1. Vitamin D Letting in the light? A Hutchesson 2011

2. Vitamin D Anti-rachitic factor in cod liver oil 1921; distinguished from vitamin A –named vitamin D 1923; ‘light equals vitamin D” (Hess) 1932-6; two main forms (D 2 and D 3 )

3. Vitamin D deficiency Rickets (children) –bone deformity –muscle weakness –low calcium, phosphate Osteomalacia (adults) –bone pain –lethargy –proximal muscle weakness –falls, fractures –Low calcium, phosphate

4. Vitamin D - Sources D2 - Ergocalciferol –Yeast, mushrooms D3 - Colecalciferol –Cod liver oil –Oily fish –Sunlight, UVB

5. Vitamin D 3 - Synthesis 7-dehydrocholesterol Previtamin D 3 Colecalciferol (D 3 ) UVB (270-300 nm) Spontaneous reaction (~12 days) Skin Lumisterol

6. Vitamin D - Metabolism Vitamin D (D 2 /D 3 ) 25(OH)DVitD-BP 1,25(OH) 2 D PTH 24,25(OH) 2 D Vit D receptor Protein synthesis Kidney (monocytes) + + + Liver -

7. Vitamin D - Actions Vitamin D receptor Intestine Bone Macrophages/ Monocytes Parathyroids Tissues  calcium/phosphate absorbtion 1,25(OH) 2 D  remodelling Immunity/ autoimmunity/ atopy?  proliferation  differentiation  PTH Other endocrine  activity

8. Vitamin D - Effects Increased calcium and phosphate absorbtion. Increased bone mineralisation  reduced fractures (25(OH)D > 75 nmol/L) Improved muscle strength, gait  reduced falls; RR 0.84 (0.76-0.93)

9. Vitamin D – possible effects Cancer protection? –Associations with colon, breast, pancreas, prostate –1100 units D 3 /day  RR 0.232 after 1 year (Lappe et al; 2007) Autoimmune disease, atopy? –Associations with MS, diabetes type 1, asthma Infections? – TB, HIV, RTI –Associations with 25(OH)D levels, VDR polymorphisms –Macrophages convert 25(OH)D  1,25(OH)2D Ischaemic heart disease –Low 25(OH)D associated with IHD –BUT,  risk in Women’s Health Initiative study (Bolland et al, 2011)

10. Vitamin D deficiency - Causes Poor sun exposure –skin colour –latitude –lifestyle –clothing –sunscreen Malabsorbtion –CF –Crohn’s disease –bariatric surgery Chronic kidney disease Chronic liver disease Medications –anticonvulsants –HAART –cholestyramine –antifungals –glucocorticoids Obesity Inherited –1-hydroxylase deficiency (pseudovitamin D deficiency) –VDR deficiency (vitamin D-resistant rickets)

11. Vitamin D - What to measure? Diagnosis -Total 25(OH)D Monitoring -25(OH)D 2 and D 3 Chronic Kidney Disease -1,25(OH) 2 D Sarcoid

12. 25(OH)D - results ng/mLnmol/L <10<25High risk of symptoms/fracture ~30~75Sufficiency PTH settles to plateau >150>365Toxicity

13. Vitamin D – how to treat 25(OH)D < 25 nmol/LHigh-dose D, 600,000 units (e.g. Dekristol, 60,000 units weekly x 8-12 weeks), then long-term low-dose (800-2000 units/day) - maintains control mechanisms for 1,25(OH) 2 D - possible effects of 24,25(OH) 2 D? 25-75 nmol/LLifestyle advice OTC low-dose D 800 – 2000 units/day (e.g. Adcal-D3) Chronic Kidney Disease1(OH)D, 1.25(OH) 2 D or analogue (e.g. Alfacalcidol, calcitriol, paricalcitol) - inability to use other forms.

14. Monitoring treatment Low-dose vitamin D - None High-dose vitamin D -Calcium x1-2/week 25-(OH)D after 1 month CKD -Calcium, phosphate, PTH