdominal pain, thirst, polyuria etc) and advised to stop taking vitamin D supplements and seek medical advice if these occur. Page 3 of 9

4 Investigation and treatment of Vitamin D deficiency / insufficiency in children Is patient a child (<18 years of age) with one of the following (in the context of child s age)? tetany reluctance to bear weight leg bowing or knock knees impaired linear growth skeletal deformity muscle pain or weakness bone pain proximal myopathy low serum calcium or high ALP Have other causes for symptoms been excluded? Vitamin D testing not required at this stage + Give appropriate advice Exclude other causes of symptoms then restart pathway Carry out tests for suspected vitamin D deficiency: 25-OHD, Ca 2+, ALP, PO 4, also U+Es, LFTs, FBC. PTH is elevated in vitamin D deficient states but routine measurement not indicated. Do any of the following apply? 25-OHD < 25nmol/L aged one year or under bone deformities (including rickets) malabsorption renal stones chronic renal disease, severe liver disease, lymphoma, metastatic cancer, parathyroid disorders, sarcoidosis, TB Atypical biochemistry (e.g. low vit D and hypercalcaemia) Pregnancy or breastfeeding Refer to specialist in secondary care. Where appropriate, consider commencing treatment in primary care until patient is seen by specialist (see below for treatment recommendations) Patient should only be transferred back to primary care with a treatment plan If specialist advice/input deemed necessary in clinician s judgement discuss with secondary care specialist and consider referral if indicated. If not treat in line with recommendations below Assess need for treatment based on total serum 25-OHD level 25-OHD < 25nmol/L Refer to specialist but where appropriate consider commencing treatment in primary care until seen by specialist see above (*) Prescribe: PO colecalciferol 3000 IU/ml liquid 25-OHD 25-49nmol/L Nutritional supplement (*) < 6 months: calciferol IU daily > 6 months: calciferol IU daily 25-OHD 50-75nmol/L Appropriate advice Doses as per BNF for children: 1-6 months: 3,000 IU daily for 8-12 weeks 6 months-12 years: 6,000 IU daily for 8-12 weeks years: 10,000 IU daily for 8-12 weeks Available Products - Healthy Start Vitamins [colecalciferol 300 IU per 5 drops] - Abidec (vitamins A, B, C, D) drops: [0.6ml contains ergocalciferol 400 IU, vitamin A 1333 units] - Dalivit (vitamins A, B, C, D) drops: [0.6ml contains ergocalciferol 400 IU, vitamin A 5000 units] + Give appropriate lifestyle advice Routine monitoring of 25-OHD not necessary See Monitoring below - Check Ca & vitamin D levels after 8-12 weeks Has patient responded to treatment? - Consider non-compliance Repeat loading dose Has patient responded to treatment? Refer to appropriate specialist in secondary care Nutritional supplement Once 25-OHD levels are optimal place on nutritional supplementation & appropriate lifestyle advice. See nutritional supplement box above. MONITORING Check serum calcium levels 4 weekly and 25-OHD levels 8-12 weekly for patients on high (treatment) dose of vitamin D * Check for allergies (some products may contain peanut (arachis) oil, sunflower oil or soya oil. Alfacalcidol & calcitrol should only be used in patients who cannot activate vitamin D and should therefore not be used for the routine treatment of primary vitamin D deficiency/insufficiency, as they carry a higher risk of toxicity and require long-term monitoring. Advise of the symptoms of hypercalcaemia (nausea, abdominal pain, thirst, polyuria etc) and advise to stop vitamin D supplements and seek medical advice if these occur. Page 4 of 9

5 Advice Sun Exposure advice The body creates most vitamin D from modest exposure to direct UVB sunlight. Regular, short periods of UVB exposure without sunscreen during the summer months are enough for most people. The more skin that is exposed, the greater the chance of making sufficient vitamin D before burning. Prolonged sunlight exposure does not lead to excess production of vitamin D. Sunscreens with sun protection factor of 15 or more may block vitamin D synthesis. It is not possible to make general recommendations for the amount of sun exposure that people need as this varies according to environmental, physical and personal factors (e.g. age, previous history of skin cancer). It has been suggested that in a fair skinned person minutes of exposure of the face and forearms 2-3 times a week in the middle of the day from spring to autumn is sufficient to achieve adequate vitamin D levels. For individuals with pigmented skin, exposure time and frequency would need to be increased (reviews have suggested by 2 to 10 fold). However, patients should be advised: o the longer they stay in the sun, especially for prolonged unprotected periods, the greater the risk of burning and skin cancer. o to stay covered up and use sunscreen (with a high UVB factor) for the majority of the time spent outside. o to always cover up or protect the skin before it starts to turn red or burn. o in view of the risk of skin cancer, sun beds are not recommended. During the winter months body stores and dietary intake maintain vitamin D status. All patients, where appropriate, should be advised about sun exposure and vitamin D and increasing safe sun exposure. Those who are unable to expose skin for long enough should be encouraged to improve their dietary intake and consider buying vitamin D supplements. Dietary Sources Patients should be advised that food in the diet can contribute to vitamin D levels, but the average daily intake is just 2 4 micrograms (80 to 160 IU). It is difficult to obtain enough vitamin D from diet alone. Vitamin D is found in oily fish (e.g. salmon, mackerel and sardines), eggs and meat. In the UK, margarine, infant formula milk, breakfast cereals, soya products, dairy products and powdered milks are often modestly fortified with vitamin D Vitamin D content of selected foods: Type of Food Average amount vitamin D per 100 grams Oily fish Fortified margarine Fortified breakfast cereals Red meat Egg yolk Mushrooms IU (5-10 micrograms) 280 IU (7 micrograms) IU (3-9 micrograms) 40 IU (1 microgram) Approximately 20 IU per egg yolk (0.5 micrograms) Small quantities All patients, where appropriate, should be encouraged to improve their dietary intake of vitamin D. Supplements A variety of oral vitamin D supplements (including multivitamin preparations) are available to buy commercially (see table on page 8). Strength may be stated in IU (international units) or micrograms IU = 25 micrograms. There are no set Reference Nutrient Intake (RNI) values for intake of vitamin D for adults over 65 years or children over 4 years of age who receive adequate sunlight exposure. The RNI for at risk adult groups to maintain adequate vitamin D status is 10 micrograms/day. The Expert Group on Vitamins and Minerals concluded that, for guidance purposes, a level of 25 micrograms/day supplementary vitamin D would not be expected to cause adverse effects in the general population when consumed regularly over a long period. Page 5 of 9

6 The Department of Health has made specific recommendations on the need for vitamin D supplementation in specific patient groups: People at risk of vitamin D Daily vitamin D supplement deficiency Infants less than 6 months Infants & children 6 months 5 years Unless they are drinking >500ml infant formula per day All pregnant/breastfeeding women People not exposed much to sun, e.g. confined indoors for long periods, those who cover their skin People aged >65 years May not need supplements as should get adequate amounts from breast milk or infant formula milk. If there is any doubt about mother s use of supplements during pregnancy and/or breastfeeding, breastfed infants will benefit from vitamin D supplements from 1 month with 340 IU/day (8.5 micrograms/day) 280 IU/day (7 micrograms/day) 400 IU/day (10 micrograms/day) 400 IU/day (10 micrograms/day) 400 IU/day (10 micrograms/day) NICE Clinical Guideline on Antenatal Care states: o all women should be informed about the importance for their own and their baby s health of maintaining adequate vitamin D stores during pregnancy and whilst breastfeeding. o In order to achieve this, women may choose to take 10 micrograms of vitamin D per day, as found in the Healthy Start multivitamin supplement. Particular care should be taken to enquire as to whether women at greatest risk are following advice to take this supplement. Pregnant/breastfeeding women and growing children who qualify can access free Healthy Start Vitamins: o women supplement provides 10 micrograms/day. o children vitamin drops provides 7.5 micrograms/day. Supplements of vitamin D containing vitamin A should not be taken in pregnancy as excessive vitamin A doses are associated with foetal CNS malformations. Patients who are at risk of vitamin D deficiency/insufficiency and unlikely to meet their vitamin D requirements through sunlight exposure and diet should be encouraged to take OTC vitamin D supplements. Some products may contain peanut (arachis), sunflower oil or soya oil. Allergy to these may lead to severe allergic reactions including anaphylaxis. Patients should be advised to raise allergies at the point of purchase to ensure the content of the product is safe to take. Eligible patients should be encouraged to access Healthy Start vitamins. Further information on Healthy Start is available at and NHS Hertfordshire Guidelines on Management of Osteoporosis The following recommendations are included in the guideline: All patients on treatments for osteoporosis (e.g. bisphosphonates) must also be prescribed calcium gram + colecalciferol 20 micrograms (800 IU) daily unless the clinician is confident the patient has adequate calcium intake and is vitamin D replete. Patients, who are frail, increased fall risk and housebound should take calcium gram and colecalciferol 20 micrograms (800IU) daily. te it may not always be clinically appropriate to give calcium and colecalciferol e.g. in primary hyperparathyroidism when calcium supplements must be avoided. Page 6 of 9

7 A range of Vitamin D products available on prescription WARNING - Some products may contain peanut (arachis) oil, sunflower oil or soya oil. Check with manufacturer if allergies are present or suspected. ADULTS Vitamin D products (loading/treatment doses) vegans Product Form Strength Contents Pack size Manufacturer Price Comments Colecalciferol (Dekristol ) capsules 20,000 IU D3 50 Pharmarama Source: lanolin unlicensed Colecalciferol (Dekristol ) capsules 20,000 IU D3 50 Martindale Source: lanolin unlicensed Colecalciferol (Dekristol ) capsules 20,000 IU D3 50 Idis Source: lanolin unlicensed Licensed/Unlicensed Medicinal product Colecalciferol (ProD3 ) capsules 20,000 IU D3 30 Synergy Biologics Source: lanolin unlicensed Colecalciferol (ColeVit D3 ) oral solution 20,000 IU/ml D3 30ml Sterling Source: lanolin unlicensed Ergocalciferol (Steriferol ) oral solution 20,000 IU/ml D2 30ml Sterling not applicable unlicensed Colecalciferol injection 300,000 IU/ml D3 10 x 1ml Idis Unknown Unknown unknown unlicensed availability problems Ergocalciferol injection 300,00 IU/ml D2 10 x 1ml Focus not applicable licensed NOT available before Jan 2012 ongoing availability problems Vitamin D products (maintenance doses) vegans Product Form Strength Contents Pack size Manufacturer Price Comments Adcal D3 chewable tablets 400 IU/ Ca 600mg per tab D3 56 ProStrakan 3.65 Source: lanolin licensed Adcal D3 caplets 200 IU/ Ca 300mg per tab D3 112 ProStrakan 3.65 Source: lanolin licensed Adcal D3 Dissolve effervescent tablets 400 IU/ Ca 600mg per tab D3 56 ProStrakan 4.99 Source: lanolin licensed Calceos tabs chewable tablets 400 IU/ Ca 500mg per tab D3 60 Galen 3.62 Source: lanolin licensed Fultium D3 capsule 800IU per cap D3 30 Jensen 3.60 Source: lanolin licensed CHILDREN Vitamin D products (loading/treatment doses) vegans Product Form Strength Contents Pack size Manufacturer Price Comments Colecalciferol (ColeVit D3 ) oral solution 3,000 IU/ml D3 30ml Sterling Source: lanolin unlicensed Ergocalciferol (Steriferol ) oral solution 3,000 IU/ml D2 30ml Sterling not applicable unlicensed Licensed/Unlicensed Medicinal product Licensed/Unlicensed Medicinal product Colecalciferol liquid 3,000 IU/ml D3 100ml rthwick Park Hospital Specials t known t known Source: lanolin, no in-use shelf life i.e.no need to discard 28 days after first opening unlicensed Colecalciferol liquid 3,000 IU/ml D3 100ml Martindale Source: lanolin unlicensed Vigantoletten Dispersible Tablets 1,000 IU D3 90 Idis Source: lanolin unlicensed Vitamin D products (maintenance doses) Product Form Strength Contents Pack size Manufacturer Price vegans Comments Licensed/Unlicensed Medicinal product Omega Abidec drops drops 400 IU/0.6ml D2 25ml Pharma units vitamin A per 0.6ml licensed Dalivit drops drops 400 IU/0.6ml D2 25ml Boston Healthcare units vitamin A per 0.6ml licensed 233micrograms vitamin A per 5 drops Available with voucher scheme or to Healthy Start Vitamins drops 300 IU/5 drops D3 10ml SSL Ltd 1.77 Unknown purchase licensed D3 = Colecalciferol D2 = Ergocalciefrol A more extensive list of available products is available at: Page 7 of 9

8 A selection of OTC vitamin D supplements Other products are available from a wide range of pharmacies & health food shops. Many are or vegans. WARNING - Some products may contain peanut (arachis) oil, sunflower oil or soya oil. Check with manufacturer if allergies are present or suspected. Colecalciferol Strength 400 IU Product Form Strength Contents Pack size Manufacturer Price vegans Comments Colecalciferol (ProD3 400 ) capsules 400 IU D3 30 Synergy Biologics 4.99 Source: lanolin Solgar Vitamin D3 softgel capsules 400 IU D3 100 Boots Herbal Stores 5.11 Source: fish oil liver Colecalciferol Strength 1,000 IU Product Form Strength Contents Pack size Manufacturer Price vegans Comments Colecalciferol (ProD ) capsules 1,000 IU D3 30 Synergy Biologics 6.99 Source: lanolin Biolife Colecalciferol chewable tablets 1,000 IU D3 90 Natural Health 9.95 Unknown Source: lanolin Solgar Vitamin D3 softgel capsules 1000 IU D3 100 Boots Herbal Stores 7.05 Source: fish oil liver Solgar Vitamin D3 tablets 1000 IU D3 90 Boots Herbal Stores 6.53 Source: lanolin Ergocalciferol Strength 800IU (use for vegans) Product Form Strength Contents Pack size Manufacturer Price vegans Comments DEVA Vegan Vitamin D2 800iu Tablets 800 IU D2 90 IDIS 5.99 not applicable A more extensive list of available products is available at: Page 8 of 9

9 References Barnet and Chase Farm Hospitals NHS Trust Management of Vitamin D Deficiency in Adults, vember Barts and The London Clinical Effectiveness Group Vitamin D guidance, January Bjelakovic et al Vitamin D supplementation for prevention of mortality in adults (Review), Cochrane Review, Issue 7, British Association of Dermatologists, Cancer Research UK, Diabetes UK, the Multiple Sclerosis Society, the National Heart Forum, the National Osteoporosis Society and the Primary Care Dermatology Society - Consensus Vitamin D position statement, Dec British National Formulary for children, British National Formulary, September Department of Health Vitamin D leaflet, East and South East England Specialist Pharmacy Services Vitamin D deficiency and insufficiency, using appropriate available products, vember Shortage/Vitamin-D-product-availability/ East and South East England Specialist Pharmacy Services Vitamin D deficiency and insufficiency in adults and paediatrics: a guideline collation document for London and East and South-East England, August Area/Evidence/Guidelines/Vitamin-D-Guideline-Collation-Document/ Holick MF et al Evaluation, Treatment, and Prevention of Vitamin D Deficiency, J Clin Endocrin Metab, 96(7), July Institute of Medicine Dietary Reference Intakes for Calcium and Vitamin D, v NHS rth Central London Diagnosis and Management of Vitamin D deficiency/insufficiency in Camden, May NHS Wandsworth Vitamin D Deficiency in Adults August 2010 NICE Clinical Guideline 62 Antenatal Care, March Pearce SH and Cheetham TD - Diagnosis and management of vitamin D deficiency, BMJ 340: , January 2010 Scientific Advisory Committee on Nutrition Update on Vitamin D, _november_2007.html UKMI, Medicines Q&As - Is there a suitable vitamin D product for a patient with a peanut or soya allergy? January UKMI, Medicines Q&As What dose of vitamin D should be prescribed for the treatment of vitamin D deficiency, October A/What-dose-of-vitamin-D-should-be-prescribed-for-the-treatment-of-vitamin-Ddeficiency/?query=vitamin+d&rank=100 Vitamin D advice on supplements for at risk groups February 2012 UK CMO CAS Letter Vitamin D pdf Approved by Hertfordshire Medicines Management Committee September/vember 2011 Page 9 of 9