Absorption of dimethoxycinnamic acid derivatives in vitro and pharmacokinetic profile in human plasma following coffee consumption

Scope: This study reports the 24 h human plasma pharmacokinetics of 3,4-dimethoxycinnamic acid (dimethoxycinnamic acid) after consumption of coffee, and the membrane transport characteristics of certain dimethoxycinnamic acid derivatives, as present in coffee. Methods and results: Eight healthy human volunteers consumed a low-polyphenol diet for 24 h before drinking 400 mL of commercially available coffee. Plasma samples were collected over 24 h and analyzed by HPLC-MS 2. Investigation of the mechanism of absorption and metabolism was performed using an intestinal Caco-2 cell model. For the first time, we show that dimethoxycinnamic acid appears in plasma as the free aglycone. The time to reach the C max value of approximately 0.5 μM was rapid, T max = 30 min, and showed an additional peak at 2-4 h for several subjects. In contrast, smaller amounts of dimethoxy-dihydrocinnamic acid (C max ∼ 0.1 μM) peaked between 8 and 12 h after coffee intake. In the cell model, dimethoxycinnamic acid was preferentially transported in the free form by passive diffusion, and a small amount of dimethoxycinnamoylquinic acid hydrolysis was observed. Conclusion: These findings show that dimethoxycinnamic acid, previously identified in plasma after coffee consumption, was rapidly absorbed in the free form most likely by passive diffusion in the upper gastrointestinal tract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Peer Reviewe

Circulating Structurally Related (-)-Epicatechin Metabolite Species and Levels after Sustained Intake of a Cocoa Powder High in Polyphenols Are Comparable to Those Achieved after a Single Dose

Background: While the bioavailability of cocoa polyphenols, particularly of the monomer (-)-epicatechin, has been investigated after a single-dose intake, the effect of sustained cocoa consumption on the metabolic profile of the structurally related (-)-epicatechin metabolites (SREMs) has not been investigated. Methods: A randomized, controlled crossover clinical trial in healthy young adults (18–40 year) was conducted to evaluate SREMs after consumption of a single-dose and after daily consumption of 1.3 g of polyphenol-rich cocoa powder for 28 days. The circulating SREMs were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results: Twenty subjects (eleven males and nine females) were enrolled. The SREMs concentrations increased to 1741 ± 337 nM after a single-dose and to 1445 ± 270 nM after sustained supplementation. Sulfate conjugates showed higher levels in females (p < 0.05). The epicatechin-3′-glucuronide (E3′G) and epicatechin-3′-sulfate (E3′S) were the most abundant metabolites in all subjects. A high intra-individual correlation (r = 0.72, p < 0.001) between SREMs concentrations after single-dose and sustained supplementation was observed. The antioxidant capacity of plasma did not change in response to the intervention and was not correlated with any of the SREMs. Conclusion: The individual SREMs profile and concentrations after a 28-day supplementation are comparable to those after a single dose

Concentrations of Carotenoids and Tocopherols in Breast Milk from Urban Chinese Mothers and Their Associations with Maternal Characteristics: A Cross-Sectional Study

Milk composition remains the best estimate of infant requirements. The aims of this study were to quantify carotenoids and tocopherols in human milk from healthy Chinese mothers, and to explore their associations with lactation stage, region, socio-economic and obstetric characteristics, and dietary intake. Human milk was obtained from 509 healthy mothers, and concentrations of carotenoids and tocopherols were analyzed by Ultra High Performance Liquid Chromatography. The mothers’ socio-economic and obstetric characteristics and dietary intake through a single 24-h dietary recall were evaluated. The median concentrations (μg/100 mL) of each component of 0–4 days, 5–11 days, 12–30 days, 31–60 days, 61–120 days, and 121–240 days postpartum were respectively as follows: β-carotene 8.0, 2.8, 2.1, 1.7, 1.9, 1.8; β-cryptoxanthin 6.2, 3.4, 2.4, 1.7, 1.8, 2.1; lutein 5.7, 7.0, 2.2, 2.9, 2.8, 3.7; lycopene 6.3, 2.5, 1.8, 1.4, 1.4, 1.5; zeaxanthin 1.0, 1.4, 0.8, 0.8, 1.0, 1.1; α-tocopherol 645, 382, 239, 206, 212, 211; γ-tocopherol 68, 63, 70, 73, 68, 88. The levels of those components varied significantly among different lactation stages and presented regional differences. Associations of carotenoid contents with maternal education, delivery mode, and present body mass index were found in multivariate analyses. These results suggested that lactation stage, region, and socio-economic and obstetric factors were associated with human milk concentrations of carotenoids and tocopherols in healthy Chinese mothers

Regional, socioeconomic, and dietary factors influencing B-vitamins in human milk of urban Chinese lactating women at different lactation stages

BACKGROUND: Adequate B-vitamins concentrations in human milk are considered to be a prerequisite for healthy development of infants in early life. This study aims to determine the concentrations of B-vitamins in human milk from Chinese women and the relationships between their concentrations and different geographical origin, lactation stages, socioeconomic characteristics, and dietary intake. METHODS: Human milk was obtained from 443 healthy lactating women from Beijing (n = 150), Suzhou (n = 146), and Guangzhou (n = 147) cities. Thiamine, riboflavin, vitamin B3 (nicotinamide and nicotinic acid), and vitamin B6 (pyridoxal, pyridoxine, and pyridoxamine) in human milk were analyzed by high performance liquid chromatography-tandem mass spectrometry. Pantothenic acid, biotin, and folates in human milk were analyzed by microbiological assay. The information from one 24-h dietary recall and socioeconomic characteristics were collected by interview and structured questionnaire, respectively. RESULTS: B-vitamins concentrations in human milk varied greatly among individuals. The median concentrations of B-vitamins of postpartum 5–11 d, 12–30 d, 31–60 d, 61–120 d, and 121–240 d were respectively as follows: thiamine 3.13, 5.07, 4.28, 5.65, 6.28 (μg/100 g); riboflavin 20.8, 20.2, 11.9, 13.6, 15.6 (μg/100 g); vitamin B3 194.0, 300.0, 261.0, 212.5, 218.0 (μg/100 g); pantothenic acid 236.5, 291.0, 254.0, 179.0, 189.0 (μg/100 g); vitamin B6 6.34, 7.58, 8.60, 9.34, 10.20 (μg/100 g); biotin 0.462, 0.834, 0.606, 0.523, 0.464 (μg/100 g); folates 0.730, 2.390, 2.440, 2.420, 2.330 (μg/100 g). The levels of B-vitamins presented regional differences and varied significantly among different lactation stages. The inversely associations of thiamine, vitamin B6, and folates with maternal BMI were found in multivariate analyses (p < 0.05), as well as higher pantothenic acid, folates, and biotin concentrations in lactating women with supplement intake when compared with those without (p < 0.05). Riboflavin concentrations associated with regular exercise was found in multivariate analyses (p < 0.05). CONCLUSIONS: The present study indicated regional and socioeconomic factors, lactation stage, and supplement intake may influence B-vitamins concentrations of human milk in healthy Chinese mothers. Further studies on accurate and complete analysis of all vitamin forms are crucial for giving a more comprehensive understanding of vitamin status in human milk. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01971671. Registered 13 October 2013

Double-balloon jejunal perfusion to compare absorption of vitamin E and vitamin E acetate in healthy volunteers under maldigestion conditions

BACKGROUND/OBJECTIVES: The vitamin E derivative, alpha-tocopheryl acetate, is often included in formulations used in enteral nutrition. In this respect, we compared alpha-tocopherol and alpha-tocopheryl acetate absorption under 'maldigestion' conditions, such as occurring during enteral tube feeding, using differentially labeled RRR-[5,7-methyl-(21-16)]-alpha-tocopherol and RRR-[5-methyl-H-2(3)]-alpha-tocopheryl acetate allowing direct comparison between free and esterified forms. SUBJECTS/METHODS: The two derivatives were given together in a single dose to six volunteers directly into the jejunum using a double-balloon perfusion system. Perfusion lasted for 1 h, and the collected blood and effluent samples were analyzed by liquid chromatography-mass spectrometry. RESULTS: In the isolated 20-cm length of exposed jejunum, on average similar to 6% of the two vitamin E forms were absorbed >1 h based on subtraction of effluent from influent. There was substantial difference in the absolute absorbed quantity between individuals, but no significant differences were observed in the absorption between the two labeled forms as assessed in the plasma. H-2(3)-alpha-tocopherol was not present in the influent, but appeared in the effluent, indicating that the acetylated form of vitamin E is cleaved by brush border enzymes in the small intestine. CONCLUSIONS: This study shows that even in the absence of digestive enzymes and bile salts, the appropriately solubilized acetylated form of alpha-tocopherol exhibits the same bioavailability as free alpha-tocopherol. This suggests that both forms can be absorbed equally under maldigestion conditions such as present clinically during enteral tube feeding. European Journal of Clinical Nutrition (2013) 67, 202-206; doi:10.1038/ejcn.2012.183; published online 5 December 201