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Nutritional genomicshttp://bmj.com/cgi/content/full/324/7351/1438
Clinical reviewScience, medicine, and the future Nutritional genomicsRuan Elliott a Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, b Clinical Research development, TNO BIBRA, Carshalton SM5 4DS Correspondence to: Ruan Elliott ruan.elliott@bbsrc.ac.uk The link between diet and health is well established, but renewed interest in which dietary components are biologically active and how they exert their effects is being fuelled by the development of nutritional genomics. Nutritional genomics is the application of high throughput functional genomic technologies in nutrition research. These technologies can be integrated with databases of genomic sequences1 and inter-individual genetic variability,2 enabling the process of gene expression to be studied for many thousands of different genes in parallel. Such techniques can facilitate the definition of optimal nutrition at the level of populations, particular groups, and individuals. This in turn should promote the development of food derived treatments and funtionally enhanced foods to improve health. This review discusses both the science and its potential.
This article is based on a review of the literature and our combined personal
experience of 19 years working in clinical and molecular nutrition
research. It also draws on consensus views for future challenges and
opportunities reached at a recent EU funded workshop addressing
nutritional genomics, hosted by the Institute of Food
Research.
Evidence that diet is a key environmental factor affecting the incidence of
many chronic diseases is overwhelming. 3
4 The precise extent of this contribution is
difficult to judge, but a reduction of 35% in the age standardised
incidence of cancer in the United States has been proposed to be
achievable via "practicable dietary means."5
Clearly, there is the potential for immense socioeconomic benefit
through successful characterisation and exploitation of health
promoting factors in foods. The spectrum of the population able to
benefit from such research will depend on how the information is used
by scientists, the food industry, and policy makers.
The food we eat contains thousands of biologically active substances, many of
which may have the potential to provide substantial health benefits.
3 6 Indeed, several
food derived compounds The full extent of biologically active components in our diet is unknown, and
our understanding of their mechanisms of action is even more limited.
Much of the available data has been derived from in vitro studies
with purified compounds in forms and concentrations to which the
tissues in our bodies may never be exposed. While this work provides
a starting point, more physiologically relevant model systems
A range of technologies form the practical basis of nutritional genomics (fig 1).8-10 These are still largely untested in nutritional science, but their potential is underlined by their rapid adoption in disciplines such as pharmaceutical, toxicological, and clinical research. As with these disciplines, the main challenges for nutritional genomics lie in the design of meaningful studies for use of these techniques; the design of studies capable of deciphering the complex interactions between individuals' genetic differences, predisposition to disease, and compound-gene interactions; and the integration and interrogation of the vast data sets that such studies will produce.
Inter-individual genetic variation is a critical determinant of differences in nutrient requirements. The commonest type of genetic variability is the single nucleotide polymorphism, a single base substitution within the DNA sequence. These occur roughly once every 1000-2000 nucleotides in the human genome.2 Polymorphism is the "quality of existing in several different forms." It can be the result of genetic predisposition or environmental influence, or a combination of both. In broad terms this is the basis for observed variations in all life forms and individuals. Recent development of extensive genetic polymorphism databases and high throughput genetic screening now make meaningful study of inter-individual variation not only possible but also critical for the future of nutrition and clinical research. Several genetic polymorphisms of importance to nutrition have been identified (see table).11-16 For example, common polymorphisms in genes that control folate metabolism have been linked to conditions such as neural tube defects, Down's syndrome, homocystineamia, and cancer. 11 12 If the mechanisms by which these polymorphisms disturb folate metabolism and alter disease risk can be elucidated, it should be possible to develop dietary or therapeutic strategies for "at risk" individuals to redress the balance. Polymorphisms have also been identified in genes involved in lipid metabolism that are important in determining an individual's plasma low density lipoprotein cholesterol concentration, a marker of cardiovascular disease risk.15
As more such links between polymorphisms and disease conditions are characterised, the scope for targeting dietary information and recommendations to specific subpopulations will increase. However, before committing ourselves to this approach, it is vital that we consider the logistics and costs of routine genetic screening for many genes, the provision of appropriate counselling, and public attitudes and ethical issues associated with such screening in relation to, say, life insurance and family planning. Furthermore, resolving the relative roles of gene-gene and gene-environment
interactions in polygenic diseases (disorders modulated by multiple
genes and polymorphisms within them) is extremely challenging. With
osteoporosis, for example, twin and sibling studies suggest that
genetic factors are the main determinant of bone mineral density and
structure, accounting typically for 50-85% of the phenotypic
variance, with environmental factors contributing the rest.
14 17 However,
although some gene polymorphisms have been linked to variations in
bone mineral density, these associations are still contentious.17
It seems likely that several genetic polymorphisms, each making a
relatively small contribution, interact to comprise the genetic
component associated with osteoporosis. Under such circumstances,
candidate gene studies, which seek to find an association between
specific gene polymorphisms and markers of disease risk, lack power
and may give spurious results. The best strategies for resolving the
genetic and environmental contributors to such polygenic disorders
are still unclear. 14 17
18
Fortified foods and functional foods are intended to supplement human nutritional needs. Certain foods, such as breakfast cereals, are already routinely fortified with vitamins and minerals, and there is an ever increasing range of functionally enhanced foods with alleged health promoting effects. Nutraceuticals (or nutriceuticals) are bioactive natural compounds that have health promoting or disease preventing properties. One example is the antihypertensive effect of dietary peptides derived from milk protein, mediated by angiotensin converting enzyme inhibition.19 Although epidemiological data and preclinical studies are promising, clinical studies of the effect of these milk peptides on human blood pressure have not yet been done.19 It is crucial that prospective clinical trials incorporate nutrigenomic technologies, especially when comparing these nutritionally derived peptides with synthetically produced angiotensin converting enzyme inhibitors, because responses to the latter possibly depend on gene polymorphism.20 People with osteoarthritis might benefit from nutraceuticals such as glucosamine and chondroitin sulphate. A meta-analysis by McAlindon et al and recent findings by Reginster et al suggest that glucosamine sulphate had disease modifying effects and led to symptomatic improvements. 21 22 However, issues of study quality and bias, true efficacy, and toxicity continue to cause uncertainty. 23 24 Further evidence is required from larger high quality clinical trials. Although some clinical trials of nutraceuticals have shown encouraging results, medical and scientific communities remain sceptical, partly because of concerns about quality control and rigour of scientific testing. Putative nutraceutical compounds are found in a variety of products from the food industry, herbal and dietary supplement producers, pharmaceutical companies, and agribusiness companies. Consequently, the potency and the purity of these agents can vary substantially. Thus, although certain food substances might qualify for health claims if they meet the requirements of the UK Food Standards Agency or the US Food and Drug Administration, they are not as strictly regulated as drugs, which gives rise to concern about routine long term use. The European Commission has adopted a proposal, arising from the white paper
on food safety of 14 January 2000, for a directive on food
supplements. This will harmonise the rules for the sale and labelling
of vitamins and minerals as dietary supplements. These measures may
signal a first step to more comprehensive tightening of legislation,
as it is suggested that future amendments could be made to cover
products containing other nutrients or ingredients.
Functional genomics techniques are ideal for elucidating the effects of novel functional foods, dietary supplements, and nutraceuticals on global gene expression and cell function without making assumptions about what to look for in terms of risk. The same approaches are also directly applicable to the assessment of the safety of genetically manipulated foods. For innovative food products with health benefits to be successful, consumer
perception of such products must be positive. Products most likely to
succeed are new foods that look and taste good and provide health
benefits that consumers understand and desire. The only way to ensure
this is to involve consumers in product development. Marketing of new
food products with no clear benefit to consumers or that fail to meet
expectations will be detrimental for nutrition research and the food
industry alike.
The greatest potential for benefit from dietary modification is likely to be in health maintenance, blocking or slowing the early stages of disease development. However, currently available biomarkers measure parameters that represent steps too far along the disease process (such as subclinical nutritional deficiency or early disease symptoms). Nutritional genomics provides the means to develop molecular biomarkers of early, pivotal changes between health maintenance and disease progression. Two distinct approaches have been proposed to exploit this opportunity (fig 2). The first focuses on the disease state and tracks back through the mechanism of development to identify the earliest genes involved. These genes might then be used as targets to identify nutritional agents capable of modulating their expression. The second approach starts with the healthy condition and examines the effects of dietary components on global patterns of gene expression without prejudice or expectation. Specific effects on patterns of gene expression would provide the focus to seek links to disease development processes. These approaches need not be mutually exclusive and may be complementary, potentially meeting at the level of the key early genes.
Such work will be complicated by the fact that the natural components of
foods we already eat can have both beneficial and adverse effects.
These may impinge on quite different health or disease processes and
at overlapping doses. For example, moderate to low intake of alcohol
is associated with a reduced risk of heart disease but an increased
risk of cancer. New approaches for determining maximal benefit and
minimal risk will be required to cope with such effects.
Contributors: This article was conceived, designed, and written by RE and TJO, who are guarantors for it. Professor Sue Southon assisted in its preparation by providing information and editorial advice. The participants of the recent workshop on "nutrigenomics," funded by the European Commission, DG Research, contributed to the underlying concepts through their discussions at the meeting.
Competing interests: None declared.
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ALL INFORMATION, DATA, AND
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Copyright 2012 by Vaccination News, A Non-Profit Corporation. All Rights Reserved. This content may not be copied unless permission in writing from Sandy Gottstein has been obtained. 
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Methods
The impact of
diet...
such
as sulphoraphane, curcumin, lycopene, and tea polyphenols
