Spore exines increase vitamin D clinical bioavailability by mucoadhesion and bile triggered release.

Sporopollenin exine capsules (SpECs) are microcapsules derived from the outer shells (exines) of plant spore and pollen grains. This work reports the first clinical study on healthy volunteers to show enhanced bioavailability of vitamin D encapsulated in SpECs from Lycopodium clavatum L. spore grains vs vitamin D alone, and the first evidence (in vitro, ex vivo and in vivo) of mechanisms to account for the enhancement and release of the active in the small intestine. Evidence for mucoadhesion of the SpECs contributing to the mechanism of the enhancement is based on: (i) release profile over time of vitamin D in a double blind cross-over human study showing significant release in the small intestine; (ii) in vivo particle counting data in rat showing preferred retention of SpECs vs synthetic beads; (iii) ex vivo99mTc labelling and counting data using rat small intestine sections showing preferred retention of SpECs vs synthetic beads; (iv) in vitro mucoadhesion data. Triggered release by bile in the small intestine was shown in vitro using solid state NMR and HPLC.

The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47phox expression.

SCOPE: Quercetin is reported to reduce blood pressure in hypertensive but not normotensive humans, but the role of endothelial redox signaling in this phenomenon has not been assessed. This study investigated the effects of physiologically obtainable quercetin concentrations in a human primary cell model of endothelial dysfunction in order to elucidate the mechanism of action of its antihypertensive effects. METHODS AND RESULTS: Angiotensin II (100 nM, 8 h) induced dysfunction, characterized by suppressed nitric oxide availability (85 ± 4% p<0.05) and increased superoxide production (136 ± 5 %, p<0.001). These effects were ablated by an NADPH oxidase inhibitor. Quercetin (3 µM, 8 h) prevented angiotensin II induced changes in nitric oxide and superoxide levels, but no effect upon nitric oxide or superoxide in control cells. The NADPH oxidase subunit p47(phox) was increased at the mRNA and protein levels in angiotensin II-treated cells (130 ± 14% of control, p<0.05), which was ablated by quercetin co-treatment. Protein kinase C activity was increased after angiotensin II treatment (136 ± 51%), however this was unaffected by quercetin co-treatment. CONCLUSION: Physiologically obtainable quercetin concentrations are capable of ameliorating angiotensin II-induced endothelial nitric oxide and superoxide imbalance via protein kinase C-independent restoration of p47(phox) gene and protein expression.

Aspartame sensitivity? A double blind randomised crossover study.

BACKGROUND: Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. METHODS: This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. RESULTS: Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. CONCLUSION: Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans. TRIAL REGISTRATION: ISRCTN Registry ISRCTN39650237.

The Occurrence, Fate and Biological Activities of C-glycosyl Flavonoids in the Human Diet.

The human diet contains a wide variety of plant-derived flavonoids, many of which are glycosylated via an O- or less commonly a C-glycosidic linkage. The distribution, quantity, and biological effects of C-glycosyl flavonoids in the human diet have received little attention in the literature in comparison to their O-linked counterparts, however, despite being present in many common foodstuffs. The structural nature, nomenclature, and distribution of C-glycosyl flavonoids in the human diet are, therefore, reviewed. Forty-three dietary flavonoids are revealed to be C-glycosylated, arising from the dihydrochalcone, flavone, and flavan-3-ol backbones, and distributed among edible fruits, cereals, leaves, and stems. C-linked sugar groups are shown to include arabinose, galactose, glucose, rutinose, and xylose, often being present more than once on a single flavonoid backbone and occasionally in tandem with O-linked glucose or rutinose groups. The pharmacokinetic fate of these compounds is discussed with particular reference to their apparent lack of interaction with hydrolytic mechanisms known to influence the fate of O-glycosylated dietary flavonoids, explaining the unusual but potentially important appearance of intact C-glycosylated flavonoid metabolites in human urine following oral administration. Finally, the potential biological significance of these compounds is reviewed, describing mechanisms of antidiabetic, antiinflammatory, anxiolytic, antispasmodic, and hepatoprotective effects.

Caffeoylquinic acids and flavonoids in the immature inflorescence of globe artichoke, wild cardoon, and cultivated cardoon.

The species Cynara cardunculus is consumed as part of the Mediterranean diet and consists of the globe artichoke [var. scolymus (L.) Fiori], the cultivated cardoon (var. altilis DC.), and the wild cardoon [var. sylvestris (Lamk) Fiori]. The objective of this study was to investigate, in immature inflorescences, the main flavonoids and phenolic acids (caffeoylquinic acids, apigenin, and luteolin derivatives) by HPLC/diode array detection/mass spectrometry. Apigenin derivatives represented the major class in all samples investigated, highest in cardoon forms. Caffeoylquinic acids and luteolin derivatives were observed in var. scolymus only. Data allowed discrimination of globe artichoke from the related species on the basis of the profile of compounds analyzed. Our results suggest the possible use of cultivated and wild cardoon as a source of phenolic acids and flavonoids and indicate that artichoke consumption is an excellent dietary source of apigenin and other flavones.

The C-glycosyl flavonoid, aspalathin, is absorbed, methylated and glucuronidated intact in humans.

Human bioavailability of the flavonoid dihydrochalcones is little understood, and no evidence exists for C-glycosyl flavonoid absorption in humans. The present study uses catechol-O-methyltransferase to generate methylated metabolites of aspalathin (a C-glycosyl dihydrochalcone from rooibos tea). One of the methylated forms, both with and without glucuronidation, was detected using LC-MS/MS in the urine of human subjects (n = 6), demonstrating that deglycosylation is not a prerequisite for C-glycosyl flavonoid absorption. Methylation is catalysed by both intestine and liver cytosolic extracts. The results show that flavonoid C-glycosides are methylated and glucuronidated in vivo in an intact form in humans.