Nutrigenetics

Nutrigenetics (Nutrition + Genetics) studies assess how genes & diet (and sometimes lifestyle) interact, where the effect of one component is dependent on the status of the other. A classic example is the Lactase (LCT) gene and lactose intolerance. In Europe there are predominantly two very common versions of this gene, one leads to lactose tolerance, i.e. it remains possible for the individual to consume lactose rich foods (mainly dairy produce) throughout adult life since he/she continues to produce the lactase enzyme in high levels and this is the enzyme which digests lactose, the sugar found in milk.

The other version of the gene leads to lactose intolerance – infants can digest lactose but as they get older, usually between 5-8years old, the gene that produces lactase slows down, much less enzyme is produced and lactase is not digested properly. It is utilised by bacteria in the intestines, creating a type of fermentation process and gas production which causes mild to severe gastric symptoms in the affected person. The important point about lactose intolerance is that it is only a problem when lactose containing products are consumed – as long a no, or only small amounts, of lactose are consumed then the individual can lead a perfectly normal life, in fact lactose intolerance is the normal state – the vast majority of the world’s population can only tolerate lactose during the early years of infancy, while feeding on the mother’s milk.

The variation that leads to lactose tolerance (also called lactose persistence) appeared relatively recently in human history and in is present almost entirely in people of middle European origin – in Italy lactose intolerance is very widespread, averaging about 70% but depends on the region.

The important point about lactose intolerance is that it is only a problem when lactose containing products are consumed – as long a no, or only small amounts, of lactose are consumed then the individual can lead a perfectly normal life, in fact lactose intolerance is the normal state – the vast majority of the world’s population can only tolerate lactose during the early years of infancy, while feeding on the mother’s milk. The variation that leads to lactose tolerance (also called lactose persistence) appeared relatively recently in human history and in is present almost entirely in people of middle European origin – in Italy lactose intolerance is very widespread, averaging about 70% but depends on the region.

Many, many studies have shown that people with the T variant, especially if they are homozygous 677TT (i.e. they received the same T version from both mother and father) require higher levels of folic acid in order to keep homocysteine levels within the normal range (homocysteine is a biomarker that is assessed as a risk factor for cardiovascular diseases).

The recommended daily intake of folate acid is 400 µg in Europe and 400 µg in the USA. Several intervention studies have shown that these levels are not adequate to maintain normal levels of homocysteine so these individuals are advised to consume at least 600 µg per day plus higher levels of vitamins B6 and B12, whereas, for those with the 677C version, 300µg is recommended.

Other genes analysed in the nutrigenetic test are involved in various metabolic systems including lipid metabolism (saturated fats, MUFA, PUFA, cholesterol), removal of oxidative stress products, removal of toxins (e.g. from airborne pollution, cigarette smoke, grilled meat, etc), glucose and insulin control, inflammatory processes, utilization of vitamin D and calcium.

Other genes analysed in the nutrigenetic test are involved in various metabolic systems including lipid metabolism (saturated fats, MUFA, PUFA, cholesterol), removal of oxidative stress products, removal of toxins (e.g. from airborne pollution, cigarette smoke, grilled meat, etc), glucose and insulin control, inflammatory processes, utilization of vitamin D and calcium.

Nutrigenetics (DNA-Based Diet and Nutrition) can be used to modify existing standard guidelines and provide an element of personalisation to the otherwise “one size fits all” advice. It can be beneficial when it is added to other information such as gender, height, weight, age, state of health etc., it is not used in isolation nor does it override other parameters. Nutrigenetics is part of everyday nutrition – it is not specifically therapeutic and does not depend on the use of nutraceuticals or supplements.

In general use, it is not intended for specific disease prevention but as an aid in optimising diet and lifestyle for promoting long term health based on the best evidence that is available. Nutrigenetic, and indeed nutritional advice in general, is useful for maintaining health and its primary purpose is not for treating disease.

These points are all important for determining the threshold of evidence required to support nutrigenetic advice and in this context the appropriate level of evidence should be the same as that applied to existing nutritional guidelines in the first place. This is the case for several gene x diet interactions and there is evidence that nutrigenetic advice is better understood and more likely to be followed compared to general dietary advice plus it can be beneficial for example in long-term weight control.

Nutrigenetics represents right now a valuable tool in the hands of the individual and the health professional, especially for dieticians and nutritionists who should incorporate evidence-based gene/diet information when devising nutrition programs for their clients. Health professionals routinely evaluate a range of biological data (biomarkers, height, weight, gender, ethnicity, health issues, etc.) when formulating personalised diets and it is entirely logical that genotype should also be included where the evidence is sufficient.

This is the case for the genes GSTT1 and GSTM1, subjects of well-studied gene–diet interaction with cruciferous vegetables, which were shown to be associated with reduced lung cancer in GSTT1- and GSTM1-null individuals, but not in individuals who had working copies of both genes (Brennan et al.2005).

Other authors have demonstrated gene–diet-dependent effects on reduced DNA damage (Palli et al.2004), reduced prostate cancer risk (Steinbrecher et al.2010), and increased levels of GST alpha (Lampe et al. 2000). These interactions among genotype, cruciferous vegetables, and lung cancer risk have also been confirmed in a systematic analysis (Lam et al. 2009).

In summary, nutrigenetics is part of the information that contributes to personalized nutrition as a whole. Where there is supporting evidence, it should be added to other phenotypic information (such as health status, ethnicity, and gender), and genetic evidence should be assessed at the same level as phenotypic evidence.

Preliminary studies suggest that including genetic information may be useful in long-term weight loss (Arkadianos et al. 2007), and a recent randomized control trial reported that genotype-based personalized dietary advice was better understood and more likely to be followed than general dietary advice (Nielsen and El-Sohemy2012).

There is good evidence of some clinical and personal utility with respect to genotype based personalized nutrition, and this should be made more widely available to allow individual decisions to be made.

A healthy diet contributes to a long and healthy life, but exactly what is a healthy diet? Is it the same for everyone? No. One size does not fit all and one diet, or one “Recommended Daily Dose” does not suit all.

Nutrigenetics involves the study of how individual genetic variation affects interaction with components of the diets, including micro & macronutrients and toxins. Genetic variation has been demonstrated to affect uptake, transport, metabolism and elimination of food components and also affects individual daily requirements for some essential nutrients. Indeed there has been good evidence available for at least 10 years that:

With the identification of polymorphisms, or common mutations, in vitamin metabolism, large percentages of the population may have higher requirements for specific vitamins

Prof. Rima Rozen, Am. J. Clin. Nutr. 76(2), 301–2 (2002)

Healthy eating is not a straight forward proposition in the modern world, and expert committees charged with the responsibility of making dietary recommendations have to do so in the context of complex and incomplete information. The goal of personalized nutrition is not to substitute the official guidelines but to enhance or modify them for the individual where there is available evidence to do so. The level of evidence for nutrigenetic advice should be assessed according to the same standards as traditional nutritional advice.

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