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Vitamin D: from bone to Vitamin D: from bone to cancer therapycancer therapy

Henk R. FrankeHenk R. Franke

The Hague, 12/4/2013

22

Who knows their vitamin D Who knows their vitamin D serum level?serum level?

33

Vitamin D serum level of Vitamin D serum level of an elderly youngsteran elderly youngster

43 weeks: 1000 IE daily13 weeks: 3600 IE daily

44

OutlineOutline

Vitamin D in shortVitamin D in short Cancer stem cell theoryCancer stem cell theory Breast cancerBreast cancer In vitro proofIn vitro proof Practical guidelinesPractical guidelines

55

How do we acquire our vitamin D ?How do we acquire our vitamin D ?

Sun-bathing 10 -20000 IE

Margarine 20 - 30 IE / slice of bread

Fatty fish 600 - 1000 IE/100g

Food only supplies < 10 % of our needs

Multivitamins 200 IE/daily

66Vieth, J Steroid Biochem Mol Biol 2004;89-90:575

NL 52°N

77

Muskiet et al, Ned Tijdschr Klin Chem Labgeneesk 2007;32:150

88

Vitamin DVitamin D

Regulates 200 genes that influences cell growth and Regulates 200 genes that influences cell growth and differentiation which probably leads to a lesser extent differentiation which probably leads to a lesser extent of malignant degeneration (Holick, 2008)of malignant degeneration (Holick, 2008)

Induces apoptosis of the cancer (stem) cellInduces apoptosis of the cancer (stem) cell Desired serum level is at least 100 nmol/l (Binkley et Desired serum level is at least 100 nmol/l (Binkley et

al, 2008)al, 2008)

99

OutlineOutline

Vitamin D in shortVitamin D in short Cancer stem cell theoryCancer stem cell theory Breast cancerBreast cancer In vitro proofIn vitro proof Practical guidelinesPractical guidelines

1100

Cancer stem cell theoryCancer stem cell theory

Vermeulen et al, NTvG, 2009;153:286

1111

Kakarala et al, Cancer J 2007;13:271

1122

Breast Tumor Content Breast Tumor Content

A tumor consists of a small stem cell A tumor consists of a small stem cell compartment (3 -35%) and a large compartment (3 -35%) and a large population of differentiated cellspopulation of differentiated cells

Number of divisions of a differentiated Number of divisions of a differentiated tumor cell: 50-60, division time: 19,5 tumor cell: 50-60, division time: 19,5 hours, total lifetime 1170 hourshours, total lifetime 1170 hours

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Breast Tumor ContentBreast Tumor Content

Tumor doubling time 50-100 dagenTumor doubling time 50-100 dagen Number of doublings needed to Number of doublings needed to

increase the tumor to 1 cm is 30-35increase the tumor to 1 cm is 30-35

1144

Breast Cancer and HT: early detectionBreast Cancer and HT: early detection

Wertheimer et al. JAMA 1986;255:1311

The Mammographic Window

1 2 3 4 5 6 7 8 9 10 11 12 13 14 Years

1012

1010

108

106

104

1

1mm

1cm

2.5cm

Premammographic Preclinical Clinical

1155

OutlineOutline

Vitamin D in shortVitamin D in short Cancer stem cell theoryCancer stem cell theory Breast cancerBreast cancer In vitro proofIn vitro proof Practical guidelinesPractical guidelines

1166

5% more breast cancers present in the left breast

1177

In The Netherlands each day 68 women and 63 In The Netherlands each day 68 women and 63 men die from cardiovascular events¹men die from cardiovascular events¹

In The Netherlands each day 9 die from breast In The Netherlands each day 9 die from breast cancer²cancer²

¹Wassertheil-Smoller et al Hypertension 2000;36:780²Sluman et al NTvG 2006;150:2018

1188

Breast cancer prevalence in the USABreast cancer prevalence in the USA

1199

Crew et al 2009;2(6):598

The association

2200

OutlineOutline

Vitamin D in shortVitamin D in short Cancer stem cell theoryCancer stem cell theory Breast cancerBreast cancer In vitro proofIn vitro proof Practical guidelinesPractical guidelines

2211

‘All roads lead to death’

2222

ApoptosisApoptosis

physiological, programmed cell death, physiological, programmed cell death, during the adult lifespan each day 10during the adult lifespan each day 1099 cells diecells die

It means falling of leaves and was first It means falling of leaves and was first mentioned by Kerr in 1972mentioned by Kerr in 1972

2233

NECROSIS: cell murder

APOPTOSIS: cell suicide

2244

HELA cell, cervix carcinoma cell

QuickTime™ en eenCinepak-decompressor

zijn vereist om deze afbeelding weer te geven.

2255

Development of the hand of an embryo of about 7 weeks gestational age

QuickTime™ en eenCinepak-decompressor

zijn vereist om deze afbeelding weer te geven.

2266

In vitro proofIn vitro proofApoptosis proliferation ratioApoptosis proliferation ratio

Mark Londema 2009

2277

OutlineOutline

Vitamin D in shortVitamin D in short Cancer stem cell theoryCancer stem cell theory Breast cancerBreast cancer In vitro proofIn vitro proof Practical guidelinesPractical guidelines

2288

Advice Vitamin D Council, USAAdvice Vitamin D Council, USA

Children till 1 year 1000 IU/dailyChildren till 1 year 1000 IU/daily Children 1 to 4 years 2000 IU/dailyChildren 1 to 4 years 2000 IU/daily Children 4 to 10 years 3000 IU/dailyChildren 4 to 10 years 3000 IU/daily Adults 2000-5000 IU/dailyAdults 2000-5000 IU/daily

www.vitamindcouncil.org

2299

Practical AdvicePractical Advice

Every 2 weeks 50.000 IUEvery 2 weeks 50.000 IU

That is 3570 IU/dailyThat is 3570 IU/daily

Half time of vitamin D: 4-5 weeksHalf time of vitamin D: 4-5 weeks

3300

€ 49,50Daily costs € 0,11

€ 22,15Daily costs € 0,16

3311

3322

Calcium/vit D and cardiovascularCalcium/vit D and cardiovascular

Bolland et al, BMJ 2011;342:d2049

3333

Calcium/vit D and cardiovascularCalcium/vit D and cardiovascular

Bolland et al, BMJ 2011;342:d2049

33443344

3355

@hrfranke@hrfranke

www.henkfranke.comwww.henkfranke.com