Bioavailability of phenolic compounds

Karakaya, S., Bioavailability of phenolic compounds. Crit. Revs. Food ScL Nutr., 44,453-464, 2004. 

Weinhrenner, T., Fito, M., Fane-Albaladejo, M. et al. (2004). Bioavailability of phenolic compounds liom oUve oil and oxidative/antioxidant status at postprandial state in healthy humans. Drugs tender Experimental and Clinical Research, 30, 207-212. 

Lafay, S. and Gil-Izquierdo, A. 2008. Bioavailability of phenolic compounds. Phytochemistry Reviews, 7,301-311. 

There is growing evidence from human feeding studies that the absorption and bioavailability and thus bioactivity of phenolic compounds and flavonoids are very much dependent on the nature of their chemical structure. Their chemical classification and dietary occurrence is briefly discussed in the following section. 

Ferulic acid has often been reported as a model compound for the investigation of bioavailability of phenolic acids, as free or esterified forms (Table 2.3), since it is abundantly present in food. Absorption via the gastrointestinal tract has also been found for dimers of ferulic acid, or diferulic acids, released from cereal brans [Andreasen et al., 2001b]. 

Dopamine receptor agonists used in the therapy against Parkinson s disease often possess phenolic or catecholic moieties, which lead to low oral bioavailabilities for these compounds since they undergo considerable metabolic degradation in the liver.161 Because of the low oral bioavailability of hydroxylated compounds, there has been a lot of interest in the development of prodrugs of such compounds, thereby circumventing the metabolic degradation. 

Using microdialysis experiments the relative oral bioavailabilities of the compounds 34, 35, 11, 80, 12, 83 and 9 could be calculated. These data show that a compound with a catechol or a phenol possesses a low relative oral bioavailability (compounds 11, 80, 12 and 9). To circumvent such a low relative oral bioavailability a bioisostere of a phenol could be introduced or a prodrug approach could be applied. Compounds 34 and 35 are examples of a bioisosteric replacements and compound 83 is a prodrug of a catecholic or a phenolic 2-aminotetralin. Both types of compounds show an improved relative oral bioavailability, as compared to the... 

Fruits and vegetables are excellent sources of phenolic compounds, which are widely recognized for their health benefits. Therefore, it is necessary to establish and consolidate phenolic compound databases in these matrices because these compounds are of importance to develop epidemiological studies, and their bioavailability should be deeply understood. 

In that context, the present chapter gives insights into the relevance of phenolic compounds in human nutrition. We will primarily discuss bioavailability and biological properties of isoflavones and lignans in the context of human health and disease, our main focus being the metabolic activities of intestinal bacteria. 

Fig. 78.1 Phenolics in human nutrition A microbiological perspective. Bioavailability of dietary compounds depends on the sum of molecular mechanisms underlying liberation of the compounds from dietary matrices, absorption, distribution into body tissues via blood circulation, metabolism (in the GI tract or target tissues), and elimination from the body. The keypad shows parameters of relevance to phenolic bioavailability. The two enlarged windows illustrate the diversity of both phenolics in food and microbial functions involved in phenolic conversion, with a focus on isoflavones and hgnans. Estimates of blood concentration of daidzein, equol, and enterolignans are...

Tomas-Barberan, F.A., Gil-Izquierdo, A., Moreno, D.A., McClements, D.J., and Decker, E.A. 2009. Bioavailability and metabolism of phenolic compounds and glucosinolates.. In D. J. McClements and E. A. Decker (eds). Designing functional foods measuring and controlling food structure breakdown and nutrient absorption, pp. 194-229. CRC Press Cambridge, UK. 

Absorption - Atier ora administration, ezetimibe is absorbed and extensively conjugated to a pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). After a single 10 mg dose of ezetimibe to fasted adults, mean ezetimibe peak plasma concentrations (Cmax) of 3.4 to 5.5 ng/mL were attained within 4 to 12 hours (Tmax)- The absolute bioavailability of ezetimibe cannot be determined, as the compound is virtually insoluble in aqueous media suitable for injection. Ezetimibe has variable bioavailability the coefficient of variation, based on intersubject variability, was 35% to 60% for area under the curve (AUC) values. 

In search of novel natural antioxidant compounds that might posses a good brain bioavailability, our laboratory has focused attention on the phenolic compound ferulic acid ethyl ester (FAEE) (Fig. 18.1). Ferulic acid is a ubiquitous plant constituent that occurs primarily in seeds and leaves both in its free form and covalently linked to lignin and other biopolymers. Due to its phenolic nucleus and an extended side chain conjugation, it readily forms a resonance stabilized phenoxy radical that accounts for its potent antioxidant potential [Kanski et al., 2002 Kikuzaki et al., 2002], Ferulic acid has been shown to be protective against oxidative stress in vitro it is absorbed and excreted by humans, and may be a promising candidate for therapeutic intervention in AD [Yan et al., 2001]. Although ferulic acid has been demonstrated to be effective in vitro, the low lipophilicity impairs its in vivo efficiency, bioavailability, and stability. 

Another important field of application concerns food and beverages, especially wine, juices, and tea (A2, A11, A17, B4, K12, V7, Yl). The antioxidant components of food include vitamin E (a-tocopherol), vitamin A (retinoids), vitamin C (ascorbic acid), and also fi-carotene (provitamin A), other carotenoids (of which more than 600 compounds have been identified), flavonoids, simple phenols, and glucobrasicins (H3). Unfortunately, the TAC value of a food is not informative on the bioavailability of its antioxidants. It has been estimated that polyphenols are normally present in blood plasma at concentrations of 0.2-2 //M (PI). However, it has been demonstrated that feeding rats a quercetin-augmented diet can increase their plasma levels of quercetin and its metabolites up to 10-100 //M (M27), and transient increases in the concentration of plant-derived phenolic compounds can take place after ingestion of food and beverages, which may affect blood plasma TAC (see later). 

The uptake if iron often requires Fe(II) as the bioavailable form, and uptake from soils containing insoluble Fe(III) is accomplished by phenolic compounds which are exuded by certain plants (Chaney and Bell, 1987). A particular use of staining has been in the study of the sites if iron reduction in plants, using Prussian blue stain (PB) (Ambler et al., 1971 Brown and Ambler, 1974). The method consists of placing the roots in a nutrient solution containing Fe(III) and ferricyanide. Since PB can be produced both from Fe(III) and Fe(CN)64 and from Fe(II) and Fe(CN)63, reduction of either source of iron in the presence of the roots will produce PB at the sites of... 

The impact of plant products on the metabolism of synthetic dmgs results from the inhibition or activation of cytochrome P-450 (CYP) enzymes. Evaluation of the potential activation of CYP by administration of natural plant products or dietary supplements is important for prediction of interactions between their components and dmgs. Therefore, attention is directed to research on the impact of products available on the food market known as natural non-nutritive substances on dmg absorption. Non-nutritive dietary components are mainly secondary plant metabolites, which include, among others, phenolic compounds such as phenolic acids and flavonoids. The health effects of non-nutritive substances are not yet known. So far, there is no answer on the extent to which they are absorbed and metabolized by the body, and there is no information on the permitted daily intake for these compounds. This information is particularly important because certain non-nutritive natural substances are simultaneously considered to be anti-nutritional factors, mainly because they inhibit digestion and reduce the bioavailability of nutrients or dmgs. It is also possible that they form undesirable interactions with dmgs. The positive health effects of non-nutritive natural substances are not only attributed to their antioxidant properties. These substances are involved in various metabolic... 

In conclusion, toxic chlorinated phenol intermediates formed during the chemical, photochemical and/or enzymatic degradation of chlorophenoxyalkanoic compounds would temporarily be detoxified when they are incorporated into the humic acid, since their bioavailability and movement into terrestrial and aquatic ecosystems would be greatly reduced. However, the knowledge of the potential toxicity problems which these bound-residues could give rise to in the environment is still very limited. Xenobiotic chemicals incorporated into humic polymers are not really removed from the ecosystem and they may maintain their identity and toxic properties for unknown time spans, eventually causing time-delayed pollution problems, if and when they will be released from humic substances. 

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