Introduction

Inter-individual differences in responses to food intake were already recognised in the early nutritional research, and phenotypes were described. With the progress in genetics, biochemical disorders with high nutritional relevance were linked to specific genetic origins. More recently, gene polymorphisms have been described that have consequences for human nutritional status. For example, carriage of the unusual variant of a relatively common polymorphism (C677T) in the gene that encodes methylenetetrahydrofolate reductase (MTHFR) results in reduced enzyme activity, elevated plasma concentrations of homocysteine and lowered circulating concentrations of folate. Those who are homozygous for the TT version of this polymorphism may have increased risk of neural-tube defects [1] and cardio- and cerebrovascular diseases [2] but, perhaps surprisingly, a lower risk some cancers [3].

However, causes of chronic diseases in general are complex and cannot be linked to a single genetic factor [4]. In nutrigenomics research therefore, the focus is on using radically new approaches to improve understanding of the underlying mechanisms of nutrition-health relationships. Modern nutritional science applies the sciences of genomics, transcriptomics, proteomics and metabolomics to human nutrition. Human studies of various designs involve increasingly more than one study centre (multi-centric) and more than one country. In the context of this kind of research, ethical implications become more complicated. Therefore, bioethics study systematically, pluralistically and in an interdisciplinary fashion and the ethical issues raised by medicine and life sciences as applied to human beings and their relationship with the biosphere. This includes also issues relating to the availability and accessibility of scientific and technological developments and their applications by the public [5].

In general, in connection with modern genetic research, the following ethical issues had been raised [6]:

• Genomic research could potentially lead to stigmatization of individuals or populations and by that to discrimination and promotion of racism
• Loss of access to genetic discoveries for research purposes due to patenting and commercialization
• Reduction of individuals to their DNA sequences, i.e. attribution of societal factors to genetic causes
• Violation of the values, traditions and integrity of populations, families or individuals
• Inadequate engagement of the scientific community with genetic research as well as a higher valuation of genetic research compared to other disciplines

In conducting human studies on nutrition and disease risk that use genetic information, the first of these issues has to be considered. As long as there is no law protecting study participants who give consent to donate biological material for genetic analyses, the problem of potential stigmatization and discrimination by insurers or employers is present [7]. Even with anonymized samples, study results involving genetic information of different ethnic groups could be misused by stigmatizing all group members [8].

Regardless of this more general problem that exists with genetic information, in the context of nutrigenomics research, we identified four relevant issues that need to be addressed:

• genotype information
• bio banks
• exchange of data and samples between researchers
• informed consent

Particularly in the recent past, many important documents and instruments for bioethics have been developed. Of them, the most important for our theme are the

• Helsinki Declaration of the World Medical Association (WMA), last updated 2002 [9]
• Convention on Human Rights and Biomedicine of the Council of Europe [10]
• International Guidelines for Biomedical Research Involving Human Subjects of the Council of International Organizations of Medical Sciences (CIOMS)[11].

These three documents are relevant in the field of bioethics because they document the principles and standards that are internationally adopted. [5]

Beyond these three, another internationally relevant document is the

• Universal Declaration on the Human Genome and Human Rights (1998) [12],

Working groups of the International Bioethics Committee (IBC, see appendix 1), invited by the UNESCO, followed up on the Universal Declaration in further valuable reports and documents:

• Report on Confidentiality and Genetic data (2000) [7],
• Human Genetic Data: Preliminary Study by the IBC on its Collection, Processing, Storage and Use (2002) [13]
• International Declaration on Human Genetic Data (2003) [14].
• Preliminary Draft Declaration on universal Norms on Bioethics (2005) [15]

However, in the day-to-day use of genomics in human-based nutritional genomics research, practical guidelines illustrating how to apply these general rules are missing. Therefore it is not surprising that in 2004 European Nutrigenomics Organization (NuGO) scientists reported during an online inquiry a large heterogeneity of regulations claimed by their Ethics Committees. As stated in the international guidelines and recommendations [11, 16], interaction of national and international legislation will have to be harmonized to a certain extent in order to promote international cooperation.

This first aim of this document is to compile several sources of information on bioethics including relevant international documents and papers and the outcomes of an inquiry of scientists about their experiences with getting approval for nutrigenomics studies. Secondly, this document contains a draft set of guidelines designed specifically for use by those conducting nutrigenomics research with human volunteers or using samples or data from such studies.

These draft guidelines will be presented and discussed during the NuGO Bioethics Workshop in Potsdam on 19 and 20 May 2005 .

The finalized guidelines will be published in an appropriate journal with the authorship of a working group to be defined during the workshop.