Vitamin D

1. Vitamin D Simon Pearce Consultant Endocrinologist, RVI, Newcastle

2. Vitamin D • Basic background • Public health • Cases & Clinical scenarios

3. Skin Liver Kidney Active vitamin D hormone Calcium & skeletal homeostasis Immune system tissues Metabolic & vascular tissues Cellular Homeostasis & apoptosis Synthesis, activation & action

4. Vitamin D- natural sources • Ergocalciferol • ‘Vitamin D2’ • UV irradiated fungi/ yeast • Colecalciferol • ‘Vitamin D3’ • UV irradiated plankton • UV irradiated animal skin/ fur

5. Vitamin D- natural sources • >90% of humankind’s vitamin D comes from UV-B exposure of skin • 20-30 min of direct skin exposure to midday sun on face and arms, 2 or 3 times weekly provides sufficient for a fair-skinned person • Above 43oN, the angle of sun to atmosphere filters out useful UV wavelengths between October and April.

6. Vitamin D- natural sources • Sun block lotion SPF-8 prevents 95% of dermal vitamin D synthesis • Wearing a hat, veil or head scarf very substantially reduce skin vitamin D synthesis • Pigmented skin or elderly (thin skin) needs more exposure for same vit D production • Impossible to overdose on skin synthesised vitamin D; possible to sunburn

7. Scale of the public health problem • Seasonal & geographic variation in prevalence of 25-OHD <40nmol/L • MRC 1958 birth cohort at age 45yrs =7437 whites • Spring nadir for 25OHD <20 nmol/L =16% <50 nmol/L =50% Hyppönen & Power 2007

8. Vitamin D- natural sources • Food • Oily fish (top of the marine ecosystem) • Salmon, trout, mackerel, herring, fresh tuna, sardines, pilchards, anchovies • Fish oils (cod liver oil) • 2 portions of oily fish weekly (100-125g) sufficient to provide sufficient Vit D • Less Vitamin D in farmed fish • Heavy metals in some sea fish

9. Vitamin D- natural sources • Common misconceptions • Negligible amount of vit D in milk • None in green vegetables • Small amounts in Egg yolk (20 yolks per day sufficient) • Small amount in mushrooms (100 per day sufficient) • Small amounts in animal liver (inc. seal liver) • Statutory supplementation in UK • Infant milk formula (500 IU/l) • Margarines (150-300 IU/100g)

10. How to determine vitamin D status? • Measure serum 25 hydroxyvitamin D (25-OHD) • Robust marker of vit D stores • Half-life 3-4 weeks • Don’t measure 1,25 dihydroxyvitamin D • Active ‘D hormone’ • Circulating levels reflect PTH action and calcium supply • Often falsely normal or even elevated in D deficiency

11. How to determine vitamin D status?

12. Interpretation of serum 25-OHD Men (n=3725) Women (n=3712) • UK-wide white cohort born 1958 Hypponen & Power 2007

13. Interpretation of serum 25-OHD Men (n=3725) Women (n=3712) • UK-wide white cohort born 1958 Hypponen & Power 2007

14. Case 1

15. 35 yo, Pakistani-born Lady • Living in Fenham for 11 yrs • Migratory aches and pains, hips, legs, back during 3rd pregnancy • GP re-assured, but ? Depressed • 4/12 post partum-feels low, aches and pains persist= Fluoxetine 20mg od • Presents limping, with pain in R hip

16. GP did blood tests • Calcium =1.89 mmol/l (2.12-2.6) • Alk Phos = 231 KIU/l (<120) • Rh factor negative • Refer endocrinology

17. Endocrinology blood tests • PTH 684 ng/l • 25-OH vitamin D = 7 nmol/l • Diagnosis = Osteomalacia

18. Generalised Aches & Pains =not always depression Sievenpiper J et al. BMJ

19. Treatment • Oral ergocalciferol 10,000 IU daily for 3 months • Feels a lot better, aches and pains gone, smiling in clinic • But……..

20. After topping up her vitamin D levels, she will need long-term maintenance • 1000 to 2000 IU calciferol daily • Regular sunlight exposure • Don’t forget the baby: who was slow to walk and had rickets with tibial deformities

21. NICE antenatal care guideline

22. Case 2

23. 20 month old girl • Mother reports lower limb deformity • 4th child, term birth, no problems • Breast fed until 8 months • Pain on walking, difficulty climbing stairs • Nigerian mother, asylum seeker housed in tower block • 3 older brothers born in Nigeria, no problems

24. Ca 1.92 mmol/l (2.3-2.7) • PO4 1.26 mmol/l (1.1-1.85) • Alk Phos 1077 KIU/l (<375) • Treatment • Ergocalciferol oily solution, 3,000 IU/ml. 2mls daily • Mother and brothers, also to take supplements: Dalivit 0.6 mls daily

25. Healthy Start/ Sure Start • The UK health departments recommend a daily dose of vitamins A, C and D for: • breastfed infants from 6 months (or from 1 month if there is any doubt about the mother's vitamin status during pregnancy) • formula-fed infants who are over 6 months and taking less than 500 ml infant formula per day • children under 5 years of age • This recommendation is particularly important for children who are picky or fussy eaters, those of Asian, African, Afro-Caribbean or middle eastern origin and those living in northern areas of the UK.

27. Case 3

28. 45 yo woman • Multiple sclerosis diagnosed age 29 • Only 2 major attacks • Feeling increasingly weak for 30 months • Painful to move legs, can’t stand up • Using wheelchair, even in house • Needs husband to pull her out of bed in morning

29. Fell out of bed one day • Wedge # of L2 vertebral body • BMD measured; T score -3.4 at spine • Bone chemistry • (PTH 43) • Treated with calcichew D3 one daily

30. Allergic to fish; none since teenager • Not really leaving the house due to mobility • No overseas holiday for 5 yrs

31. Treatment • Oral colecalciferol 20,000 IU capsules, 3 per week (Dekristol; pharmacy special order, approved by APC) • Vomiting and diarrhoea (contains fish oil!) • IM ergocalciferol 300,000 IU monthly for 3 months, • Oral vitamin D3 2 x 25ug capsules daily (2000 IU) from Holland and Barrett • 1 year later; walks unaided up to 200 m, no pain

32. How to determine vitamin D status?

34. Also OTCBoots (12.5 ug capsules) £2.99 for 90 Holland & Barrett (25 ug capsules) £6.99 for 100

35. Dosing issues • 100 IU calciferol daily increases serum 25-OHD by 2.5 nmol/l • RDA is 400 IU (10 ug) • Increase serum 25-OHD by 10 nmol/l • Typical Newcastle patient with vitamin D insufficiency has levels between 20 and 30 nmol/l • Need to aim for 70 nmol/l or better • Toxicity seen at levels of 500 nmol/l or higher • 1- 2000 IU daily is appropriate maintenance dose (Adults)

36. Tips on treatment • Most people who you suspect are D deficient, are D deficient • Supplementation is not the same as treatment • If a child has rickets, the siblings and mother should also be treated • Compliance with calcium containing preparations (calcichew D3) is poor, better to prescribe D only compounds for longterm use

37. The End

38. Questions •Is it worth screening all new patients from overseas at risk of vit D? -When people first arrive, they aren’t deficient -Probably takes 5 years or a pregnancy to manifest severe D deficiency -Worth giving dietary/sunlight exposure advice to all at risk groups

39. Questions • Treatment- injection vs oral medication and how long for? -Oral is better (all round); but current supply issues. -In severe deficiency a short course of monthly IM insures treatment is received -If GI problem, IM worthwhile

40. Questions • How often to monitor bloods once on treatment? -Depends on manifestations, but maybe never or once in a year until dietary intake is no longer an issue -If Alk. Phos raised, recheck in 3 and 6 months; although it may take longer to normalise

41. Questions • When to refer?- and who to endocrine vs bone clinic • Doubt about diagnosis; conflicting biochem (eg. Hypercalcaemia) • Failure to respond to treatment • Other nutritional issues (IDA frequently co-exists) • Childhood with bone disease - Vitamin D is actually a hormone

42. Questions • Patients with aches and pains and confirmed vit D def- should we be x-raying joints I generally don’t, unless there is very localised pain (not generalised aches & pains) Pain not improved by 3 months treatment should trigger an X-ray

43. 10,000 U/d 5,000 U/d 1,000 U/d Placebo Dosing of colecalciferol in Autumn From Heaney RP et al.