Human intervention trials

More recently, large human intervention trials were undertaken with P-carotene alone, or in combination with non-dietary amounts of vitamin E. These trials were undertaken because of promising animal studies that suggested that these antioxidants could offer chemo-preventive action against oxidative stress. The results, which are summarised in Table 11.1, were disappointing. Although the study population in two of the studies (ATBC and CARET)... 

Table 11.1 Summary of human intervention trials with 3-carotene...

In summary, OATPs appear to play an important role in the influx of a number of drugs into enterocytes and hepatocytes. The inhibition of OATP activity has been demonstrated for orange and GFJ in in vitro experiments. The clinical relevance of this mechanism remains to be investigated in further human intervention trials. 

Pool-Zobel, B.L. et al.. Consumption of vegetables reduces genetic damage in humans first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis, 18, 1847, 1997. 

Following this experimental design, approximately 700 plant materials have been evaluated and this has resulted in over 6,500 bioassay results. A number of active principles have been obtained that are active with the in vitro test systems, and several of the isolates have retained activity by preventing formation of preneoplastic lesions in mammary organ culture. Thus far, three lead compounds have been shown to mediate considerable cancer chemopreventive activity in full-term tumorigenesis models (28,34,45,46) and are being studied in more advanced test systems. We remain hopeful that one or more discoveries resulting from this project will be deemed worthy of human intervention trials. 

Human Intervention Trials In several human intervention trials, significant cancer-preventive effects of supplemental selenium have already been demonstrated, and several other studies are pres-... 

Before considering the bioavailability of phytochemicals in a food matrix and relating these to biological effects in humans, it is important and necessary to understand that phytochemicals are mostly minor plant constituents whose concentration varies considerably according to, for example, seasonal and agronomic factors, the variety, age, and part of the plant examined. Such variability can lead to serious problems of interpretation of results from epidemiologal studies or human intervention trials if the dose of the phytochemical applied is not determined. 

The interactions between dietary polyphenols and the host-gut co-metabonome take place in different metabolic compartments, and take place at different time-scales. Unravelling these interactions in the human super-organisms would require longitudinal sampling in different metabolic compartments (Figure 1). Due to ethical considerations one can mostly only obtain urine, plasma and faeces in human intervention trials. Metabolic profiles from... 

NMR-based metabonomics is able to detect the subtle metabolic effects of dietary interventions of polyphenols in human intervention trials. For this purpose trial design, metabolic profiling and data-analysis need to be well interknitted. 

With respect to GTs, less evidence of their beneficial effects on human subjects has been provided. Despite the fact that tannic acid, PGG, and some plants containing high amounts of GA and GTs have shown several beneficial effects by using in vitro and in vivo models, insights related to human intervention trials are very scarce. 

TABLE 11.1 Obesity-Related Human Intervention Trials of Probiotics, Prebiotics and Synbiotics in Adult Subjects ... 

Verhagen H, de Vries A, Nijhoff WA, et al. Effect of Brussels sprouts on oxidative DNA-damage in man. Cancer Lett. 1997 114 127-130. Hoelzl C, Glatt H, Meinl W, et al. Consumption of Brussels sprouts protects peripheral human Ijnnphocytes against 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) and oxidative DNA-damage results of a controlled human intervention trial. Mol Nutr Food Res. 2008 52 330-341. 

There are large interindividual differences in the ability to metabolize plant phenolics in the gut High-throughput sequencing and metabolite analysis will allow dynamic characterization of the gut microbial ecosystem in human intervention trials... 

In consequence, manufacturers have to collaborate actively with academic researchers in order to provide the scientific evidence to substantiate health claims. This substantiation has to address three main points the characterization of the ingredient, the relevance of the claimed effect, and the establishment of a cause and effect relationship between the ingredient s intake and the claimed effect by efficacy studies on human intervention trials. These trials have to follow strict criteria of quality and design in order to be successful, especially by choosing adequate participants, outcomes, and biomarkers. 

Wang, IS., Luo, H., Wang, P. et al. (2008). Validation of green tea polyphenol biomarkers in a phase II human intervention trial. Food Chemical Toxicology, 46,232-240. 

The number of papers published in the field of nutritional metabo-lomics has increased rapidly over the past few years. While a detailed literature review of all papers is beyond the scope of this chapter, a more focused overview of some of the studies using functional ingredients will be presented. There are a number of studies which have investigated the effects of pol henols on metabolic effects in humans. Grun and colleagues developed a GC-MS metabolomis method to profile phenolic microbial fermentation products (Gmn et al. 2008). They successfully applied this in a cross-over human intervention trial where... 

Evidence from intervention trials is of variable quality and conflicting animal studies have shown positive results but have often used very high does of antioxidants, and the relevance to human health is unclear large human intervention trials completed to date, such as the a-Tocopherol / -Carotene Cancer Prevention Study, Gruppo Italiano per lo Studio Delia Sopravivenza nellTnfarto Miocardico, the Heart Protection Study, the Heart... 

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