The Best Dietetic Principles To Life Extension


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Das ist ein Vortrag, den Dr. Clarence P. Davis im Jahre 2007 im Rahmen eines Anti-Aging Kongresses in Paris gehalten hat.
Er beinhaltet theoretisches Basis- und Hintergrundswissen zu den verschiedenen Diaettypen, sowie einige praktische Beispiele aus dem aerztlichen Alltag.
Der Vortrag ist auf Englisch und einem hohen Niveau. Er richtet sich ausschliesslich an professionelle Leser mit fundierten Vorkenntnissen.

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The Best Dietetic Principles To Life Extension

  1. 1.
  2. 2. The best dietetic principles to life extensionA review of the studies<br />Dr. Clarence P. Davis<br />Bergstrasse 8<br />CH-8702 Zollikon<br />
  3. 3. Causes of Death in the US<br />McGinnis JM, Foege WH. JAMA. 1993 Nov 10;270(18):2207-12 <br />
  4. 4. Causes of Death in the US<br />                                                                                                                   <br />Table 2. Actual Causes of Death in the United States in 1990 and 2000<br />Mokdad AH et al. JAMA. 2004 Mar 10;291(10):1238-45<br />
  5. 5. Causes of Death in the US<br />                                                                                                                   <br />Table 1. Leading Causes of Death in the United States in 2000*<br />Mokdad AH et al. JAMA. 2004 Mar 10;291(10):1238-45 <br />
  6. 6. Caloric Restriction<br />Early studies date back to 1914: Reducing food intake inhibits the occurrence of spontaneous tumors in rodents<br /><ul><li>Rous F. The influence of diet on transplant and spontaneous tumors. J Exp Med. 1914 20:433-451</li></ul>1915/1917: Restricted food intake leads to an increase in fertility and longevity in female rats<br />Osborne TL, Mendel LB. The resumption of growth after long continued failure to grow. J Biol Chem. 1915 23:439-454<br />Osborne TL, Mendel LB. The effect or retardation of growth upon the breeding period and duration of life in rats. Science. 1917:294-295<br />Many studies followed showing all a significant increase in longevity for a vast group of poikilothermic and homeothermic species<br />
  7. 7. Number of <br />Surviving Rats<br />Rats +<br />ad libitum diet<br />Rats + caloric diet<br />1400<br />-1499<br />1100-1199<br />21-399 days<br />500-599<br />700-799<br />900-999<br />1300-1399<br />Age <br />(days)<br />Rats + ad libitum diet + cancer (29 % = 72/250)<br />Rats +  cal. diet<br /> + cancer (19 % = 48/250)<br />A  calorie diet =&gt;  mean & maximal life span & delays risk of cancer<br />Ross MH, Bras G. J Nutr 1973 Jul;103(7):944-63<br />
  8. 8. Sedentary rats (W = 271 g)<br />+ ad libitum diet<br />55<br />Rats (W = 170 g) +physical exercise<br />Rats (W = 170 g) +low caloric diet<br />0<br />0<br />Rats were followed from age 40 days =&gt; At 50 days they received a series of DMBA injections =&gt; 18 weeks later: only rats fed an ad libitum diet & sedentary hadmammary tumors<br />Physical exercise or  Calorie diet =&gt; delays &  risk of cancer in rats<br />Number of <br />Female Rats<br />with <br />mammary <br />tumor<br />Moore C, Tittle PW. Surgery. 1973 Mar;73(3):329-32<br />
  9. 9. Dietary Restriction in Mice beginning at 1 Year of Age<br />Body weights and survival of two different strains of mice fed on control and restricted diets.<br />Each point in the survival curves represents one mouse.<br />Weindruch R, Walford RL. Science. 1982 Mar 12;215(4538):1415-8<br />
  10. 10. Periodically diet-restricted rats <br />(food regimen: alternate day ad libitum <br />Diet-<br /> Rats <br />9 days <br />after t. i. <br />unrestricted <br />surviviving <br />80<br />10 days <br />control rats <br />(%)<br />after t. i. <br />60<br />66.7%<br />9 days after <br />tumor <br />50 %<br />10 days <br />ttumor-bearing <br />40<br />inoculation<br />after t. i. <br />Fisher rats)<br />20<br />20.8 %<br />12.5 %<br />0<br />Short-term alternate day-dietary-restriction initiated 1 week before intraperitoneal inoculation of ascites tumor cells <br />Short-term calorie restriction =&gt;  longevity of tumor-bearing rats<br />feeding followed by alternate day fasting)<br />n = 3-4-month-old <br />Siegel I, et al. Cancer Invest. 1988;6(6):677-80<br />
  11. 11. Repeatedly <br />Fasting mice<br />Control <br />(4 consecutive days, <br />mice <br />every 2 weeks)<br />Mean Survival Time (weeks) <br />+ 34 %<br />80<br />60<br />64.0 weeks<br />40<br />47.9 weeks<br />20<br />0<br />Short-term repeated fasting mice survived sign.longer than full-fed mice in spite of the fasting group having a heavier body weight than controls.<br /> Short-term repeated fasting manipulation was also effective on the rolongation of life-span in autoimmune-prone mice<br />Short-term calorie restriction <br />=&gt;  longevity of mice<br />Sogawa H, et al. Mech Ageing Dev. 2000 May 18;115(1-2):61-71<br />
  12. 12. Ad libitum-fed mice<br />Chronic calorie <br />Periodically calorie-<br />restricted mice<br /> restricted mice<br />Mammary tumor development<br />In mouse species prone to MT (%) <br />(matches calorie <br />(3-week intervals of ad <br />intake of weight-<br />libitum food intake <br />80<br />cycled mice)<br />followed by 3-week <br />intervals of food restriction <br />77 %<br />60<br />40<br />44 %<br />20<br />3 %<br />0<br />n = 1/30<br />n = 15/33<br />n = 23/30<br />Periodic restriction of food intake by 3-weeks interval starting in adulthood (10 weeks of age) drastically reduces the incidence of mammary tumors & the mean weight of the tumor & delays its detection.<br />Peridocal calorie-restriction <br />=&gt; reduces mammary tumor development<br />Cleary MP, et al. Cancer Epidemiol Biomarkers Prev. 2002;11(9):836-43<br />
  13. 13. Effects of CR<br />Reduced body weight and fat<br />Mixed effect model of body weight as a function of age in male and female rhesus monkeys on a control diet (CON) or caloric restriction (CR).<br />This result is not surprising <br />considering that generally a 30–<br />40% reduction in caloric intake is imposed.<br />Mattison JA et al. Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46<br />
  14. 14. Effects of CR<br />Reduced trunk fat<br />CR reduces abdominal (trunk) fat. Each bar represents the mean<br />amount of trunk fat determined by dual energy X-ray<br />absorptiometry after 6 (females) or 11 (males) years on CR. The effect of CR on reducing trunk fat was significant for both genders p&lt;0.05.<br />Lane MA et al. 1999a. Toxicol. Sci. 52 (suppl), 41–48<br />
  15. 15. Effects of CR<br />Reduced body temperature<br />Subcutaneous body temperature during CON feeding and 3 months at 30% CR for monkeys in a short-term study.<br />Lane MA et al. 1996. Proc. Natl Acad. Sci. USA 93, 4159–4164<br />
  16. 16. Effects of CR<br />Reduced decrease of DHEAS<br />CR slows the rate of decline in serum DHEAS. Each point represents the mean DHEAS level at a given age. Ages represent the average (± 0.3 year) age of young adult male rhesus monkeys for years 3–6 of the longitudinal study. The rate of change was significantly slower in CR monkeys<br />P&lt;0:005.<br />Lane MA et al. 1997b J. Clin. Endocrinol. Metab. 82, 2093–2096<br />
  17. 17. Effects of CR<br />Reduced decrease of Melatonin<br />An age-related decline of melatonin is not evident in the monkeys that are maintained on restriction for a 12-<br />year period. In fact, melatonin levels in old CR monkeys are significantly greater than that observed in the age-matched controls.<br />Roth GS et al. 2001 J. Clin. Endo. Metab. 86, 3292–3295<br />
  18. 18. The Biosphere 2 Project<br />Walford RL et al. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11533-7<br />
  19. 19. The Biosphere 2 Project: Effect of caloric Restriction on metabolic Parameters<br />Mean systolic BP for males (M, four subjects) and females (F, four subjects) preclosure (period 0) and during the following 6 months. *, P &lt; 0.05; **, P &lt; 0.01.<br />Walford RL et al. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11533-7<br />
  20. 20. The Biosphere 2 Project: Effect of caloric Restriction on metabolic Parameters<br />Mean diastolic BP for males (M) and females (F) preclosure (period 0) and during the following 6 months. **, <br />P &lt; 0.01.<br />Walford RL et al. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11533-7<br />
  21. 21. The Biosphere 2 Project: Effect of caloric Restriction on metabolic Parameters<br />Mean fasting serum total cholesterol (●) and HDL<br />cholesterol (▲) preclosure (period 0) and during the following 6<br />months *, Difference (P &lt; 0.05) compared to period 0; **, <br />P &lt; 0.01.<br />Walford RL et al. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11533-7<br />
  22. 22. CR in Humans<br />Subjects in the BLSA are NOT CR. Genetic or environmental factors that contribute to the CR-like metabolic effects are unknown.<br />Roth GS et al. Science. 2002 Aug 2;297(5582):811<br />
  23. 23. Hypotheses of CR and longevity<br />Reduced caloric intake leads to a decrease of oxidative stress<br /><ul><li>Caveat: The role of oxidative stress in aging has not yet been clearly demonstrated</li></ul>Alteration of the glucose-insulin system<br /><ul><li>CR causes decrease in plasma glucose and insulin levels
  24. 24. Hyperglycemia and hyperinsulinemia have damaging effects similar to those occurring in senescence</li></ul>Alteration of the GH-IGF-1 Axis<br /><ul><li>CR decreases GH secretion and lowers plasma [IGF-1]</li></ul>Hormesis (=beneficial action resulting from the response of an organism to a low-intensity-stressor)<br /><ul><li>CR causes a moderate increase in daily levels of plasma free corticosterones
  25. 25. CR enhances the induction of stress proteins in response to damage
  26. 26. Single-gene mutations that extend the life of invertebrate species also increase the ability of these organisms to cope with damaging agents</li></li></ul><li>Feasibility of CR in Humans and Outlook<br />Is CR relevant to human aging?<br /><ul><li>Yes and no
  27. 27. A caloric restriction of 30-50% of total daily caloric intake is hardly feasible for the general population (much less as a lifetime intervention…)</li></ul>can mechanisms of CR relevant to human aging be identified?<br /><ul><li>Yes
  28. 28. Glycolytic inhibition
  29. 29. IGF-1 signaling pathway
  30. 30. Insulin sensitivity
  31. 31. PPARs (peroxisome proliferator activated receptors)
  32. 32. Sirtuins
  33. 33. Lipids
  34. 34. Body temperature
  35. 35. DHEA and immunosenescence (and other hormonal actions)</li></ul>can interventions be identified that operate through these mechanisms to mimic CR?<br /><ul><li>Yes</li></li></ul><li>CRMs<br />Criteria for a candidate to be used as a CRM<br /><ul><li>It mimics the metabolic, hormonal, and physiological effects of CR
  36. 36. it does not significantly reduce long-term food intake
  37. 37. it activates stress response pathways observed in CR and provides protection against a variety of stressors
  38. 38. It produces CR-like effects on longevity, reduction of age-related disease and maintenance of function</li></ul>Some examples of promising candidates<br /><ul><li>2-deoxy-D-glucose (inhibition of the enzyme phosphohexose isomerase and thus reduction of glycolytic processing)
  39. 39. All inhibitors of the IGF-1 pathway (retinoids, soy isoflavones (e.g. genistein and daidzein), flavonoids (e.g. quercetin and kaempferol), somatostatin analogues (e.g. octreotide), and selective estrogen receptor modulators (e.g. tamoxifen))
  40. 40. Insulin sensitizers (e.g. metformin)
  41. 41. Resveratrol
  42. 42. agonists for peroxisome proliferator activated receptors (PPARs)
  43. 43. Hypolipidemic drugs?</li></li></ul><li>Possible life extending eating behavior<br />Avoid sugar<br />Insulin resistance<br />CVD<br />cancer<br />Avoid caffeinated drinks<br />Cancer?<br />Eat vegetables/fruits<br />Lowers cancer rate<br />Drink alcohol in moderate dose<br />Preventive effects for CVD<br />
  44. 44. Avoid<br />Sugar<br />
  45. 45. Average life span of the 70 mice <br />Average life span of 7 oldest mice <br />-6,4 %<br />1000<br />Survival <br />20 % glucose diet<br />Control diet <br />800<br />-10 %<br />(days )<br />600<br />400<br />200<br />0<br />n = 70<br />n = 70<br />n = 7<br />n = 7<br />p &lt; 0.05<br />p &lt; 0.05<br /> Glucose diet =&gt;  life span of mice<br />Mlekusch W et al. Mech Ageing Dev 1996 Nov 29;92(1):43-51<br />
  46. 46. HIGHEST quintile of intake of<br />Prostate cancer (odds Ratio)<br />Starch <br />LOWEST <br />1.5<br />Linolenic<br />acid (3)<br />Linoleic<br />acid (6)<br />quintile<br />+40 %<br />1<br />-20%<br />large-scale Italian cohort study; 1294 cases <br />-30 %<br />0.5<br />1.4<br />0.8<br />0.7<br />0<br />p &lt; 0.05<br />p&lt; 0.05<br />p&lt; 0.05<br />Starch intake =&gt;  risk of Prostate cancer<br />Bidoli E et al. Ann Oncol. 2005 Jan;16(1):152-7<br />
  47. 47. Cancer<br />Stroke<br />CVD<br />Apoptosis –<br />Cell proliferation +<br />Hypertension Atherosclerosis Diabetes Dyslipidemia<br />Metabolic Syndrome<br />Gonadal and adrenal<br />stimulation<br />IGF1<br />Bioavailability +<br />Sex<br />Hormones +<br />Pathogenesis<br />Insulin +<br />SHBG -<br />Insulin resistance (IR)<br />FFA +<br />TNF a +<br />IL-6 +<br />Resistin +<br />Adiponectin -<br />NADPH oxidase +<br />Antioxidant<br />enzymes -<br />Aromatase +<br />Oxidative Stress<br />Inflammation<br />ER Stress<br />ROS<br />Risc Factor<br />Genetics<br />Lifestyle Environment<br />Obesity<br />Adapded from: Jee SH et al. Yonsei Med J. 2005 Aug 31;46(4):449-55<br />
  48. 48. Relationship between fasting serum glucose and risk of cancer<br />Hazard ratios for all cancer deaths by fasting serum glucose levels in Korean men according to body mass index, 1993-2002<br />Jee SH et al. JAMA 2005 Jan 12;293(2):194-202 <br />
  49. 49. Avoid<br />Caffeinated Drinks<br />
  50. 50. Female C3H mice<br />spontaneous BC<br />Change in <br />Female BD2F1 mice<br />incidence <br /> DMBA-induced BC<br />Caffeine 500 mg/l<br />of <br />+ 117 %<br />mammary <br />120<br />carcinoma<br />Caffeine 500 mg/l<br />Caffeine 250 mg/l<br />100<br />80<br />+ 40 %<br />+ 20 %<br />Caffeine 250 mg/l<br />60<br />+ 13 %<br />(% more mice <br />40<br />with <br />20<br />breast cancer) <br />0<br />NS<br />NS<br />p &lt; 0.05<br />p &lt; 0.05<br />Increased incidence of DMBA carcinogen-induced mammary carcinoma’s in BD2F1 & C3H mice drinking caffeine in drinking water starting at 8 weeks of age to experiment termination. Mammary gland development was sign. increased in high caffeine BALB/c mice.<br />Caffeine drinking =&gt;  mammary carcinoma incidence<br />Welsch CW et al. Cancer Res 1988 Apr 15;48(8):2078-82 <br />
  51. 51. Heavier women<br />Lean women<br />(BMI ≥ 24) <br />(BMI ≤24) <br />Drinking ≥ 5 cups/day <br />2.5<br />2<br />Drinking &lt; 2 cups of coffee/day<br />Drinking &lt; 2 cups of coffee/day<br /> 2.1 <br />1.5<br />Drinking ≥ 5 cups/day <br />Risk)<br />1<br />1<br />1<br />0.5<br /> 0.5<br />0<br />Coffee consumption reduces the risk of breast cancer in lean women, but might increase it in relatively obese women. This interaction between coffee intake & BMI was statist. sign.<br />n = 152 breast cancer cases among 14,593 Norwegian women ; mean follow-up = 12 yrs<br />Coffee =&gt; breast cancer risk: in lean women, in obese women<br />Breast <br />Cancer<br />(Relative <br />Vatten et al. Br J Cancer. 1990 Aug;62(2):267-70<br />
  52. 52. Heaviest smokers<br />(highest quartile)<br />Heaviest coffee drinkers<br />(highest quartile)<br />2.7<br />2,5<br />2.1 <br />2<br />(95% CI:<br />Relative risk of bladder cancer <br />Lowest quartile<br />1.8 to 4.0)<br />1,5<br />(95% CI:<br />1.3-3.2)<br />1<br />1<br />0,5<br />p &lt; 0.05<br />p &lt; 0.05<br />0<br />Coffee =&gt;  risk of bladder cancer<br />Coffeeconsumption was assoc. + increased risk for bladder cancer among the heaviest coffee drinkers after adjustment for cigarette smoking & other dietary risk factors. The effect was more pronounced among nonsmokers, esp. among those 65 yrs & older. These findings support the contention that coffee is a weak carcinogen. After adjustment for age, education, & dietary risk factors by multiple regression, risk of bladder cancer was found to increase with increasing pack-years of cigarette use.<br />Vena JE et al. Ann Epidemiol. 1993;3(6):586-91<br />
  53. 53. Caffeine increases BP<br />Laboratory studies over the last 20 yrs =&gt; consistently demonstrated <br />=&gt; caffeine dose of 2 to 3 cups of brewed coffee <br />=&gt;  blood pressure (BP) at rest: + 7 to + 10 mm Hg<br />when administered either to &quot;caffeine-naive&quot; individuals or to habitual coffee drinkers after overnight abstinence. <br />=&gt;  BP reach a max. 30 to 60 minutes after caffeine administration & persist for several hours.<br />Lane JD et al. Psychosomatic Med 2002; 64:595-603<br />
  54. 54. Serum Cholesterol<br />200<br />(mg/dl)<br />Increase of 1 cup of coffee per day = increase of 2 mg/dl total cholesterol <br />196<br />192<br />(p &lt; 0.001)<br />188<br />184<br />n = 2109 healthy nonsmokers aged 25-65 yrs <br />(mean follow-up = 16.7 months)<br />180<br />176<br />0<br />1<br />2<br />3<br />4<br />5<br />6<br />7<br />8<br />9<br />10<br />cups/day<br />Coffee =&gt;  serum cholesterol<br />A dose-response was found among those who decreased regularcoffee consumption, those who continued the same dose, & those who increased consumption. The same trend was observed among those who quit drinking regular coffee, those who never drank coffee, & those who started to coffee.<br />Wie M et al. J Clin Epidemiol. 1995 Oct;48(10):1189-96<br />
  55. 55. Eat<br />Vegetables & Fruits<br />
  56. 56. CITRUS FRUIT<br />consumption<br />SUPPLEMENT intake <br />LOW<br />HIGH <br />LOW <br />(&lt; 1 x/wk)<br />HIGH<br />(≥ 2 x/wk)<br />HIGH LINOLEIC ACID<br />HIGH<br />VIT. C<br />1<br />VIT. B2<br />1.0<br />-48 %<br />-50 %<br />-60 %<br />MORTALITY<br />0.5<br />0.52<br />(95% CI = <br />0.28 - 0.95)<br />0<br />5-year cohort study among n = 162 self-sufficient residents in a public home for elderly <br /> citrus fruits &  intake of vit. C, vit. B2 & linoleic acid =&gt;  all- cause mortality in very elderly people<br />Frequent consumption of citrus fruit, and high intake of vitamin C, riboflavin, & linoleic (6) acid are associated with longevity <br />Fortes C et al. Epidemiology. 2000 Jul;11(4):440-5<br />
  57. 57. 0.87 <br />0.78 <br />(0.68-<br />(0.61-<br />1.10) <br />1.01) <br /> Fruit & vegetable intake =&gt;  mortality<br />Relative risk <br />Fruit & vegetable intake<br />of dying <br />(11-yr mortality)<br />th<br />th<br />th<br />(2<br />) Lowest <br /> (3<br />) Average<br />(4<br />) Higher <br />th<br />st<br />(5<br />) Highest <br />(1<br />) Lowest <br />quintile<br />quintile<br />quintile<br />quintile<br />quintile <br />1.2<br /> - 6 %<br /> - 11 %<br /> - 22 %<br />1<br />1.08 <br />1.0<br />0.8<br />(0.88-<br />0.94 <br />1.33) <br />(0.75-<br />0.6<br />1.17) <br />0.4<br />0.2<br />0<br />n = 15,792 <br />(age 45-64 yrs)<br />P for trend = 0.02<br />Over an 11-y follow-up period, the relative hazards of death for quintiles 2-5 of fruit & vegetable intake were 1.08 (95% CI:0.88-1.33) , 0.94 (0.75-1.17) , 0.87 (0.68-1.10) , & 0.78 (0.61-1.01), resp. Neither fruit, nor vegetable fiber intake were associated with incident cardiovascular death (P =.98, =.95 resp.) <br />Steffen LM et al. Am J Clin Nutr. 2003 Sep; 78(3): 383-90<br />
  58. 58. Upper quintiles<br />Lowest <br />Relative risk (adjusted prevalence odds ratio) <br />quintile<br />Fruit <br />consumption<br />1<br />Vegetable <br />1<br />consumption<br />Fruit & vegetable consumption <br />0.8<br />n = 4393<br />0.6<br />0.68 <br />0.58 <br />(95 % CI: <br />0.4<br />(95 % CI: <br />0.23 <br />0.43- 1.09)<br />0.36-0.91)<br />(95 % CI: <br />0.2<br />0.43- 1.09)<br />0<br />P = 0.001<br />P = 0.10<br />P = 0.01<br />Fruit & vegetable intake =&gt;  risk of hypertension<br />In a Mediterranean population with an elevated fat consumption (37 % of diet),a high fruit & vegetable intake is inversely associated with BP levels<br />Alonso A et al. Br J Nutr. 2004;92(2):311-9<br />
  59. 59. FRUIT & VEGETABLE INTAKE ≥ 3x/day<br />Relative risk of disease or death <br />Ischemic heart disease mortality <br />Cardiovascular disease disease mortality <br />All cause mortality <br />1<br />&lt;1x/day <br />Stroke<br />incidence<br />Stroke<br />mortality<br />0.8<br />0.6<br />- 27%<br />- 24%<br />- 27%<br />- 15%<br />- 42%<br />0.4<br />0.2<br />0.85<br />0.73<br />0.73<br />0.58<br />0.76<br />0<br />n = 9608 adults aged 25-74 yr<br />(average 19-yr follow-up)<br /> P = 0.02 <br />Fruit & vegetable intake =&gt; cardiovascular and all cause mortality<br />An inverse association of fruit & vegetable intake with therisk of cardiovascular disease & all-cause mortality was observed in the general US population.<br />Bazzano LA et al. Am J Clin Nutr. 2002 Jul; 76(1): 93-9<br />
  60. 60. Liver<br />Overall cancer mortality <br />Stomach &<br />cancer<br />lung cancer<br />(Almost) daily<br />(Almost) daily green-<br />Mean<br />(Amost) daily<br />FRUIT intake<br />yellow VEGETABLE <br />Risk<br />FRUIT intake<br />intake<br />- 8 %<br />- 12 %<br />- 20%<br />1<br />- 25%<br />0.8<br />0.6<br />0.75<br />1.0<br />0.92<br />0.8<br />0.88<br />95%CI<br />0.4<br /> 0.94-<br />= 0.80<br />0.60-<br />0.65-<br />0.2<br />1,01)<br />-0,96)<br />0,95)<br />0.98)<br />0<br /> P &lt; 0.05<br /> P &lt; 0.05<br /> P &lt; 0.05<br /> P &lt; 0.05<br />38 540 men & women who were atomic-bomb survivors in Hiroshima & Nagasaki, Japan, were followed-up for cancer deaths until March 1998, during which time 3136 cancer deaths were identified. <br />Fruit & vegetable intake =&gt; cancer mortality<br />Relative risk of dying from cancer <br />Daily consumption of fruit & vegetables reduces the mortality from total cancer, &specifically cancers of stomach, liver, & lung. Not statist. sign. associations were found w/ oesophageal cancer, but none w/ breast & colorectal cancer.<br />Sauvaget C et al. Br J Cancer. 2003; 88(5): 689-94<br />
  61. 61. Anti cancer action of vegetables<br />VEGETABLE intake has a STRONG PROTECTIVE EFFECT:<br /><ul><li>independent of vitamins C, E, folic acid & fiber (Freudenheim 1996)
  62. 62. dependent on -carotene & lutein + zeaxanthin (RR = 0.5 => 0.80)(Freudenheim 1994)
  63. 63. still some unexplained protectionattributable to total intake of vegetables
  64. 64. possible synergetic effectof vit. E & beta-carotene (Krinsky 1993)</li></ul>other substances may be protective:<br /><ul><li>indolesin cabbage, broccoli (Michnovicz 1991, Tivari 1994) : chemoprevention
  65. 65. sterols(Jellinck 1991, Michnovicz 1991, Bradlow 1991) :  oxidation of E2 in liver ( catecholestrogen production) =>  secretion of 2-hydroxy-E1, -E3
  66. 66. lignans(phytoestrogens like enterolactone + other dephenols; Adlercreutz 1991):  aromatase competitively w/ testosterone + androstenedione in peripheral & cancer cells =>  estrogens (Adlercreutz 1993); have 1/75 - 1/360 potency of estrogens phytoestrogens
  67. 67. isoflavonoids(phytoestrogens) : some of these substances can  E-metabolism (Adlercreutz 1993)</li></li></ul><li>No or <br />Moderate amounts <br />of alcohol<br />
  68. 68. Coffee + Alcohol + smoking =&gt;  risk of pancreatic cancer<br /> Smoking<br />+ Alcohol<br />+ Coffee<br />Pancreatic <br />30<br />Alcohol<br />Cancer<br />+ Coffee<br /> 26.3<br />20<br />(Relative <br />Risk)<br />13.9<br />10<br />1<br />0<br />p = 0.02<br />p = 0.13<br />n = 29 cases + pancreatic cancer & 29 controls<br />The combination of 2 to 3 risk factors increases considerably therisk of pancreatic cancer.<br />Considered independently, only alcohol & coffee consumption were found to be sign. assoc. + pancreas cancer <br />Pfeffer F et al. Rev Invest Clin. 1989 Jul-Sep;41(3):205-8<br />
  69. 69. Alcohol =&gt;  risk of breast cancer<br />Follow-up: daily alcohol of 24 g continues<br />Daily initial alcohol consumption of 24 g (2 drinks)<br />Non drinkers<br />1,7<br />(95% CI, 1.4-2.2)<br />1,4<br />(95% CI, 1.0-1.8) <br />Risk of breast cancer in daily alcohol drinkers & non-drinkers<br />Longnecker MP et al. JAMA. 1988 Aug 5;260(5):652-6<br />
  70. 70.  <br /> <br /> ALCOHOL consumption =&gt; predisposes to BREAST CANCER?<br /> <br /> <br /> <br /> <br />
  71. 71. Alcoholusers<br />&gt;96 <br />Prostate<br />22-96 <br />grams<br /> cancer<br />&lt;22 grams <br />grams<br />risk <br />4<br />+210%<br />alcohol <br />(Rel. Risk) <br />+160 %<br />3<br />per week <br />3.1<br />2<br />large-scale <br />Nonusers<br />2.6<br />+10 %<br />Iowa Cohort <br />1<br />study; <br />1.1<br />110 (?) cases <br />0<br />NS<br />p&lt; 0.05<br />p&lt; 0.05<br />Increased risk of prostate cancer in alcohol consumers<br />Alcohol =&gt;  risk of Prostate cancer<br />Putnam SD et al. Ann Epidemiol. 2000 Aug;10(6):361-9<br />
  72. 72. Mediterranean diet =&gt; mortality<br />Alonso A, Martinez-Gonzalez MA. JAMA. 2005 Feb 9;293(6):674<br />
  73. 73. Thank you for your attention<br />