The DNA Diet
By Parslow, Virginia
The development of personalised diets tailored to our genes will help us to both maintain health and relieve disease. Current dietary guidelines provide a “one-size fits all” approach that ignores the genetic differences between individuals. However, studies of the interaction of genes and diet are now coming of age as a result of the sequencing of the human, mouse and rat genomes, improved understanding of the mechanisms that underlie chronic inflammation, and new understandings of the ways in which macronutrients and micronutrients interact with our genetic make-up.
Macronutrients and micronutrients influence the metabolic programming of cells and help control homeostasis. But equally important is how any one person’s body will use and respond to nutrients, which is driven at least in part by their genetic make- up.
Prof Bruce Ames of the University of California, Berkeley, says that micronutrient deficiencies are widespread and may be a major preventable cause of the diseases of ageing. Ames” theory states diat the degenerative diseases that accompany ageing, such as immune dysfunction, cancer, cognitive decline and stroke, might be delayed by the inexpensive intervention of micronutrient supplementation. About 40 micronutrients are needed for metabolism, including minerals, vitamins, amino acids and fatty acids.
Micronutrient deficiency is widespread in both affluent and poor societies. Concern over this fact is low because the effects of such deficiency are not immediate. Rather, our long-term health is compromised by DNA damage (future cancer), adaptive immune dysfunction (future severe infection) and mitochondria! decay (future cognitive dysfunction and accelerated ageing).
There is plenty of evidence to support Ames” theory. For example, vitamin B12 and folate both reduce the number of chromosome breaks in an organism, hence reducing the level of DNA damage.
Most importantly, Ames argues that an individual’s genetic make- up must be known to ensure that no harm is caused by micronutrient supplementation. He suggests that biomarkers are needed for the community so that they can manage themselves to a reasonable extent.
Along related lines, Dr Michael Fenech of CSIRO Human Nutrition is researching dietary prevention of DNA damage and its dependence on genotype. His group’s studies have identified nine key micronutrient deficiencies that are associated with DNA damage in lymphocytes. These nutrients are folate, vitamin B12, nicotinic acid, calcium, vitamin E, retinol, riboflavin, pantothenic acid and biotin.
The results of Fenech’s studies show that DNA damage can be reduced by supplementation with the appropriate micronutrients. These observations have led to the concept of a genome health clinic named Reach 100, which is aimed at diagnosing and nutritionally preventing DNA damage on an individual basis. Fenech and CSIRO will provide Reach 100 with a simple diagnostic blood test that will measure DNA damage. They will also generate knowledge relating to the nutritional, lifestyle and environmental factors that affect DNA damage. In turn, the results from Reach 100 testing will contribute to CSIROs databases on DNA damage in the Australian population and the factors that affect DNA damage.
Fenech says that a recent report detailing adverse effects of supplementation involved extremely high doses of supplements. His own preference is to take supplements once or twice a week so that the body doesn’t “get used to them”, and therefore makes better use of them.
Fenech insists that with diseases such as phenylketonuria, in which protein accumulation causes mental retardation and seizures, neither the genetic risk factor nor the environmental exposure that triggers the disease have any effect by themselves – both need to be present and interacting to cause the disease.
OXIDATIVE STRESS AND INFLAMMATION
Dr Jim Joseph of the USDA Human Nutrition Research Center on Aging at Tufts University describes oxidative stress and inflammation as the “twin evils” of ageing, and is investigating the concept of “berrying” the aged brain. Findings from his group’s research suggest that berries may improve behaviour in the aged by enhancing neuronal signalling associated with learning, memory and neuronal communication while decreasing signalling of oxidative stress. This could be of particular benefit in protection against diseases such as Alzheimer’s, Parkinsons, heart disease, vascular dementia, cancer and arthritis.
While oxidative stress is a “known villain” that causes cellular damage and death, inflammation is a more complex character because inflammatory processes are an essential part of the immune system. However, when inflammation persists long after the original trigger it can become chronic. Chronic inflammation can also occur following a number of episodes of acute inflammation. Chronic inflammation is thought to be a common underlying mechanism of several non- communicable diseases, including cardiovascular disease, diabetes, cancer, inflammatory bowel disease, Alzheimer’s disease, asthma and rheumatoid arthritis.
Whole genome association studies have identified genes that affect a person’s susceptibility to inflammation. When the genes that influence immune response involve polymorphisms – common genetic variations that occur in more than 1 % of the population – they will affect a person’s susceptibility to disease. Other genes that influence antioxidant effects, cell death and cell signalling will also interact Thus understanding the genetic polymorphisms of an individual or group may assist with developing more precise dietary strategies that will reduce chronic inflammation and its long-term consequences.
Different nutrients or non-nutrients (so named because they don’t have a defined role in nutrition) may modulate processes that lead to chronic inflammation and increased risk of disease. Among these, numerous macronutrients are emerging as important in the inflammatory process, including amino acids such as glutamine and arginine, lipids such as omega-3 fatty acids, and certain novel carbohydrates. Vitamins C and E, alongwith the minerals zinc and selenium, are also showing significant impact on the immune system, as are some plant- and fruit-derived chemical compounds along with probiotics and prebiotics. Because each of the stages involved in inflammation is likely to respond to a different dietary intervention, a complementary approach may be necessary to reduce symptoms.
INFLAMMATORY BOWEL DISEASE
Our team at Nutrigenomics New Zealand, a collaboration between the University of Auckland, AgResearch, Crop & Food Research and HortResearch, is researching the area of genes, diet and inflammatory bowel disease (IBD). IBD arises in part from a genetic predisposition. Although approximately only one in 5000 people develop the disease, around 20% of people with IBD have a blood relative who is also affected.
The two main types of IBD are Crohn’s disease and ulcerative colitis. We are focusing on Crohn’s disease, using genomic technologies to genotype a study population of both Crohn’s disease and control participants so that we can ascertain which genes and gene variants are most common among those with the disease.
Three metabolic pathways are closely involved with the chronic inflammation that underlies Crohn’s disease. These three pathways are linked with three kinds of genes:
* those affecting bacterial recognition, which in Crohn’s disease means that the immune system inappropriately responds to gut bacteria, leading to chronic inflammation;
* those affecting transport of metabolites, causing chronic inflammation;
* those affecting the intracellular processing of bacteria or damaged organelles (autophagy).
It is already clear that diet plays an important role in how severe the Crohn’s disease is and how people manage the disease. Crohn’s disease sufferers find that many dietary items either benefit or worsen their condition.
In many cases Crohn’s disease is controlled using elemental diets, which are liquid diets that contain all the nutrients needed by the body. Once a person’s disease has been stabilised with the elemental diet, elimination diets are often used to individualise dietary requirements.
The ability to determine a person’s unique genetic make-up will mean that any person’s dietary requirements can be finely tuned. It could also mean that not only would someone know which foods to avoid, but they could also learn what foods are good for them and should be included in their regular diet.
Hence IBD is an excellent example in which both the incidence and the severity of the disease could be modulated by developing dietary recommendations according to genotype. It is an especially valuable example as the food is expected to have its effect in the gut rather than needing to be absorbed and active in the blood or tissues.
RESEARCH OBJECTIVES
Our overall objective is to discover and develop foods that can be matched to individual human genotypes for maximum health maintenance, disease amelioration and, where possible, disease prevention or even cure. Underpinning this aim is our bioinformatics platform, which maintains a unique relational database of information gathered from our study group of Crohn’s disease and control participants.
Both groups complete a lifestyle questionnaire and provide a blood sample that undergoes genomic analysis to determine how both genotype (what genes we have) and phenotype (the way our genes are expressed) relate to lifestyle. Crohn’s disease participants also complete a dietary questionnaire to assist us in learning about which foods are beneficial to Crohn’s disease sufferers and which are not. While there is great diversity in the responses to the dietary questionnaire, some “offenders” stand out. For example, one in 16 Crohn’s disease participants indicate a wheat or gluten intolerance. Items such as energy and carbonated drinks plus mixed foods, especially hot curry dishes, also rate highly in the “adverse effect” responses. Conversely, a number of common vegetables are generally very beneficial.
One particular gene we have studied doesn’t seem to be a consistent indicator for Crohn’s disease on its own, although there has been quite some debate about this gene. However we have found that when people with this gene consume a particular common vegetable (which we cannot reveal at this time) they report adverse effects. Our analysis of the people who reported adverse effects, along with those who reported beneficial effects, produced exciting gene-specific results that are statistically significant. It is early days for this part of our research, but we may be looking at our first pronounced gene-diet interaction in Crohn’s disease.
We are gradually working our way through the data being generated from our dietary questionnaires, and selecting some foods that are often named as being highly beneficial or highly adverse to take on for further testing.
This involves high throughput screening to study the action of multiple food components on a single gene, and genomics techniques to genotype people and populations. In our high throughput screening work we grow cells that mimic genetic variants found in our human Crohn’s disease population. Selected food components are then mixed with these cells and we then look for two different effects: food components that show inflammatory or anti-inflammatory activity, and food components that have a “restorative” effect in balancing the gene variants involved in Crohn’s disease.
Whereas this work studies the effect of food components on a single gene in vitro, a further strand of our research studies the action of food components on multiple cells and genes in vivo. Here we use mice that spontaneously develop IBD to test food components that have shown a promising response in vitro.
The final strand of our research extracts and separates foods into defined fractions that can then be tested in vitro and in vivo. This includes the creation of food libraries, personalised diets and novel foods. This forms a knowledge base for the development of gene- specific foods that could ultimately be used to create individualised diets. There is no genetic engineering involved – only what nature has provided is used to develop foods and/or food products that will give positive health benefits.
We are also identifying active compounds through advanced chemical techniques such as NMR and mass spectrometry. This allows us to home in on the active compound and then find other foods that also contain these compounds.
Once we have promising food components that do well in the small animal trials we will be ready to take these foods through to a human clinical trial, with the aim of both coming up with dietary recommendations for Crohn’s disease sufferers based on genotype, and developing novel foods that will be highly suitable for our Crohns disease population.
Ultimately we plan to apply this approach to other disease targets and population groups. While it is no simple task, in that we are working with multiple nutrients acting in multiple ways on multiple genes, the prospect of developing highly personalised diets to both maintain health and relieve disease is becoming more feasible as our research progresses.
Virginia Parslow is administrator of the New Zealand Centre for Research Excellence in Nutrigenomics at the University of Auckland.
Copyright Control Publications Pty Ltd Sep 2008
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