Bioavailability of flavonoids and cinnamic acids and their effect on plasma homosysteine in humans

Dietary antioxidants might prevent oxidative damage to tissues and therefore protect against cardiovascular disease and cancer. Dietary phenols are strong antioxidants in vitro but their role in vivo is uncertain. Furthermore, there are only limited data on their bioavailability in humans. The aim of this thesis was to investigate whether bioavailability data on flavonoids and cinnamic acids support the hypothesis that they can affect health in humans . Because the group of phenols in foods is huge, we focussed our research on major phenols in foods; the flavonol quercetin, black tea phenols and chlorogenic acid (5-caffeoylquinic acid). We studied their bioavailability and effect on plasma homocysteine in humans, a potential risk factor for cardiovascular disease.The bioavailability of quercetin and chlorogenic acid depends upon their conjugated moieties. Hollman et al. found that the bioavailability of quercetin-3-rutinoside, a major flavonol in tea, was only 20% of that of quercetin-4'-glucoside. We found that transformation of quercetin-3-rutinoside into quercetin-3-glucoside will improve its bioavailability because the 3-glucoside had the same high bioavailability as the 4'-glucoside. Caffeic acid is a major phenol in coffee, but it is present as a conjugate with quinic acid, called chlorogenic acid. We found that the conjugation of caffeic acid with quinic acid hinders absorption in humans: absorption of chlorogenic acid was only 30% of that of its caffeic acid moiety.Furthermore, we found that chlorogenic acid, black tea solids and quercetin-3-rutinoside are extensively metabolized in the human body, mainly before they reach the circulation. Their metabolites have no, or less, antioxidant activity in vitro than their parent phenols. Therefore the role of dietary phenols as antioxidants in vivo might be less important than suggested by their in vitro antioxidant activity.Coffee consumption increases plasma homocysteine, a potential risk factor for cardiovascular disease. Chlorogenic acid from coffee is partly responsible for the homocysteine-raising effect of coffee, because we found that it increased plasma homocysteine. Black tea solids also raised plasma homocysteine, whereas quercetin-3-rutinoside did not. Furthermore, we found that glycination of metabolites of phenols in the body is not involved in the homocysteine-raising effect of phenols.In conclusion, chlorogenic acid, tea phenols and quercetin are available in the human body, but their effects on health are uncertain. Further research on bioavailability and health effects of dietary phenols is needed.</p

Effects of Betaine Intake on Plasma Homocysteine Concentrations and Consequences for Health

High plasma concentrations of homocysteine may increase risk of cardiovascular disease. Folic acid lowers plasma homocysteine by 25% maximally, because 5-methyltetrahydrofolate is a methyl donor in the remethylation of homocysteine to methionine. Betaine (trimethylglycine) is also a methyl donor in homocysteine remethylation, but effects on homocysteine have been less thoroughly investigated. Betaine in high doses (6 g/d and higher) is used as homocysteine-lowering therapy for people with hyperhomocysteinemia due to inborn errors in the homocysteine metabolism. Betaine intake from foods is estimated at 0.5-2 g/d. Betaine can also be synthesized endogenously from its precursor choline. Studies in healthy volunteers with plasma homocysteine concentrations in the normal range show that betaine supplementation lowers plasma fasting homocysteine dose-dependently to up to 20% for a dose of 6 g/d of betaine. Moreover, betaine acutely reduces the increase in homocysteine after methionine loading by up to 50%, whereas folic acid has no effect. Betaine doses in the range of dietary intake also lower homocysteine. This implies that betaine can be an important food component that attenuates homocysteine rises after meals. If homocysteine plays a causal role in the development of cardiovascular disease, a diet rich in betaine or choline might benefit cardiovascular health through its homocysteine-lowering effects. However betaine and choline may adversely affect serum lipid concentrations, which can of course increase risk of cardiovascular disease. However, whether the potential beneficial health effects of betaine and choline outweigh the possible adverse effects on serum lipids is as yet unclea

Chlorogenic acid and caffeic acid are absorbed in humans

Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileostomy subjects. In such subjects, degradation by the colonic microflora is minimal and absorption can be calculated as the amount ingested minus the amount excreted in ileostomy effluent. The ileostomy subjects ingested 2.8 mmol chlorogenic acid and 2.8 mmol caffeic acid on separate days in random order and subsequently collected ileostomy fluid and urine for 24 h. Absorption of chlorogenic acid was 33 ± 17ømean ± SD) and of caffeic acid 95 ± 4ÐTraces of the ingested chlorogenic acid and 11␘f the ingested caffeic acid were excreted in urine. Thus, one third of chlorogenic acid and almost all of the caffeic acid were absorbed in the small intestine of humans. This implies that part of chlorogenic acid from foods will enter into the blood circulation, but most will reach the colon

Is the intake of sugar-containing beverages during adolescence related to adult weight status?

Objective To investigate the relationship between the intake of sugar-containing beverages (SCB) at the age of 13 years and adult weight status 24-30 years later. Design A longitudinal study with 30 years of follow-up from adolescence (age 13 years in 1976) to adulthood (up to 2000 and 2006). Dietary intake was assessed through cross-check dietary history face-to-face interviews by a dietitian. Beverages were divided into two categories: (i) total SCB and (ii) SCB excluding 100% fruit juices. Percentage of total fat (%total fat) and percentage of trunk fat (%trunk fat) were obtained through dual-energy X-ray absorptiometry measurements; body weight and height were measured by trained staff. Setting Amsterdam Growth and Health Longitudinal Study, the Netherlands. Subjects One hundred and fourteen males and 124 females. Results In males, but not in females, each additional daily serving of SCB excluding 100% fruit juices at 13 years was associated with 1·14 % higher %total fat (95 % CI 0·04, 2·23 %; P = 0·04) and 1·62 % higher %trunk fat (95 % CI 0·14, 3·10 %; P = 0·03) in adulthood after correction for confounders. No statistically significant relationship was found between the intake of SCB excluding 100% fruit juices at the age of 13 and BMI in both sexes. In addition, no statistically significant relationships were found between the intake of total SCB and all measures of adult weight status in both sexes. Conclusions Intake of SCB excluding 100% fruit juices at the age of 13 years was positively associated with adult %total fat and %trunk fat in males, but not in females. © 2011 The Authors

Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men

Background: A high homocysteine concentration is a potential risk factor for cardiovascular disease that can be reduced through betaine supplementation. Choline is the precursor for betaine, but the effects of choline supplementation on plasma total homocysteine (tHcy) concentrations in healthy humans are unknown. Objective: The objective was to investigate whether supplementation with phosphatidylcholine, the form in which choline occurs in foods, reduces fasting and postmethionine-loading concentrations of plasma tHcy in healthy men with mildly elevated plasma tHcy concentrations. Design: In a crossover study, 26 men ingested 2.6 g choline/d (as phosphatidylcholine) or a placebo oil mixture for 2 wk in random order. Fatty acid composition and fat content were similar for both treatments. A methionine-loading test was performed on the first and last days of each supplementation period. Results: Phosphatidylcholine supplementation for 2 wk decreased mean fasting plasma tHcy by 18% (¿3.0 µmol/L; 95% CI: ¿3.9, ¿2.1 µmol/L). On the first day of supplementation, a single dose of phosphatidylcholine containing 1.5 g choline reduced the postmethionine-loading increase in tHcy by 15% (¿4.8 µmol/L; 95% CI: ¿6.8, ¿2.8 µmol/L). Phosphatidylcholine supplementation for 2 wk reduced the postmethionine-loading increase in tHcy by 29% (¿9.2 µmol/L; 95% CI: ¿11.3, ¿7.2 µmol/L). All changes were relative to placebo. Conclusions: A high daily dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as postmethionine-loading plasma tHcy concentrations in healthy men with mildly elevated tHcy concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in human

Consumption of high doses of chlorogenic acid, present in coffee, or black tea increases plasma total homocysteine concentrations in humans

In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. OBJECTIVE: We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples. DESIGN: In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order. RESULTS: Total homocysteine in plasma collected 4-5 h after supplement intake was 12ø1.2 micromol/L; 95␌I: 0.6, 1.7) higher after chlorogenic acid and 11ø1.1 micromol/L; 95␌I: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4ø0.4 micromol/L; 95␌I: 0.0, 0.8) higher after chlorogenic acid and 5ø0.5 micromol/L; 95␌I: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations. CONCLUSIONS: Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established

Effect of sugar-sweetened beverages on body weight in children: design and baseline characteristics of the Double-blind, Randomized INtervention study in Kids.

Background: Intake of sugar-sweetened beverages is associated with overweight in observational studies. A possible explanation is that liquid sugars do not satiate and that their intake is not compensated by reduced caloric intake from other foods. However, evidence from intervention studies for this hypothesis is inconclusive because previous studies were not blinded. Hence results may have been influenced by expectations and behavioral cues rather than by physiological mechanisms. Methods: We designed the Double-blind, Randomized INtervention study in Kids (DRINK) to examine the effect on body weight of covertly replacing sugar-sweetened by sugar-free beverages. Children were only eligible if they habitually drank sugar-sweetened beverages. We recruited 642 healthy children (mean age 8.2, range 4.8-11.9). We designed, tested and produced custom-made beverages containing 10% sugar and sugar-free beverages with the same sweet taste and look. Children receive one 250. mL can of study beverage daily for 18. months. We perform body measurements at 0, 6, 12 and 18. months. The primary outcome is the z-score of BMI for age. The maximum predicted difference in this score between groups is 0.72, which corresponds with a difference in body weight of 2.3. kg. Discussion: The double-blind design eliminates behavioral factors that affect body weight. If children gain less body fat when drinking sugar-free than when drinking sugar-sweetened beverages that would show that liquid sugar indeed bypasses biological satiation mechanisms. It would also suggest that a reduction in liquid sugars could decrease body fat more effectively than reduction of other calorie sources. © 2011 Elsevier Inc