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

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

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

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 ( g) 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 ( 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?
25-OHD
(nmol/l)
Vit D status
Manifestation
Action
<25
Deficient
Rickets
Osteomalacia
Treat with
high dose D
25-50
Insufficient
Associated with disease risk
Supplement with vit D
50-75
Adequate
Healthy
Lifestyle advice
>75
Optimal
None

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. Treatment 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
Serum
Feb
April
Calcium
2.60
2.30
PO4
1.11
0.77
Alk Pase 62 48
25-OHD 10 11

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?
25-OHD
(nmol/l)
Vit D status
Manifestation
Action
<25
Deficient
Rickets
Osteomalacia
Treat with
high dose D
25-50
Insufficient
Associated with disease risk
Supplement with vit D
50-75
Adequate
Healthy
Lifestyle advice
>75
Optimal
None

34. Also OTC Boots (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
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. Dosing of colecalciferol in Autumn
Placebo
10,000 U/d
5,000 U/d
1,000 U/d
From Heaney RP et al.