McGinnis JM, Foege WH. JAMA. 1993 Nov 10;270(18):2207-12

Causes of Causes of DeathDeath in in thethe USUS

JAMA. 1993 Nov 10;270(18):2207-12. Links Comment in: JAMA. 1994 Mar 2;271(9):659-60; author reply 660-1. JAMA. 1994 Mar 2;271(9):659; author reply 660-1. JAMA. 1994 Mar 2;271(9):660; author reply 660-1. JAMA. 1994 Mar 2;271(9):660; author reply 660-1. JAMA. 1994 Mar 2;271(9):660; author reply 660-1. Actual causes of death in the United States. McGinnis JM, Foege WH. US Department of Health and Human Services, Washington, DC 20201. OBJECTIVE--To identify and quantify the major external (nongenetic) factors that contribute to death in the United States. DATA SOURCES--Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and complications of vital statistics and surveillance data were also obtained. STUDY SELECTION--Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity. DATA EXTRACTION--Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates. DATA SYNTHESIS--The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400,000 deaths), diet and activity patterns (300,000), alcohol (100,000), microbial agents (90,000), toxic agents (60,000), firearms (35,000), sexual behavior (30,000), motor vehicles (25,000), and illicit use of drugs (20,000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations. CONCLUSIONS--Approximately half of all deaths that

occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities. PMID: 8411605 [PubMed - indexed for MEDLINE]

Mokdad AH et al. JAMA. 2004 Mar 10;291(10):1238-45

Causes of Causes of DeathDeath in in thethe USUS

Table 2. Actual Causes of Death in the United States in 1990 and 2000

JAMA. 2004 Mar 10;291(10):1238-45. Links Erratum in: JAMA. 2005 Jan 19;293(3):293-4. JAMA. 2005 Jan 19;293(3):298. Comment in: JAMA. 2004 Jun 23;291(24):2941-2; author reply 2942-3. JAMA. 2004 Jun 23;291(24):2941; author reply 2942-3. JAMA. 2004 Jun 23;291(24):2941; author reply 2942-3. JAMA. 2004 Jun 23;291(24):2942; author reply 2942-3. JAMA. 2004 Jun 23;291(24):2942; author reply 2942-3. JAMA. 2004 Mar 10;291(10):1263-4. Actual causes of death in the United States, 2000. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Division of Adult and Community Health, Centers for Disease Control and Prevention, Atlanta, Ga, USA. amokdad@cdc.gov CONTEXT: Modifiable behavioral risk factors are leading causes of mortality in the United States. Quantifying these will provide insight into the effects of recent trends and the implications of missed prevention opportunities. OBJECTIVES: To identify and quantify the leading causes of mortality in the United States. DESIGN: Comprehensive MEDLINE search of English-language articles that identified epidemiological, clinical, and laboratory studies linking risk behaviors and mortality. The search was initially restricted to articles published

during or after 1990, but we later included relevant articles published in 1980 to December 31, 2002. Prevalence and relative risk were identified during the literature search. We used 2000 mortality data reported to the Centers for Disease Control and Prevention to identify the causes and number of deaths. The estimates of cause of death were computed by multiplying estimates of the cause-attributable fraction of preventable deaths with the total mortality data. MAIN OUTCOME MEASURES: Actual causes of death. RESULTS: The leading causes of death in 2000 were tobacco (435 000 deaths; 18.1% of total US deaths), poor diet and physical inactivity (365 000 deaths; 15.2%) [corrected], and alcohol consumption (85 000 deaths; 3.5%). Other actual causes of death were microbial agents (75 000), toxic agents (55 000), motor vehicle crashes (43 000), incidents involving firearms (29 000), sexual behaviors (20 000), and illicit use of drugs (17 000). CONCLUSIONS: These analyses show that smoking remains the leading cause of mortality. However, poor diet and physical inactivity may soon overtake tobacco as the leading cause of death. These findings, along with escalating health care costs and aging population, argue persuasively that the need to establish a more preventive orientation in the US health care and public health systems has become more urgent. PMID: 15010446 [PubMed - indexed for MEDLINE] Related Links Actual causes of death in the United States. [JAMA. 1993] PMID: 8411605 The modifiable factors contributing to leading causes of death in South Carolina. [J S C Med Assoc. 1999] PMID: 10389384 Youth risk behavior surveillance--United States, 2001. [MMWR Surveill Summ. 2002] PMID: 12102329 Youth risk behavior surveillance--United States, 1999. [MMWR CDC Surveill Summ. 2000] PMID: 12412614 Surveillance for traumatic brain injury deaths--United States, 1989-1998. [MMWR Surveill Summ. 2002] PMID: 12529087 See all Related Articles... Display

Siegel I, et al. Cancer Invest. 1988;6(6):677-80

Short-term calorie restriction => ↑ longevity of tumor-bearing rats

n = 3-4-month-old

feeding followed by alternate day fasting)

0

20

40

60

80Diet-

unrestrictedcontrol rats

Short-term alternate day-dietary-restriction initiated 1 week beforeintraperitoneal inoculation of ascites tumor cells

Rats surviviving

(%)

ttumor-bearingFisher rats)

9 days aftertumor

inoculation

Periodically diet-restricted rats(food regimen: alternate day ad libitum

66.7%

9 daysafter t. i.

10 daysafter t. i.

10 daysafter t. i.

50 %

20.8 %12.5 %

Siegel I, Liu TL, Nepomuceno N, Gleicher N. Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. Cancer Invest. 1988;6(6):677-80 Department of Obstetrics and Gynecology, Mount Sinai Hospital Medical Center, Chicago, Illinois.We studied the effects of short-term dietary restriction on the survival of3-4-month-old tumor-free and tumor-bearing Fisher rats. The diet-restricted foodregimen consisted of alternate day ad libitum feeding followed by alternate dayfasting. Diet-unrestricted control rats were fed ad libitum daily. Sixtumor-free rats on the diet-restricted regimen compensated for the dietaryrestriction by an increase in food consumption during the alternate feedingdays, and lost an average of only 2-3% of their weight in 13 days. Sixtumor-free rats on a daily ad libitum feeding regimen gained an average of 6.8%in 15 days. The above dietary-restricted regimen was initiated 1 week before 24rats were inoculated intraperitoneally with 15 million Mat 13762 ascites tumorcells. Sixteen of 24 (66.7%) diet-restricted tumor-bearing hosts and 5/24(20.8%) diet-unrestricted tumor-bearing hosts survived at 9 days after tumorinoculation (p less than 0.005). Twelve of 24 (50%) diet-restrictedtumor-bearing hosts, and 3 of 24 (12.5%) diet-unrestricted tumor-bearing hosts,survived at 10 days after tumor inoculation (p less than 0.025). Thus, thesurvival of tumor-bearing rats was enhanced by short-term relatively milddietary restrictions. We suggest that relatively mild dietary restrictionsshould be included in clinical trials designed to inhibit cancer growth and enhance the survival of human cancer patients.PMID: 3245934 [PubMed - indexed for MEDLINE]

Mlekusch W et al. Mech Ageing Dev 1996 Nov 29;92(1):43-51

↑↑ Glucose diet => Glucose diet => ↓↓ lifelife spanspan ofof micemice

0

200

400

600

800

1000Survival

(days )

n = 70

Control diet 20 % glucosediet

-10 %

-6,4 %

Average life span of the 70 mice

Average life spanof 7 oldest mice

n = 70p < 0.05 p < 0.05

n = 7 n = 7

Mech Ageing Dev. 1996 Nov 29;92(1):43-51. Links A glucose-rich diet shortens longevity of mice. Mlekusch W, Lamprecht M, Ottl K, Tillian M, Reibnegger G. Institute of Medical Chemistry and Pregl Laboratory, Karl-Franzens-Universitat-Graz, Austria.

High plasma levels of glucose and insulin over long-time periods play an important role in the genesis of diabetic complications. There is evidence that the long term consumption of glucose-rich diet by rats is detrimental to insulin sensitivity. We investigated the effect of a glucose-rich diet on longevity of 70 female mice which were compared to 70 mice on a control diet. The average age of death of the control group was 568 +/- 139 days compared to 511 +/- 170 for the glucose group and the seven oldest mice of the control group died at age 890 +/- 52 days, while the seven oldest mice of the glucose group died at 833 +/- 49 days. These differences are statistically significant (P < or = 0.05). Our work shows that a life-long intake of a diet with 20% of total energy derived from glucose leads to a significant reduction of the average and maximal life-span in female mice and thus, supports previous observations of detrimental effects of high glucose intake over long periods. PMID: 9032754 [PubMed - indexed for MEDLINE]

Bidoli E et al. Ann Oncol. 2005 Jan;16(1):152-7

Starch intake => Starch intake => ↑↑ riskrisk ofof Prostate cancerProstate cancer

0

0.5

1

1.5

large-scaleItalian cohortstudy; 1294 cases

Starch

1.4

-20%

LOWEST quintile

Linolenicacid (Ω3)

Linoleicacid (Ω6)

0.7 0.8

-30 %

Prostate cancer(odds Ratio)

+40 %

p < 0.05 p< 0.05 p< 0.05

HIGHEST quintile of intake of

Ann Oncol. 2005 Jan;16(1):152-7. Links Macronutrients, fatty acids, cholesterol and prostate cancer risk. Bidoli E, Talamini R, Bosetti C, Negri E, Maruzzi D, Montella M, Franceschi S, La Vecchia C. Servizio di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (PN), Italy. epidemiology@cro.it BACKGROUND: The role of selected macronutrients, fatty acids and cholesterol in the etiology of prostate cancer was analyzed using data from a case-control study carried out in five Italian areas between 1991 and 2002. PATIENTS AND METHODS: Cases were 1294 men with incident, histologically confirmed prostate cancer, and admitted to the major teaching and general hospitals of study areas. Controls were 1451 men admitted for acute,

non-neoplastic conditions to the same hospital network. Information on dietary habits was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for increasing levels of nutrient intake. RESULTS: A direct association with prostate cancer was found for starch intake (OR = 1.4 in the highest versus the lowest quintile of intake; 95% CI: 1.1-1.8), whereas an inverse association emerged for polyunsaturated fatty acids (OR = 0.8; 95% CI: 0.6-1.0). Among polyunsaturated fatty acids, linolenic acid (OR = 0.7; 95% CI: 0.6-0.9) and linoleic acid (OR = 0.8; 95% CI: 0.6-1.0) were inversely related to prostate cancer. When the six major macronutrients were included in the same model, the adverse effect of high intake of starch and monounsaturated fatty acids was statistically significant together with the protective effect of polyunsaturated fatty acids. Results were consistent in separate strata of age, body mass index and family history of prostate cancer. CONCLUSIONS: Starch and monounsaturated fatty acids were directly associated with prostate cancer risk and polyunsaturated fatty acids were inversely associated. PMID: 15598953 [PubMed - indexed for MEDLINE]

Adapded from: Jee SH et al. Yonsei Med J. 2005 Aug 31;46(4):449-55

Metabolic SyndromeHypertension Atherosclerosis Diabetes Dyslipidemia

Genetics Lifestyle EnvironmentObesity

Insulin resistance (IR)

Oxidative StressInflammation

ER Stress ROS

Risc Factor

Pathogenesis

FFA +TNF a +IL-6 +

Resistin +Adiponectin -

NADPH oxidase +Antioxidantenzymes -

Insulin +

IGF1Bioavailability +

Apoptosis –Cell proliferation +

CancerStroke CVD

SHBG -

SexHormones +

Gonadal and adrenalstimulation

Aromatase +

Yonsei Med J. 2005 Aug 31;46(4):449-55. Links Obesity, insulin resistance and cancer risk. Jee SH, Kim HJ, Lee J. Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. jsunha@yumc.yonsei.ac.kr Obesity is a known cause of metabolic syndrome which includes Type II diabetes, hypertension, and dyslipidemia. It is well documented that insulin resistance contributes to the mortality and the incidence of metabolic syndromes including central obesity, dyslipidemia, hyperglycemia and hypertension. Both obesity and diabetes are emerging topics for researchers to consider as having a possible causal association with cancer since the two factors have been viewed as risk factors for cancer. The present paper introduced the

hypothesis of a possible causal relationship between obesity, insulin resistance and cancer and reviews relevant existing studies in this area. More efforts and studies are needed to clarify the mechanisms and the common risk factors which might be incorporated into interventions to prevent cancer and cardiovascular diseases as top causes of death. PMID: 16127767 [PubMed - indexed for MEDLINE]

Relationship between fasting serum Relationship between fasting serum glucose and risk of cancerglucose and risk of cancer

Hazard ratios for all cancer deaths by fasting serum glucose levels in Korean men according to body mass index, 1993-2002

Jee SH et al. JAMA 2005 Jan 12;293(2):194-202

JAMA. 2005 Jan 12;293(2):194-202. Links Comment in: JAMA. 2005 Jan 12;293(2):235-6. JAMA. 2005 May 11;293(18):2210-1; author reply 2211. Fasting serum glucose level and cancer risk in Korean men and women. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea. jsunha@yumc.yonsei.ac.kr CONTEXT: Diabetes is a serious and costly disease that is becoming increasingly common in many countries. The role of diabetes as a cancer risk factor remains unclear. OBJECTIVE: To examine the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea. DESIGN, SETTING, AND PARTICIPANTS: Ten-year prospective cohort study of 1,298,385 Koreans (829,770 men and 468,615 women) aged 30 to 95 years who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation in 1992-1995 (with follow-up for up to 10 years). MAIN OUTCOME MEASURES: Death from cancer and registry-documented incident cancer or hospital admission for cancer. RESULTS: During the 10 years of follow-up, there were 20,566 cancer deaths in men and 5907 cancer deaths in women. Using Cox proportional hazards models and controlling for smoking and alcohol use, the stratum with the

highest fasting serum glucose (> or =140 mg/dL [> or =7.8 mmol/L]) had higher death rates from all cancers combined (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.22-1.37 in men and HR, 1.23; 95% CI, 1.09-1.39 in women) compared with the stratum with the lowest level (<90 mg/dL [<5.0 mmol/L]). By cancer site, the association was strongest for pancreatic cancer, comparing the highest and lowest strata in men (HR, 1.91; 95% CI, 1.52-2.41) and in women (HR, 2.05; 95% CI, 1.43-2.93). Significant associations were also found for cancers of the esophagus, liver, and colon/rectum in men and of the liver and cervix in women, and there were significant trends with glucose level for cancers of the esophagus, colon/rectum, liver, pancreas, and bile duct in men and of the liver and pancreas in women. Of the 26,473 total cancer deaths in men and women, 848 were estimated as attributable to having a fasting serum glucose level of less than 90 mg/dL. For cancer incidence, the general patterns reflected those found for mortality. For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL (6.9 mmol/L), risks for cancer incidence and mortality were generally elevated compared with those without diabetes. CONCLUSION: In Korea, elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers, and the risk tends to increase with an increased level of fasting serum glucose. PMID: 15644546 [PubMed - indexed for MEDLINE]

CaffeineCaffeine drinkingdrinking => => ↑↑ mammarymammarycarcinomacarcinoma incidenceincidence

Welsch CW et al. Cancer Res 1988 Apr 15;48(8):2078-82

020406080

100120

Female BD2F1 miceDMBA-induced BC

+ 117 %

Change in incidence

of mammarycarcinoma

(% more micewith

breast cancer) NS

Female C3H micespontaneous BC

NSp < 0.05 p < 0.05

+ 40 %+ 13 %

Caffeine 500 mg/l

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 experimenttermination. Mammary gland development was sign. increased in high caffeine BALB/c mice.

Caffeine 250 mg/l

+ 20 % Caffeine 250 mg/l

Caffeine 500 mg/l

Cancer Res. 1988 Apr 15;48(8):2078-82. Links Influence of caffeine consumption on carcinomatous and normal mammary gland development in mice. Welsch CW, DeHoog JV, O'Connor DH. Department of Anatomy, Michigan State University, East Lansing 48824. The influence of caffeine consumption on the development of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in BD2F1 female mice and spontaneous mammary carcinomas in nulliparous C3H mice was examined. Caffeine (250 and 500 mg/liter of drinking water) was administered to BD2F1 mice commencing 1 week after a series of 6 weekly 7,12-dimethylbenz(a)anthracene intubations, until experiment

termination. Caffeine was administered to C3H mice (via drinking water) commencing at 8 weeks of age to experiment termination. In BD2F1 mice receiving 250 and 500 mg of caffeine, mammary carcinoma multiplicity (number of mammary carcinomas/mouse) was increased by 20 and 40%, respectively. In C3H mice receiving 250 and 500 mg caffeine, mammary carcinoma multiplicity was increased by 13 and 117%, respectively. In both BD2F1 and C3H mice, the higher dose level of caffeine resulted in a significant (P less than 0.05) increase in mammary carcinoma multiplicity. Caffeine consumption did not significantly effect the percentage of mice bearing mammary carcinomas or the mean latency period of mammary tumor appearance. In a second series of studies, the influence of caffeine consumption on mammary gland development in female BALB/c mice was assessed in vivo and in vitro (organ culture). In mice consuming caffeine (500 mg/liter of drinking water), mammary gland development was significantly (P less than 0.05) increased compared to control mice; this difference in mammae development was more conspicuous in mice treated with mammotropic hormones. In the organ culture studies, mammary glands derived from caffeine (500 mg/liter of drinking water) consuming BALB/c mice were more responsive in vitro to a mammotropic hormonal developmental growth stimulus than were mammae derived from control mice (P less than 0.05). These results provide evidence that caffeine consumption can enhance mammary tumorigenesis in C3H and carcinogen-treated BD2F1 female mice and, in addition, enhance developmental growth of the normal female mouse (BALB/c) mammary gland. PMID: 3127046 [PubMed - indexed for MEDLINE]

CoffeeCoffee => => breastbreast cancer cancer riskrisk:: ↓↓ in in leanlean womenwomen,,↑↑ in in obeseobese womenwomen

Vatten et al. Br J Cancer. 1990 Aug;62(2):267-70

(Relative

BreastCancer

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.n = 152 breast cancer cases among 14,593 Norwegian women ; mean follow-up = 12 yrs

0

0.5

1

1.5

2

2.5

Risk)1

2.1

0.5

Drinking ≥ 5 cups/day

Lean women(BMI ≤ 24)

Drinking < 2 cups of coffee/day

Heavier women(BMI ≥ 24)

1

Drinking < 2 cups of coffee/day

Drinking ≥ 5 cups/day

Br J Cancer. 1990 Aug;62(2):267-70. Links Coffee consumption and the risk of breast cancer. A prospective study of 14,593 Norwegian women. Vatten LJ, Solvoll K, Loken EB. Department of Oncology, University Hospital, Trondheim, Norway. The association between coffee consumption and the incidence rate of breast cancer has been analysed in 152 incident cases of breast cancer that developed among 14,593 Norwegian

women during a mean follow-up of 12 years. At the time of inquiry they were between 35 and 51 years of age, and at the end of follow-up between 46 and 63. There was an overall weak negative association between daily intake of coffee and risk of breast cancer, which was not statistically significant. However, the association with coffee varied, depending on the body mass index (BMI) of the women. In the lean (Quetelet less than 24; population mean) there was an inverse relation between coffee intake and risk of breast cancer (chi 2 trend = 5.07, P = 0.02). In this group, women who reported drinking 5 cups or more per day had an age-adjusted IRR of 0.5 (95% confidence intervals, 0.3 and 0.9) compared to women who had 2 cups or less. In women with Quetelet's index equal to or greater than 24 there was a positive relation between coffee intake and breast cancer risk (chi 2 trend = 2.33, P = 0.13), where the corresponding age-adjusted IRR was 2.1 (95% confidence intervals, 0.8 and 5.2). This interaction effect between coffee intake and BMI was statistically significant (chi 2 interaction = 10.2, 3 d.f., P = 0.02). In summary, the results of this study suggest that coffee consumption reduces the risk of breast cancer in lean women, whereas coffee might have the opposite effect in relatively obese women. PMID: 2386741 [PubMed - indexed for MEDLINE]

Coffee Coffee => => ↑↑ risk of bladder cancerrisk of bladder cancer

Vena JE et al. Ann Epidemiol. 1993;3(6):586-91

Coffee consumption 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.

Relative risk of bladdercancer

Heaviest coffeedrinkers

(highest quartile)

Lowest quartile

Heaviestsmokers

(highest quartile)

0

0,5

1

1,5

2

2,5

1

2.1

(95% CI:1.3-3.2)

p < 0.05

2.7

(95% CI:1.8 to 4.0)

p < 0.05

Ann Epidemiol. 1993 Nov;3(6):586-91. Links Coffee, cigarette smoking, and bladder cancer in western New York. Vena JE, Freudenheim J, Graham S, Marshall J, Zielezny M, Swanson M, Sufrin G. Department of Social and Preventive Medicine, School of Medicine and Biomedical Sciences, State University of New York at Buffalo. The association between consumption of coffee and bladder cancer and the effect modification of cigarette smoking was investigated as part of a comprehensive case-control study. The study population consisted of 351 case patients with histologically confirmed

transitional cell carcinomas of the bladder among white males and 855 white male control subjects selected from Erie, Niagara, and Monroe counties in New York from 1979 to 1985. Usual diet, coffee consumption, and cigarette use were estimated by comprehensive interviews using a detailed food frequency questionnaire. After adjustment for age, education, and dietary risk factors by multiple logistic regression, risk was found to increase with increasing pack-years of cigarette use with an odds ratio in the highest quartile of 2.7 (95% confidence interval, 1.8 to 4.0) when compared to the lowest quartile. Coffee consumption was associated with an increased risk for bladder cancer among the heaviest coffee drinkers after adjustment for cigarette smoking and other dietary risk factors (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.2). The effect was more pronounced among nonsmokers, especially among those 65 years and older. These findings support the contention that coffee is a weak carcinogen. PMID: 7921304 [PubMed - indexed for MEDLINE]

Caffeine increases BPCaffeine increases BPLaboratory studies over the last 20 yrs => Laboratory studies over the last 20 yrs => consistently demonstrated consistently demonstrated => caffeine dose of => caffeine dose of 2 to 3 cups of brewed coffee 2 to 3 cups of brewed coffee => => ↑↑ blood pressure (BP) blood pressure (BP) at rest:at rest: + 7 to + 10 mm Hg+ 7 to + 10 mm Hgwhen administered either to "caffeinewhen administered either to "caffeine--naive" individuals or to naive" individuals or to habitual coffee drinkers after overnight abstinence. habitual coffee drinkers after overnight abstinence. => => ↑↑ BPBP reach a reach a max. 30 to 60 minutes aftermax. 30 to 60 minutes after caffeine caffeine administration & administration & persist for several hours.persist for several hours.

Lane JD et al. PsychosomaticPsychosomatic MedMed 2002; 64:5952002; 64:595--603603

Psychosom Med. 2002 Jul-Aug;64(4):595-603. Links Caffeine affects cardiovascular and neuroendocrine activation at work and home. Lane JD, Pieper CF, Phillips-Bute BG, Bryant JE, Kuhn CM. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. jdlane@acpub.duke.edu OBJECTIVE: This study investigated the effects of moderate doses of caffeine on ambulatory blood pressure and heart rate, urinary excretion of epinephrine, norepinephrine, and cortisol, and subjective measures of stress during normal activities at work and at home in the evening. METHODS: Healthy, nonsmoking, habitual coffee drinkers (N = 47) participated in 3 days of ambulatory study. After a day of ad lib caffeine consumption, caffeine (500 mg) and placebo were administered double-blind in counter-balanced order on separate workdays. Ambulatory blood pressure and heart rate were monitored from the start of the workday until bedtime.

Urinary excretion of catecholamines and cortisol was assessed during the workday and evening. RESULTS: Caffeine administration significantly raised average ambulatory blood pressure during the workday and evening by 4/3 mm Hg and reduced average heart rate by 2 bpm. Caffeine also increased by 32% the levels of free epinephrine excreted during the workday and the evening. In addition, caffeine amplified the increases in blood pressure and heart rate associated with higher levels of self-reported stress during the activities of the day. Effects were undiminished through the evening until bedtime. CONCLUSIONS: Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. Furthermore, caffeine may exaggerate sympathetic adrenal-medullary responses to the stressful events of normal daily life. Repeated daily blood pressure elevations and increases in stress reactivity caused by caffeine consumption could contribute to an increased risk of coronary heart disease in the adult population. PMID: 12140349 [PubMed - indexed for MEDLINE]

Coffee Coffee => => ↑↑ serum cholesterolserum cholesterol

Wie M et al. J Clin Epidemiol. 1995 Oct;48(10):1189-96

A dose-response was found among those who decreased regular coffee 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.

176

180

184

188

192

196

200

0 1 2 3 4 5 6 7 8 9 10cups/day

Serum Cholesterol(mg/dl)

n = 2109 healthy nonsmokers aged 25-65 yrs(mean follow-up = 16.7 months)

(p < 0.001)

Increase of 1 cup of coffee per day = increase of 2 mg/dl total cholesterol

J Clin Epidemiol. 1995 Oct;48(10):1189-96. Links The impact of changes in coffee consumption on serum cholesterol. Wei M, Macera CA, Hornung CA, Blair SN. Department of Internal Medicine, School of Medicine, University of South Carolina, Columbia 29208, USA. To investigate the possible association between changes in coffee consumption and serum cholesterol levels, information was obtained from 2109 healthy nonsmokers aged 25-65 years at two clinic visits to a preventive medical center between 1987 and 1991 (mean interval between visits: 16.7 months). After adjusting for age and changes in other potential confounders, about 2 mg/dl total cholesterol increase was associated with an increase of one cup of regular coffee per day (p < 0.001). A dose-response was found among those who decreased regular coffee consumption, those who continued the same dose, and those who

increased consumption. The same trend was observed among those who quit drinking regular coffee, those who never drank coffee, and those who started to drink coffee. No change in cholesterol level was found among those continuing to consume the same quantity of regular coffee compared to those who never drank coffee. The change in cholesterol level was not related to consumption of decaffeinated coffee, regular tea, decaffeinated tea, or cola with caffeine. To our knowledge, this is the first follow-up study correlating change in coffee consumption with change in serum cholesterol in a large group of men and women. PMID: 7561980 [PubMed - indexed for MEDLINE]

↑↑ citrus fruits & citrus fruits & ↑↑ intake of intake of vitvit. C, . C, vitvit. B2 & . B2 & linoleiclinoleic acid acid => => ↓↓ allall-- cause mortality in very elderly peoplecause mortality in very elderly people

Fortes C et al. Epidemiology. 2000 Jul;11(4):440-5

0

0.5

1

MO

RTA

LITY

5-year cohort study among n = 162 self-sufficient residents in a public home for elderly

1.0

CITRUS FRUITconsumption SUPPLEMENT intake

LOW

0.52(95% CI = 0.28 - 0.95)

HIGH (≥ 2 x/wk)

LOW(< 1 x/wk)

-50 %

HIGHVIT. C HIGH

VIT. B2

-60 %

HIGH LINOLEIC

ACID-48 %

Frequent consumption of citrus fruit, and high intake of vitamin C, riboflavin, & linoleic (Ω6) acid are associated with longevity

Epidemiology. 2000 Jul;11(4):440-5. Links Diet and overall survival in a cohort of very elderly people. Fortes C, Forastiere F, Farchi S, Rapiti E, Pastori G, Perucci CA. Department of Epidemiology, Lazio Regional Health Authority, Rome, Italy. We conducted a 5-year cohort study among 162 self-sufficient residents in a public home for the elderly in Rome, Italy, to evaluate the association between the consumption of specific food groups and nutrients and overall 5-year survival. We used a validated, semiquantitative food-frequency questionnaire to assess diet at baseline. Individuals consuming citrus fruit at least twice a week had an adjusted risk of dying that was half that of individuals who consumed citrus fruit less than once a week [relative risk (RR) = 0.52; 95% confidence interval (CI) = 0.28-0.95] (with adjustment for gender, age, education, body mass index, smoking status, cognitive function, and chronic diseases). The adjusted RRs of mortality were 0.38 (95% CI = 0.14-1.01) for consumption of milk and yogurt at least three times a week vs less than once a week; 0.21 (95% CI = 0.08-0.35) for moderate consumption of espresso coffee (1-2 cups weekly) vs less than once a week; and 0.35 (95% CI = 0.17-0.69) for > 2 cups a week of espresso coffee vs less than once a week. High levels of intake of ascorbic

acid, riboflavin, and linoleic acid were associated with 50-60% decreases in mortality risk. High consumption of meat was associated with a higher risk of mortality (RR = 9.72; 95% CI = 2.68-35.1) among subjects with chronic diseases. Our findings indicate that frequent consumption of citrus fruit, milk, and yogurt; low consumption of meat; and high intake of vitamin C, riboflavin, and linoleic acid are associated with longevity. PMID: 10874552 [PubMed - indexed for MEDLINE]

↑↑↑↑ Fruit & vegetable intake => Fruit & vegetable intake => ↓↓ mortalitymortality

Steffen LM et al. Am J Clin Nutr. 2003 Sep; 78(3): 383-90

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.)

00.20.40.60.8

11.2

Fruit & vegetable intake(2th) Lowest

quintile(5th) Highest

quintile

(3th) Averagequintile

(4th) Higherquintile

n = 15,792 (age 45-64 yrs) P for trend = 0.02

(1st) Lowestquintile

Relative riskof dying

(11-yr mortality)

0.78 (0.61-1.01)

0.87 (0.68-1.10)

0.94 (0.75-1.17)

1.08 (0.88-1.33)

1.0- 22 %- 11 %- 6 %

Am J Clin Nutr. 2003 Sep;78(3):383-90. Links Comment in: Am J Clin Nutr. 2003 Sep;78(3):357-8. Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Steffen LM, Jacobs DR Jr, Stevens J, Shahar E, Carithers T, Folsom AR. Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, 55454, USA. steffen@epi.umn.edu BACKGROUND: Recent epidemiologic study results showed that subjects who had high intakes of whole-grain foods had lower risks of death and heart disease than did subjects who had low intakes. However, the findings were inconsistent for fruit and vegetable intake. OBJECTIVE: The relations of whole-grain, refined-grain, and fruit and vegetable intakes with the risk of total mortality and the incidence of coronary artery disease (CAD) and ischemic stroke were studied in the Atherosclerosis Risk in Communities (ARIC) cohort (baseline: age 45-64 y, n = 15,792). DESIGN: Proportional hazards regression analyses were used to assess the relations of whole-grain, refined-grain, and fruit and vegetable intakes with the risk of death and the incidence of CAD and ischemic stroke, with adjustment for age, sex, ethnicity,

energy intake, and cardiovascular disease risk factors. Dietary intakes were assessed by using a food-frequency questionnaire. RESULTS: Over an 11-y follow-up period, whole-grain intake was inversely associated with total mortality and incident CAD. The relative hazards of death for quintiles 2-5 of fruit and vegetable intake were 1.08 (95% CI: 0.88, 1.33), 0.94 (0.75, 1.17), 0.87 (0.68, 1.10), and 0.78 (0.61, 1.01), respectively; P for trend = 0.02. An inverse association between fruit and vegetable intake and CAD was observed among African Americans but not among whites (P for interaction = 0.01). The risk of ischemic stroke was not significantly related to whole-grain, refined-grain, or fruit and vegetable consumption. CONCLUSION: These observational findings suggest a beneficial effect of whole-grain and fruit and vegetable consumption on the risks of total mortality and incident CAD but not on the risk of ischemic stroke. PMID: 12936919 [PubMed - indexed for MEDLINE]

Fruit & vegetable intake Fruit & vegetable intake => => ↓↓ riskrisk ofofhypertensionhypertension

Alonso A et al. Br J Nutr. 2004;92(2):311-9

In a Mediterranean population with an elevated fat consumption (37 % of diet), a high fruit & vegetable intake is inversely associated with BP levels

0

0.2

0.4

0.6

0.8

1

Upper quintiles

Relative risk(adjustedprevalenceodds ratio) n = 4393

Fruit & vegetable

consumption

P = 0.001P = 0.10

0.58 (95 % CI: 0.36-0.91)

Fruitconsumption

0.68 (95 % CI:

0.43- 1.09) 0.23 (95 % CI:

0.43- 1.09)

P = 0.01

Vegetableconsumption1

Lowestquintile

Br J Nutr. 2004 Aug;92(2):311-9. Links Fruit and vegetable consumption is inversely associated with blood pressure in a Mediterranean population with a high vegetable-fat intake: the Seguimiento Universidad de Navarra (SUN) Study. Alonso A, de la Fuente C, Martin-Arnau AM, de Irala J, Martinez JA, Martinez-Gonzalez MA. Department of Epidemiology and Public Health, University of Navarra, Pamplona, Spain. There is evidence that a diet rich in fruit and vegetables reduces blood pressure (BP). Characteristically, the Mediterranean diet is rich in plant-derived foods and also in fat, but studies conducted in Mediterranean countries to relate diet to BP are scarce. We studied the association between fruit and vegetable consumption and BP in a cross-sectional analysis of 4393 participants in the Seguimiento Universidad de Navarra (SUN) Study, an ongoing dynamic cohort study in Spain. Diet was measured using a food-frequency questionnaire

previously validated in Spain. Fat represented more than 37 % total energy intake. Subjects were considered to have undiagnosed hypertension if they reported systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg, and not a medical diagnosis of hypertension. The adjusted prevalence odds ratio of undiagnosed hypertension (upper v. lowest quintile) was 0.58 (95 % CI 0.36, 0.91; P for trend 0.01) for vegetable consumption and 0.68 (95 % CI 0.43, 1.09; P for trend 0.10) for fruit consumption. Comparing those in the highest quintile of both fruit and vegetable consumption with those in the lowest quintile of both food groups, the prevalence odds ratio was 0.23 (95 % CI 0.10, 0.55; P = 0.001), after adjusting for risk factors for hypertension and other dietary exposures. In a Mediterranean population with an elevated fat consumption, a high fruit and vegetable intake is inversely associated with BP levels. PMID: 15333163 [PubMed - indexed for MEDLINE]

↑↑ Fruit & Fruit & vegetablevegetable intakeintake =>=> ↓↓cardiovascularcardiovascular andand allall cause cause mortalitymortality

Bazzano LA et al. Am J Clin Nutr. 2002 Jul; 76(1): 93-9

An inverse association of fruit & vegetable intake with the risk of cardiovascular disease & all-cause mortality was observed in the general US population.

0

0.2

0.4

0.6

0.8

1

FRUIT & VEGETABLE INTAKE ≥ 3x/dayRelative risk of disease or death

P = 0.02

0.85

<1x/day

n = 9608 adults aged 25-74 yr

Strokeincidence

- 27%

Ischemicheart

diseasemortality

- 24%

Strokemortality

- 42%

0.730.73 0.58 0.76

(average 19-yr follow-up)

Cardiovasculardiseasediseasemortality

- 27%

All cause mortality

- 15%

Am J Clin Nutr. 2002 Jul;76(1):93-9. Links Comment in: Am J Clin Nutr. 2002 Jul;76(1):1-2. Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L, Whelton PK. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA. BACKGROUND: Epidemiologic studies report inconsistent findings on the association of fruit and vegetable intake with the risk of cardiovascular disease. OBJECTIVE: The objective was to examine the relation between fruit and vegetable intake and the risk of cardiovascular

disease. DESIGN: We studied 9608 adults aged 25-74 y participating in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study and free of cardiovascular disease at the time of their baseline examination between 1971 and 1975. Fruit and vegetable intake at baseline was measured with a food-frequency questionnaire. The incidence of and mortality from cardiovascular disease were obtained from medical records and death certificates. RESULTS: Over an average of 19 y, 888 strokes (218 fatal), 1786 ischemic heart disease events (639 fatal), 1145 cardiovascular disease deaths, and 2530 all-cause deaths were documented. Consuming fruit and vegetables > or = 3 times/d compared with <1 time/d was associated with a 27% lower stroke incidence [relative risk (RR): 0.73; 95% CI: 0.57, 0.95; P for trend = 0.01), a 42% lower stroke mortality (0.58; 0.33, 1.02; P for trend = 0.05), a 24% lower ischemic heart disease mortality (0.76; 0.56, 1.03; P for trend = 0.07), a 27% lower cardiovascular disease mortality (0.73; 0.58, 0.92; P for trend = 0.008), and a 15% lower all-cause mortality (0.85; 0.72, 1.00; P for trend = 0.02) after adjustment for established cardiovascular disease risk factors. CONCLUSION: We showed an inverse association of fruit and vegetable intake with the risk of cardiovascular disease and all-cause mortality in the general US population. PMID: 12081821 [PubMed - indexed for MEDLINE]

↑↑ Fruit & Fruit & vegetablevegetable intakeintake =>=> ↓↓ cancer cancer mortalitymortality

Sauvaget C et al. Br J Cancer. 2003; 88(5): 689-94

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.

Relative riskof dying

from cancer

0

0.2

0.4

0.6

0.8

1

(Almost) dailyFRUIT intake

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.

P < 0.05

95%CI= 0.80-0,96)

0.751.0 0.920.88

Overall cancer mortality Stomach &

lung cancer

Livercancer

(Almost) daily green-yellow VEGETABLE

intake

MeanRisk

0.8

0.94-1,01)

0.60-0,95)

0.65-0.98)

- 12 %- 25% - 20%

- 8 %

P < 0.05 P < 0.05P < 0.05

(Amost) dailyFRUIT intake

Br J Cancer. 2003 Mar 10;88(5):689-94. Links Vegetables and fruit intake and cancer mortality in the Hiroshima/Nagasaki Life Span Study. Sauvaget C, Nagano J, Hayashi M, Spencer E, Shimizu Y, Allen N. Department of Epidemiology, Radiation Effects Research Foundation, Minami-ku, Hiroshima, Japan. sauvaget@rerf.jp

The association between green-yellow vegetables and fruit consumption and risk of cancer death was investigated in a prospective study of 38 540 men and women who were atomic-bomb survivors in Hiroshima and Nagasaki, Japan. Study participants completed a dietary questionnaire in 1980-1981 and were followed-up for cancer deaths until March 1998, during which time 3136 cancer deaths were identified. Daily or almost daily fruit consumption was associated with a significant 12% reduction in total cancer mortality (RR=0.88; 95% CI, 0.80-0.96 for daily intake compared with intake once per week or less). Daily or almost daily green-yellow vegetables consumption was associated with a marginally significant 8% reduction in total cancer mortality (0.92; 0.94-1.01). Green-yellow vegetables consumption was associated with a significant reduction in liver cancer mortality (0.75; 0.60-0.95). Fruit consumption was associated with a significantly reduced risk of stomach cancer and lung cancer mortality (0.80; 0.65-0.98). Green-yellow vegetables and fruit consumption was associated with a reduction in oesophageal cancer, but these associations were not statistically significant. Neither green-yellow vegetables nor fruit consumption was associated with colorectal cancer or breast cancer mortality. These results support the evidence that daily consumption of fruit and vegetables reduces the risk of total cancer, and specifically cancers of the stomach, liver, and lung. PMID: 12618875 [PubMed - indexed for MEDLINE]

Coffee + Alcohol + smoking Coffee + Alcohol + smoking => => ↑↑ riskrisk ofofpancreaticpancreatic cancercancer

Pfeffer F et al. Rev Invest Clin. 1989 Jul-Sep;41(3):205-8

The combination of 2 to 3 risk factors increases considerably the risk of pancreatic cancer.Considered independently, only alcohol & coffee consumption were found to be sign. assoc. + pancreas cancer

0

10

20

30Pancreatic

Cancer

(Relative Risk)

1

n = 29 cases + pancreatic cancer & 29 controls

p = 0.02

26.3

13.9

p = 0.13

Smoking+ Alcohol+ Coffee

Alcohol+ Coffee

Rev Invest Clin. 1989 Jul-Sep;41(3):205-8. Links [Smoking, consumption of alcoholic beverages and coffee as factors associated with the development of cancer of the pancreas] [Article in Spanish] Pfeffer F, Avilas Rosas H, Vargas F, Villalobos JJ. The purpose of this study was to evaluate retrospectively the role of alcohol intake, smoking and coffee consumption as risk factors in the development of cancer of the pancreas. Twenty nine cases with pancreatic cancer and 29 controls matched by sex, socioeconomic status and age were evaluated. Information on alcohol, tobacco and coffee consumption was obtained by

specially designed questionnaires. Odds ratios were calculated and analyzed by chi square testing. The combination of the 3 factors gave an odds ratio of 26.3, whereas alcohol and coffee consumption gave an odds ratio of 13.9. Considered independently, only alcohol and coffee consumption were found to be significantly associated with cancer of the pancreas. PMID: 2813993 [PubMed - indexed for MEDLINE]

Alcohol => Alcohol => ↑↑ risk of breast cancerrisk of breast cancer

Longnecker MP et al. JAMA. 1988 Aug 5;260(5):652-6

Risk of breast cancer in daily alcohol drinkers & non-drinkers

0

0.5

1

1.5

2

Non drinkers

Daily initial alcohol

consumption of 24 g (2 drinks)

Follow-up: daily alcohol

of 24 g continues

1,4(95% CI, 1.0-1.8)

1,7(95% CI, 1.4-2.2)

JAMA. 1988 Aug 5;260(5):652-6. Links A meta-analysis of alcohol consumption in relation to risk of breast cancer. Longnecker MP, Berlin JA, Orza MJ, Chalmers TC. Department of Epidemiology, Harvard School of Public Health, Boston, MA. Epidemiologic findings regarding the relation between alcohol consumption and risk of breast cancer have been inconsistent. We performed a meta-analysis (a quantitative review) of the available data. To evaluate whether there was a dose-response relation between alcohol consumption and risk of breast cancer, we fitted mathematical models to the pooled data. There was strong evidence to support a dose-response relation in both the case-control and follow-up epidemiologic data. Using the dose-response curves that we calculated, the risk of breast cancer at an alcohol intake of 24 g (1 oz) of absolute alcohol daily (about two drinks daily) relative to nondrinkers was 1.4 (95% confidence interval, 1.0 to 1.8) in the case-control data and was 1.7 (95% confidence interval, 1.4 to 2.2) in the follow-up data. We interpret these findings not as proof of causality, but as strongly supportive of an association between alcohol consumption and risk of breast cancer. PMID: 3392790 [PubMed - indexed for MEDLINE]

Alcohol => Alcohol => ↑↑ riskrisk ofof Prostate cancerProstate cancer

Putnam SD et al. Ann Epidemiol. 2000 Aug;10(6):361-9

Increased risk of prostate cancer in alcohol consumers

0

1

2

3

4

large-scaleIowa Cohort

study; 110 (?) cases

<22 gramsalcohol

per week

1.1

+210%

Nonusers

22-96 grams

Alcoholusers>96

grams

2.63.1

+160 %

Prostatecancer

risk(Rel. Risk)

+10 %

NS p< 0.05 p< 0.05

Ann Epidemiol. 2000 Aug;10(6):361-9. Links Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men. Putnam SD, Cerhan JR, Parker AS, Bianchi GD, Wallace RB, Cantor KP, Lynch CF. Department of Preventive Medicine and Environment Health, University of Iowa, College of Medicine, Iowa City, IA, USA. PURPOSE: Several lines of evidence suggest that prostate cancer has a hormonal etiology. We evaluated factors known to modulate the endocrine system, including alcohol and tobacco use, physical activity, and obesity as risk factors for prostate cancer. METHODS: Cancer-free controls who participated in a population-based case-control study from 1986-1989 (81% response rate) were followed through 1995 for cancer incidence by linkage to the Iowa Cancer Registry; 101 incident prostate cancers were identified. RESULTS: Compared with non-users of alcohol, men who consumed <22 grams alcohol per week (relative risk [RR] = 1.1; 95% Confidence Interval [CI] 0.6-2.1), 22-96 grams alcohol per week (RR = 2.6; 95% CI 1.4-4. 6) and >96 grams alcohol per week (RR = 3.1; 95% CI 1.5-6.3) were at increased risk of prostate cancer after adjustment for age, family history of prostate cancer, body mass index, total energy, and intake of carbohydrate, linoleic acid, lycopene, retinol, and red meat (p for trend < 0.0001). The respective RRs were similar when assessing type of alcohol consumed (beer, wine or liquor) or when well-differentiated, localized tumors were excluded. Body mass index was only weakly and positively associated with prostate cancer after adjustment for age, but this association strengthened after multivariate adjustment and exclusion of well-differentiated, localized tumors. For the latter tumors, men with a BMI of 24.1-26.6 kg/m(2) and >26.6 kg/m(2) were at elevated risk compared to men with a BMI <24.1 kg/m(2). Tobacco use (cigarettes, cigar/pipe, chewing tobacco and snuff use), height, weight, and both leisure and occupational physical activity were not associated with risk of

prostate cancer in this cohort. CONCLUSIONS: These data suggest that in white men obesity is a risk factor for more clinically significant prostate cancer and confirm limited previous reports showing that alcohol consumption is positively associated with prostate cancer and that this risk is not limited to any specific type of alcohol. PMID: 10964002 [PubMed - indexed for MEDLINE]

MediterraneanMediterranean dietdiet => => mortalitymortality

Alonso A, Martinez-Gonzalez MA. JAMA. 2005 Feb 9;293(6):674

JAMA. 2005 Feb 9;293(6):674; author reply 674-5. Links Comment on: JAMA. 2004 Sep 22;292(12):1433-9. Mediterranean diet, lifestyle factors, and mortality. Alonso A, Martinez-Gonzalez MA. PMID: 15701904 [PubMed - indexed for MEDLINE]