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Biomedical subjects

M B Katan

Publications and source records attributed to M B Katan.

At least 73 records · Page 4Linked to original sources

Tea flavonols in cardiovascular disease and cancer epidemiology.

Tea is an important dietary source of flavonols in countries such as the Netherlands, the United Kingdom and Japan. Flavonols may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumor development in animal studies. The association between flavonol intake and cancer risk was investigated in three prospective studies (Zutphen Elderly Study in the Netherlands, a Finnish cohort, and the Netherlands Cohort Study). Only one study (Finnish cohort) showed an inverse association with cancer mortality. The intake of flavonols with subsequent cardiovascular disease was studied in six prospective epidemiological studies. In some populations (Seven Countries Study, Zutphen Elderly Study, a Finnish cohort) a clear protective effect was observed. In a large US cohort, a protective effect was only found in a subgroup with previous history of coronary heart disease, whereas in Welsh men, flavonol intake, mainly from tea, was associated with an increased risk of coronary heart disease. These conflicting results may be due to confounding by coronary risk factors associated with tea consumption. The question of whether flavonols protect against cardiovascular disease remains still open; a protective effect of flavonols against cancer is less likely.

Antioxidants↗

The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man.

Flavonoids are antioxidants present in plant foods. They occur mainly as glycosides, i.e. linked with various sugars. It is uncertain to what extent dietary flavonoid glycosides are absorbed from the gut. We investigated how the nature of the sugar group affected absorption of one major flavonoid, quercetin. Quercetin linked with glucose, i.e. quercetin glucoside and quercetin linked with rutinose, i.e. quercetin rutinoside, both occur widely in foods. When we fed these compounds to nine volunteers, the peak concentration of quercetin (Cmax) in plasma was 20 times higher and was reached (Tmax) more than ten times faster after intake of the glucoside (Cmax = 3.5+/-0.6 microM (mean +/- SE); Tmax < 0.5 h) than after the rutinoside (Cmax = 0.18+/-0.04 microM; Tmax = 6.0+/-1.2 h). The bioavailability of the rutinoside was only 20% of that of the glucoside. We suggest that quercetin glucoside is actively absorbed from the small intestine, whereas quercetin rutinoside is absorbed from the colon after deglycosylation. Absorption of other food components might also be enhanced by attachment of a glucose group.

Absorption↗

Health effects and bioavailability of dietary flavonols.

Flavonoids are polyphenolic compounds that are ubiquitously present in foods of plant origin. Flavonoids are categorised into flavonols, flavones, catechins, flavanones, anthocyanidins, and isoflavonoids. They may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumour development in animal studies. It is estimated that the human intake of all flavonoids is a few hundreds of milligram per day. Flavonoids present in foods used to be considered non-absorbable because they are bound to sugars as beta-glycosides. However, we found that human absorption of the quercetin glycosides from onions (52%) is far better than that of the pure aglycone (24%). The sugar moiety is an important determinant of their absorption and bioavailability. Flavonol glycosides might contribute to the antioxidant defences of blood. The average intake of the flavonols quercetin, myricetin and kaempferol and the flavones luteolin and apigenin in the Netherlands was 23 mg/day. The intake of these flavonols and flavones was inversely associated with subsequent coronary heart disease in some but not all prospective epidemiological studies. A protective effect of flavonols on cancer was found in one prospective study; two others showed no association. Thus the epidemiological evidence does not yet allow a decision on the involvement of flavonols in the etiology of either cardiovascular diseases or cancer.

Animals↗

Possible mechanisms underlying the cholesterol-raising effect of the coffee diterpene cafestol.

Cafestol, a coffee diterpene present in unfiltered coffee brews, potently raises serum lipids in humans. The mechanism through which this dietary compound influences liporotein metabolism is largely unknown. Unravelling the mechanism of action might lead to new insights into the regulation of serum cholesterol levels in humans. This review summaries ways in which cafestol may act on serum lipids.

CCAAT-Enhancer-Binding Proteins↗

Cholesterol lowering by diet: what can be achieved?

The cholesterol concentration in the plasma is poorly regulated by the human organism and is therefore easily influenced by lifestyle. Indeed cholesterol levels differ between populations. An important question is how much diet can be held responsible for differences in cholesterol level between e.g. Finland and Japan at the beginning of the Seven Countries Study around 1960. This difference can partly be explained by a difference in saturated fat intake but there was probably an accumulation of both genetic cholesterol elevating factors present in the Finnish society and of cholesterol-lowering factors in the Japanese society. However, controlled trials do show a major effect of diet on cholesterol. With iso-caloric diets low in saturated fat and high in fibre a reduction in total cholesterol of 20-30% can be realized. The reduction can be larger if weight loss also occurs. Further reductions may occur when novel foods are introduced on the market e.g. margarines enriched with plant sterols that give an additional reduction in total cholesterol of about 10%. It can be concluded that diet can reduce total cholesterol levels substantially. The value of novel foods in this context has to be evaluated.

Asian People↗

[Dietary trans-fatty acids: a risk factor for coronary disease].

Unsaturated fatty acids with their double bond in trans configuration raise serum low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels, and lower high-density lipoprotein (HDL) cholesterol in humans when substituted for cis unsaturated fatty acids in the diet. These effects should increase the risk of coronary heart disease, which is confirmed by epidemiological studies. Trans fatty acids are formed from cis unsaturated fatty acids during hydrogenation of vegetable oils in food industries. Until recently, major dietary sources of trans fatty acids in the Netherlands were frying fats, shortenings, and margarines, which in the past contained up to 50% of trans fatty acids. Nowadays, most shortenings and margarines sold in the Netherlands have a low trans fatty acid content due to manufacturing changes in the recent past. However, frying fats used in fast-food outlets still contain over 30% of trans fatty acids. French fries sold in these outlets provide 7-8 g of trans fatty acids per portion. Producers of frying fats for fast-food outlets therefore should also reduce the trans fatty acid content of their products as much as possible.

Cholesterol↗

[Less fat or a different fat?].

Current dietary advice with a view to avoiding cardiovascular pathology is to replace fatty foodstuffs and those rich in saturated fat and cholesterol by food rich in complex carbohydrates. Although substitution of carbohydrates for fat lowers the blood level of low-density lipoprotein (LDL) cholesterol, it also lowers the level of high-density lipoprotein (HDL) cholesterol, thereby adversely influencing the risk profile for cardiovascular disease. Neither does a low fat diet appear to reduce obesity, another risk factor. A modern advice based on published research reads: obese persons should reduce their intake of saturated and trans-fatty acids by lowering the consumption of dairy fat, meat and hardened oils (bakery products and catering products fried in hardened fats), and in addition should consume less products with added sugars and refined starch. Carbohydrates should be provided by fruits, vegetables, leguminous plants and whole-wheat products. Persons of about the ideal weight should replace saturated and trans-fatty acids in their diet by unsaturated plant oils, and products with refined carbohydrates by fruits, vegetables and whole-wheat products.

Cardiovascular Diseases↗

Bioavailability and health effects of dietary flavonols in man.

Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Over 4000 different flavonoids have been described, and they are categorized into flavonols, flavones, catechins, flavanones, anthocyanidins, and isoflavonoids. Flavonoids have a variety of biological effects in numerous mammalian cell systems, as well as in vivo. Recently much attention has been paid to their antioxidant properties and to their inhibitory role in various stages of tumour development in animal studies. Quercetin, the major representative of the flavonol subclass, is a strong antioxidant, and prevents oxidation of low density lipoproteins in vitro. Oxidized low density lipoproteins are atherogenic, and are considered to be a crucial intermediate in the formation of atherosclerotic plaques. This agrees with observations in epidemiological studies that the intake of flavonols and flavones was inversely associated with subsequent coronary heart disease. However, no effects of flavonols on cancer were found in these studies. The extent of absorption of flavonoids is an important unsolved problem in judging their many alleged health effects. Flavonoids present in foods were considered non-absorbable because they are bound to sugars as beta-glycosides. Only free flavonoids without a sugar molecule, the so-called aglycones were thought to be able to pass through the gut wall. Hydrolysis only occurs in the colon by microorganisms, which at the same time degrade flavonoids. We performed a study to quantify absorption of various dietary forms of quercetin. To our surprise, the quercetin glycosides from onions were absorbed far better than the pure aglycone. Subsequent pharmacokinetic studies with dietary quercetin glycosides showed marked differences in absorption rate and bioavailability. Absorbed quercetin was eliminated only slowly from the blood. The metabolism of flavonoids has been studied frequently in various animals, but very few data in humans are available. Two major sites of flavonoid metabolism are the liver and the colonic flora. There is evidence for O-methylation, sulfation and glucuronidation of hydroxyl groups in the liver. Bacterial ring fission of flavonoids occurs in the colon. The subsequent degradation products, phenolic acids, can be absorbed and are found in urine of animals. Quantitative data on metabolism are scarce.

Biological Availability↗

Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin.

An expert workshop reviewed the health effects of n-3 polyunsaturated fatty acids (PUFA), and came to the following conclusions. 1. Consumption of fish may reduce the risk of coronary heart disease (CHD). People at risk for CHD are therefore advised to eat fish once a week. The n-3 PUFA in fish are probably the active agents. People who do not eat fish should consider obtaining 200 mg of very long chain n-3 PUFA daily from other sources. 2. Marine n-3 PUFA somewhat alleviate the symptoms of rheumatoid arthritis. 3. There is incomplete but growing evidence that consumption of the plant n-3 PUFA, alpha-linolenic acid, reduces the risk of CHD. An intake of 2 g/d or 1% of energy of alpha-linolenic acid appears prudent. 4. The ratio of total n-3 over n-6 PUFA (linoleic acid) is not useful for characterising foods or diets because plant and marine n-3 PUFA show different effects, and because a decrease in n-6 PUFA intake does not produce the same effects as an increase in n-3 PUFA intake. Separate recommendations for alpha-linolenic acid, marine n-3 PUFA and linoleic acid are preferred.

Animals↗

Release of peptide YY and inhibition of gastric acid secretion by long-chain and medium-chain triglycerides but not by sucrose polyester in men.

METHODS: In the present study, we have investigated the effects of intraduodenal perfusion of long-chain and medium-chain triglycerides and of sucrose polyester on the release of peptide YY in healthy men. RESULTS: Perfusion of medium-chain triglycerides (180 mmol fatty acids) increased the plasma concentration of peptide YY from 7.9 pmol L(-1) (SEM 0.2, n=8) to 10.7 pmol L(-1) (SEM 0.5, n=8), whereas perfusion of long-chain triglycerides (180 mmol fatty acids) had a significantly greater effect, increasing peptide YY concentration from 8 6 pmol L(-1) (SEM 0.2, n=8) to 18.9 pmol L(-1) (SEM 2.4, n=8, P < 0.008). A smaller quantity of long-chain triglycerides (90 mmol fatty acids) increased plasma concentration of peptide YY from 7.4 pmol L(-1) (SEM 0.4, n=8) to 13.3 pmol L(-1) (SEM 1.5, n=8), whereas sucrose polyester (90 mmol fatty acids) did not change peptide YY concentration. In a previous study, we investigated gastrin-stimulated gastric acid output in response to these treatments. The correlation between increases in peptide YY in response to all treatments and the decrease in acid output was r=0.72 (n=48, P < 0.0001). These results show that both long-chain and medium-chain triglycerides, but not sucrose polyester, stimulate the release of peptide YY. CONCLUSION: We speculate that peptide YY may play an important role in the inhibition of gastrin-stimulated gastric acid secretion by long-chain and medium-chain triglycerides.

Adult↗

Absorption and urinary excretion of the coffee diterpenes cafestol and kahweol in healthy ileostomy volunteers.

OBJECTIVES: To determine the absorption and urinary excretion of the cholesterol-raising coffee diterpenes cafestol and kahweol in humans. SUBJECTS AND DESIGN: Nine healthy ileostomists consumed a dose of one, two or three cups of French-press coffee together with a standardized breakfast on three separate days in random order. Subsequently, ileostomy effluent was collected for 14 h and urine for 24 h. Stability of cafestol and kahweol was also assessed under simulated gastrointestinal tract conditions. MAIN OUTCOME MEASURES: Absorption of diterpenes, stability of diterpenes during incubation with gastrointestinal fluids, and urinary excretion of diterpenes. RESULTS: Corrected mean absorptions expressed as percentages of the amount consumed and the amount entering the duodenum were 67 and 88%, respectively, for cafestol, and 72 and 93%, respectively, for kahweol. We found losses of diterpenes during incubation in vitro with gastric juice (cafestol, 24%; kahweol, 32%), during storage with ileostomy effluent (cafestol, 18%; kahweol, 12%), and during freeze-drying (cafestol, 26%; kahweol, 32%). Mean excretion of glucuronidated plus sulphated conjugates in urine was 1.2% of the ingested amount for cafestol and 0.4% of the ingested amount for kahweol. CONCLUSIONS: About 70% of the ingested cafestol and kahweol is absorbed in ileostomy volunteers. Possibly, undetected metabolites are present in ileostomy effluent, resulting in lower absorption percentages. Only a small part of the diterpenes is excreted as a conjugate of glucuronic acid or sulphate in urine. Therefore, these compounds are extensively metabolized in the human body.

Adult↗

Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study.

Intake of dietary flavonols and flavones was inversely associated with risk for cardiovascular disease in several epidemiologic studies. This may have been due to effects on hemostasis because flavonoids have been reported to inhibit platelet aggregation in vitro. We indeed found that 2500 micromol/L of the flavonol quercetin and the flavone apigenin significantly inhibited collagen- and ADP-induced aggregation in platelet-rich plasma and washed platelets by approximately 80-97%. However, lower concentrations, such as might occur in vivo, had no effect. To test this in vivo we fed 18 healthy volunteers 220 g onions/d providing 114 mg quercetin/d, 5 g dried parsley/d providing 84 mg apigenin/d, or a placebo for 7 d each in a randomized crossover experiment with each treatment period lasting 2 wk. Onion consumption raised mean plasma quercetin concentrations to 1.5 micromol/L; plasma apigenin could not be measured. No significant effects of onions or parsley were found on platelet aggregation, thromboxane B2 production, factor VII, or other hemostatic variables. We conclude that the antiaggregatory effects of flavonoids seen in vitro are due to concentrations that cannot be attained in vivo. Effects of dietary flavonols and flavones on cardiovascular risk are possibly not mediated by hemostatic variables.

Adult↗

Effect of low-fat diets on plasma high-density lipoprotein concentrations.

Low concentrations of HDLs in plasma are a strong predictor of risk for coronary as well as other cardiovascular diseases. There is increasing evidence that this relation is causal and that interventions that change HDL concentrations also change risk. One such intervention is exchanging fat and carbohydrate. In controlled trials, low-fat, high-carbohydrate diets decrease HDL concentrations. The effect is strongest when carbohydrates replace saturated fatty acids, but is also seen when carbohydrates replace mono- and polyunsaturated fatty acids carbohydrates. The effect is seen in both short- and long-term trials and therefore appears to be permanent. This finding is supported by epidemiologic studies in which populations eating low-fat, high-carbohydrate diets were shown to have low HDL concentrations. Weight losses with consumption of low-fat diets could theoretically counter effects on HDL, but in published trials weight losses have been modest and insufficient to offset the decrease in HDL concentrations induced by carbohydrates. Thus, replacement of saturated fat by carbohydrates adversely affects plasma HDL concentrations; replacement of saturated fat by unsaturated fatty acids deserves consideration as an alternative.

Dietary Carbohydrates↗

Linoleic acid intake and cancer risk: a review and meta-analysis.

Replacement of saturated fat by the major dietary polyunsaturated fat linoleic acid reduces blood cholesterol concentrations and the risk of coronary artery disease. However, there is concern that long-term consumption of large amounts of linoleic acid might increase cancer risk. We reviewed the epidemiologic and experimental literature on linoleic acid intake and cancer risk and performed additional meta-analyses of risk estimates from case-control and prospective cohort studies. None of the combined estimates from within-population studies indicated a significantly increased risk of cancer with high compared with low intakes of linoleic acid or polyunsaturated fat. For case-control studies, the combined relative risks were 0.84 (95% CI: 0.71, 1.00) for breast, 0.92 (95% CI: 0.85, 1.08) for colorectal, and 1.27 (95% CI: 0.97, 1.66) for prostate cancer. For prospective cohort studies, combined relative risks were 1.05 (95% CI: 0.83, 1.34) for breast, 0.92 (95% CI: 0.70, 1.22) for colon, and 0.83 (95% CI: 0.56, 1.24) for prostate cancer. Ecologic comparisons of populations showed positive associations between cancer rates and per capita use of animal or saturated fat, but less so with per capita use of vegetable oil or polyunsaturated fat. Controlled studies of coronary artery disease in men did not, except for 1 study, show an increased cancer incidence after consumption of diets with a very high linoleic acid content for several years. Animal experiments indicated that a minimum amount of linoleic acid is required to promote growth of artificially induced tumors in rodents; but above this threshold, linoleic acid did not appear to have a specific tumor-promoting effect. Although current evidence cannot exclude a small increase in risk, it seems unlikely that a high intake of linoleic acid substantially raises the risks of breast, colorectal, or prostate cancer in humans.

Animals↗

Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake.

Flavonols are antioxidants that may reduce the risk of heart disease. Two major flavonols in the diet are quercetin and kaempferol, and their main sources in The Netherlands are tea and onions. We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans could be used as biomarkers of intake. We provided 15 subjects with strong black tea (1600 mL/d) or fried onions (129 g/d) for 3 d each in random order separated by a 4-d washout period. The tea provided 49 mg quercetin and 27 mg kaempferol daily and the onions provided 13 mg quercetin and no kaempferol. Flavonols from both foods were clearly absorbed. However, the excretion of unmodified quercetin was 0.5% of intake after tea and 1.1% after onions. Thus, the absorption of quercetin from tea was half of that from onions. The onion treatment was repeated 7-14 d later to estimate within-subject CVs as a measure of reproducibility when the same treatment is given twice. CVs for quercetin were 30% in plasma and 42% in urine. The magnitude of these variations relative to actual variations of approximately 60% between free-living subjects indicates that concentrations of quercetin in plasma and urine are applicable as biomarkers of its intake. We conclude that flavonols in plasma and urine reflect short-term flavonol intake and that they could be used as biomarkers to distinguish between high and low flavonol consumption in epidemiologic studies.

Adult↗