Anti-aging medicine and breast safety.

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1 Anti-aging medicine and breast safety. A Nutriceutical for Healthy Aging Frank Comhaire M.D. Ph.D.

2 Why take a nutriceutical to postpone telemore shortening To preserve brain function To protect blood vessels To maintain bone density To counteract effects of stress To reduce cancer risk

3 Nutriceutical formulaltion for healthy aging Antioxidants Pine bark extract Vinca minor, phosphatidylserine Vit. B6, B9, B12, Zinc Linseed extract, Broccoli extract Lepidium meyenii Dioscorea villosa

4 Antioxidants Addressing cell membrane, Mitochondria ATP-production and DNA Vit C, Liponic acid, Tocopherols, Selenium (-methionine), Glutathion, Ubiquinone Q10.

5 Telomeres

6 Telomeres Protect the tips of chromosomes from degeneration upon DNA-replication during cell division. Telomeres are repetitive DNA-sequences rich in Guanine Oxidative overload damages Guanine, reducing the number of cell divisions, and shortening life span. Antioxidants reduce DNA damage to telomeres

7 Effect of antioxidant on ROS before Astaxanthin during before Placebo during

8 5 (Phosphate end) Oxidative DNA-damage 3 (Hydroxyl end) T A G A G C A 8-OH-2dG A T C T C G T 3 (Hydroxyl end) Transition mutagenesis 5 (Phosphate end)

9 8-OH-22 deoxyguanosine P< Before After

10 Protecting blood vessels Antioxidant and lag time of low- density lipoprotein cholesterol. Pine bark extract (Pycnogenol ) ) inhibiting 5-lipoxygenase

12 Heistad D, NEJM 2003;349:2285

13 max time OD Lag Phase Time

14 % increase of lag-time after 8 weeks of antioxidant intake 100 Lag-phase (% change) Dose

15 Protecting blood vessels Antioxidant and lag time of low- density lipoprotein cholesterol. Pine bark extract (Pycnogenol ) ) inhibiting 5-lipoxygenase

16 Cell membrane

17 Cell membrane Fatty acids

18 -LNA LNA 18:3 18: :4 18:4 3 E 20:4 20: :5 3 E 22:5 22:5 3 E 24:5 24: :6 24:6 3 RC RC 22:6 22:6 3 DHA DHA LA LA 18:2 18:2 6 18:3 18:3 6 20:3 20:3 6 20:4 20:4 6 Metabolism Metabolism Diet Diet Vegetable oils Vegetable oils Fish oil Fish oil PG1 leukotriene A4 Nutrition Nutrition 5-LOX LOX

20 Protecting bones Discorea villosa (diosgenin) has anti-osteoporotic activity in ovariectmized rats, preventing bone loss induced by oestrogen deficiency Sustains periosteal bone formation. Does not bind to the human oestrogen receptor (ERBA-test) = breast safe

21 Dioscorea (Wild Yam)

22 Diosgenin

24 Breast safety Antioxidants and Adaptogens Xeno-estrogens estrogens Fytoestrogens: Soya: Genistein, Daidzein, Equol Hop: 8-pregnylnaringenin. 8 Linseed: enterodiol, enterolactone

25 DNA-Replication

26 5 (Phosphate end) Oxidative DNA-damage 3 (Hydroxyl end) T A G A G C A 8-OH-2dG A T C T C G T 3 (Hydroxyl end) Transition mutagenesis 5 (Phosphate end)

27 8-OH-22 deoxyguanosine P< Before After

28 Stress increases the concentration of adrenaline, which causes DNA-damage through several steps Stress decreases the activity of the repair protein P 53 DNA-damage accumulates, causing diseases due to mutations, including cancer.

29 Lepidium meyenii (MACA) Is a phyto-adaptogen Increases stress resistance though activating the heatshock protein P 70 Epidemiological and animal experiments suggest anti-cancer effect

30 Breast safety Antioxidants Xeno-estrogens estrogens Fytoestrogens: Soya: Genistein, Daidzein, Equol Hop: 8-pregnylnaringenin. 8 Linseed: enterodiol, enterolactone

31 Hormones, Pesticides and Phenol-esters esters (2) Methylparaben

32 Bisphenol A CH 3 HO C OH CH 3

34 Breast safety Antioxidants Xeno-estrogens estrogens Fytoestrogens: Hop: : 8-pregnylnaringenin. 8 Soya: Genistein, Daidzein, Equol Linseed: enterodiol, enterolactone

35 8-pregnylnaringenin

36 Hop extract Enriched in 8-Pregnynaringenin 8 100µg Reduction of Kupperman index, after 6 weeks, not after 12 weeks. Unlikely to elicit estrogenic response in breast issue Probably breast safe,, but probably inactive.

37 Breast safety Antioxidants Xeno-estrogens estrogens Fytoestrogens: Hop: 8-pregnylnaringenin. 8 Soy-isoflavones isoflavones: Genistein, Daidzein, Equol Linseed lignans: enterodiol, enterolactone

38 Genisteine Daidzein

39 Soy isoflavones Questionable presence in breast tissue In vitro stimulation of breast cancer cells Interferes with Tamoxifen No effect on radiodensity

40 Soy isoflavones Increase oestradiol in saliva of 1/3 of postmenopausal women Increase 2OH/16ɑOH ratio. No significant effect on menopausal symptoms Probable protection against osteoporosis

41 Soy isoflavone Possible protective effect against breast cancer, if: Given from puberty (or earlier) Together with Asian diet In equol producers (intestinal bacteria)

42 Soy isoflavones and 2OH/16α0H ratio

43 Breast safety Antioxidants Xeno-estrogens estrogens Fytoestrogens: Hop: 8-pregnylnaringenin. 8 Soy isoflavones: Genistein, Daidzein, Equol Linseed lignans: : enterodiol, enterolactone

44 Linseed: source of oil and lignans

45 Lignans Enterodiol Enterolacton

46 Lignans Decrease hot flashes in 1/3 of women Decrease mortality from breast cancer (HR: ) 0.60) Decrease aromatase activity (lower intracellular estradiol-load) load) Block in vitro effect of soy-isoflavones on breast cancer cells. Increase 2OH/16αOH ratio

47 Lignans and 2OH/16α0H ratio

48 Nutriceutical formulaltion for healthy aging should also protect against breast cancer Antioxidants Pine bark extract Vinca minor, phosphatidylserine Vit. B6, B9, B12, Zinc Linum,, Broccoli extract Lepidium meyenii Dioscorea villosa

49 If medical doctors do not become nutritionists, nutritionists will become the doctors of tomorrow.

50 Thank you for your attention!

dna oestrogen GENOTYPE REPORT Patient Name: Date of Birth: Sample Number: Referring Practitioner: Date Reported:

dna oestrogen GENOTYPE REPORT Patient Name: Date of Birth: Sample Number: Referring Practitioner: Date Reported: BACKGROUND TO THE ANALYSIS The importance of both oestrogen and progesterone in breast cancer