Chlorogenic acids are natural polyphenolic compounds that are found in coffee and many fruits and vegetables. Their potential health benefits have led Denis Barron and colleagues at the Nestlé Research Center in Switzerland to synthesise potential human metabolites of these compounds. Here, Dr Barron gives an insight into his work. 

1. Could you explain the significance of your article to the non-specialist? 

Chlorogenic acids are important constituents of coffee beans and of coffee brew. Thus coffee drinkers are regularly exposed to these compounds. Due to the potential health benefits of chlorogenic acids, it is important to understand how these compounds are absorbed and metabolized by the human body. The purpose of our work was to chemically synthesize the potential human metabolites of chlorogenic acids. These standard compounds will be of great help in obtaining future evidence for the presence of chlorogenic acid derivatives in human biological fluids.

2. What has motivated you to conduct this work? 

Our motivation was threefold: 

1) Due to the lack of availability of standards of polyphenol conjugates, most bioavailability studies have been based so far on the enzymatic hydrolysis (sulphatase, b-glucuronidase) of the blood conjugates, followed by an extraction and quantification of the released aglycone. However, in this case, only a partial picture of the metabolite profile of blood is deduced. No information is available on the real conjugated circulating form. 

2) In absence of suitable standard metabolites, the extraction and the quantification of chlorogenic acid metabolites from human blood would be a difficult challenge. Thus these analytical problems must be solved before we move to high cost human clinical studies. Obtaining the standards of chlorogenic acid conjugates is the first unavoidable step of this sequence of events. 

3) The metabolites represent the real forms the tissues or cells will be exposed to. Thus this is more relevant to investigate the biological activity of the metabolites, rather than that of the original forms present in food. Again the poor information on this subject is due to the lack of availability of standard metabolites. In most cases, only organic synthesis would give access to sufficient amounts of compounds for biological studies. 

3. Where do you see this work developing in the future? 

To accurately follow the absorption of beneficial constituents of coffee by humans and also to apply a similar synthetic approach to the preparation of metabolites of related coffee constituents (such as dicaffeoylquinic acids). 

4. Are there any particular challenges facing future research in this area? 

Some dietary polyphenols like chlorogenic acids (coffee), procyanidins (cocoa), or anthocyanins (berries) are polar compounds that are more difficult to extract from biological materials. The sulfate and glucuronic acid conjugates of these compounds are expected to be even more polar. In the absence of proper standards for these conjugates, the optimization of the extraction process and of the chromatographic conditions for these compounds would be extremely difficult. This could explain in part why, so far, no evidence for the presence of such conjugates in blood has been provided.