Beta-carotene and cancer prevention: the Basel Study.

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.

Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study.

BACKGROUND: Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol. OBJECTIVE: The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins. DESIGN: Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed. RESULTS: Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer. CONCLUSIONS: Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C.

For the prolongation of life expectancy and reduction of ischemic heart disease (IHD) dietary guidelines generally recommend lowering saturated mammalian fat with partial replacement by vegetable oils and increasing generously vegetables, legumes, and fruits, which provide more essential antioxidants. Plasma antioxidants as assayed in epidemiological studies of complementary type (ie the cross-cultural MONICA Vitamin Substudy reevaluation considering the "Finland-Factor", the Edinburgh Angina-Control Study, and the Basel Prospective Study) consistently revealed an increased risk of IHD (and stroke) at low plasma concentrations of antioxidants, with the rank order as follows: lipid-standardized vitamin E >> carotene = vitamin C > vitamin A, independently of classical IHD risk factors. Decreasing IHD risk through nutrition may be possible when plasma concentrations have the following values: > 27.5-30.0 mumol vitamin E/L, 0.4-0.5 mumol carotene/L, 40-50 mumol vitamin C/L and 2.2-2.8 mumol vitamin A/L. Thus, previous prudent regimens may now be updated, aiming at an optimal status of all essential and synergistically linked antioxidants.

Inverse correlation between essential antioxidants in plasma and subsequent risk to develop cancer, ischemic heart disease and stroke respectively: 12-year follow-up of the Prospective Basel Study.

There is accumulating evidence that free radicals may contribute to various diseases such as cancer or cardiovascular disease. Possible health hazards can to some extent be prevented by the body's multilevel defense system against free radicals, which comprises, besides others, antioxidant vitamins. The 12-year mortality follow-up of 2,974 participants of the Basal Study allowed to test the hypothesis that low antioxidant vitamin plasma concentrations (vitamin A, C, E and carotene) were associated with increased death from cancer of various sites and death from atherosclerosis such as ischemic heart disease and stroke, respectively. For the analysis 204 cancer cases, 132 fatalities from ischemic heart disease (IHD) and 31 deaths from cerebral vascular disease were available. Cancer mortality. Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer had also lower mean vitamin C and lipid-adjusted vitamin A levels than survivors (p less than 0.05). Calculating the relative risk with exclusion of mortality during the first two years of follow-up, low plasma carotene was associated with an increased risk for bronchus cancer (RR 1.8, p less than 0.05), and the small number of stomach cancer cases (RR 2.95, p less than 0.05) low plasma levels of carotene and vitamin A with all cancer types (RR 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than 60 years) with lung cancer (RR 2.17, p less than 0.05). Studies in other cohorts with a poor vitamin E status revealed an increased risk of subsequent cancer at low vitamin E levels as well. It is concluded that low plasma levels of all major essential antioxidants are associated with an increased risk of subsequent cancer mortality. Cardio-vascular mortality. Plasma carotene concentration below quartile 1 was associated with an increased risk for IHD (RR 1.53, p = 0.02). The same was true for low levels of both carotene and vitamin C (RR = 1.96, p = 0.022). The risk of cerebrovascular death was elevated in subjects with low carotene in the presence of low vitamin C plasma concentration (RR 4.17, p less than 0.01). These data confirm and extend recent findings on an inverse correlation of beta-carotene and vitamin C respectively to CVD.(ABSTRACT TRUNCATED AT 400 WORDS)

Dietary nitrates, nitrites, and N-nitroso compounds and cancer risk: a review of the epidemiologic evidence.

Experimental animal studies have shown N-nitroso compounds (NOC) to be potent carcinogens. Epidemiologic evidence of the carcinogenic potential of dietary NOC and precursor nitrates and nitrites in humans remains inconclusive with regard to the risk of stomach, brain, esophageal, and nasopharyngeal cancers. Inadequate available data could obscure a small to moderate effect of NOC.

Daily consumption of (red) meat or meat products in Switzerland: results of the 1992/93 Swiss Health Survey.

OBJECTIVE: The present study aimed to examine the frequency of daily meat and meat product consumption and the preference for red meat in Switzerland. DESIGN: Cross-sectional Study. SETTINGS AND SUBJECTS: Data were taken from the 1992/1993 Swiss Health Survey, which collected data on a random sample of persons aged 15 and over, living in Switzerland. The survey, which had a response rate of 71%, included 7930 male and 7358 female respondents. Bivariate analyses and multivariate logistic regressions controlling for sociodemographic and lifestyle factors were performed. RESULTS: Daily consumption of meat or meat products (25%) and more frequent consumption of red than white meat (26% of meat eaters) were prevalent in Switzerland. Men, middle-aged persons, participants with a low level of education, persons living in the German or Francophone regions of Switzerland, those with Swiss nationality, smokers, overweight and obese people, those with daily alcohol consumption and physically inactive persons were found to consume daily meat or meat products more frequently. A preference for red meat rather than white meat was more often observed in men, young people, persons living in the German or Francophone regions of Switzerland, smokers and participants who consumed alcohol at least once daily. CONCLUSIONS: The analysis of data from the 1992/1993 Swiss Health Survey shows that in specific subgroups of the Swiss population meat and meat product consumption is still more frequent than recommended, but crude comparisons with older and more recent studies indicate a decrease in meat consumption. The observed clustering of daily meat consumption with other risk factors underscores the necessity to include dietary recommendations in health programs addressing other unhealthy lifestyles. European Journal of Clinical Nutrition (2000) 54, 136-142

Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence.

It is only recently that folate deficiency has been implicated in the development of cancer. The mechanisms by which folate might protect against cancer are not clear but may relate to its role in DNA methylation and DNA synthesis. All case-control, cohort and intervention trials reported in English, French, or German, on folate intake or blood levels in relation to the risk of colorectal, breast, and cervix cancer were reviewed. Twenty case-control, and 12 nested case-control or cohort studies were identified. The epidemiological studies consistently show an inverse association between intake and/or levels of folate and the frequency of colorectal carcinomas, and less clearly of adenomas. Long-term use of supplements of folate seems to be of greater benefit than dietary intake. The effect of folate seems to be modulated by alcohol, methionine, and MTHFR polymorphisms. Results from animal studies suggest that folate supplementation might decrease or increase cancer risk depending on dosage and timing. Recent studies also suggest an inverse association between folate intake and breast cancer among women who regularly consume alcohol. Conversely, epidemiological evidence remains uncertain for the role of folate in cervical cancer prevention; the results of two intervention trials on rates of cervical intraepithelial neoplasia regression or progression were negative. An effect of folate later in carcinogenesis is not supported by the few (nested) case-control studies on invasive cervical cancer. Some of the conflicting results may be due to the fact that dietary intake or blood levels of folate do not accurately reflect folate concentrations in the cells of cancer origin. Furthermore, only a few studies have taken into account the modulating effect of alcohol, methionine, and MTHFR polymorphisms in their analyses. The observed inverse associations between folate and risk of cancer, on the other hand, may be confounded by various factors, especially by other potentially protective constituents in fruits and vegetables. Ongoing intervention studies can strengthen evidence for causality by excluding such confounding, but the optimal dose, duration, and stage of carcinogenesis and the appropriate (genetically predisposed) study group for folate chemoprevention are not yet defined.

Is there a hypocholesterolemic factor in milk and milk products?

Cow's milk is considered to be related to atherosclerosis since more than 50% of its energy comes from fat in which saturated fatty acids are predominant. But many investigators have reported that milk or milk products have actually a hypocholesterolemic effect in man and animals and a number of milk constituents have been suggested as hypocholesterolemic factors.

The role of folate, antioxidant vitamins and other constituents in fruit and vegetables in the prevention of cardiovascular disease: the epidemiological evidence.

Evidence that fruit and vegetables may protect against coronary heart disease is accumulating. It is unclear which constituents of fruit and vegetables are responsible for this protective effect. Folate as a co-substrate in homocysteine metabolism may be important. An intake of about 400 micrograms folate equivalents/day seems to be required to achieve stable low homocysteine blood levels. Five of eight epidemiologic studies show significant inverse associations between folate and cardiovascular disease. These associations could be confounded by antioxidant vitamins and/or other substances. In trials examining an association between folate and cardiovascular disease such confounding must be excluded, before specific recommendations can be given. Observational studies suggest that vitamin C plays a role in the aetiology of cardiovascular disease, but there are no completed intervention trials of this vitamin alone. With regard to vitamin E two cohort studies point to cardiovascular benefits with the long-term use of supplements of at least 100 IU/day, but the results of controlled trials are inconclusive. There is some evidence from observational studies of an inverse association between beta-carotene and cardiovascular disease, particularly in smokers. Intervention trials do not support this hypothesis, rather, they suggest a possible harmful effect of beta-carotene supplements in smokers. Nevertheless, protective effects of beta-carotene and vitamin E in different dosages, durations of administration, or different combinations are still possible. The last paragraph of this review discusses limitations of the present and priorities of future research.

[Should dietary recommendations be revised?]. / Müssen die Ernährungsempfehlungen revidiert werden?

The dietary recommendations of the Second Swiss Nutrition Report are in part based on incomplete knowledge about nutritional patterns of the Swiss population and on controversial results of relations between nutritional status and health, thus do not fulfill completely the WHO requirements for dietary guidelines. A new set of recommendations would not be based on better knowledge. However, efforts to prevent the widespread chronical diseases, e.g. by dietary measures are understandable. We therefore recommend to apply dietary guidelines never without considering their controversial incomplete scientific basis and to prevent by this a possible negative impact of dietary guidelines.

[Inadequate fruit and vegetable consumption in Switzerland: results of the Swiss Health Survey 1992/93]. / Ungenügender Früchte- und Gemüsekonsum in der Schweiz: Resultate der Schweizerischen Gesundheitsbefragung 1992/93.

Inadequate consumption of fruit and vegetables increases the risk of various (chronical) diseases. It is therefore recommended to eat at least three portions of vegetables and two portions of fruit every day. The present study aims to determine the prevalence of inadequate fruit and vegetable (potatoes are not regarded as vegetables in Switzerland) consumption in Switzerland and to determine sociodemographic and lifestyle correlates of inadequate consumption. Data presented in this study were taken from the first national representative health survey for Switzerland (conducted 1992/1993) including 7930 men and 7358 women (response rate 71%), age 15 and over. Bivariate analyses and multivariate logistic regressions controlling for sociodemographic and lifestyle factors were done. Inadequate consumption of fruit and vegetables was common among the study population. Less than daily consumption of fruit was reported by about 30%, of vegetables by 17%. About 25% of study participants do not eat fruit or vegetables every day, for 11% the consumption of both is insufficient. Men, young people, study participants with a low educational background, people living in the French and Italian speaking part of Switzerland, smokers and participants with low physical activity reported more often inadequate fruit and vegetable intake than women, older people, well educated study participants, inhabitants of the German speaking part of Switzerland, nonsmokers, and less physically active people. These results stress the need for nutrition education programs aimed at increased consumption of fruit and vegetables in Switzerland.

[Disabilities and impairment in activities of daily living as possible risk factors in dementia: prospective study in Basel 1986]. / Behinderungen und Einschränkungen der Aktivitäten des täglichen Lebens als mögliche Risikofaktoren für Demenz: Prospektive Basler-Studie 1986.

Because of the increasing number of old people in our society more and more dementia cases will be expected. The etiology of dementia is far from being clear. To get some idea about risk factors 4200 participants (on average 60 years old) of the Prospective Basel Study were asked by letter questions about their health and their way of life. One of the hypotheses to be tested is whether or not disabilities or impairments of activities of daily living could be risk factors for dementia. At present only the results of the basic survey can be discussed. Impairments of hearing, of mobility, of cutting toe-nails and of general physical activity were the conditions which were most frequently named. These results of people being mainly healthy with regard to dementia, will make it possible in the future--in contrast to the cross-sectional studies mentioned in the literature--to test the risk of physical disabilities and impairments of activities of daily living for dementia without being confounded by impairments due to dementia.

[Nutrition and cancer]. / Ernährung und Krebs.

The complex process of carcinogenesis is mainly due to environmental factors and therefore preventable. Diet may account for about 35% of cancer. This review presents the nutritional evidence for the development of the four most common cancers in Switzerland. The clearest risk factors for breast cancer are those associated with hormonal and reproductive factors. In relation to dietary factors, high alcohol intake, weight gain and adipositas (postmenopausal breast cancer) probably increase the risk of breast cancer. The evidence is less clear for the consumption of (animal) fat, meat, fruit and vegetables (inverse association). Hormones may also play an important role in the development of prostate cancer. There is no convincing evidence that any dietary factors modify the risk of prostate cancer. Diets high in vegetables are possibly protective, regular consumption of fat and meat possibly increase the risk. Intervention trials revealed protective effects of supplementation with selen or alpha-tocopherol. The main cause of lung cancer is cigarette smoking, and smokers whose diet is protective nevertheless remain at high risk. The evidence that diets high in vegetables and fruit protect against lung cancer is convincing, but it is not clear what constitutents are responsible for this effect. Intervention trials revealed no protective effect of beta-carotene, and in high risk groups, lung cancer risk was even increased. There is convincing evidence that diets high in vegetables decrease the risk of colorectal cancer. The same is true for regular physical activity. Alcohol and consumption of diets high in (red) meat, probably increase the risk of colorectal cancer. For cancer prevention it is recommended to choose a predominantly plant-based diet, to avoid obesity, to reduce the intake of fat, (red) meat, alcohol and salt, not to smoke and to be physically active. The main aim of nutritional therapy of cancer patients is to improve quality of life, whereas the effect on life expectancy is very limited.

[The significance of nutrition in primary prevention of cancer]. / Die Bedeutung der Ernährung in der Primärprävention von Krebs.

The complex process of carcinogenesis is mainly due to environmental factors and therefore preventable. Diet may account for about 35% of cancer cases; risk factors and protective factors are discussed. Accordingly, obesity is associated with an increased risk of endometrial and postmenopausal breast cancers. Less clear is the relationship with colorectal and prostate cancer. The observed inverse association of body weight with lung cancer risk is most probably confounded by smoking habits and/or the effect of preclinical cancer. The risk factor fat has been studied mainly in relation to colorectal, breast and prostate cancer; the results are controversial. More consistent are the associations between (red) meat consumption and risk of colorectal and prostate cancer. Alcohol is a risk factor for tumors of the upper gastrointestinal tract, the hepatocellular carcinoma and the (distal) colorectal cancer. Even small amounts of alcohol seem to increase the risk of breast cancer. Residues, contaminants, mycotoxins and additives like benzopyrene, nitrosamine(s), and aflatoxine are associated with a smaller risk of cancer than "overnutrition". High intake of fruit and vegetables is related to a reduced risk of lung cancer and cancer of the upper gastrointestinal tract. What the specific chemicals in fruits and vegetables are that are responsible for this association are still unclear. Despite only weak associations between dietary factors and cancer risk, for potential protective effects it is recommendable to increase the consumption of fruit and vegetables, to avoid obesity, to reduce the intake of fat, meat and alcohol and to avoid cured, pickled, smoked, and mouldy food.

Racial variation in sex steroid hormone concentration in black and white men: a meta-analysis.

Sex steroid hormones are associated with chronic diseases and mortality with risk associations that differ between racial and ethnic groups. However, it is currently unclear whether sex steroid hormone levels differ between black and white men. The aim of this study was to assess racial variation in circulating testosterone, free testosterone, sex hormone-binding globulin (SHBG) and estradiol levels in men. We searched PubMed for articles comparing circulating hormones in black and white men. A meta-analysis was performed using weighted mean differences (WMD) to compare hormones levels between black and white men. Fifteen eligible studies were identified; three did not report adjusted means. After age adjustment, free testosterone levels were significantly higher in black than in white men (WMD = 4.07 pg/mL, 95% CI 1.26, 6.88). Depending on the free testosterone concentration in white men, this WMD translates into a racial difference ranging from 2.5 to 4.9%. Total testosterone (WMD = 0.10 ng/mL, 95% CI -0.02, 0.22), estradiol (WMD = 0.67 pg/mL, 95% CI -0.04, 1.38) and SHBG (WMD = -0.45 nmol/L, 95% CI -1.75, 0.85) concentrations did not differ comparing blacks with whites. After adjustment for age, black men have a modestly but significantly 2.5 to 4.9% higher free testosterone level than white men. Based on previous studies on effects of sex steroid hormones on risk of chronic diseases or mortality, this modest difference is unlikely to explain racial differences in disease risk.

Revised D-A-CH intake recommendations for folate: how much is needed?

The D-A-CH reference value (D-A-CH arises from the initial letters of the common country identification for the countries Germany (D), Austria (A) and Switzerland (CH)) for folate equivalents had been set at 400 µg/d for adults in the year 2000. By that time, the prevention of cardiovascular diseases through reduction of homocysteine was considered an important target of the reference value. Since that time a number of research papers revealed that in spite of an inverse association between folate-rich diet and chronic diseases, a preventive effect of folic acid intake on cardiovascular events was not supported by randomized controlled trials, and the reduction of plasma homocysteine levels to around 10-12 µmol/l did not reduce the risk for thromboembolic and cardiovascular diseases in persons already affected by these diseases. These results together with the observation that folate intakes below 400 µg/d result in a sufficient folate status justified a review of the current literature and-consequently-a reduction of the reference value to 300 µg/d for adults. This reference value is expressed as dietary folate equivalents that take into account the difference in bioavailability between folic acid and all types of folates in food. The recommendation to take a daily supplement of 400 µg of synthetic folic acid for women who intend to get pregnant and until the end of the first trimester of pregnancy is maintained.

Meat consumption and diet quality and mortality in NHANES III.

BACKGROUND/OBJECTIVES: There is growing evidence that meat consumption is associated with total and cause-specific mortality. Our objective was to evaluate the association of meat intake and the healthy eating index (HEI) with total mortality, cancer and cardiovascular disease (CVD) mortality. SUBJECTS/METHODS: Analyses are based on 17, 611 participants from Third National Health and Nutrition Examination Survey (NHANES III) (1986-2010). Meat intake was assessed using a food frequency questionnaire administrated at baseline. Adherence to the HEI was analyzed with a single 24-h dietary recall. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality according to five categories of meat consumption and three categories of the HEI score. RESULTS: During the follow-up period, 3683 deaths occurred, of which 1554 were due to CVD and 794 due to cancer. After multivariable adjustment, neither red and processed meat, nor white meat consumption were consistently associated with all-cause or cause-specific mortality. In men, white meat consumption tended to be inversely associated with total mortality (P for trend=0.02), but there was no such association among women. Significantly decreased mortality was observed in the top compared with the bottom third of the HEI score (HR=0.70, 95% CI 0.52-0.96). This association was only observed in men, but not in women. CONCLUSIONS: Meat consumption was not associated with mortality. A healthy diet according to HEI, however, was associated with a decreased total mortality in men, but not in women.

[Data on overweight and nutrition in the 2007 Swiss Health Survey]. / Daten zum Ubergewicht und zu Ernährungsgewohnheiten aus der Schweizerischen Gesundheitsbefragung 2007.

The 2007 Swiss Health Survey is the fourth survey conducted by the Federal Office of Statistics in intervals of five years. Data are collected from a random sample (n = 18760) of persons aged 15 and over, living in Switzerland: 29% are overweight, and additional 8% are obese, but between 2002 and 2007 no increases in the prevalence of overweight and obesity were observed anymore. In relation to nutritional habits, nearly 30% of the interviewed persons do not care about their nutrition. Only 30% of the population eat the recommended five portions of fruits and vegetables per day, and only 10% consume the recommended three servings of milk and milk products. 37% do rarely or never consume fish. Nearly 20% eat meat or meat products every day. According to the four Swiss Health Surveys nutritional habits have hardly improved during the last fifteen years in Switzerland.

[Is periconceptional use of folic acid associated with a reduced risk of cleft lip with or without cleft palate?]. / Reduziert die perikonzeptionelle Gabe von Folsäure auch das Risiko von Lippen-Kiefer-Gaumenspalten?

A recently observed decrease in the prevalence of cleft lip with or without cleft palate in the United States was associated with the folic acid fortification of enriched cereal grains, which became mandatory in 1998. Several case-control and one prospective study found an inverse association between intake of folic acid and/or multivitamins and the risk of cleft lip with or without cleft palate. A randomized trial to prove causality would be unethical, due to the established relationship between neural tube defects and periconceptional folic acid use. Until the results of carefully carried out cohort studies will be available, all women of childbearing age not under contraceptives should consume a diet rich in folate and take an additional daily dose of at least 0.4 (better 0.8) mg folic acid, preferably with a multivitamin, and until the end of the first twelve weeks after conception. With these recommendations for the prevention of neural tube defects, the risk of cleft lip with or without cleft palate may also be reduced.