What’s all the fussabout vitamin D?

Dr Margaret OziemskiDermatologist

Brisbane

www.sunsafetyqld.com.au

Professor Michael KimlinAusSun Research Lab QUT

The Sunday Courier Mail 11/11/2009

75% of Brisbane residents are vitamin D deficient

Slip, Slop, Crack :The Vitamin D crisis

The Age Dec 2007

Message to cover up has led to vitaminD deficiencies between 30% - 70% ofthe population

Osteoporosis Australia link low levels ofvitamin D to massive increase inosteoporosis related diseases costing$ 1.9 billion a year

The Challenge

Australia has the highest rate of skincancer in the world

Over 1000 lives lost each yearSkin cancer rates continuing to increaseMelanoma is the commonest life

threatening cancer in 15 – 25 year oldsCosts to health budget significant –

$ 264 million spent on nonmelanoma skincancer in 2000-01

Our Lifestyle

Sun worshipping continues People underestimate the intensity of the sun

in the Sunshine State when timetablingactivities for leisure, school, sport or work

Sunburn frequently reported

Public education - Prevention

Slip, Slop, SlapUV Index/ UV AlertProtect in Five ways from skin cancer

What is Vitamin D?

Bulk of vitamin D is made in the skinSmall amount is obtained from foodVitamin D is more of a hormone than a

vitaminMost tissues posses vitamin D receptor

and can convert circulating vitamin D toactive

Vitamin D insufficiency

MUSCULOSKELETALRicketsBone painMuscle achesFallsFracturesOsteomalaciaOsteoporosis

A Place for Vitamin D

VulvitisRespiratory tractinfectionsRicketsRhA

MacrophagesAnti-melanomaMorpheaMusclesMS

Hair growthHeadacheHeartHIVHypertension

DementiaDepressionDiabetes type 1and 2

UC/CrohnsUrticaria

Parkinson’sPeriodontitisPCODPhotoprotectionPre-ecclampsiaPregnancyProstatePsoriasis

Lichen sclerosusLymphomas - NHLLung cancer

GIT - UC/CrohnsGlucocorticosteroidinduced osteoporosisprevention

CathelicidinCalciphylaxisCardiomyopathyColorectaladenomasCystic fibrosisCrohns

Tuberculosisprevention andtreatmentTransplantpatients

ObesityOsteomalaciaOsteoporosisOvarian cancer

KeratodermaKidneys

Fall preventionFatigueFolliculitis

BonesBowel cancerBreast cancer/aromatase inducedarthralgiaBurns

SchizophreniaSCC of head andneckSLESystemic sclerosisStatin inducedmyalgia

NailsNeonatal tetany

Immune systemInfertilityInfluenzapreventionInsulin resistance

EczemaEpidermolysis bullosaEpileptic drugs interferewith metabolismEPP

AcneAlzheimersAMIAnti-bacterialAsthmaAutoimmune

Molecular basis of the potentialof Vitamin D to prevent Cancer

1,25 (OH)2 D3 - Calcitriol - and functional VDRrequired for normal control of cell cycle

Calcitriol has antiproliferative effects related to cellcycle control involving p21, p27 and p53

Calcitriol influences genes affecting apoptosis Calcitriol changes shape of cancer cells which

become more adhesive ?reduces metastases Calcitriol targets BRCA1 - breast cancer susceptibility

protein involved in tumour suppression

Current Medical Research and Opinion vol 24, No 1, 2008, p 139-149

Vitamin D and Melanoma

1,25 (OH)2 vitD3 is antiproliferative inmelanoma cellsClin Cancer Res 2000 Feb;6(2):498-504

VDR polymorphism associated withoccurrence and outcome of melanomaBr J Dermatol 2002 Aug;147(2):197-213

Vitamin D and Melanoma

High vitamin D status associated withimproved survival for melanomaCurr Opin Clin Nutr Metab Care 2007 Jan;10(1):6-11

Reduced serum 25 OH vitamin D levels instage IV melanomaAnticancer Res 2009 Sep;29(9):3669-74

SMU Vit D and MelanomaANZCTR 2009

http://www.anzctr.org.au/trial_view.aspx?ID=83884

75 patients, 23 monthsRandomised blind Vit D3 vs placeboVit D3 level >75 nmol/lPrimary, histologically resected stage Iib, Iic,

IIIa(N1a) and IIIb(N1a,N2a) cutaneousmelanoma

50,000IU D3 x10 on Day 1, then 50,000IU D3once a month for the 23 months

Vitamin D Metabolism

7-dehydrocholesterol

UVB

Previtamin D3 Vit D Thermalisomerisation

Chen et al Arch Biochem Biophys2007(460);213-217

Time of dayLatitudeSeasonClothesSunscreenMelaninAge

Skin Liver

Kidney

25 OH Vit D3

1,25 (OH)2 Vit D3

FoodD3, D2

Calcitriol

Tissues1,25 (OH)2 Vit D3

Time of the Day

Reproduced with permission from Nutrition and Bone Health ed. Michael Holick and Bess Dawson-Hughes, 2004 2004

Month of the Year

Reproduced with permission from Nutrition and Bone Health ed. Michael Holick and Bess Dawson-Hughes, 2004 2004

Sunscreen effect

Reproduced with permission from Nutrition and Bone Health ed. Michael Holick and Bess Dawson-Hughes, 2004

Effect of Age

Reproduced with permission from Nutrition and Bone Health ed. Michael Holick and Bess Dawson-Hughes, 2004

Most Australians needsunprotection when the UV index is3 or above.

It is safe to go outside without sunprotection in the early morning andlate afternoon when the UV Indexis below 3.

Safe Sun concept

WHO Global Solar UV Index

Safe Sun

Brisbane

Extreme

Very high

High

Moderate

Low

Can we make vitamin D when theUV is less than 3?”

“Recent results from our lab and others suggestthat not a lot of vitamin D is made when the UVBwavelengths of even as low as 311 nm,suggesting that not much if any D would bemade if the UV index is <3”.

Professor Rebecca MasonHead, Physiology Bosch Institute SydneyEmail 4 June 2008

Womans DayJuly 2010

“few minutes of sunlight on either side of the peak UV periods on most days of the week”

WHO Global Solar UV Index

When UV is over3

practicesunprotection

“few minutes of sunlight on either side of the peak UV periods on most days of the week”

Peak UV undex in Darwin in Extreme or VeryHigh range on average

Peak UV index in Melbourne in Low orModerate range for 6 months of year

Problems in Policy

The advice to sunprotect when theUV index is over 3 includes the

time when vitamin D is made bythe action on UVB on the skin

You do not make vitamin D when theUV index is less than 3

It is the same UVB which isneeded to make vitamin D that

causes damage to the skinlongterm if the skin is

overexposed

If we are not in the sun howcan we achieve adequate

Vitamin D levels?

Vitamin Dand the diet

Salmon 360 IU Mackerel 345 IU Sardines 270 IU Milk Physical approx100 IU Berri Australian Fresh Tropical Fruit Juice 100 IU Cereal 99 IU Margarine* 40 IU Cheese* 40 IU Beef liver 30 IU Egg yolk 25 IU

Note:Cod liver oil 1 tbsp = 1360IU D3 but high vitamin A content can cause birth defects

Vit D3 Supplements

Ostevit D or Ostelin 1000 IU D3Balckmores D3 1000 IU D3Elevit 500 IU D3Citracal with D 500 IU D3Caltrate with D 200 IU D3Bioceuticals drops 333.3 IU D3 per drop

What should the Vitamin Dblood level be?

Vitamin D status

Vitamin D sufficiency > 75 nmol/lSub-optimal levels 50 - 75 nmol/lVitamin D insufficiency 25 - 50 nmol/lVitamin D deficiency 15 - 25 nmol/lSevere Vitamin D deficiency < 15 nmol/l

Joshi D, Center J and Eisman J.Australian Prescriber 2010 Aug vol 33 No 4 p103-106

Sufficient Vitamin D

For Bone health Recommended Daily Intake(RDI)

19 - 50 yo 200 IU/d 51 - 70 yo 400 IU/d >70 yo 600 IU/d

For Better bones vitamin D blood level over80 nmol/l recommended

Vitamin D levels for OtherHealth Outcomes

50% of colon cancer incidence in NthAmerica could be prevented by vit D levelof > 85 nmol/l

50% of breast cancer incidence in NthAmerica could be prevented by vit D level>130 nmol/lGarland et alNutrition Reviews Aug 2007;65(8):S91-S95

Maintaining sufficient vitamin D

Replacement with 1000 - 5000 IU a dayvitamin D3 for 2 - 3 months and repeat25 OH vitamin D level

Titrate dose of vitamin D3 supplement toblood level at least over 80nmol/l

May require 1000 - 5000IU a daymaintenance

Monitor 25 OH vit D3, calcium and U&E3 - 6 monthly once stable

Can you have too muchVitamin D?

Vitamin D toxicity: due to raised blood calcium:anorexia, nausea, headache, thirst, polyuria,constipation, twitching, soft tissue calcification,kidney stones, confusion, coma

Reported if vitamin D blood level > 350 nmol/lSome side effects of supplements not related to

hypercalcemia: itch, headache, upset digestion,cramps if Magnesium low

Vitamin D Conference4 - 8 October,2009Bruges, Belgium

“At Risk” Groups ofVitamin D Deficiency

Dark skinnedReligious/ Cultural coveringElderlyBabies of vitamin D deficient

mothersHousebound/ Institutionalised

Practice Audit

Period of 6 months March to August2007, Brisbane private dermatologypractice

Patients during consultation questionedabout amount of time in the sun on dayto day basis

Sunprotective measures recorded

57/170(33.5%)

19/61( 31.1%)

5/9(55.6%)

Otherconditions

12/170( 7.1%)

8/61(13.1%)0/9

Immunosuppressed/Photosensitive

101/170(59.4%)

34/61(55.7%)

4/9(44.4%)

PH Melanoma,NMSC, or both,

DN, FH Mel

57.4 yrs(22 - 93)

56.3 yrs(30 - 93)

48.7 yrs(32 - 87)

Mean age50141 M

120478 Sex F

170/310(54.8%)

61/310(19.7%)

9/310(2.9%)

Number< 75 nmol/l< 50 nmol/l < 25 nmol/l

DN - Dysplastic naevi

NMSC - Non melanoma skin cancer

Additional “At risk” groups ofVitamin D deficiency Reported

Past history of melanoma, non melanomaskin cancer, dysplastic naevi, or family historyof melanoma

Photosensitive conditions or medicationsImmunosuppressed conditions or medicationsWorking indoors

Check Vitamin D after Skin Cancer Diagnosis- Dr Margaret OziemskiMedical Observer 3 April 2008

Recent Practice Audit1/1/04-25/8/09

2380 vitamin D tests, Brisbane privatedermatology practice

< 25 nmol/l 27 ( 1%)< 50 nmol/l 304 ( 13%)< 75 nmol/l 1047 ( 44%)< 150 nmol/l 2344 ( 99%)

The vitamin D status ofAustralian Dermatologists

Bruce et al, Clin & Exp Dermatol 34;2009: 621-638

Southern Australia winter 200647 dermatologists6 had levels > 50nmol/l15% had levels <20 nmol/l

QML Clinical Audit Aug 09

1/11/08-28/1/09 in Brisbane15,000 vitamin D studies35% vit D level> 75 nmol/l41% level 50 - 75 nmol/l24% level in deficient range <50 nmol/l

Our Obligation

If we advise sunprotection, we shouldmonitor for vitamin D sufficiency

If a patient is sunprotecting, we shouldmonitor for vitamin D sufficiency

If a patient is not in the sun, we shouldmonitor for vitamin D sufficiency

A Tale of Two Sisters

43 yo indoor workerFreckles, black hairSolar lentigos, DSAPBurned easily in

childhood2004 Level 1

Melanoma on leg as38 yo

47 yo indoor workerFreckles, red hairDSAPBurned easily in

childhood2006 BCC left cheek

as 45 yo

A B

FH

Breast cancer mother aged 64

A (23/3/07) B (26/4/07)

25 OH D 21

Bone Density - mild osteopeniaL4 T -1.0

Supplemental D315,000IU/d25 OH D 138

25 OH D 28

Bone Density -low normalL4 T -0.3

Supplemental D34000IU/d

25 OH D 148

It is important to maintainadequate Vitamin D levels for a

whole host ofHealth Outcomes

not only for Musculoskeletal health

Summary Points

It is possible to supplementvitamin D and monitor with

blood levels rather thanrecommend sun exposure to

achieve sufficiency

Vitamin D insufficiency is underreported and its impact on our health

underestimated

More clinical trials are needed to look atdosage, timing of supplementation and

health outcomes

SLIP SLOP SLAP

SLIDE ON SOME SHADES SWALLOW A SUPPLEMENT

SEEK A SKIN CHECK