A systematic literature review of the effect of anthocyanins on gut microbiota populations.

BACKGROUND: Evidence has shown that anthocyanins, a subclass of polyphenol, are metabolised in the gut, modulate bacterial species and exert bioactive effects through this interaction. METHODS: A systematic literature review was undertaken to determine the level of current evidence for the association between anthocyanin intake and changes in gut microbiota populations. The studies included were also assessed for the different techniques used in microbiota determination. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, scientific databases, including Scopus, PubMed, ScienceDirect, Web of Science and MEDLINE, were searched up to June 2017. Details on population/sample, study design, intervention/control, dosage and method of microbiota determination were extracted. RESULTS: Six studies (three in vitro, two animal and one human trials) were included in the review, which showed that anthocyanins induced a significant proliferative effect on Bifidobacterium spp., known for their wide use in probiotics and for the treatment of irritable bowel syndrome. There was also an observed inhibition of Clostridium histolyticum, which was shown to be pathogenic in humans. The depth of analysis is an important consideration for the choice of microbiota determination technique with respect to a comprehensive, high-resolution microbiota analysis or analysis of the main microbiota taxa. CONCLUSIONS: Very limited research has been carried out in the area of anthocyanins and gut microbiota; beneficial effects have generally been observed, and further clinical trials in humans are needed to confirm changes to gut microbes in relation to dietary anthocyanin intake and potential health benefits.

Food-based anthocyanin intake and cognitive outcomes in human intervention trials: a systematic review.

BACKGROUND: Preclinical evidence suggests that the anthocyanins, which comprise a subclass of dietary flavonoids providing the purple and red pigmentation in plant-based foods, may have a beneficial impact on cognitive outcomes. METHODS: A systematic review was conducted to identify the published literature on food-based anthocyanin consumption and cognitive outcomes in human intervention trials. The literature search followed PRISMA guidelines and included six databases, as well as additional hand searching. RESULTS: Seven studies were included in this review, comprising acute trials (n = 4) and longer-term (n = 3) interventions that assessed multiple cognitive outcomes in children, adults and older adults with cognitive impairment. Six of seven studies reported improvements in either a single, or multiple, cognitive outcomes, including verbal learning and memory, after anthocyanin-rich food consumption. As a result of methodological limitations and the large clinical and methodological diversity of the studies, the pooling of data for quantitative analysis was not feasible. CONCLUSIONS: The impact of food-based anthocyanin consumption on both acute and long-term cognition appears promising. However, adequately powered studies that include sensitive cognitive tasks are needed to confirm these findings and allow the translation of research into dietary messages.

Optimisation of extraction procedure and development of LC-DAD-MS methodology for anthocyanin analysis in anthocyanin-pigmented corn kernels.

An ultra-high-performance liquid chromatography-diode array detector-mass spectrometry method was developed for characterisation and quantification of anthocyanin components in complex corn-kernel matrices. The anthocyanin profiles and total anthocyanin content (TAC) of mature seeds of five types of anthocyanin-pigmented corn were reported. Internal standard was used to validate the efficiency of extraction and optimise the liquid extraction procedure for anthocyanins. A total of eighteen anthocyanins were identified and quantified. Cyanidin-based glucosides were the major pigments of purple-pericarp sweetcorn (75.5% of TAC) and blue-aleurone maize (91.6%), while pelargonidin-based glucosides composed the main anthocyanins of reddish-purple-pericarp sweetcorn (61.1%) and cherry-aleurone maize (74.6%). Importantly, previous studies reported the presence of acetylated and succinylated anthocyanins in corn kernels; these compounds were found to be artefact pigments, generated during the extraction process. These crucial findings provide the correct anthocyanin profiles of pigmented corns, and emphasise the importance of using acidified solutions for the extraction of corn-based anthocyanins.

Anthocyanin composition and changes during kernel development in purple-pericarp supersweet sweetcorn.

The current study reports the anthocyanin profile of purple 'supersweet' sweetcorn, recently developed from purple Peruvian maize, and the effect of kernel maturity on anthocyanin accumulation. Twenty anthocyanin compounds, consisting of cyanidin-, peonidin-, and pelargonidin-based glucosides, were identified and quantified in purple- and reddish-purple-pericarp sweetcorn accessions. For the first time, four isomers of cyanidin-3-malonylglucoside, four isomers of pelargonidin-3-malonylglucoside and two to three isomers each of cyanidin-3-dimalonylglucoside, peonidin-3-malonylglucoside and pelargonidin-3-dimalonylglucoside, were identified in the new pigmented sweetcorn. While cyanidin-based glucosides predominated in the purple-pericarp accession, pelargonidin-based glucosides predominated in the reddish-purple accession. Total anthocyanin concentration increased significantly (p < 0.05) during the optimum sweetcorn eating period (23 to 28 DAP) and continued to increase as the kernels further matured (>28 DAP). As kernels continued to mature, pigment coverage across the pericarp progressively increased from a small spot at the stigma end of the kernel, to gradually spreading over the entire kernel.

Absorption and excretion of elderberry (Sambucus nigra L.) anthocyanins in healthy humans.

Pharmacokinetic variables of several dietary anthocyanins (potent natural antioxidants) following consumption of elderberry (Sambucus nigra L.) extract were evaluated in urine and plasma of six healthy volunteers. They were given a single oral dose of either 30 ml (278 mg total anthocyanins) or 200 ml (1852 mg total anthocyanins) of a commercially available elderberry extract. Within 7 h, the fraction of orally administered total anthocyanins (calculated as the sum of cyanidin-3-sambubioside and cyanidin-3-glucoside) excreted unchanged was 0.39% and 0.27% following ingestion of 30 and 200 ml, respectively. The elimination half-life of total anthocyanins was slightly lower following the consumption of 278 mg (1.85 h) than that after the consumption of 1852 mg (2.57 h). The renal clearance (median) of total anthocyanins was 196 and 169 ml/min, respectively. The peak and average systemic exposure to the major elderberry anthocyanidin glycosides in plasma as well as their renal excretion exhibited approximate dose-proportional characteristics within the administered range. The low dose-normalized area under the concentration-time curve (AUC) and the fraction of orally administered anthocyanins recovered unchanged in urine indicate a low bioavailability of these compounds.

Anthocyanin-rich plum juice reduces ambulatory blood pressure but not acute cognitive function in younger and older adults: a pilot crossover dose-timing study.

Consumption of anthocyanins from fruit sources may exert protection against hypertension and improve cognition. However, the effect of dose timing in studies is rarely considered. We hypothesized that timed-dose consumption of juice from an anthocyanin-rich Japanese plum variety (Queen Garnet plum, QGP) will have acute and dose-timing effects on cardiovascular responses, cognition, and urinary anthocyanin excretion profiles. Our study objective was to investigate the impact of plum juice on these health parameters. Twelve older (65+ years) and 12 younger (18-45 years) adults participated in an acute crossover study. Participants received, randomly, either 1 × 300 mL or 3 × 100 mL plum juice over 3 hours on 2 different occasions with a 2-week washout period. A battery of cognitive tasks was administered at 0 and 6 hours on each study day. Blood pressure (BP) and urinary anthocyanin/metabolite excretion profiles were measured over 24 hours. Area under the curve for BP was calculated (0-6 hours). A significant reduction in BP and cardiovascular responses was observed in both age groups which was more obvious in the older age group on the single dose for systolic BP, diastolic BP, mean arterial pressure, and heart rate (P values = .035, .028, .017, and .006, respectively). No significant difference was observed between dose-timing regimens for either age group. There was no observed effect on cognition. Native QGP anthocyanins, as well as methylated/glucuronidated metabolites, were detected in urine with no significant differences between age groups or dose timing. High-anthocyanin plum juice significantly reduced BP, but dose timing did not appear to be a significant factor in the potential acute BP-lowering effect of QGP juice.

Urinary pharmacokinetics of cyanidin glycosides in healthy young men following consumption of elderberry juice.

We investigated the urinary pharmacokinetics of monomeric anthocyanins in seven healthy volunteers. The volunteers were administered a single oral dose of 3.57 g total anthocyanins contained in 150 ml of a concentrated elderberry juice under fasting conditions. Within 24 h the urinary excretion of unchanged cyanidin-3,5-diglucoside (cyanidin-3-sambubioside-5-glucoside and cyanidin-3,5-diglucoside were calculated as cyanidin-3,5-diglucoside equivalents), cyanidin-3-glucoside, cyanidin-3-sambubioside and total anthocyanins (i.e., the sum of all quantifiable anthocyanidin glycosides) was 0.16, 0.06, 0.05 and 0.06% of the administered doses, respectively. Maximum excretion rates were determined within 1.0 h after intake. The estimates (arithmetic mean +/- SD) of t1/2 were 1.25 +/- 0.25, 1.53 +/- 0.36, 1.38 +/- 0.20 and 1.35 +/- 0.18 h for cyanidin-3,5-diglucoside, cyanidin-3-glucoside, cyanidin-3-sambubioside and total anthocyanins, respectively. The urinary excretion of intact anthocyanins was fast and the decline of excretion rates appeared to be monophasic, suggesting a one-compartment pharmacokinetic model. The low urinary excretion of dietary anthocyanidin glycosides with values below 1% indicates that a large proportion of these plant pigments consumed are metabolized before entry into the circulation.

Effect of inhaled amiloride on the bronchial response to methacholine and cold air hyperventilation challenges.

Inhaled amiloride has been recently demonstrated to have an effect on the decline of pulmonary function in patients with cystic fibrosis. Other diuretics have been demonstrated to provide protection against bronchoconstriction in asthmatic subjects. We report on the effect of inhaled amiloride on cold air hyperventilation challenge (CAHC) and methacholine challenge in asthmatics. We studied nine subjects with mild-moderate asthma in a double-blind, placebo-controlled, crossover study. Our results showed amiloride did not significantly protect against the bronchoconstriction induced by CAHC. Inhaled amiloride did not affect FEV1 in the hour after inhalation, and there was no significant difference between placebo or amiloride on the dose of methacholine causing a 20 percent fall in FEV1. Inhaled amiloride appears not to have a profile of action as previously seen with inhaled furosemide.

Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats.

In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

Bioactive anthocyanins detected in human urine after ingestion of blackcurrant juice.

Anthocyanins are a group of very efficient bioactive compounds that are widely distributed in plant food. Several fruits (blackcurrant, blackberry, red grape) and some vegetables (eggplant, onion, red radish) are rich sources of these natural pigments. Extracts of some of them are used as food colorants as well as components of pharmaceutical preparations and functional foods. Anthocyanins, through their ability to inhibit radical reactions, are considered to exert several protective effects in the human body. Until now there has been only a small amount of data available on their capability, in intact or metabolized form, to reach the systemic circulation of humans. The present study was designed to determine the potential bioavailability in humans of the most important anthocyanins of blackcurrants: delphinidine-3-glucoside, delphinidine-3-rutinoside, cyanidine-3-glucoside, and cyanidine-3-rutinoside. Urinary samples from 4 healthy volunteers (2 women and 2 men) were collected before (baseline) and over a period of 5 hours with intervals of 30 minutes after the ingestion of 200 mL of blackcurrant juice (containing 153 mg of anthocyanins). Using high-performance liquid chromatography (HPLC), it was possible to quantify the 4 main anthocyanins of blackcurrants, excreted unchanged in the urine (0.020-0.050% of the oral doses). We present data on the bioavailability in humans of blackcurrant anthocyanins, which are dietary antioxidants with possible biological effects.

Bioavailability of anthocyanidin-3-glycosides following consumption of elderberry extract and blackcurrant juice.

Pharmacokinetic parameters and the bioavailability of several dietary anthocyanins following consumption of blackcurrant juice and elderberry extract were compared exploratorily in 6 healthy volunteers. They were given a single oral dose of either 137 ml of blackcurrant juice (144.8 mg total anthocyanins) or 30 ml of elderberry extract (147.3 mg total anthocyanins). Within 7 hours, the urinary excretion of total anthocyanins (i.e. the sum of all assayed anthocyanidin glycosides) was 0.04% and 0.37% of the administered dose following blackcurrant juice and elderberry extract ingestion, respectively. Pharmacokinetic parameters based on non-compartmental methods for plasma and urine concentrations exhibited higher variability in urinary excretion after ingestion of elderberry extract. Anthocyanin absorption was significantly greater following the intake of elderberry extract than after the intake of blackcurrant juice as shown by the 5.3- and 6.2-fold higher estimates of dose-normalized Cmax and AUC(0-tZ) of total anthocyanins, respectively. The geometric means of t(1/2) were not significantly different following elderberry extract (1.74 h) and blackcurrant juice ingestion (1.73 h, p > 0.05). The urinary excretion rate of intact anthocyanins was fast, appeared to be monoexponential for both blackcurrant juice and elderberry extract. However, in order to evaluate the contribution of anthocyanins to the health-protecting effects of blackcurrant juice and elderberry extract it will be necessary to perform further studies on the unchanged glycosides and their in vivo metabolites in human plasma and urine.

Bioavailability of water- and lipid-soluble thiamin compounds in broiler chickens.

The bioavailability of thiamin mononitrate, thiamin chloride-hydrochloride and benfotiamin was compared in broiler chickens. A thiamin-deficient diet was supplemented with either 1.8 and 1.5 mg/kg thiamin equivalent as water-soluble salts, or with 1.5 and 1.2 mg/kg thiamin equivalent as benfotiamin, respectively, and fed to 3 replicate groups/treatment for 21 days. Weight gain, feed consumption and feed conversion rate were not significantly affected by solubility or dietary level of thiamin. Likewise, using biochemical indices of thiamin status (erythrocyte transketolase activation coefficient, and thiamin concentrations in blood and liver), no differences were found between the water-soluble thiamin salts, indicating that they have identical potency. In contrast, biochemical indices of thiamin status showed a significantly higher bioavailability for benfotiamin than for the water-soluble sources.

Anaphylaxis: clinical presentation, immunologic mechanisms, and treatment.

Anaphylaxis is a devastating allergic catastrophe. It is described as a systemic, immediate-type hypersensitivity reaction induced by exposure to a specific antigen and is immunologically based. The clinical manifestations may be mild but are often rapidly progressive, leading to respiratory distress and cardiovascular collapse. In addition to avoiding exposure to the antigen, treatment includes general supportive measures and specific therapeutic modalities. The purpose of this article is to review the current concepts of anaphylaxis and discuss the etiologic agents, immunologic mechanisms, clinical presentation, and treatment of this true allergic emergency.

Binding of polyphenols to plant cell wall analogues - Part 2: Phenolic acids.

Bacterial cellulose and cellulose-pectin composites were used as well-defined model plant cell wall (PCW) systems to study the interaction between phenolic acids (PA) derived from purple carrot juice concentrate (PCJC) and PCW components. Significant PA depletion from solution occurred, with pure cellulose initially (30s-1h) absorbing more than cellulose-pectin composites in the first hour (ca 20% cf 10-15%), but with all composites absorbing similar levels (ca 30%) after several days. Individual PAs bound to different relative extents with caffeic acid>chlorogenic acid>ferulic acid. Extrapolation of data for these model systems to carrot puree suggests that nutritionally-significant amounts of PAs could bind to cell walls, potentially restricting bioavailability in the small intestine and, as a consequence, delivering PAs to the large intestine for fermentation and metabolism by gut bacteria.