Does nutrition need a new research paradigm?

When you consider how highly complex food systems interact with highly complex human systems, it is a bit overwhelming.  Then consider the thousands of different food species, nutrients, dietary patterns and combinations, how these interact with differing activities and other environmental variables, and elucidating an ideal diet seems an impossible task.  Though we know a lot about some aspects of food, we are more confused than ever on others.  I think this reflects a limited cognitive capacity to account for all of these variables (the human tendency is to look at few variables at a time and discount the importance of others), and human cognitive bias’ that push us toward seeing patterns that might not be there, or misinterpreting data in in the wrong context.

Existing nutritional research is often difficult to interpret and seemingly contradicting, until you meticulously consider design and potential residual confounders that are so difficult to mathematically account for.

Until recently, studying nutrition used classic study design to attempt to tease out the effects of individual variables.  While this has given us a lot of insight on some mechanisms in the body, it has also unfairly demonized certain foods and partly pushed us into a health epidemic.  We are discovering more and more how nutrients and pathways interact in the body, and it goes far beyond what appears on nutrition labels.  Designing diets tailored to recommended doses of well studied nutrients is simply missing the forest for the trees.

Instead new methods of studying nutrition are being adopted, ushered in by the age of nutrigenomics.  A recent video interview of Dr. Jim Kaput, director of the Division of Personalized Nutrition and Medicine in the FDA offers a refreshing, conservative opinion on the field of nutrigenomics, that is borrowing ideas and technologies from other science disciplines to analyze massive amounts of data to bring a personalized understanding to nutrition.  And hopefully it will give us a bigger picture view of nutrient-pathway interactions so we don’t make mistakes that cause unwarranted restrictions as did the lipid hypothesis.

View it here.

For some great commentary and examples on the limitations of current studies and how genetics is improving our understanding, check Keith Grimaldi’s posts here and here.

Though maybe we will find that marrying nutrition and genetic/-omics will make establishing ideal diets an even more daunting task?  The road will be long and arduous…

Video link via @nutrigenomics

  • http://metavolismos.com/en/ Andreas Zourdos

    Nutrition does not need a research paradigm but “nutrigenomics” sounds too cool to fail, evidence is not needed, two scientefic terms together is all the evidence some people need.My view on the topichttp://metavolismos.com/en/?p=62

  • http://www.recomp.com Colby

    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.

  • http://twitter.com/eurogene keith grimaldi

    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!

  • http://twitter.com/eurogene keith grimaldi

    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!

  • http://twitter.com/eurogene keith grimaldi

    Re Saukko et al: http://bit.ly/9ylYfg “Dr. Muin Khoury and colleagues from the U.S. Office for Genomics and Disease Prevention, Centers for Disease Control, which was in charge of developing ways to use genomic research to prevent disease, stated in the prestigious journal Nature Genetics that the science of using genetics to enhance healthy lifestyle “holds great promise” but was “not ready for prime time” (Haga, Khoury, & Burke, 2003: 350). “Yes – 1) not ready for prime time, OK I agreed at the time, but it does not mean not ready full stop. 2) “holds great promise” – this was in 2003, still holds proimse and in the intervening years some progress has been made as well

  • http://metavolismos.com/en/ Andreas Zourdos

    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.

  • http://twitter.com/eurogene keith grimaldi

    Andreas,I get it about the paper, any study involving non-academics must be suspect because of commercial conflicts, correct? So if a company tries to do research, the research is tainted, if a company does no research then that company is criticised for having no scientific credentials.Hcy – note that the actual effect of low folate on DNA damage has been directly demonstrated, in vitro, to be mediated by Hcy. The effects have also been seen in vivo – read the Fenech body of work to understand more about MTHFR, folate, Hcy and DNA damageCan you please cite the evidence of Prof Weissberg – BBC2006 is not good enough. All studies that show no benefit of folate on heart attacks have been performed in diseased people, who already have heart disease. Please see http://bit.ly/aWPUEQ to understand why this has nothing to do with primary preventionPlease can you show me definitive evidence of long term health benefits of any piece of nutritional advice (beyond the obvious curing of severe vitamin deficiencies). What would you consider to be good dietary advice? What is the definitive evidence. My point is (as should be clear in my blog) that such evidence is impossible to obtain.Was the study well conducted? You think not, luckily it was not your opinion that mattered but those of the referees (as I said, you can go to the journal site and read the referees comments, it also gives you their names). Our study was also passed by our science advisory board before being submitted (the SAB included Jose Ordovas and Wally Gilbert, Nobel prize winner).LCT/lactose intolerance – trial and error? Yes of course it can, and it can be a painful process, especially for children. Lactose intolerance is not itself a disease, or even a great problem. But you should be aware that lactose intolerance can also be the result of serious problems – the reasons for the intolerance can be genetic or due to intestinal disease (celiac, Crohn’s, etc). If you don’t know the genotype the danger is you will just assume normal lactose intolerance and miss the disease.http://www.nugo.org – I really don’t have much to say about your answer. Did you look at the website? Nugo was formed several years ago by a network of academic departments in Europe. You still don’t believe that there is a scientific basis – your problemSaukko – your interpretation is wrong. They present a theory of how it was marketed and are not determining whether it is science or not. They DO NOT make that statement

  • http://twitter.com/eurogene keith grimaldi

    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

  • http://metavolismos.com/en/ Andreas Zourdos

    Keith, Through this conversation you tend to focus on pretty much anything to confirm your preformed views. The goal post keeps moving and moving. Additionally, the fact that you selectively ignore to answer my question concerning the importance of energy equilibrium in the weight loss study is very serious and tells a lot about your objectivity. I made my case and I will not continue debating because it is pointless.Andreas Zourdos

  • http://twitter.com/eurogene keith grimaldi

    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).

  • http://www.recomp.com Colby

    “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.”

    There is a potential conflict of interest in many studies, but it doesn't mean anything unless you have evidence of tampering. I don't need to defend Keith, as he already pointed out, the study was not about energy balance. He gave clear statements about the limitations and that this area of research is young. You unfairly reported this:

    “By carefully reading this study it is striking that it does not take in account energy balance and fails to report the calories of both diets.That is if there was a difference at this variable then increased weight loss should not be attributed to some hypothetical diet-gene interaction but to the plain obvious, increased negative energy balance.”

    Did you read it carefully? It clearly suggests that compliance was most likely the main reason for more weight loss in the personalized group, not some “hypothetical diet-gene interaction.” I think it is much too early to think about personalized diets, and this is only one aspect of nutrigenomics. You are still thinking too narrowly. Nutrigenomics offers tools to examine the biomolecular differences in individuals to groups- this could help explain why for example some cultures seem to have greater risks for various diseases compared to others when adopting certain diets or exposed to certain nutrients (allergies/intolerances could be better studied as well). And who knows- maybe we will find that some people respond significantly different to diet patterns or nutrients in that certain people should adopt specific macronutrient ratios or micronutrient doses to achieve varying degrees of success- consider that rodent studies generally use animals of the same genotype, while human studies are with heterogeneous populations. Are we missing patterns that aren't being detected? Sub-analysis by genotype or others could reveal previously hidden relationships. Obesity is clearly multi-factorial and I would agree that a large part is probably related to food environment. Weight is most certainly determined by calories in = calories out, however lots of things go on to influence what foods go in, how they are processed and what effects they have on the body, and how much energy comes out- and processes influence all of these at the molecular level. To quote Michael Muller (@nutrigenomics on twitter) and Sander Kersten from their 2003 paper: http://www.nature.com/nrg/journal/v4/n4/abs/nrg

    … although personalized diets would be an interesting application of nutrigenomics, we believe that the implementation of such an approach lies far ahead of us. Although there are many that disagree, we think that over the next 10 years the focus should be on understanding how nutrients interact with the genome at the molecular level.

    Please try to see that personalized nutrition is only one aspect of the science of nutrigenomics, an aspect still very controversial even among academics. Nutrigenomics should not be demonized because of a focus from some groups and the media on this aspect.

  • http://twitter.com/eurogene keith grimaldi

    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

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  • http://www.facebook.com/people/Paolo-Manzelli/100003183321923 Paolo Manzelli

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