Absorption, distribution, and biliary excretion of cafestol, a potent cholesterol-elevating compound in unfiltered coffees, in mice.

Cafestol is a diterpene present in unfiltered coffees. It is the most potent cholesterol-elevating compound present in the human diet. However, the precise mechanisms underlying this effect are still unclear. In contrast, cafestol is also known as a hepatoprotective compound, which is likely to be related to the induction of glutathione biosynthesis and conjugation. In the present study, we investigated whole-body distribution, biliary excretion, and portal bioavailability of cafestol in mice. First, dissection was used to study distribution. Five hours after an oral dose with (3)H-labeled cafestol, most activity was found in small intestine, liver, and bile. These results were confirmed by quantitative whole-body autoradiography in a time course study, which also showed elimination of all radioactivity within 48 h after administration. Next, radiolabeled cafestol was dosed intravenously to bile duct-cannulated mice. Five hours after the dose 20% of the radioactivity was found in bile. Bile contained several metabolites but no parent compound. After intestinal administration of radioactive cafestol to portal vein-cannulated mice, cafestol was shown to be rapidly absorbed into the portal vein as the parent compound, a glucuronide, and an unidentified metabolite. From the presence of a glucuronide in bile that can be deconjugated by a bacterial enzyme and the prolonged absorption of parent compound from the gastrointestinal tract, we hypothesized that cafestol undergoes enterohepatic cycling. Together with our earlier observation that epoxidation of the furan ring occurs in liver, these findings merit further research on the process of accumulation of this coffee ingredient in liver and intestinal tract.

[Confounding in nutritional epidemiology; is Mendelian randomization the answer?] / Het probleem met de voedingsepidemiologie.

Observational studies have reported many beneficial effects of vitamin and mineral supplements on cardiovascular and other diseases, but randomized controlled trials have failed to confirm these. This could be due to the failure of statistical adjustment to eliminate residual and unmeasured confounding by known risk factors. A Mendelian randomization study now suggests a similar problem for the observed beneficial effects of moderate alcohol intake. When 500,000 Chinese people were ranked by self-reported alcohol intake, stroke risk showed a U-shaped curve, risk being lowest at 1-2 units per day. However, when subjects were ranked by genetically conditioned intake, risk was lowest in abstainers and went up linearly with intake. Mendelian randomization may be more suitable for elucidating the effects of diet on health than conventional epidemiology.

[The role of diet in the development of type 2 diabetes mellitus: calories play the leading role]. / De rol van voeding bij het ontstaan van diabetes mellitus type 2: calorieën in de hoofdrol.

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.

[Elimination of all trans fatty acids]. / Alle transvetzuren de wereld uit.

At the start of the 20th century, the production of trans fatty acids was originally largely driven by the increasing demand for margarine. The two Dutch margarine firms Van den Bergh and Jurgens played an important role in this early development. In the early 1990s it was shown that trans fatty acids increase the risk of heart disease. Unilever, the successor to Van den Bergh and Jurgens, then took the lead in eliminating trans fatty acids from retail foods worldwide. As a result, intake in The Netherlands fell from 15 g per day in 1980 to 3 g per day in 2003. Dairy products and meat are now the major source of trans fatty acids. The effects on health of these ruminant trans fatty acids are unclear. There are three lessons to be learned from the rise and fall of trans fatty acids. First, a history of safe use does not guarantee safety of food components, because routine surveillance will fail to detect adverse effects on common illnesses with long incubation periods. Second, it shows that it is more effective and easier to change the composition of foods than to change consumer behaviour. And third, governments can have a major impact on consumers' health by mandating the use of healthier food ingredients.

[The probiotic yogurt Activia shortens intestinal transit, but has not been shown to promote defecation]. / De probiotische yoghurt Activia: versnelde darmpassage wel aangetoond, maar bevordering van de stoelgang niet.

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.

[Fish fatty acids and cardiovascular diseases--an update]. / Visvetzuren en hart-en vaatziekten--een update.

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.

[Alcohol should not be recommended for the prevention of heart disease]. / Alcohol geen goed middel om een hartinfarct te voorkomen.

Encouraging teetotallers to drink may reduce the risk of heart disease, but it is not likely to improve public health. The reason is that even one drink a day increases the risk of breast cancer, and alcohol causes serious non-fatal diseases that exceed the reduction in heart disease. Other lifestyle and drug interventions are safer and more effective.

[City hall holds the key to weight control]. / De sleutel tot vetzucht ligt op het stadhuis.

Doctors can play a major role in reducing obesity in the community, but that requires an unconventional approach. Treatment of individual patients with diet or drugs is largely ineffective. In contrast, comprehensive community interventions such as one pioneered by EPODE in France have successfully reduced the prevalence of corpulence in children. Such a community approach requires simultaneously engagement by town governments, retailers, associations, restaurants, caterers, media, schools and kindergartens to cooperate in improving diets, reducing caloric intake and increasing activity. Physicians are by far the most highly trusted source of information when it comes to health matters. Therefore, a few words from a doctor at the right time and in the right place, e.g. at a city council meeting, could tip the scales. Individual doctors cannot cure patients' obesity by themselves in their offices, but a few hours per year spent on persuading key stakeholders might help to turn the tide on obesity in the community.

[Fish oil in pregnancy: can it prevent asthma in children?] / Visolie tijdens de zwangerschap.

Taking fish oil supplements in the third trimester of pregnancy was associated with significantly less wheezing or asthma in the child at the age of 3-5 years, according to a randomized clinical trial by Bisgaard et al., NEJM 2017. However, the results of this study should be interpreted with caution. The primary end points were modified at a late stage in the study, and two primary end points, eczema in the first 3 years of life and allergic sensitization at 18 months of age, were demoted to secondary end points, and showed no significant effect of treatment. Furthermore, the age range for the published primary end point, persistent wheeze, differed from that in the protocol. Additional concerns include the emphasis on outcomes by omega-3 fatty acid levels in the blood, a post hoc subgroup analysis not included in the protocol. In our opinion, this study does not justify advising routine fish oil supplements in pregnancy.

Trans monounsaturated fatty acids in nutrition and their impact on serum lipoprotein levels in man.

Trans-C18:1 in the diet originate predominantly from partially hydrogenated oils, with beef, mutton and dairy products being an additional source. These fatty acids are absorbed and incorporated into lipids. Their estimated consumption is about 5-7% of total fatty acids, although reliable data are lacking. In addition, large variations between individuals exist. There is no evidence that trans fatty acids accumulate in human tissues. Elaidic acid and its positional isomers do, however, raise LDL cholesterol and apoprotein B and Lp(a) and probably depress HDL cholesterol and apoprotein A-I, compared with the cis isomer, oleic acid. In view of these adverse effects, patients at high risk for atherosclerosis, in addition to reducing their intake of saturated fatty acids and of cholesterol might also do well to avoid excessive intakes of trans fatty acids. Still, trans fatty acids form only a minor component of the diets of most patients and therefore even marked relative reductions in intake will probably have less of an impact on LDL cholesterol than a sizeable reduction in saturated fatty acids and cholesterol will produce.

[Uncertain effects of folic acid on disorders other than neural-tube defects]. / Onzekere effecten van foliumzuur op andere aandoeningen dan neuraalbuisdefecten.

Periconceptional supplemention with folic acid prevents neural-tube defects in infants. However, contrary to expectations, clinical trials found no beneficial effect of folic acid on the recurrence of cardiovascular disease. Trial evidence on folic acid and cognitive decline or dementia is scarce, though observational studies suggest that high folate intake may prevent these disorders. In contrast, animal studies suggest that high doses of folic acid enhance the growth of existing tumours. However, recent clinical trials failed to show significant effects of folic acid on cancer incidence and mortality. There are also speculations that folic-acid fortification may increase the number of newborns with the thermolabile variant of methylene tetrahydrofolate reductase. There appears to be little evidence that folic-acid supplementation may mask vitamin-B12 deficiency. In view of these controversies, it is unlikely that The Netherlands will mandate folic-acid fortification of staple foods in the near future. Therefore, women who are planning a pregnancy should be urged to take folic-acid supplements.

[Negligible amounts of cholesterol-raising diterpenes in coffee made with coffee pads in comparison with unfiltered coffee]. / Verwaarloosbare hoeveelheden cholesterolverhogende diterpenen in koffie gezet met de koffiepadzetmethode bij vergelijking met ongefilterde kookkoffie.

OBJECTIVE: To determine the amounts of the serum-cholesterol raising diterpenes cafestol and kahweol in coffee made with coffee pads and the Senseo coffee machine as opposed to filtered and unfiltered coffee. DESIGN: Observational. METHOD: In five cities in the Netherlands coffee was purchased in three major supermarkets resulting in a total of 30 samples of coffee pads. The levels of cafestol and kahweol were determined by gas chromatography. As controls, the diterpene levels in filtered and unfiltered coffee were also measured. RESULTS: Coffee prepared using coffee pads contained on average 0.76 mg/l cafestol (95% CI: 0.69-0.82) and 0.85 mg/l kahweol (95% CI: 0.77-0.94). Filtered coffee contained 0.76 mg/l cafestol (95% CI: 0.63-0.88) and 0.81 mg/l kahweol (95% CI: 0.63-0.99). Unfiltered coffee contained 72.5 mg/l cafestol (95% CI: 48.5-96.4) and 71.5 mg/l kahweol (95% CI: 45.0-98.1). CONCLUSION: Coffee prepared using coffee pads and the Senseo coffee machine contained minute levels of diterpenes comparable to those of filtered coffee. Its effect on serum-cholesterol levels is therefore likely to be negligible.

Replacement of dietary saturated fatty acids by trans fatty acids lowers serum HDL cholesterol and impairs endothelial function in healthy men and women.

We tested whether trans fatty acids and saturated fatty acids had different effects on flow-mediated vasodilation (FMD), a risk marker of coronary heart disease (CHD). Consumption of trans fatty acids is related to increased risk of CHD, probably through effects on lipoproteins. Trans fatty acids differ from most saturated fatty acids because they decrease serum high-density lipoprotein (HDL) cholesterol, and this may increase the risk of CHD. We fed 29 volunteers 2 controlled diets in a 2x4-week randomized crossover design. The "Trans-diet" contained 9.2 energy percent of trans fatty acids; these were replaced by saturated fatty acids in the "Sat-diet." Mean serum HDL cholesterol after the Trans-diet was 0.39 mmol/L (14.8 mg/dL), or 21% lower than after the Sat-diet (95% CI 0.28 to 0.50 mmol/L). Serum low density lipoprotein and triglyceride concentrations were stable. FMD+SD was 4.4+/-2.3% after the Trans-diet and 6.2+/-3.0% after the Sat-diet (difference -1.8%, 95% CI -3.2 to -0.4). Replacement of dietary saturated fatty acids by trans fatty acids impaired FMD of the brachial artery, which suggests increased risk of CHD. Further studies are needed to test whether the decrease in serum HDL cholesterol caused the impairment of FMD.

[How much vitamin B6 is toxic?]. / Hoeveel vitamine B6 is toxisch?

Vitamin B6 (pyridoxine) causes neuropathy at intakes of 1000 mg per day or more, which is about 800 times the daily intake from foods. There have also been occasional reports of toxicity at intakes of 100-300 mg per day. The US authorities set the no-observed-adverse-effect-level at 200 mg per day and the safe upper limit at 100 mg per day. A report of neurotoxicity in 2 patients who had taken 24 mg and 40 mg of vitamin B6 per day respectively, may be coincidence rather than a true toxic effect of such relatively low doses. However, physicians need to remain alert to high intakes of vitamin B6 as a cause of unexplained neuropathy.

[Cost of foods fortified with plant sterols refunded by a health insurance company]. / Halvarine met plantensterolen van de verzekering.

The Dutch health insurance company VGZ recently decided to refund part of the cost of using spread, yogurt and milk fortified with plant sterols. Plant sterols lower plasma cholesterol concentrations but they do so less effectively than statins. For health insurance companies wishing to improve the health of their clients, it would be more logical to reimburse costs of folic acid supplements for the prevention of neural tube defects, and vitamin-D-enriched products to prevent fractures in elderly people.

Effect of decaffeinated versus regular coffee on blood pressure. A 12-week, double-blind trial.

The effect of decaffeinated versus regular coffee on blood pressure and heart rate was investigated. In a randomized double-blind, crossover trial, 45 healthy volunteers (23 women and 22 men, 25-45 years old) with a habitual intake of 4-6 cups coffee/day received 5 cups of regular coffee each day for a period of 6 weeks, and 5 cups of decaffeinated coffee for the next 6 weeks or vice versa. The background diet was kept constant. The total amount of caffeine ingested was 40 mg during the decaffeinated coffee period and 445 mg during the regular coffee period. Use of decaffeinated coffee led to a significant but small decrease in systolic (mean +/- SEM, -1.5 +/- 0.4 mm Hg; p = 0.002) and diastolic (-1.0 +/- 0.4 mm Hg; p = 0.017) ambulant blood pressure and to a small increase in ambulant heart rate (+1.3 +/- 0.6 beats/min; p = 0.031). Individual differences in rate of caffeine metabolism did not explain differences in long-term response of blood pressure to caffeine. We conclude that in normotensive adults replacement of regular by decaffeinated coffee leads to a real but small fall in blood pressure. However, it remains to be established whether a mass switch from regular to decaffeinated coffee would significantly reduce the total incidence of hypertension-related disorders.

Boiled coffee and blood pressure. A 14-week controlled trial.

The question of whether long-term elimination of coffee from the diet lowers blood pressure has not been settled. Consumption of Scandinavian-style "boiled coffee" is associated with coronary heart disease. However, little is known about the effect of brewing method on the blood pressure-raising potential of coffee. We have studied the effects on blood pressure and heart rate of total elimination of coffee and tea in comparison with drinking boiled coffee consumed as such, or boiled coffee consumed after filtration through paper filter. Thirty-one women and 33 men first consumed 6 cups/day of boiled and filtered coffee for 17 days. Then they were randomly divided into three groups, which for the next 79 days received either unfiltered boiled coffee (caffeine content 860 mg/l), boiled-and-filtered coffee (887 mg caffeine/l), or no coffee, the latter being replaced by fruit juice and mineral water. Total elimination of coffee did not significantly affect blood pressure or heart rate relative to boiled-and-filtered coffee. In subjects who drank boiled coffee, mean ambulant systolic blood pressure rose significantly relative to those who consumed boiled-and-filtered coffee (mean difference +/- SEM, 3.1 +/- 1.1 mm Hg, p = 0.006). This response showed a tendency to be stronger for women (4.5 +/- 1.8 mm Hg) than for men (1.7 +/- 1.2 mm Hg). We conclude that elimination of filtered coffee has no substantial long-term effect on blood pressure, but consumption of unfiltered boiled coffee may cause a slight but significant rise in systolic blood pressure.

Absorption and disposition kinetics of the dietary antioxidant quercetin in man.

Quercetin is a dietary antioxidant that prevents oxidation of low-density lipoproteins in vitro by scavenging to free oxygen radicals. Its intake was inversely associated with coronary heart mortality in Dutch elderly men. However, data on absorption of quercetin in man are scarce and contradictory. We studied the time course of the plasma quercetin concentration in two subjects after ingestion of fried onions containing quercetin glucosides equivalent to 64 mg of quercetin aglycone. Peak plasma levels of 196 ng/ml were reached after 2.9 h, with a half-life of absorption of 0.87 h. The half-life of the distribution phase was 3.8 h, and of the subsequent elimination phase 16.8 h. After 48 h the plasma concentration was about 10 ng/ml. We conclude that quercetin glucosides from onions are absorbed and are eliminated slowly throughout the day. Thus, the dietary antioxidant quercetin could increase the antioxidant capacity of blood plasma.

Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man.

Quercetin is a strong antioxidant and a major dietary flavonoid. Epidemiological studies suggest that consumption of quercetin protects against cardiovascular disease, but its absorption in man is controversial. We fed nine subjects a single large dose of onions, which contain glucose conjugates of quercetin, apples, which contain both glucose and non-glucose quercetin glycosides, or pure quercetin-3-rutinoside, the major quercetin glycoside in tea. Plasma levels were then measured over 36 h. Bioavailability of quercetin from apples and of pure quercetin rutinoside was both 30% relative to onions. Peak levels were achieved less than 0.7 h after ingestion of onions, 2.5 h after apples and 9 h after the rutinoside. Half-lives of elimination were 28 h for onions and 23 h for apples. We conclude that conjugation with glucose enhances absorption from the small gut. Because of the long half-lives of elimination, repeated consumption of quercetin-containing foods will cause accumulation of quercetin in blood.

High-oil compared with low-fat, high-carbohydrate diets in the prevention of ischemic heart disease.

Reducing the intake of saturated fatty acids reduces the risk of coronary disease. This paper reviews the merits of two types of diets reduced in saturated fat. Low-fat, high-carbohydrate diets lower plasma low-density lipoprotein (LDL) but also lower high-density lipoprotein (HDL) concentrations and raise plasma very-low-density lipoprotein. The predicted net effect on coronary risk is zero. Weight loss with low-fat diets is modest and insufficient to offset the fall in HDL. Evidence for other beneficial effects of low-fat diets in incomplete. In contrast, diets low in saturated fat but high in unsaturated oils improve the ratio of HDL to LDL in plasma and thus reduce the predicted coronary risk. Recommendations to reduce total fat intake are therefore too imprecise; guidelines should aim specifically at saturated and probably also at trans fatty acids, whereas recommendations for restriction of cis-unsaturated fatty acids are not supported by firm scientific evidence.