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Vitamin D: from bone to cancer
 therapy

            Henk R. Franke


The Hague, 12/4/2013          1
Who knows their vitamin D serum
level?




                           2
Vitamin D serum level of an
 elderly youngster




43 weeks: 1000 IE daily
13 weeks: 3600 IE daily        3
Outline
   Vitamin D in short
   Cancer stem cell theory
   Breast cancer
   In vitro proof
   Practical guidelines



                              4
How do we acquire our vitamin D ?




Sun-bathing     Fatty fish 600 -   Multivitamins 200   Margarine 20 - 30 IE /
10 -20000 IE    1000 IE/100g       IE/daily            slice of bread



       Food only supplies < 10 % of our needs
                                                              5
NL 52°N


Vieth, J Steroid Biochem Mol Biol 2004;89-90:575
                                            6
Muskiet et al, Ned Tijdschr
Klin Chem Labgeneesk
2007;32:150 7
Vitamin D

   Regulates 200 genes that influences cell growth
    and differentiation which probably leads to a lesser
    extent of malignant degeneration (Holick, 2008)
   Induces apoptosis of the cancer (stem) cell
   Desired serum level is at least 100 nmol/l (Binkley
    et al, 2008)




                                               8
Outline
   Vitamin D in short
   Cancer stem cell theory
   Breast cancer
   In vitro proof
   Practical guidelines



                              9
Cancer stem cell theory




                Vermeulen et al, NTvG,   10

                2009;153:286
Kakarala et al, Cancer J 2007;13:27
                   11
Breast Tumor Content
   A tumor consists of a small stem cell
    compartment (3 -35%) and a large
    population of differentiated cells
   Number of divisions of a differentiated tumor
    cell: 50-60, division time: 19,5 hours, total
    lifetime 1170 hours


                                           12
Breast Tumor Content

   Tumor doubling time 50-100 dagen
   Number of doublings needed to increase
    the tumor to 1 cm is 30-35




                                      13
Breast Cancer and HT: early detection



           The Mammographic Window                                    2.5cm
1012
1010
                                              1cm
108
106                         1mm
104
 1


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

               Premammographic           Preclinical       Clinical




                                                                               14
                                                    Wertheimer et al. JAMA 1986;255:1311
                                                                                14
Outline
   Vitamin D in short
   Cancer stem cell theory
   Breast cancer
   In vitro proof
   Practical guidelines



                              15
5% more breast
cancers present in
the left breast




            16
   In The Netherlands each day 68 women and 63 men die
    from cardiovascular events¹
   In The Netherlands each day 9 die from breast cancer²




                       ¹Wassertheil-Smoller et al Hypertension 2000;36:780
                       ²Sluman et al NTvG 2006;150:2018       17
Breast cancer prevalence in the USA




                                      18
The association




                  Crew et al 2009;2(6):598
                                   19
Outline
   Vitamin D in short
   Cancer stem cell theory
   Breast cancer
   In vitro proof
   Practical guidelines



                              20
‘All roads lead to death’




                            21
Apoptosis
   physiological, programmed cell death, during
    the adult lifespan each day 109 cells die
   It means falling of leaves and was first
    mentioned by Kerr in 1972




                                              22
NECROSIS: cell murder


APOPTOSIS: cell suicide

                          23
HELA cell, cervix
                 QuickTime™ en een
               Cinepak-decompressor              carcinoma cell
zijn vereist om deze afbeelding weer te geven.




                                                              24
Development of the
                QuickTime™ en een                hand of an embryo
              Cinepak-decompressor
zijn vereist om deze afbeelding weer te geven.   of about 7 weeks
                                                 gestational age




                                                                25
In vitro proof
  Apoptosis proliferation ratio




                                  Mark Londema 26
                                               2009
Outline
   Vitamin D in short
   Cancer stem cell theory
   Breast cancer
   In vitro proof
   Practical guidelines



                              27
Advice Vitamin D Council, USA

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



                                 www.vitamindcouncil.org
                                                      28
Practical Advice

Every 2 weeks 50.000 IU
That is 3570 IU/daily
Half time of vitamin D: 4-5 weeks




                                    29
€ 49,50              € 22,15
Daily costs € 0,11   Daily costs € 0,16
                                          30
31
Calcium/vit D and cardiovascular




                 Bolland et al, BMJ 2011;342:d2049
                                               32
Calcium/vit D and cardiovascular




                 Bolland et al, BMJ 2011;342:d2049
                                               33
34
@hrfranke




            www.henkfranke.com
                           35

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Vitamin D and cancer

  • 1. Vitamin D: from bone to cancer therapy Henk R. Franke The Hague, 12/4/2013 1
  • 2. Who knows their vitamin D serum level? 2
  • 3. Vitamin D serum level of an elderly youngster 43 weeks: 1000 IE daily 13 weeks: 3600 IE daily 3
  • 4. Outline  Vitamin D in short  Cancer stem cell theory  Breast cancer  In vitro proof  Practical guidelines 4
  • 5. How do we acquire our vitamin D ? Sun-bathing Fatty fish 600 - Multivitamins 200 Margarine 20 - 30 IE / 10 -20000 IE 1000 IE/100g IE/daily slice of bread Food only supplies < 10 % of our needs 5
  • 6. NL 52°N Vieth, J Steroid Biochem Mol Biol 2004;89-90:575 6
  • 7. Muskiet et al, Ned Tijdschr Klin Chem Labgeneesk 2007;32:150 7
  • 8. Vitamin D  Regulates 200 genes that influences cell growth and differentiation which probably leads to a lesser extent of malignant degeneration (Holick, 2008)  Induces apoptosis of the cancer (stem) cell  Desired serum level is at least 100 nmol/l (Binkley et al, 2008) 8
  • 9. Outline  Vitamin D in short  Cancer stem cell theory  Breast cancer  In vitro proof  Practical guidelines 9
  • 10. Cancer stem cell theory Vermeulen et al, NTvG, 10 2009;153:286
  • 11. Kakarala et al, Cancer J 2007;13:27 11
  • 12. Breast Tumor Content  A tumor consists of a small stem cell compartment (3 -35%) and a large population of differentiated cells  Number of divisions of a differentiated tumor cell: 50-60, division time: 19,5 hours, total lifetime 1170 hours 12
  • 13. Breast Tumor Content  Tumor doubling time 50-100 dagen  Number of doublings needed to increase the tumor to 1 cm is 30-35 13
  • 14. Breast Cancer and HT: early detection The Mammographic Window 2.5cm 1012 1010 1cm 108 106 1mm 104 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Years Premammographic Preclinical Clinical 14 Wertheimer et al. JAMA 1986;255:1311 14
  • 15. Outline  Vitamin D in short  Cancer stem cell theory  Breast cancer  In vitro proof  Practical guidelines 15
  • 16. 5% more breast cancers present in the left breast 16
  • 17. In The Netherlands each day 68 women and 63 men die from cardiovascular events¹  In The Netherlands each day 9 die from breast cancer² ¹Wassertheil-Smoller et al Hypertension 2000;36:780 ²Sluman et al NTvG 2006;150:2018 17
  • 18. Breast cancer prevalence in the USA 18
  • 19. The association Crew et al 2009;2(6):598 19
  • 20. Outline  Vitamin D in short  Cancer stem cell theory  Breast cancer  In vitro proof  Practical guidelines 20
  • 21. ‘All roads lead to death’ 21
  • 22. Apoptosis  physiological, programmed cell death, during the adult lifespan each day 109 cells die  It means falling of leaves and was first mentioned by Kerr in 1972 22
  • 24. HELA cell, cervix QuickTime™ en een Cinepak-decompressor carcinoma cell zijn vereist om deze afbeelding weer te geven. 24
  • 25. Development of the QuickTime™ en een hand of an embryo Cinepak-decompressor zijn vereist om deze afbeelding weer te geven. of about 7 weeks gestational age 25
  • 26. In vitro proof Apoptosis proliferation ratio Mark Londema 26 2009
  • 27. Outline  Vitamin D in short  Cancer stem cell theory  Breast cancer  In vitro proof  Practical guidelines 27
  • 28. Advice Vitamin D Council, USA  Children till 1 year 1000 IU/daily  Children 1 to 4 years 2000 IU/daily  Children 4 to 10 years 3000 IU/daily  Adults 2000-5000 IU/daily www.vitamindcouncil.org 28
  • 29. Practical Advice Every 2 weeks 50.000 IU That is 3570 IU/daily Half time of vitamin D: 4-5 weeks 29
  • 30. € 49,50 € 22,15 Daily costs € 0,11 Daily costs € 0,16 30
  • 31. 31
  • 32. Calcium/vit D and cardiovascular Bolland et al, BMJ 2011;342:d2049 32
  • 33. Calcium/vit D and cardiovascular Bolland et al, BMJ 2011;342:d2049 33
  • 34. 34
  • 35. @hrfranke www.henkfranke.com 35

Editor's Notes

  1. Hoeveel in 15 minuten hoofd en armen? Hoeveel vit D per dag nodig ?? Aangegeven is de wilde zalm, bij gekweekte slechts ca ¼ van de wilde zalm
  2. Max 250 ug/dag toelaatbaar