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Latest Paper:
Stella Trompet,
J Wouter Jukema,
Martijn B Katan,
Gerard J Blauw,
Naveed Sattar,
Brendan Buckley,
Muriel Caslake,
Ian Ford,
Jim Shepherd,
Rudi G J Westendorp,
Anton J M de Craen
Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR)= 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = .86, 95% CI: .50, 1.47) or cancer mortality (HR = .70, 95% CI: .30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.
Saskia T J van Cruchten,
Laura H J de Haan,
Patrick P J Mulder,
Cindy Kunne,
Mark V Boekschoten,
Martijn B Katan,
Jac M M J G Aarts,
Renger F Witkamp
Department of Human Nutrition, Wageningen University, 6700 EV, Wageningen, The Netherlands; Top Institute of Food and Nutrition, 6709 PA, Wageningen, The Netherlands.
Cafestol and kahweol are diterpene compounds present in unfiltered coffees. Cafestol is known as the most potent cholesterol-raising agent that may be present in the human diet. Remarkably, the mechanisms behind this effect have only been partly resolved so far. Even less is known about the metabolic fate of cafestol and kahweol. From the structure of cafestol, carrying a furan moiety, we hypothesized that epoxidation may not only be an important biotransformation route but that this also plays a role in its effects found. In bile duct-cannulated mice, dosed with cafestol, we were able to demonstrate the presence of epoxy-glutathione (GSH) conjugates, GSH conjugates and glucuronide conjugates. In addition, it was shown that cafestol was able to induce an electrophile-responsive element (EpRE). Using a murine hepatoma cell line with a luciferase reporter gene under control of an EpRE from the human NQO1 regulatory region, we also found that metabolic activation by CYP450 enzymes is needed for EpRE induction. Furthermore, raising intracellular GSH resulted in a decrease in EpRE-mediated gene induction, whereas lowering intracellular GSH levels increased EpRE-mediated gene induction. In conclusion, evidence suggests that cafestol induces EpRE, apparently via a bioactivation process that possibly involves epoxidation of the furan ring. The epoxides themselves appear subject to conjugation with GSH. The effects on EpRE can also explain the induction of GSH which seems to be involved in the reported beneficial effects of cafestol, for example, when administered with aflatoxin B1 or other toxic or carcinogenic compounds.
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Ingeborg A Brouwer,
Merritt H Raitt,
Carla Dullemeijer,
Dale F Kraemer,
Peter L Zock,
Cynthia Morris,
Martijn B Katan,
William E Connor,
John A Camm,
Evert G Schouten,
John McAnulty
TI Food and Nutrition, Wageningen, The Netherlands.
Aims To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. Methods and results We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR .90; 95% CI .67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline ( .79; .60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = .79). Conclusion These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.
Vrije Universiteit, Instituut voor Gezondheidswetenschappen, De Boelelaan 1085, 1081 HV Amsterdam. katan99@falw.vu.nl
Diets high in saturated fat, trans fat and glycaemic load and low in fibre and polyunsaturated fat are associated with a 25 to 50% increase in the risk of type 2 diabetes. However, obesity increases this risk by 500 to 1000%. Effects ascribed to dietary composition might therefore be due to unmeasured effects of body size. In clinical trials, a weight loss of 3-5 kg plus twice to min of walking per day reduced the incidence of diabetes by 58%. The size of this effect is remarkable. It points to the solution to the diabetes epidemic, which is to reconstruct cities so as to make people eat less and move more. There is an analogy here with the cholera epidemics, which also could be solved only by changing the urban environment.
Vrije Universiteit, Instituut voor Gezondheidswetenschappen, De Boelelaan 1085,1081 HV Amsterdam.
Epidemiologic observational research shows that higher intake of fish fatty acids is associated with a lower risk of fatal heart disease and sudden death, but this effect is not observed with non-fatal heart disease. Currently available trials with clinical endpoints provide no convincing evidence that supplementation with fish oil prevents cardiovascular disease. The theory that fish fatty acids can prevent cardiac arrhythmias is not supported by the trials performed in patients with life-threatening cardiac arrhythmias. For the specific group of patients who have previously experienced a ventricular tachycardia and who have not been prescribed an anti-arrhythmia medication for this, there are indications that the intake of fish oil might even lead to a slightly increased risk ofsevere cardiac arrhythmias. However, other subgroups of patients, such as patients with a recent myocardial infarction may benefit from taking fish oil to prevent cardiac arrhythmias. The advice of the Health Council of the Netherlands to eat fish twice per week, of which fatty fish once per week, or to take 450 mg of the combination eicosapentaenic acid (EPA) and docosahexaenic acid (DHA) per day remains justifiable until the results from current studies become available. However, patients with a ventricular arrhythmia who do not receive specific anti-arrhythmic medication should be careful about taking fish oil capsules.
Top Institute of Food & Nutrition, Wageningen, Netherlands.
BACKGROUND: Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries. Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status. OBJECTIVE: The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherlands, where folic acid fortification is not taking place. DESIGN: Men and women aged 50-75 y were randomly assigned in this 12-wk double-blind, placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily (n = 72) or unfortified bread (n = 70). RESULTS: The consumption of fortified bread increased serum folate concentrations by 45%(mean: 6.3 nmol/L; 95% CI: 4.5, 8.1 nmol/L) and serum vitamin B-12 concentrations by 49%(mean: 102 pmol/L; 95% CI: 82, 122 pmol/L) relative to the placebo group. Fortified bread increased erythrocyte folate concentrations by 22% and holotranscobalamin concentrations by 35%; it decreased homocysteine concentrations by 13% and methylmalonic acid concentrations by 10%. Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations (<133 pmol/L) from 8% at enrollment to % after 12 wk. CONCLUSION: Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people. This trial was registered at clinicaltrials.gov as NCT00353353.
Renate M Winkels,
Ingeborg A Brouwer,
Petra Verhoef,
Floor V A van Oort,
Jane Durga,
Martijn B Katan
Top Institute Food and Nutrition, 6709PA Wageningen, The Netherlands.
The recommended dietary allowance (RDA) differs between men and women for some vitamins, but not for folate. The RDA for folate is derived mainly from metabolic studies in women. We assessed if men differ from women in their response of erythrocyte folate to folic acid supplementation. We used data from 2 randomized placebo-controlled trials with folic acid: a 3-y trial in which subjects ingested 800 mug/d of folic acid (294 men and 112 women) and a 12-wk trial in which 187 men and 129 women ingested , 50, 100, 200, 400, 600, or 800 microg/d of folic acid in a parallel design (n = 38-42 per treatment group). In the 3-y trial, the erythrocyte folate concentration increased 10%(143 nmol/L,[95%CI 46, 241]) less in men than in women. In the 12-wk trial, regression analysis showed that the response of erythrocyte folate upon folic acid intake for men was 47 nmol/L lower than for women (P for beta(gender)= .022); for an intake of 800 microg/d folic acid, this resulted in a 5% lower response in men than in women. Differences in lean body size explained 56% of the difference in response of erythrocyte folate between men and women in the 3-y trial and 70% in the 12-wk trial. Men need more folic acid than women to achieve the same erythrocyte folate concentration, mainly because men have a larger lean body mass. This could be an indication that the RDA for folate should be higher for men than for women, or that the RDA should be expressed per kilogram of lean body mass.
Vrije Universiteit, Instituut Gezondheidswetenschappen, De Boelelaan 1085, 1081 HV Amsterdam. katan99@falw.vu.nl
Activia is a yogurt product containing the probiotic bacterium Bifidobacterium animalis DN-173 010. Five clinical trials have been carried out. Four of these show that dairy products containing this bacterium shorten intestinal transit in volunteers. However, except in a subgroup of 19 out of 267 patients in one study, no significant effect of Activia was reported on the frequency, quantity or consistency of stools. In its marketing in the Netherlands, the company that produces Activia, Danone, claims that Activia promotes defecation. There is insufficient scientific evidence to support this claim.
