Jakob Linseisen

Association between Pre-Diagnostic Circulating Vitamin D Concentration and Risk of Colorectal Cancer in European Populations: a Nested Case-Control Study

Objective To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls Main outcome measures Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. Results 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 ( FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes.

The present study gives further evidence for the recently found association between variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and PUFA in blood phospholipids and explores this association for cellular fatty acids in erythrocyte membranes. In a subgroup of adults participating in the Bavarian Nutrition Survey II, a cross-sectional population-based study conducted in Bavaria, Germany, allelic variation in three selected loci of the FADS1 FADS2 gene cluster was analysed and used for haplotype construction. Associations with plasma phospholipid PUFA (n 163) and PUFA in erythrocyte membranes (n 535) were investigated by regression analysis. All haplotypes of the original five-loci haplotypes of our previous study could be replicated. In addition, associations with serum phospholipid PUFA were confirmed in the present data set. Although less pronounced, associations between FADS1 FADS2 haplotypes and PUFA in erythrocyte membranes, particularly arachidonic and dihomo-gamma-linolenic acid, could be established. We provide the first replication of the association of the FADS1 FADS2 gene cluster with PUFA in blood phospholipids. For the first time, such associations were also shown for PUFA in cell membranes.

DIETARY PHYTOESTROGEN INTAKE AND PREMENOPAUSAL BREAST CANCER RISK IN A GERMAN CASE-CONTROL STUDY

A diet high in isoflavonoids (soy) is associated with lower breast cancer risk in Asian populations. Due to the low soy intake, dietary lignans may be the more important phytoestrogen class in Western populations. We used a population‐based case‐control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of different phytoestrogens and premenopausal breast cancer risk. Dietary information was collected from 278 premenopausal cases and 666 age‐matched controls, using a validated FFQ. Using multivariate logistic regression, the highest vs. lowest intake quartiles of daidzein and genistein yielded significantly reduced ORs (95% CI) for breast cancer risk of 0.62 (0.40–0.95) and 0.47 (0.29–0.74), respectively. The protective effects of daidzein and genistein were found only for hormone receptor‐positive tumors. High intake of other isoflavonoids, e.g., formononetin and biochanin A, as well as the sum of isoflavonoids were not associated with a decrease in risk. Breast cancer risk significantly decreased with a high intake of the plant lignan matairesinol (OR = 0.58, 95% CI 0.37–0.94) but not secoisolariciresinol or the sum of plant lignans. However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61 (0.39–0.98) and 0.57 (0.35–0.92), respectively. No effect was found for total phytoestrogen intake. Our results suggest an important role of dietary intake of daidzein and genistein, despite low levels, as well as of matairesinol and mammalian lignans to reduce premenopausal breast cancer risk in this study population.

Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC)

BACKGROUND In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet-disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe. OBJECTIVE Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS Plasma levels of six carotenoids--alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin--were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids. RESULTS Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35 micromol l(-1) for men in Malmö, Sweden vs. 2.79 micromol l(-1) for men in Ragusa/Naples, Italy; 1.61 micromol l(-1) for women in The Netherlands vs. 3.52 micromol l(-1) in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (alpha-carotene: 0.06 micromol l(-1) for men in Murcia, Spain vs. 0.25 micromol l(-1) for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R(2)=27.3%), followed by BMI (partial R(2)=5.2%), gender (partial R(2)=2.7%) and smoking status (partial R(2)=2.8%). Females had higher total carotenoid levels than males across Europe. CONCLUSIONS Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.

Absorption of Cholesterol Oxidation Products from Ordinary Foodstuff in Humans

Background: Information on the absorption of cholesterol oxidation products (COP) from ordinary foodstuff in humans is scarce. Methods: Five healthy young men were offered a salami- and Parmesan-containing meal naturally rich in COP. Plasma and lipoprotein COP concentrations were measured over the following 9 h. Results: The mean plasma free (nonesterified) COP concentration showed its maximal increase 3 and 5 h after meal consumption. In contrast, the raise in plasma total COP concentration began 6 h after the meal with a maximum at 8 h and was statistically significant for 7α- and 7β-hydroxycholesterol and 7-ketocholesterol. The increase in plasma total cholesterol concentration was comparable to that of total COP. Comparing the COP composition of the chylomicrons and the test meal, cholestanetriol, 7-ketocholesterol, and to a lesser extent cholesterol-α-epoxide were underrepresented in the chylomicrons as was the opposite for 7β-hydroxycholesterol. In very-low-density lipoprotein, a steady increase in the COP:cholesterol ratio was observed from 6 h on. Conclusion: COP from ordinary foodstuff were absorbed in the human intestinal tract but differences in the bioavailability of the single COP compounds were found.

Flavonoidzufuhr Erwachsener in einem bayerischen Teilkollektiv der Nationalen Verzehrsstudie

ZusammenfassungFlavonoide sind natürlich vorkommende Inhaltsstoffe von Lebensmitteln pflanzlichen Ursprungs; aufgrund ihrer biologischen Wirkungen (antioxidativ, antimutagen, anticancerogen) ergeben sich interessante Ansätze für die Arteriosklerose- und Krebs-Prophylaxe beim Menschen. In Nährwerttabellen sind Flavonoide nicht ausgewiesen und somit sind Angaben zur Flavonoidzufuhr beim Menschen spärlich (Flavonole) oder gar nicht vorhanden. Deshalb wurde anhand von Literaturangaben eine Datenbank zum Flavonoidgehalt von Lebensmitteln erstellt und mit deren Hilfe 7-Tage-Ernährungsprotokolle von 119 Personen (63 Frauen und 56 Männer, Alter 19–49 Jahre) aus einem bayerischen Teilkollektiv der Nationalen Verzehrsstudie (NVS) ausgewertet.Im Mittel (Median) über alle Personen werden täglich 54,0 mg Flavonoide (berechnet als Aglykon) aufgenommen, wobei die Streubreite der Einzelwerte sehr hoch ist. Den größten Anteil stellen Flavonole (12,0 mg/d), Catechine (8,3 mg/d) und Flavanone (13,2 mg/d), gefolgt von Anthocyanidinen (2,7 mg/d), Proanthocyanidinen (3,7 mg/d) und Phloretin (Dihydrochalcon) (0,7 mg/d). Ein Geschlechterunterschied ist statistisch nicht nachzuweisen. Die Lebensmittelgruppe „Obst/-produkte/-säfte“ ist die wichtigste Flavonoidquelle. Die Flavonolzufuhr wird etwa zur Hälfte durch den Verzehr von Gemüse/-produkten/-säfte gedeckt. Dementsprechend korreliert die Gesamtaufnahme von Flavonoiden statistisch signifikant (p<0,001) mit der Zufuhr von Vitamin C (r=0,59) und Ballaststoffen (r=0,49).Im Vergleich mit anderen Ländern ist die Flavonolzufuhr im betrachteten Kollektiv eher als niedrig einzustufen. Durch die erstellte Datenbank war es erstmals möglich, neben Flavonolwerten auch Zufuhrdaten für weitere Flavonoide zu berechnen. Verglichen mit der täglichen Zufuhrmenge anderer Antioxidantien (z.B. Vitamine C und E) ist die pro Tag aufgenommene Menge an Flavonoiden beachtlich hoch und sollte somit in Untersuchungen zur Bedeutung der Ernährung bei bestimmten Krankheiten berücksichtigt werden.SummaryFlavonoids as naturally occuring compounds of plant derived foodstuff reveal some biological effects (antioxidative, antimutagenic, anticarcinogenic) which makes them interesting substances in the prevention of atherosclerosis and cancer in humans. Data on the flavonoid content of food are not considered in food composition tables, and human intake data are scarce (flavonols) or missing. Consequently, after installing a flavonoid data base by means of literature data, 7-d dietary protocols of 119 adults (63 women and 56 men, age 19–49 years) representing a bavarian subgroup of the German National Food Consumption Survey (NVS) were evaluated.In all subjects, average intake of all flavonoids (calculated as aglycons) amounts to 54,0 mg/d (median) with a great range of variability. The most important flavonoid groups are flavonols (12,0 mg/d), catechins (8,3 mg/d), and flavanons (13,2 mg/d), followed by anthocyanidins (2,7 mg/d), proanthocyanins (3,7 mg/d) and phloretin (dihydrochalcone) (0,7 mg/d). Sex differences did not reach statistical significance. Fruits, fruit products and fruit juices were the most important flavonoid sources. Vegetables and its products provided about half of the flavonol intake. Therefore, statistically significant correlations (p<0.001) exist between total flavonoid intake and the intake of vitamin C (r=0.59) or dietary fiber (r=0.49).Compared to other countries, flavonol intake of the investigated group of persons is rather low. With the built data base it was possible for the first time to calculate the intake of further flavonoids besides flavonols. In comparison to the intake of other antioxidants (e.g. vitamins C and E) the amount of flavonoids in the diet is considerably high and therefore should be regarded in further investigations on the role of diet in certain diseases.Flavonoids as naturally occurring compounds of plant derived foodstuff reveal some biological effects (antioxidative, antimutagenic, anticarcinogenic) which makes them interesting substances in the prevention of atherosclerosis and cancer in humans. Data on the flavonoid content of food are not considered in food composition tables, and human intake data are scarce (flavonols) or missing. Consequently, after installing a flavonoid data base by means of literature data, 7-d dietary protocols of 119 adults (63 women and 56 men, age 19-49 years) representing a bavarian subgroup of the German National Food Consumption Survey (NVS) were evaluated. In all subjects, average intake of all flavonoids (calculated as aglycons) amounts to 54.0 mg/d (median) with a great range of variability. The most important flavonoid groups are flavonols (12.0 mg/d), catechins (8.3 mg/d), and flavanons (13.2 mg/d), followed by anthocyanidins (2.7 mg/d), proanthocyanins (3.7 mg/d) and phloretin (dihydrochalcone) (0.7 mg/d). Sex differences did not reach statistical significance. Fruits, fruit products and fruit juices were the most important flavonoid sources. Vegetables and its products provided about half of the flavonol intake. Therefore, statistically significant correlations (p < 0.001) exist between total flavonoid intake and the intake of vitamin C (r = 0.59) or dietary fiber (r = 0.49). Compared to other countries, flavonol intake of the investigated group of persons is rather low. With the built data base it was possible for the first time to calculate the intake of further flavonoids besides flavonols. In comparison to the intake of other antioxidants (e.g. vitamins C and E) the amount of flavonoids in the diet is considerably high and therefore should be regarded in further investigations on the role of diet in certain diseases.

Origin, metabolism, and adverse health effects of cholesterol oxidation products

Cholesterol oxidation products (COP), also called oxysterols, enter the organism by intake of COP-containing foodstuff or are generated in vivo by enzymatic or non-enzymatic oxidation (peroxidation) of cholesterol. COP are transported in lymph and blood with lipoproteins (mainly fatty acyl monoesters at the 3β-position) or bound to albumin. As being substrates for acyl CoA: cholesterol acyltransferase (ACAT), lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP), COP are esterified and exchanged between lipoproteins and are distributed in the whole organism. Kupffer cells and hepatocytes are the target cells for COP transformation and excretion via bile secretion. Regarding biological activities, COP reveal widespread effects on cholesterol metabolism as well as on structure and function of cellular membranes. Throughout their actions, COP were shown to be cytotoxic but they were also suggested to be regulatory agents. Their detrimental part in atherogenesis seems to be still underestimated, while valid data on the role of COP in carcinogenesis are still missing. Herkunft, Stoffwechsel und gesundheitsschadigende Wirkungen von Cholesterinoxidationsprodukten Cholesterinoxidationsprodukte (COP), auch Oxysterole genannt, gelangen durch den Verzehr von Lebensmitteln, die COP enthalten, in den Organismus oder entstehen bei der korpereigenen enzymatischen und nichtenzymatischen (Peroxidation) Oxidation von Cholesterin. COP werden in der Lymphflussigkeit und im Blut zusammen mit Lipoproteinen (hauptsachlich als Monofettsaureester an der 3β-Position) oder an Albumin gebunden transportiert. Sie sind Substrate fur die Acyl-CoA-Cholesterol-Acyltransferase (ACAT), die Lecithin-Cholesterol-Acyltransferase (LCAT) und das Cholesterolester-Transferprotein (CETP). Somit konnen COP verestert, zwischen Lipoproteinen ausgetauscht und im ganzen Korper verteilt werden. Kupfferzellen und Hepatozyten sind verantwortlich fur die Transformation und Ausscheidung von COP uber die Gallenflussigkeit. COP weisen eine Reihe von Wirkungen auf den Cholesterinstoffwechsel sowie die Struktur und die Funktionen von biologischen Membranen auf. Daraus erklart sich ihre zytotoxische Wirkung. COP konnten jedoch auch regulatorische Funktionen zukommen. Die Bedeutung von COP bei der Entstehung der Arteriosklerose erscheint noch zu wenig beachtet. Dagegen ist ihre Rolle bei der Tumorentwicklung weiterhin unklar.

Association of carotenoids, tocopherols and vitamin C in plasma with allergic rhinitis and allergic sensitisation in adults

OBJECTIVES Antioxidant nutrients like carotenoids, tocopherols and vitamin C have been suggested to protect against allergic rhinitis and allergic sensitisation but scientific evidence is scarce. The aims of the study were to measure the plasma concentration of six carotenoids, alpha- and gamma-tocopherol and vitamin C as biomarkers of the intake, absorption and subsequent metabolism of these nutrients, and to assess their association with allergic rhinitis and sensitisation. METHOD Data from a cross-sectional study on representative dietary and lifestyle habits of the population of Bavaria, Germany, were analysed. The plasma levels of six carotenoids (alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, canthaxanthin and cryptoxanthin) as well as of alpha-tocopherol, gamma-tocopherol and vitamin C were measured in 547 adults aged between 19 and 81 years. Participants with specific serum immunoglobulin E > or =700 U l(-1) were categorised as sensitised. The association of plasma antioxidant levels, allergic rhinitis and allergic sensitisation was assessed by means of unconditional logistic regression models. RESULTS We observed a negative association between plasma total carotenoids and the prevalence of allergic rhinitis, with odds ratio (95% confidence interval) of 1.13 (0.54-2.39) for the second, 0.72 (0.33-1.58) for the third and 0.44 (0.19-1.03) for the fourth quartile of total carotenoids concentration (P for trend=0.0332); results for lycopene failed to reach statistical significance (P=0.0608). Other single carotenoids, tocopherols and vitamin C were unrelated to allergic rhinitis. Allergic sensitisation was negatively associated with plasma gamma-tocopherol, with odds ratio (95% confidence interval) of 0.92 (0.51-1.65) for the second, 1.00 (0.56-1.80) for the third and 0.45 (0.23-0.88) for the fourth quartile of plasma gamma-tocopherol concentration (P for trend=0.0410). No other antioxidant was significantly related to allergic sensitisation. CONCLUSIONS High plasma carotenoid concentrations reflecting a diet high in various fruits and vegetables might have a protective effect on allergic rhinitis in adulthood.

Association of fatty acids in serum phospholipids with hay fever, specific and total immunoglobulin E

The dietary intake of certain fatty acids might contribute to the development of allergic diseases such as hay fever and asthma. We investigated the association between the concentrations of fifteen fatty acids in serum phospholipids, as a marker of dietary intake and metabolism, and hay fever, allergic sensitisation and total IgE in adults. Data from a population-based cross-sectional study on respiratory health, including the measurement of fatty acids in the serum phospholipids of 740 adults between 20 and 64 years of age, were analysed. Positive associations were found between hay fever and arachidonic acid, and allergic sensitisation and oleic acid. No other fatty acids showed any association with hay fever or allergic sensitisation. Elevated levels of total IgE were not related to fatty acids. Concentrations of long-chain n-3 fatty acids, trans fatty acids or saturated fatty acids in serum phospholipids were not associated with allergic diseases in adults in this study. The present result on the association between hay fever and arachidonic acid is consistent with current hypotheses but warrants further research.

Dietary conjugated linoleic acid (CLA) intake assessment and possible biomarkers of CLA intake in young women

OBJECTIVE The habitual intake of the conjugated linoleic acid (CLA) isomer C18:2 c9t11 (rumenic acid, RA) was assessed and compared with plasma biomarkers. DESIGN The newly developed food-frequency questionnaire (FFQ) comprised 46 food items and was validated by means of a 7-day estimated record (7-d ER). Additionally, the dietary intake results of the FFQ, 7-d ER, the last day (1-d ER) and the last two days (2-d ER) before blood sampling of the 7-d ER were compared to the content of C18:2 c9t11 in plasma phospholipids (PL) and triglycerides (TG) as possible biomarkers. SETTING Metabolic unit of a university institute. SUBJECTS Fifty-seven students completed both dietary instruments. From all participants fasting blood samples were taken. RESULTS Mean daily intake of rumenic acid was 246 mg day(-1) and 323 mg day(-1) as measured by the FFQ and the 7-d-ER, respectively. The degree of correspondence between both assessment methods was acceptable; this is indicated by a total kappa value of kappa = 0.31 (P < 0.01) and a Pearson correlation coefficient of r = 0.46 (P < 0.01). Rumenic acid content in plasma triglycerides was twice as high as found in phospholipids. The correlation between the intake results gained with the 7-d ER and the plasma PL contents of C18:2 c9t11 was statistically significant; this was also true for the C18:2 c9tl 1 values in plasma TG compared with the intake results of one or two days before blood sampling. CONCLUSIONS Regarding RA intake, the FFQ data revealed an acceptable degree of correspondence with the 7-d ER data but failed to show significant correlations to the potential biomarkers. However, with respect to the results of the 7-d ER, the RA content in plasma PL and TG are possible biomarkers of short-term and medium-term intake, respectively.