Andreas,I think you are misunderstanding the umbrella term nutrigenomics and making some unfair statements. Nutrigenomics is more than simply tailoring diets to genotype (nutrigenetics), is it also the study of the epigenome, transcriptome, proteome, and metabolome and integrating these tools into a better understanding of how nutrition effects the body at the molecular level.To me, the most important aspects of nutrigenomics are the technologies it brings to the table that allow for deep probing of molecular pathways in relationship to nutrients and diet patterns. It yields more accurate associations by grouping genotypes (see links to Keith Grimaldi's posts, who was the principal investigator in the “Greek study” you commented on) and should lead to better biomarkers for disease risk than what we currently have (which are often controversial and not necessarily reflective of what they intend).And I would be surprised if any (credible) scientists in this field discount environmental effects on health in favor of reading the genotype to predict health, or suggest that genes are a major explanation for the obesity epidemic. Those are unfair assumptions. There is a lot of literature on correlations to various SNPs and obesity and to my understanding the effect is small. Obviously obesity and associated disease are multi-factorial, but that doesn't mean people won't respond better to certain diets based on genotype, whether that means through compliance, or through physiological mechanisms that current studies have not detected because of averaging, or for other reasons. With nutrigenomic tools, the influence of non-nutrition variables can be isolated as well, better than we have been able to previously.I do agree with you that the idea of tailoring nutrients to genotype in general is probably a poor one, and it is much too early to doing this. I think the most important findings here will show that ethnicity should be a consideration for choosing how to eat, as genomics has demonstrated that recent evolution is occurring more rapidly than previously believed and the relevance to nutrition is intriguing. But it is still much too early to draw conclusions. You may be forming conclusions based on testing services that are operating prematurely.I am not a scientist in this field, but i've invited some people who are to share their insight.

OK – my answer is yes, nutrition research is simply not working – if you think it is, show the evidence. We still do not have knowledge but just opinions: sat fats raise risk of heart disease vs. sat fats are no problem. High cholesterol bad vs. high cholesterol OK. And so on, after 50 years of looking for the answers.Colby has explained very well what nutrigenomics means as a whole – I'll just address a few points in the post that Andreas links to:Nutrigenetics: this is the effect of genetic variation on nutrition. E.g. the well studied “poster gene” is MTHFR, there is a variant that Andreas refers to that is involved in metabolism of folic acid. The variant (Rs1801133) affects enzyme activity, reducing it by 2/3rds – so a homozygous TT person has only 30% activity compared to a CC individual. This has a significant and mathematical effect that has been demonstrated countless times – it's not an association but actually does CAUSE homocysteine levels to rise when the diet is poor in folic acid. TT individuals require more than the RDA to be sure of keeping homocysteine normal (for refs on this go to SNPedia and Geneopedia – http://bit.ly/bjM2KD).So what? Hcy is implicated (yes, by association) as a risk factor in cardiovascular disease, osteoporosis, cognitive problems, etc. It's not yet established if it is causal. There is also some interesting work from Michael Fenech on Hcy, low folate and DNA damage (http://bit.ly/9OSRUg and http://bit.ly/b1Pf31). So what – it's never been proven in a clinical trial. Yes, that's the point of Colby's post and thise of mine that he refers to. Potential benefit vs. risk. In this case a TT person can make sure he/she includes more B vitamins in the diet to keep Hcy low. Hcy may not be causal but at the very least it is a biomarker of a non-optimum set of pathways that lead to DNA methlyation and synthesis of nucleotides for DNA replication. These are some pretty important processes and for the sake of a few extra ugs of folate etc, still at levels well below the upper limits, it is easy to keep things running normal. Of course a piece of nutrigenetic advice to increase folic acid will not guarantee you will not get a heart attack, but it will ensure that you don't get it because of high homocysteine…There are about 20-30 other genetic variants where the gene-diet relationship is well established. Nutrigenetics does not (or should not) make claims about protection about specific diseases but just about better nutrition. I don't know why it invites such scepticism. Actually I do know why – it's related to the title of Colby's post – nutrition research was the biotech of the first half of the last century – solving deficiencies, discovering vital nutrients, etc, really saving lives. After that it became more about trying to “optimise” nutrition and has not had much success, it's seen as a “soft” science, not serious, open to be exploited by quackery, which of course we know happens. Many pseudo-nutritionists have hijacked the term nutrigenomics to sell their latest diet books, and this also harms the field and creates sceptics of people like Andreas.I also was a sceptic, as a molecular biologist working for years on DNA damage and repair the concept of diet and genes did not interest me and if ever I came across it I ignored it as another nutritionists fad…or worse. But then a well respected group of people I knew started taking it seriously and introduced me to it – the reason for my scepticism, apart from the hijacking by the scammers, was mainly pure ignorance. I was so blinkered in my speciality that I did not see outside the “purity” of molecular biology and could not see any use in nutrition as a science. I did not know about MTHFR and folate, or the fact the 50% in Europe do not possess GSTM1 activity, etc.Anyway – I got involved and we did what we did. There are genes that we know enough about to be able to make some modifications to the individual RDA of nutrient and mineral objectives and limits, that's not my opinion but is demonstrated. My opinion is that these changes will lead to better longer term health, that has not been demonstrated, just like not one single piece of nutritional advice in any of the myriad pyramids has actually been demonstrated by the so-called gold standard of randomised clinical trial. We know for certain that if we don't eat enough we will starve to death (except for a few exceptional people, usually priests or monks in Italy who are apparently able to live on a glass of water + a communion host per day, but that's another story). I am also assured that if I eat a polar bears liver I will die of vitamin A poisoning. Neither of these “facts” have been proven by clinical trial, but we have certainly OBSERVED the effects of starvation often enough.Some other mis-understandings from Andreas' post:”Is nutritional genomics a science based method?” – just go to http://www.nugo.org“Because lactose cannot be digested and absorbed , therefore it cannot cause obesity since it does not affect energy balance” Not sure of the relevance or truth of this. The version of the LCT gene that leads to lactose “intolerance” leads to unpleasant, sometimes painful, symptoms when too much lactose is ingested, the lactose is fermented by bacteria rather than digested by lactase. Most of the world population is “intolerant”. In Italy about 70% have the “intolerant” genotype, this is surprising and not commonly known in this land of mozzarella and pizza. It's is useful to know your genotype.”The propaganda of nutritional genomics also declares that many diseases such as obesity, diabetes, cardiovascular disease and hypertension are due exclusively to nutrition or to isolated nutritional preferences”This is the complete opposite actually. Nutrigenomics deals with interactions between nutrients and genes – effects on gene expression, metabolism and so on. The claims are that health and disease are NOT simply due to nutrition. It also goes beyond nutrition to embrace all aspects of lifestyle and environmental effects – but it's called nutrigenomics because that's already a long enough word – I am certainly glad that I don't work in psychoneuroimmunoendocrinology.Regarding the “Greek study” as Colby said, I was lead author – it is available here, open access at http://bit.ly/4Yk4Wg. It gets worse – Yiannis Arkadianos was indeed the distributor of the Sciona nutrigenetic test, but I was Chief Scientist at Sciona itself! Those from NTUA and Kings College London were academics. However, we published in a peer reviewed open access journal (so open access that you can even read the referees review of the work and the modifications required). Yes there was a potential conflict of interest, as declared, but any accusations that the study was fixed are specious. Furthermore, unlike other companies Sciona did not go out and create a “weight management” product based on the results.Also you misunderstood the study – we were not looking for magical effects of gene-diet interactions. The study was small, far from perfect, left many many questions unanswered, but not all of them. There was no attempt to “choose” diet according to genotype but simply to modify slightly the base diet where indicated. It’s not a classic, it’s not incontrovertible evidence that when genetics are used there is better compliance (for personal motivation or whatever), but it is some evidence. Unfortunately research is expensive and most VC money goes on marketing, pity but true – anyway the work continues in other projects and with other collaborations.“Time now for a reality check: the evidence for the effectiveness of “nutritional genomics” is non-existent” – simply not true, again, start with http://www.nugo.org. Your ref, Sauko, does not say that. Genewatch probably still do, but then they would, it’s what they do.The goals of nutrigenomics are just to help to improve health – there is no magic or pomposity, it’s just that nutrition is the most important environment that we are exposed to and our genes are pretty important too. Every single part of me is derived from what I have consumed or inhaled. When a single fertilised cell sitting inside an egg converts those proteins and lipids, carbs, minerals, etc into a bunch of muscle, fat bones and feathers, with no outside help except for a warm mother, that’s genes and nutrition at work. The thing is that nutrigenomics is not very dramatic, it’s not curing cancer, or even a headache, but it’s about small effects that over a long term become significant. Just like the process towards lung cancer starts with the first cigarette. Small effects are not to be dismissed lightly – usually they are not noticeable. I have never seen my children grow, every day they are seem to be the same height, but they keep getting bigger. Small changes in diet and lifestyle have long term consequences. A few too many calories per day can become 15 kg overweight over 20 years. A small insufficiency of a vitamin, a small lipid imbalance, etc etc etc. One of the criticisms of nutrigenetic tests is that the advice is not much different to standard dietary advice (whatever that is). Correct, it is not. But it IS different, slightly and hopefully significantly. My shoe size is 43, if I were to buy size 42 it would look almost the same, it would feel just about OK, but 8 hours later my feet would hurt. Nutrigenetics is one part of personal genetics – where we try to use the information that we have now to make choices. It’s not new – we have been making these choices for years. Most people who go to the beach (here I am in Italy in August, everyone is at the beach) will automatically buy some sun screen. I’m mostly English and I start with factor 20, wife is Neapolitan, she starts with factor 10, three children are African, they use factor 2. These are personalised products and we choose them based on our genotype – we don’t question it, we don’t think it is a scam, I don’t think anyone does. The use of these products is not supported by any clinical trials etc etc etc. Most opinion is that sun screen and other preventions are helping to reduce cancers – we are pretty sure of that, but they are still opinions, not facts. Our opinions are that nutrigenomics will help us to understand more about diet and genetics and help us with personal choices. My opinion, not shared by a lot of people in nutrigenomics, is that we do know enough now to make some small (hopefully significant) changes to diet based on the variants of a few genes. I have no FACT to prove that, what I have observed convinces me of it, and I have not seen anything that disproves it.I have never understood the comparison with the drunk man looking for his keys only where there is the light of the lamp post – it’s used as a criticism. But where should he look? Or what should he do? He can a) do nothing, b) “look” where he cannot see or c) look where the light is, which is what a sober person would do!

Colby, On your previous article you criticized ADA's sponsorship with Pepsigate and you stated clearly there is a conflict of interest.It makes one wonder how you do not see the potential for conflict of interest in the nutrigenomics study I referred to where the distributor of the nutrigenomic tests was the one providing the evidence.Keith,”Nutrigenetics: this is the effect of genetic variation on nutrition. E.g. the well studied “poster gene” is MTHFR, there is a variant that Andreas refers to that is involved in metabolism of folic acid. The variant (Rs1801133) affects enzyme activity, reducing it by 2/3rds – so a homozygous TT person has only 30% activity compared to a CC individual. This has a significant and mathematical effect that has been demonstrated countless times – it's not an association but actually does CAUSE homocysteine levels to rise when the diet is poor in folic acid. TT individuals require more than the RDA to be sure of keeping homocysteine normal (for refs on this go to SNPedia and Geneopedia – http://bit.ly/bjM2KD).So what? Hcy is implicated (yes, by association) as a risk factor in cardiovascular disease, osteoporosis, cognitive problems, etc. It's not yet established if it is causal. There is also some interesting work from Michael Fenech on Hcy, low folate and DNA damage (http://bit.ly/9OSRUg and http://bit.ly/b1Pf31).”-Like you pointed out this is an association of homocysteine levels with cardiovascular disease , whether there is a causal relationship between the variables is not established. This leaves us with a hypothesis. Concerning low folate and DNA damage, the study is investigating low folate intake, carrying a susceptible gene does not pre determine dietary intake of folate.”of course a piece of nutrigenetic advice to increase folic acid will not guarantee you will not get a heart attack, but it will ensure that you don't get it because of high homocysteine…”-Professor Peter Weissberg, medical director of the British Heart Foundation would disagree with you: “People should not be taking folic acid and vitamin B6 to stop them having a heart attack because it won't” (BBC,2006).”My opinion is that these changes will lead to better longer term health, that has not been demonstrated, just like not one single piece of nutritional advice in any of the myriad pyramids has actually been demonstrated by the so-called gold standard of randomised clinical trial. “-I see you recognise that no long term health benefits have not been demonstrated, I agree. I understand that sometimes a little faith is needed in every hypothesis ,still illogicical action is not justified by the presence of other illogical actions.”The thing is that nutrigenomics is not very dramatic, it’s not curing cancer, or even a headache, but it’s about small effects that over a long term become significant. Just like the process towards lung cancer starts with the first cigarette. Small effects are not to be dismissed lightly – usually they are not noticeable. I have never seen my children grow, every day they are seem to be the same height, but they keep getting bigger. Small changes in diet and lifestyle have long term consequences. A few too many calories per day can become 15 kg overweight over 20 years. A small insufficiency of a vitamin, a small lipid imbalance, etc etc etc. “Indeed a few too many calories per day leads to increased weight, but this also leads to increased BMR , increased adipose tissue, and increased leptin secretion which has an anorexigenic effect. I do not think the cancer-cigarette example is representative as smoking is addictive, in weight gain there are rebound mechanisms that inhibit appetite and increase energy expenditure. Regarding the “Greek study” as Colby said, I was lead author – it is available here, open access at http://bit.ly/4Yk4Wg. It gets worse – Yiannis Arkadianos was indeed the distributor of the Sciona nutrigenetic test, but I was Chief Scientist at Sciona itself! Those from NTUA and Kings College London were academics. However, we published in a peer reviewed open access journal (so open access that you can even read the referees review of the work and the modifications required). Yes there was a potential conflict of interest, as declared, but any accusations that the study was fixed are specious. Furthermore, unlike other companies Sciona did not go out and create a “weight management” product based on the results.”I can understand that's definitely an advantage in credibility for Sciona concerning the related competition in the field , this does not mean the study was well conducted and/or un-biased, at least in my opinion.”Because lactose cannot be digested and absorbed , therefore it cannot cause obesity since it does not affect energy balance” Not sure of the relevance or truth of this. The version of the LCT gene that leads to lactose “intolerance” leads to unpleasant, sometimes painful, symptoms when too much lactose is ingested, the lactose is fermented by bacteria rather than digested by lactase. Most of the world population is “intolerant”. In Italy about 70% have the “intolerant” genotype, this is surprising and not commonly known in this land of mozzarella and pizza. It's is useful to know your genotype.”Knowing your genotype certainly does not hurt. However , I am sure you are aware lactose intolerance is not that hard to diagnose through trial and error, this is pretty much common knowledge , I think you over emphasize the importance of knowing our genes.”Also you misunderstood the study – we were not looking for magical effects of gene-diet interactions. The study was small, far from perfect, left many many questions unanswered, but not all of them. There was no attempt to “choose” diet according to genotype but simply to modify slightly the base diet where indicated. It’s not a classic, it’s not incontrovertible evidence that when genetics are used there is better compliance (for personal motivation or whatever), but it is some evidence. Unfortunately research is expensive and most VC money goes on marketing, pity but true – anyway the work continues in other projects and with other collaborations.”This study was comparing weight loss under two different protocols, still it is amazing it did not report on calories of the two diets. If you disagree that weight loss is primarily regulated by energy equilibrium please feel free to reference.“Time now for a reality check: the evidence for the effectiveness of “nutritional genomics” is non-existent” – simply not true, again, start with http://www.nugo.org. Your ref, Sauko, does not say that. Genewatch probably still do, but then they would, it’s what they do.”I would like to see some form of independent source of evidence , not from a nutrigenomics web site. Genewatch is a non profit group. Their paper provides evidence for their claims. Concerning Saukko, it is clearly stated in the abstract “We argue that the companies, mirroring and negotiating the regulatory debates, were creating a newsocial space for products between medicine and consumer culture. This space was articulated through three themes: (i) how “genes” and tests were framed, (ii) how the individual was imagined vis a vis health information, and (iii) the advice and treatments offered. The themes mapped onto four frames or models for genetic testing: (i)clinical genetics, (ii) medicine, (iii) intermediate, and (iv) lifestyle.We suggest that the genomics researchers and policy makers appeared to perform what Gieryn (Gieryn, T.F. (1983). Boundary-work and the demarcation of science from non-science: strains and interests in professional ideologies of scientists. American Sociological Review, 48, 781–795.) has termed “boundary work”, i.e., to delegitimize the tests as outside proper medicine and science. Yet, they legitimated them, though in a different way, by defining them as lifestyle, and we contend that the transformation of the boundaries of science into a creation of such hybrid or compromise categories is symptomatic of current historical times.” It is clearly stated that nutrigenomic tests fall out of what is termed “science”. Science is an evidence based method.”One of the criticisms of nutrigenetic tests is that the advice is not much different to standard dietary advice (whatever that is). Correct, it is not. But it IS different, slightly and hopefully significantly.”I can relate to your enthusiasm for nutrigenomics , this is exactly how I was feeling when I heard the term. Maybe in the future there is enough solid and independent scientific evidence proving my case wrong.

I should add one caveat about clinical trials – they can be of use for determing whether a particular nutritional intervention may cause harm. e.g. high dose vitamin D, folate, etc. In some cases they do and others they don't. Nutrigenetic and general nutritional recommendations stick to what is within the IOM defined tolerable upper limits

Yes I agree, pointless. I don't answer about energy equilibrium because that was not addressed by the study (please read it carefully). You say nutrigenoimics/nutrigenetics is not a science – that's your opinion but you don't support it (in my opinion). My views are not preformed but were actually formed by the information I presented.I see from your profile that you are a nutrition student – good luck with your studies. My advice would be to be objective, keep an open mind, read widely and carefully, accept the evidence (but study the source and it's credibility), criticise it constructively and be prepared to change your opinions (as I have done often throughout my career).

In the end it's very simple: Genes act alone or Gene x Environment interactions are important. If you believe the latter, and accept that our most important env exposure is diet then you accept nutrigenetics/omics