Contact UsDietetics today – nutrigenomics tomorrow?
Siân B. Astley Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA Tel. +44 (0)1603 255219, fax. +44 (0)1603 255168, email. sian.astley@bbsrc.ac.uk
 | A patient with a family history of early death from heart attack comes to you to obtain a nutrition and lifestyle advice. As well as collecting family and diet histories, and making physical and blood biochemistry measurements, you also scan their electronic genome card. From this information, you develop a selection of targeted recommendations for diet and exercise, and drug regimens depending on their preferred lifestyle. Is this entertaining fiction or a frightening glance into the future? <concept borrowed from DeBusk et al. April 2005 Journal of the American Dietetic Association 105(4): 589-598> |
Diet and disease
There are three broad factors – all inextricably linked – that affect our risk of developing age- or diet-related diseases: life-stage, lifestyle and our genes. As we get older, our bodies are less effective at avoiding disease. Our immune systems are less able to detect and mount a defence; DNA enabling our cells to replicate becomes more error prone; and proteins are less functionally efficient. The resulting breakdown in cellular structure and function leads to those diseases we associate with old age: cancer, cardiovascular disease (CVD), type II diabetes, cataract and macula degeneration, arthritis etc. Poor diet can accelerate this process whilst 80% of case-controlled studies support the hypothesis that a diet rich in fruits and vegetables can reduce the risk of age-related illness. There are other things we can do to reduce our risk. We can maintain an appropriate weight for our height, moderate our consumption of alcohol, choose whether or not to smoke, and take regular exercise. These factors alone will determine whether the majority of the population are at high or low risk of developing age/ diet-related disease. However, individual genetic differences in response to diet have been evident for years, e.g. cholesterol and saturated fat intake.Some of us have genetic diseases that have no association with diet (e.g. sickle cell disease). Others may create specific dietary needs and the condition may be exacerbated by some foods, but it is not caused by diet per se (e.g. cystic fibrosis, coeliac and food allergy). Some people carry or acquire a high risk of developing diseases (e.g. breast cancer), which may or may not be affected by diet or other lifestyle choices. For the rest of us, diet has a role to play in the maintenance of healthy bodies as well as the development of disease [for a review see Astley & Lindsay (2002) European Research on the Functional Effects of Dietary Antioxidants - EUROFEDA]. Understanding this relationship has proven very difficult and what is obvious is that the benefits of some dietary choices are not the same for everyone.
| Molecular nutrition, nutrigenetic and nutrigenomics In the past, nutrition research has been limited to a few ‘likely’ dietary compounds, a handful of relevant biochemical pathways and latterly a small number of candidate genes (e.g. oncogenes), which might be pertinent to the disease in question. Nutrigenomics is the science examining the response of individuals to food/ food components using post-genomics technologies (‘omics) and it allows a more holistic approach. Its long-term aim is to understand how the whole body responds to real foods, and determine how individuals can benefit their health through dietary choice. The huge advantage in this approach is that the studies can examine people (i.e. populations, sub-populations – based on genes or disease – and individuals), food, life-stage and life-style without preconceived ideas. For example, to understand the role of vitamin E in the prevention of CVD, nutrigenomics enables researchers to examine lipid and lipoprotein genotypes; glucose metabolism (i.e. the insulin-glucagon regulatory mechanism); triglyceride regulation (which retinoids, and therefore some carotenoids, may act on); and fatty acid metabolism simultaneously. |
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The various techniques (i.e. transcriptomics, proteomics and metabolomics) would, however, also reveal genes, proteins and metabolites, which the researcher might not have predicted as relevant. Although much of the research in the scientific literature is still in animal or cell models not free-living humans, consideration of complex interacting biochemical pathways in parallel is a reality.Perhaps more easily understood than nutrigenomics, nutrigenetics examines gene-food compound-disease interaction. One of the best-described examples is the relationship between folate and the gene for MTHFR - 5,10-methylenetetrahydrofolate reductase. There is a variant in the gene for MTHFR that produces a less efficient form of the enzyme. Those with the unstable enzyme and low dietary folate accumulate homocysteine and have less methionine, which increases their risk of vascular disease and premature cognitive decline. Supplemented with folic acid (or increased intake of folate from food sources), these individuals quickly metabolise the excess homocysteine restoring their methionine levels to normal. Currently, we are aware of about 20 genes that that have polymorphisms that appear to confer a significant disadvantage, which may be overcome with dietary modification. There are more but it is these that are being used by companies in the US and elsewhere to sell dietary and lifestyle advice based on gene-testing. In addition to the value of such advice, over and above that which might be offered by a registered dietician with intimate knowledge of family history and diet choice, there are a number of wider issues to consider. In the first place, genotypes that confer a substantial disadvantage are not usually preserved in a population. Although unrelated to diet, those that are have been shown to offer some other benefit. For example, we now know that individuals with a single copy of genes for sickle cell diseases or blood thalassemias have inherent protection from malaria. This disease is endemic in regions where these variants are most commonly found. The fact that the most common polymorphism for the MTHFR gene is present in 15-20% of European population should at least raise the question why it and the other genes have persisted so successfully if they only bestow a disadvantage or if modern eating habits make these individuals vulnerable. Secondly, these 15-20 genes represent 0.1% of human genes. Currently, we neither know how or which of these genes interact with one another nor the consequences of modifying the response of a few on the majority and the effects of that on our immediate or long term health. Thus, whilst increasing your intake of folate may be beneficial in the long term, it may be shown at some point in the future that increased intake has unforeseen risks for some individuals or sub-populations.
Ethical, legal and societal considerations
The societal sensitivities surrounding nutrigenomics are as complex as the technical challenges. Some of the information emerging from nutrigenomics research is difficult to handle. For example, a mutation in the apolipoprotein E protein (e4/ e4), which is found in 1-3% of the UK population, is associated with increased risk of early CVD. Unlike single gene disorders, an individual with this genotype may or may not become ill in the future. He or she is only more likely to experience CVD at an earlier age than someone without this mutation; when and in what form remains uncertain because of the interaction between this gene and others associated with CVD, and lifestyle. Changing the types of dietary fat eaten can reduce this risk but this genotype is also linked with a 60% increased risk of developing Alzheimer’s disease. Currently, there is no means of preventing or curing Alzheimer’s disease, and it is not clear whether modification of the individual’s dietary lipids also reduces their risk of Alzheimer’s disease. Just as with genetic diseases, nutrigenomics must allow choice; the right to opt out of knowing whether you are a carrier of a particular genotype, and the right to full employment and insurance benefits regardless of whether you choose to access that information, and the right to ignore dietary and lifestyle advice. Not that these decisions are not without consequences or penalties but people have the right to make informed choices.The pharmaceutical industry has much to offer nutritional science in trial design, and understanding of risk-benefit. It also has much to teach us about economic access to “treatment” and their right not to be discriminated against. Promotion of healthy patterns of nutrition and lifestyle are paramount and key messages on a healthy diet are well established. We should not risk diluting these messages with premature speculation about what nutrigenomics can achieve or raise unrealistic expectations. Equally, it would be inappropriate to scare people about increased risk of age-related disease unnecessarily. The reality is, however, that poor dietary choice within a sedentary lifestyle is contributing to increased rates of death and disability from age- and diet-related diseases including Type II diabetes. The “one-size-fits-all” strategies in public health have not always been delivered consistently, which may be why they do not appear to be working to change people’s dietary habits, but more importantly consumers want ownership – the feeling that something is tailored to their needs and will over come their problems. Personalising nutrition, underpinned by nutrigenomics, may be more effective in achieving long term change. Although nutrigenomics is not an alternative to public health policy, it does have much to contribute to the discussion.
Conclusions
In the end, humans are complex and so too are their diets; these make nutrition science and the questions it must address fiendishly difficult. Although they still seem impossibly complicated, nutrigenomics and systems biology are the ideal, and perhaps, only tools able to answer the question – what should we be eating?
This article was orginally published in the May issue of Dietetics Today* in conjunction with an event held in London on 23rd May (Introduction to the ‘Dietitians, genetics and genomics: Here and Now). For more information about this event and resources for dieticians please visit The National Genetics Education and Development Centre.
* Dietetics Today is the monthly magazine for members of the British Dietetics Association. It carries news and features about nutrition and dietetics, professional development, book reviews, courses and events, and news about the association, its services, groups and branches, people and campaigns.
For more information please visit Resources for nutrition-related practice.