Vitamin D
Simon Pearce
Consultant Endocrinologist, RVI, Newcastle
Vitamin D
• Basic background
• Public health
• Cases & Clinical scenarios
Synthesis, activation & action
Skin
Liver
Kidney
Active vitamin
D hormone
Calcium &
skeletal
homeostasis
Immune
system
tissues
Metabolic &
vascular
tissues
Cellular
Homeostasis
& apoptosis
Vitamin D- natural sources
• Ergocalciferol
– ‘Vitamin D2’
– UV irradiated fungi/ yeast
• Colecalciferol
– ‘Vitamin D3’
– UV irradiated plankton
– UV irradiated animal skin/ fur
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.
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
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
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
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)
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
How to determine vitamin D
status?
25-OHD
(nmol/l)
<25
Vit D status
Action
Treat with
high dose D
Supplement
with vit D
Lifestyle
advice
None
25-50
Insufficient
50-75
Adequate
Rickets
Osteomalacia
Associated with
disease risk
Healthy
Optimal
Healthy
>75
Deficient
Manifestation
Interpretation of serum 25-OHD
Men (n=3725)
• UK-wide white cohort born 1958
Women (n=3712)
Hypponen & Power 2007
Interpretation of serum 25-OHD
Men (n=3725)
• UK-wide white cohort born 1958
Women (n=3712)
Hypponen & Power 2007
Case 1
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
GP did blood tests
• Calcium =1.89 mmol/l (2.12-2.6)
• Alk Phos = 231 KIU/l (<120)
• Rh factor negative
• Refer endocrinology
Endocrinology blood tests
• PTH 684 ng/l
• 25-OH vitamin D = 7 nmol/l
• Diagnosis = Osteomalacia
Generalised Aches & Pains =not always depression
Sievenpiper J et al. BMJ
Treatment
• Oral ergocalciferol 10,000 IU daily for 3 months
• Feels a lot better, aches and pains gone,
smiling in clinic
• But……..
• 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
NICE antenatal care guideline
Case 2
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
• 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
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.
Case 3
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
Fell out of bed one day
• Wedge # of L2 vertebral body
• BMD measured; T score -3.4 at spine
• Bone chemistry
• (PTH 43)
Serum
Feb
April
Calcium
2.60 2.30
PO4
1.11 0.77
Alk Pase 62
48
25-OHD
11
10
• Treated with calcichew D3 one daily
• Allergic to fish; none since teenager
• Not really leaving the house due to mobility
• No overseas holiday for 5 yrs
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
How to determine vitamin D
status?
25-OHD
(nmol/l)
<25
Vit D status
Action
Treat with
high dose D
Supplement
with vit D
Lifestyle
advice
None
25-50
Insufficient
50-75
Adequate
Rickets
Osteomalacia
Associated with
disease risk
Healthy
Optimal
Healthy
>75
Deficient
Manifestation
Also OTC
Boots (12.5 ug capsules) £2.99 for 90
Holland & Barrett (25 ug capsules) £6.99 for 100
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)
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
The End
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
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
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
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
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
Dosing of colecalciferol in Autumn
10,000 U/d
5,000 U/d
1,000 U/d
Placebo
From Heaney RP et al.