Altered Transport and Metabolism of Phenolic Compounds in Obesity and Diabetes: Implications for Functional Food Development and Assessment

Abstract

Interest in the application of phenolic compounds from the diet or supplements for the prevention of chronic diseases has grown substantially, but the efficacy of such approaches in humans is largely dependent on the bioavailability and metabolism of these compounds. Although food and dietary factors have been the focus of intense investigation, the impact of disease states such as obesity or diabetes on their absorption, metabolism, and eventual efficacy is important to consider. These factors must be understood in order to develop effective strategies that leverage bioactive phenolic compounds for the prevention of chronic disease. The goal of this review is to discuss the inducible metabolic systems that may be influenced by disease states and how these effects impact the bioavailability and metabolism of dietary phenolic compounds. Because current studies generally report that obesity and/or diabetes alter the absorption and excretion of these compounds, this review includes a description of the absorption, conjugation, and excretion pathways for phenolic compounds and how they are potentially altered in disease states. A possible mechanism that will be discussed related to the modulation of phenolic bioavailability and metabolism may be linked to increased inflammatory status from increased amounts of adipose tissue or elevated plasma glucose concentrations. Although more studies are needed, the translation of benefits derived from dietary phenolic compounds to individuals with obesity or diabetes may require the consideration of dosing strategies or be accompanied by adjunct therapies to improve the bioavailability of these compounds.

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6‐Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals

“…Obesity may impact pharmacokinetics of polyphenols by lowering absorption and metabolism, while increasing excretion . This may, in part, be due to altered polyphenolic transport and metabolism in the liver and colon . Concentrations of parent compounds and their metabolites in adipose tissue of obese rats were reported to be lower than in lean rats .…”

“…In contrast, in this study with mango gallotannins, there were no significant differences between lean and obese individuals at baseline. Previous reports indicate that transporters possibly involved in the absorption of polyphenols, for example, glucose transporters and monocarboxylate transporter 1, are lower in obese individuals which may lead to a lower systemic exposure. The systemic exposure to polyphenol metabolites is also shaped by the activity of hepatic phase II enzymes, including catechol‐ O ‐methyltransferase (COMT) and sulfotransferases (SULT) .…”

“…Systemic exposure to gallotannin metabolites has previously been demonstrated to exert health benefits including lowering blood pressure and cholesterol levels, reducing inflammation, and improving endothelial functions . However, efficacy of polyphenol metabolites in inflammation is thought to be dependent on their bioavailability .…”

Improving natural product research translation: From source to clinical trial

“…The likelihood of translational relevance of a preclinical model to a clinical or other experimental question can be considered in terms of different types of model validity, including face validity (similar phenotype, lower probability of successful translation), construct validity (similar mechanism and phenotype, better probability of successful translation), and clinical validity (demonstrated clinical predictive success) [153][154][155][156] (Table 4). 112,141,157,158 This demonstrates the critical importance in research on humans of considering, assessing, and reporting background diet and history, as well as standard biometric parameters. 82 Many factors that differ between preclinical in vivo models and people may influence the biological effects of a NP.…”

Influence of Diet‐Induced Obesity on the Bioavailability and Metabolism of Raspberry Ketone (4‐(4‐Hydroxyphenyl)‐2‐Butanone) in Mice

“…[ 12,13 ] For example, obese individuals normally show altered gastrointestinal mobility, xenobiotic metabolism, and microbial compositions, which can significantly impact phenolic bioavailability. [ 14,15 ] In view of the effects that RK exerts on white adipose, we hypothesize that RK and its major metabolites will accumulate at higher levels in the white adipose tissue (WAT) of obese than normal‐weight mice. In addition, as the recommended doses for commercial RK dietary supplement are at 400–1400 mg day −1 for adults, which are excessively higher than the dietary doses, [ 16 ] understanding the bioavailability and metabolism of RK will also be instrumental to the regulation and application of RK‐enriched products to avoid adverse side effects.…”