Vitamin D

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Vitamin D

• Simon Pearce
• Consultant Endocrinologist, RVI, Newcastle

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Vitamin D

• Basic background
• Public health
• Cases Clinical scenarios

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Synthesis, activation action
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Vitamin D- natural sources

• Ergocalciferol
• Vitamin D2
• UV irradiated fungi/ yeast
• Colecalciferol
• Vitamin D3
• UV irradiated plankton
• UV irradiated animal skin/ fur

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Vitamin D- natural sources

• gt90 of humankinds 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.

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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

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Scale of the public health problem

• Seasonal geographic variation in prevalence of
  25-OHD lt40nmol/L
• MRC 1958 birth cohort at age 45yrs 7437 whites
• Spring nadir for 25OHD lt20 nmol/L 16
• lt50 nmol/L 50

Hyppönen Power 2007
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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

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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)

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How to determine vitamin D status?

• Measure serum 25 hydroxyvitamin D (25-OHD)
• Robust marker of vit D stores
• Half-life 3-4 weeks
• Dont 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

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How to determine vitamin D status?
25-OHD (nmol/l) Vit D status Manifestation Action
lt25 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
gt75 Optimal Healthy None
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Interpretation of serum 25-OHD
Men (n3725) Women (n3712)
UK-wide white cohort born 1958
Hypponen Power 2007
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Interpretation of serum 25-OHD
Men (n3725) Women (n3712)
UK-wide white cohort born 1958
Hypponen Power 2007
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Case 1
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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

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GP did blood tests

• Calcium 1.89 mmol/l (2.12-2.6)
• Alk Phos 231 KIU/l (lt120)
• Rh factor negative
• Refer endocrinology

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Endocrinology blood tests

• PTH 684 ng/l
• 25-OH vitamin D 7 nmol/l
• Diagnosis Osteomalacia

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Generalised Aches Pains not always depression
Sievenpiper J et al. BMJ
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Treatment

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

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• After topping up her vitamin D levels, she will
  need long-term maintenance
• 1000 to 2000 IU calciferol daily
• Regular sunlight exposure
• Dont forget the baby who was slow to walk and
  had rickets with tibial deformities

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NICE antenatal care guideline
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Case 2
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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

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• Ca 1.92 mmol/l (2.3-2.7)
• PO4 1.26 mmol/l (1.1-1.85)
• Alk Phos 1077 KIU/l (lt375)
• Treatment
• Ergocalciferol oily solution, 3,000 IU/ml. 2mls
  daily
• Mother and brothers, also to take supplements
  Dalivit 0.6 mls daily

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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.

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Case 3
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45 yo woman

• Multiple sclerosis diagnosed age 29
• Only 2 major attacks
• Feeling increasingly weak for 30 months
• Painful to move legs, cant stand up
• Using wheelchair, even in house
• Needs husband to pull her out of bed in morning

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

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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

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How to determine vitamin D status?
25-OHD (nmol/l) Vit D status Manifestation Action
lt25 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
gt75 Optimal Healthy None
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Also OTC Boots (12.5 ug capsules) 2.99 for
90 Holland Barrett (25 ug capsules) 6.99 for
100
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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)

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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

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The End
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Questions

• Is it worth screening all new patients from
  overseas at risk of vit D?
• -When people first arrive, they arent deficient
• -Probably takes 5 years or a pregnancy to
  manifest severe D deficiency
• -Worth giving dietary/sunlight exposure advice to
  all at risk groups

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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

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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

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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

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Questions

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

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Dosing of colecalciferol in Autumn
From Heaney RP et al.