Dr Seeta Durvasula seeta.durvasula@sydney.edu.au 1
Avoid sun skin cancer risk Australia has highest rates of skin cancer in the world Epidemic of Vitamin D deficiency Lack of Vitamin D increases risk of diabetes Indoor workers suffer vitamin D deficiency Lack of vitamin D linked to cancer Lack of vitamin D may have killed Mozart Vitamin D boosts brain power in middle aged men Bald head offers no vitamin D advantage 2
What is vitamin D? Sources of vitamin D Role of vitamin D Skeletal effects Other effects Vitamin D deficiency Criteria Prevention Treatment Implications for people with intellectual disability
Hormone rather than vitamin Active form made in one organ (kidney) Has effects on other organs Two molecules Cholecalciferol (vitamin D3) main form Made by action of UVB radiation on 7-dehydrocholesterol in skin Ergocalciferol (vitamin D2) Made by UV radiation of plant steroid, ergosterol 4
Three different wavelengths Shorter the wavelength, more harmful UVC (100-280 nm) most harmful, but completely filtered by atmospheric ozone UVA (315-400 nm) most reaches Earth Penetrates deeper layers Effects immediate tanning, contributes to ageing, may enhance skin cancer development UVB (280-315 nm) -10% reaches Earth Penetrates superficial skin layers Effects - delayed tanning, ageing, skin cancer WHO - http://www.who.int/uv/faq/whatisuv/en/index.html 5
Skin 7 -dehydrocholesterol Cholecalciferol (Vitamin D3) Food Minor source Vitamin D2 Vitamin D3 Liver Kidney & other tissues 25-hydoxycholecalciferol (25 hydroxyvitamin D) 1,25-hydoxycholecalciferol (1,25 dihydroxyvitamin D) = Calcitriol Regulated by PTH, low PO4, growth, pregnancy 6
Obesity Associated with low vitamin D levels Vitamin D stored in fat Not easily released Physical activity May mobilise vitamin D from fat stores Not just due to sun exposure with outdoor exercise Low calcium intake or high PTH more rapid breakdown of vitamin D 7
Promotes calcium absorption from gut Counteracts normal urinary loss of calcium So, calcium doesn t have to be released from bone (resorption) to maintain blood levels Also Promotes bone mineralisation Suppresses bone turnover Role in muscle function 8
Vitamin D deficiency less calcium absorbed from gut low blood calcium levels increased parathyroid hormone (secondary hyperparathyroidism) stimulates release of calcium from bone reduced bone density muscle function impaired Increased fracture risk - especially in elderly 9
Decreased bone mineralisation bones soft Rickets / osteomalacia Rickets in children bone deformity, enlarged growth plates, delayed standing, walking, delayed growth, bone pan Osteomalacia in adults Bone pain Proximal muscle weakness Unsteady gait Increased risk of fractures (Osteoporosis bone is mineralised, but less bone overall, so brittle ) 10
Cells of many organs have Vitamin D receptors 1,25 OH vitamin D Regulates cell growth and differentiation in normal and malignant cells Modulates immune system 11
Autoimmune disease MS, Type I diabetes, rheumatoid arthritis Cancer Bowel, breast, prostate Type 2 diabetes - Insulin resistance Asthma, Atopic dermatitis Infection Cardiovascular disease Overall mortality Schizophrenia / Depression 12
High level evidence for preventing fractures and falls in older people Need adequate calcium for vitamin D to work 13
Some limited evidence - mostly observational studies showing associations Biological mechanisms plausible, but Causation always not proven Evidence for non-skeletal benefits of vitamin D therapy is not strong Some evidence of decreased all cause mortality Need high quality studies 14
Older people usually, less sun exposure Less 7-dehydrocholesterol with thinner skin Darker skin pigmentation Less absorption of UVB may need 3-6 times longer UV exposure than fair skinned people Less sun exposure Covering up for religious/cultural reasons Active sun avoidance Indoor work and leisure activities Chronic illness, poor mobility Sunscreen - reduces UVB penetration, but often not properly applied
Recommended Daily Allowance (USA) 1-70 years 600IU (15µg) 71 + years 800IU (20 µg) Upper Limit 4000IU (100µg) 16
Diet limited Wild-caught oily fish North sea salmon, herring, mackerel (2-5µg/100gm) Wild or UV pulsed mushrooms (up to 40µg/ 100gm) One vitamin D fortified milk (2 µg/ 250 ml) Average estimated dietary intake is only 2-3 µg/day 17
Minimal Erythema Dose (MED) = amount of UV exposure that causes faint redness of the skin 1/3 rd MED to 15% of body - hands, face, arms 25µg (1,000 IU) vitamin D On most days to maintain vitamin D levels 18
It depends. 19
Depends on Skin pigmentation Latitude Season Time of day Local weather conditions - cloud cover, haze etc. Clothing Note: sun exposure through window glass not effective little UVB transmission 20
Region Dec. Jan. 10am or 2pm* July Aug 10am or 2pm July Aug Noon Cairns 6-7 9-12 7 Brisbane 6-7 15-19 11 Sydney 6-8 26-28 16 Melbourne 6-8 32-52 25 Hobart 7-9 40-47 29 Christchurch 6-9 49-97 40 1 People with moderately fair skin * 11am or 3pm daylight saving 21
Aim for 50-60nmol/L at end of winter Suppresses parathyroid hormone Above this level, no additional benefit for bone density and muscle function Some studies, but not all indicate older people need minimum 60nmol/L for falls and fracture prevention Some propose 75-80nmol/L for prevention of non-skeletal effects, but no strong evidence for this
Adequate vitamin D 51-60 nmol/l Mild vitamin D deficiency 26-50 nmol/l Moderate vitamin D deficiency 12.5 25 nmol/l Severe vitamin D deficiency <12.5 nmol/l 23
If not at high risk of vitamin D deficiency Walk in the sun at morning or afternoon tea in summer, lunch time in winter Adequate calcium intake e.g. low fat dairy Exercise NB: Follow guidelines for safe sun exposure! Where sun exposure not desirable or practical and/or those at high risk of deficiency Vitamin D supplements at least 1,000IU/day Calcium supplements if little in diet 24
Moderate-severe deficiency 3,000 5,000IU /day for 6-12 weeks Variation in response, so check vitamin D levels after 12 weeks Once target level reached, need maintenance usually 1,000IU/day Also need daily intake of calcium of 1,000-1,300 mg/day Supplements, if can t achieve through diet 25
Toxicity hypercalcaemia Usually at levels of 500nmol/L RCT 1 of single annual dose 500,000IU for 3-5 years increased falls & fracture risk But, study of oral dose of 100,000IU every 4 months in >65 years reduced fractures Contraindications hypercalcaemia or hypercalciuria Caution with cod liver oil Also has vitamin A toxic at high doses 1 Sanders et al.(2010)jama, 303:1815-1822 26
Can t overdose through sun exposure Prolonged UV exposure breakdown of vitamin D So, brief exposures more efficient at making vitamin D 27
High prevalence 50-60% Risk factors People in large residential care Reduced mobility, availability of staffing support, chronic illness etc. reduced sun exposure Low calcium levels reduced intake, malabsorption Some antiepileptic medications e.g. phenytoin Vanlint et al (2008)
Screening all for deficiency, but can be expensive Supplement without screening Recommended in elderly population Probably justified for those at high risk Prevention safe sun exposure, as for general population Treatment as for general population 29
Mason R. (2011). Vitamin D: a hormone for all seasons. Climacteric 14(2):197-203 Thatcher T.D. & Clarke B.L. (2011) Vitamin D insufficiency Mayo Clinic Proceedings 86(1): 50-60 Vanlint S, Nugent M, Durvasula S, Downs J & Leonard H. (2008). A guide for the assessment and management of vitamin D status in people with intellectual disability. Journal of Intellectual and Developmental Disability 33(2): 184 188 30
Working Group of the Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia and Osteoporosis Australia (2005). Vitamin D and adult bone health in Australia and New Zealand: a position statement MJA 2005: 182 (6):281-285 (due to be reviewed) Risks and benefits of sun exposure Position statement (Approved by The Australian and New Zealand Bone and Mineral Society, Osteoporosis Australia, The Australasian College Of Dermatologists and Cancer Council Australia ) 2007. http://www.cancer.org.au//file/policypublications/ PSRisksBenefitsSunExposure03May07.pdf - last accessed 28.10.11 31
NPS News 72: Vitamin D (2011). National Prescribing Service http://www.nps.org.au/ health_professionals/publications/nps_news/ current/vitamind last accessed 2.2.11 32