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Personalized Nutrition

personalized nutrition personalized medicine nutrigenomics nutrigenetics

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#1 albedo

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Posted 17 May 2015 - 04:35 PM


I am reading the report of the recent study conducted on an European-wide scale by the Food4Me project on personalized nutrition (PN) which to me brings an exciting opportunity in particular for prevention and reduction of healthcare costs and parallels the "personalized medicine" which many consider the future of medicine.

 

Large corporation such as Nestlé are of course massively investing in the PN area.

 

The recent press release is HERE and the results are summarized HERE

 

The study shows effectiveness of PN to improve dietary behaviors when comparing only to population studies. And that is very good. What I found strange is there seems to be a lack of added value from using genetic information to personalize lifestyle-based interventions which to me is key.  One of the reasons might be the hesitation of consumers to provide genetic data for potential misuse. Nevertheless, I think nutrigenomics (the science underpinning the relation between dietary intake and gene expression) is a key path forward to preventive interventions. Few years ago I was thinking nutrigenomics will became mainstream in 5-10 years time frame but I was wrong.

 

There is an excellent webminar site by the Food4Me project:

http://www.food4me.o...erence-webinars

 

The second video from Prof. Dr. Hannelore Daniel is of particular interest to me as touching various existing or not-so-future technologies. I was also enervated by official report discouraging direct to consume genotyping services (min 2:33) as "linked to sale of dietary supplements or no proven value". Also the connection to the IT industry in particular the big players in the BigData and AI field is important.

 

Also, a good resource on "personalized medicine" with many free articles, including "personalized nutrition" is here:
http://www.futuremed.../pme?close=2014



#2 ta5

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Posted 17 May 2015 - 05:36 PM

This is nutrigenomics. It's exciting and the future, but we have a long way to go.


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#3 albedo

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Posted 22 May 2015 - 12:24 PM

I agree. Acceleration might come from industry both nutrition (e.g. Nestle) and IT and big data probably the only way to make sense of the hugely complex field of metabolism, genetics and nutrients interactions.


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#4 albedo

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Posted 19 August 2015 - 05:31 PM

Darryl has posted HERE an interesting link which I believe is relevant to the discussion on Personal Nutrition:

 

Gerhauser C. 2013. Cancer chemoprevention and nutri-epigenetics: state of the art and future challenges. In Natural Products in Cancer Prevention and Therapy (pp. 73-132). Springer Berlin Heidelberg.

 

 



#5 albedo

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Posted 20 August 2015 - 02:43 PM

What you people think about Personal Nutrition? How far do you think we are to hold in our hands what possibly is the future of PN?

 

On one side, how far we are to own, as consumers, inexpensive appliances or access services to test say hundreds or thousands or relevant biomarkers (from a drop of blood, small sample of urine/saliva or even skin patch)?

 

On the other side, how far we are to access to a big data and AI system (à-la-Watson or equivalent) so that you can gather personalized recommendations for foods and supplements based on your current dietary intake (macro and micronutrients), genomic profile, lifestyle (exercise, caloric expenditure etc.) mapped into published studies as they emerge and data bases? A smart phone app having access to the cognitive system would allow interaction and feedback gathering from the user and refinement of the recommendations. In parallel, anonymized data will feed back into the system under user control for research purposes.

 

I wonder if this community has come up with projects in this area.  Probably the less regulatory system in nutrition will make all this a reality before the equally important personalized medicine. I hope PN is not too much of a buzzword and all this not simply science fiction.


Edited by albedo, 20 August 2015 - 03:01 PM.


#6 albedo

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Posted 03 September 2015 - 09:50 PM

A nice example of nutrigenomic and nutrigenetics methods:

 

Dietary isoflavones in the prevention of cardiovascular disease--a molecular perspective.

 

Abstract

The Food and Drugs Administration has approved a health claim for soy based on clinical trials and epidemiological data indicating that high soy consumption is associated with a lower risk of coronary artery disease. Soy products contain a group of compounds called isoflavones, with genistein and daidzein being the most abundant. A number of cardioprotective benefits have been attributed to dietary isoflavones including a reduction in LDL cholesterol, an inhibition of pro-inflammatory cytokines, cell adhesion proteins and inducible nitric oxide production, potential reduction in the susceptibility of the LDL particle to oxidation, inhibition of platelet aggregation and an improvement in vascular reactivity. There is increasing interest in the use of nutrigenomic methods to understand the mechanisms by which isoflavones induce these changes, and in the use of nutrigenetics to understand why the effects vary between individuals. Nutrigenomics is a rapidly growing field making use of molecular biology methodologies, such as microarray technology and proteomics, to study how specific nutrients or diets affect gene expression and cellular protein levels. The analysis of differential gene expression and protein levels in endothelial cells, macrophages and smooth muscle cells is critical to elucidating the sequence of events leading to the formation of atherosclerotic lesions, and to understanding the potential anti-atherogenic properties of soy isoflavones. An increasing number of studies demonstrate a significant impact of genetic variation on changes in cardiovascular risk factors in response to dietary intervention. Nutrigenetic effects of this type have recently been reported for dietary isoflavones, and may help to explain some of the disparities in the current literature concerning isoflavones and cardiovascular health.

 

http://www.ncbi.nlm....pubmed/17689850

 


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#7 albedo

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Posted 18 October 2015 - 07:22 PM

I posted here two very interesting studies on the benefit and the usefulness of using nutrigenetics in nutritional approaches to reduce risks of certain diseases, in particular on using soy foods against prostate cancer: in general you might think it is a good idea, but you can make it worse ....



#8 albedo

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Posted 15 November 2015 - 02:32 PM

I think I found very interesting results related to the risk of prostate cancer (for me, higher than average as per my 23andMe results) and nutritional interventions based on nutrigenetics (personal nutrition). I hope you find this helpful too.

As reported here, I have introduced soy foods (in particular tempeh because of fermentation but also tofu) and a small supplementation because of the genistein/daidzein isoflavones anti-proliferative effects.  I also follow an anti-inflammatory strategy in particular consuming fatty fishes and moderately supplementing with EPA/DHA. However, I never found a nutrigenetics study support both, till today…...

In 23andMe I found I am genotype AG for the gene ESR2 SNP rs2987983. The following Swedish study (1) “…provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene…”. This would mean (in 23andMe reporting conventions) AG or GG. The decrease is as high as -37%. On the other hand, using soy, the risk increases if you are genotype AA.

 

So it is better to test this particular SNP before deciding to use soy foods or isoflavones supplementation with the hope to reduce prostate cancer risks because you can make it worse.

 

A similar results apply for fatty fish consumption when you check for the SNP rs5275 in the pro-inflammation gene PTGS2 (aka COX-2). A similar study (2) by the same authors "... found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01) ..." Risk decreases is a substantial -71% and no benefit (despite no risk increase as in the other study) without the variant.  I am genotype AG for the rs5275, so I hope to benefit from fatty fishes or supplementation too.

 

(1)
Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer.
http://www.ncbi.nlm....pubmed/16921512

(2)

Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism

http://www.ncbi.nlm....pubmed/17066444


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#9 albedo

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Posted 15 November 2015 - 02:38 PM

Another interesting proof point on the benefit of personalized nutrition. It is a pilot study and would need to be confirmed by clinical trials though:

 

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

 

"Abstract

Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study."


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#10 albedo

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Posted 15 November 2015 - 03:41 PM

Often, when looking at individuals homozygous for the MTHFR 677T variant (rs1801131), i.e. having the 677T/T genotype, and implications for cardiovascular disease (e.g. high homocysteine etc ..) we rightly read a lot about folate status and supplementation benefit (e.g. using l-methylfolate).

 

However, riboflavin status gets rarely mentioned. Here is a nice study showing the importance of riboflavin which can be even more important to prevent hypertension for these people:

 

Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial.

 

"Abstract

Intervention with riboflavin was recently shown to produce genotype-specific lowering of blood pressure (BP) in patients with premature cardiovascular disease homozygous for the 677C→T polymorphism (TT genotype) in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). Whether this effect is confined to patients with high-risk cardiovascular disease is unknown. The aim of this randomized trial, therefore, was to investigate the responsiveness of BP to riboflavin supplementation in hypertensive individuals with the TT genotype but without overt cardiovascular disease. From an available sample of 1427 patients with hypertension, we identified 157 with the MTHFR 677TT genotype, 91 of whom agreed to participate in the trial. Participants were stratified by systolic BP and randomized to receive placebo or riboflavin (1.6 mg/d) for 16 weeks. At baseline, despite being prescribed multiple classes of antihypertensive drugs, >60% of participants with this genotype had failed to reach goal BP (≤140/90 mm Hg). A significant improvement in the biomarker status of riboflavin was observed in response to intervention (P<0.001). Correspondingly, an overall treatment effect of 5.6±2.6 mm Hg (P=0.033) in systolic BP was observed, with pre- and postintervention values of 141.8±2.9 and 137.1±3.0 mm Hg (treatment group) and 143.5±3.0 and 144.3±3.1 mm Hg (placebo group), whereas the treatment effect in diastolic BP was not significant (P=0.291). In conclusion, these results show that riboflavin supplementation targeted at hypertensive individuals with the MTHFR 677TT genotype can decrease BP more effectively than treatment with current antihypertensive drugs only and indicate the potential for a personalized approach to the management of hypertension in this genetically at-risk group."

 

Also let's also remember the difference between people in US and Europe: in US (and Canada?) I read foods are fortified with riboflavin while this is not the case in Europe.


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#11 albedo

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Posted 17 November 2015 - 06:25 PM

This is nutrigenomics. It's exciting and the future, but we have a long way to go.

Ta5

 

I very much agree with you but wish to dispel maybe the impression this might give that we are talking about something exotic or just futuristic. While, a lot needs to be done and, IMHO, help will surely come with more education and the effective use of computing technology, genetics is already used in the clinical practice since long time at least where the nutritional impact on specific diseases has clearly emerged. The examples often given are phenylketonuria, which might require a low phenylalanine diet, biotidinase deficiency which might require increasing biotin, hemochromatosis requiring less iron and several others.

 



#12 albedo

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Posted 18 November 2015 - 05:11 PM

I have been looking recently at choline for several reasons including its importance as acetylcholine neurotransmitter precursor and for liver health. As men, we do not have a lot of estrogen which looks to be a strong activator of the PEMT gene (a key gene to produce choline) and we rely very much on diet. For other reasons, I tend not to consume much of eggs yolks and red meats which are very rich in choline. Also, progressing with age, my liver enzymes, while in the reference ranges, shows signs of deterioration (e.g. when I look in particular at the AST/ALT ratio which tends to rise).  In addition, my brother tends to have some degree of non-alcoholic fatty liver (NAFLD) and with him I tend to have higher triglycerides too if I do nothing with my diet. Finally, with age, I tend to loose muscle mass and I read that increased creatine kinase after choline depletion is a sign of damaged muscles.

 

So, for all these reasons, I thought a good idea to use a modest supplementation of PPC (polyenylphosphatidylcholine or unsaturated phosphatidylcholine) which I recently increased from 900 to 1800 mg.

 

While my 23andMe profile results “typical” for NAFLD, that looks to be reported based only on one study on one marker (rs3772622 for AGTR1). So, I studied other genes and, at least for two, MTHFD1 and PEMT, my pro-action with PPC seems justified:

 

(1) Rs2236225 or variant 1958A on MTHFD1 shows an increase need of choline vs.people w/o this allele. E.g. see:

 

Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans

 

I am AA and as per the study I might need about the double of choline than being GG.

 

(2) Carriers of two copies of rs7946 variants V175M on PEMT are also about 2x more likely to have NAFLD than non carriers. E.g. see:

 

Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD).

 

I am TT and so I might be more susceptible to NAFLD which is probably the case with my brother?

 

A 3rd studied variant, rs12325817 on PEMT, related to estrogen response, is unfortunately not reported by 23andMe and I am looking how I can infer that information too to support my point.

 


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#13 albedo

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Posted 18 November 2015 - 10:14 PM

Something I forgot to add to my previous post:

 

As I tend to have a slightly elevated homocysteine and not fully convinced to add massive doses of TMG (betaine) to my folate, which seems not w/o risks, my increased choline could also be helpful in the recycling of homocysteine into methionine. E.g. see the Fig. 1 in the article:

 

Attached File  Folate mediated one carbon transfer.JPG   75.15KB   5 downloads

 

http://www.pnas.org/...2/44/16025.long

 

 


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#14 aribadabar

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Posted 20 November 2015 - 03:59 PM

Thanks for sharing your findings. - very informative!

 

I think I found very interesting results related to the risk of prostate cancer (for me, higher than average as per my 23andMe results) and nutritional interventions based on nutrigenetics (personal nutrition). I hope you find this helpful too.

As reported here, I have introduced soy foods (in particular tempeh because of fermentation but also tofu) and a small supplementation because of the genistein/daidzein isoflavones anti-proliferative effects.  I also follow an anti-inflammatory strategy in particular consuming fatty fishes and moderately supplementing with EPA/DHA. However, I never found a nutrigenetics study support both, till today…...

In 23andMe I found I am genotype AG for the gene ESR2 SNP rs2987983. The following Swedish study (1) “…provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene…”. This would mean (in 23andMe reporting conventions) AG or GG. The decrease is as high as -37%. On the other hand, using soy, the risk increases if you are genotype AA.

 

So it is better to test this particular SNP before deciding to use soy foods or isoflavones supplementation with the hope to reduce prostate cancer risks because you can make it worse.

 

A similar results apply for fatty fish consumption when you check for the SNP rs5275 in the pro-inflammation gene PTGS2 (aka COX-2). A similar study (2) by the same authors "... found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01) ..." Risk decreases is a substantial -71% and no benefit (despite no risk increase as in the other study) without the variant.  I am genotype AG for the rs5275, so I hope to benefit from fatty fishes or supplementation too.

 

(1)
Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer.
http://www.ncbi.nlm....pubmed/16921512

(2)

Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism

http://www.ncbi.nlm....pubmed/17066444

 

A few questions:

- I am also AG in the rs2987983. How worse is GG compared to AG in this case?

- Is AA variation in the rs5275 polymorphism mentioned in the second study good then? 

 

I have been looking recently at choline for several reasons including its importance as acetylcholine neurotransmitter precursor and for liver health. As men, we do not have a lot of estrogen which looks to be a strong activator of the PEMT gene (a key gene to produce choline) and we rely very much on diet. For other reasons, I tend not to consume much of eggs yolks and red meats which are very rich in choline. Also, progressing with age, my liver enzymes, while in the reference ranges, shows signs of deterioration (e.g. when I look in particular at the AST/ALT ratio which tends to rise).  In addition, my brother tends to have some degree of non-alcoholic fatty liver (NAFLD) and with him I tend to have higher triglycerides too if I do nothing with my diet. Finally, with age, I tend to loose muscle mass and I read that increased creatine kinase after choline depletion is a sign of damaged muscles.

 

So, for all these reasons, I thought a good idea to use a modest supplementation of PPC (polyenylphosphatidylcholine or unsaturated phosphatidylcholine) which I recently increased from 900 to 1800 mg.

 

While my 23andMe profile results “typical” for NAFLD, that looks to be reported based only on one study on one marker (rs3772622 for AGTR1). So, I studied other genes and, at least for two, MTHFD1 and PEMT, my pro-action with PPC seems justified:

 

(1) Rs2236225 or variant 1958A on MTHFD1 shows an increase need of choline vs.people w/o this allele. E.g. see:

 

Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans

 

I am AA and as per the study I might need about the double of choline than being GG.

 

(2) Carriers of two copies of rs7946 variants V175M on PEMT are also about 2x more likely to have NAFLD than non carriers. E.g. see:

 

Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD).

 

I am TT and so I might be more susceptible to NAFLD which is probably the case with my brother?

 

A 3rd studied variant, rs12325817 on PEMT, related to estrogen response, is unfortunately not reported by 23andMe and I am looking how I can infer that information too to support my point.

 

- I am AG in  Rs2236225 so how that compares to being AA or GG?

- I am also TT in rs7946 - what recommendation have you found to act against this mutation? Also increased choline intake?


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#15 albedo

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Posted 21 November 2015 - 02:53 PM

Thanks for sharing your findings. - very informative!

 


A few questions:

- I am also AG in the rs2987983. How worse is GG compared to AG in this case?

- Is AA variation in the rs5275 polymorphism mentioned in the second study good then? 

 

- I am AG in  Rs2236225 so how that compares to being AA or GG?

- I am also TT in rs7946 - what recommendation have you found to act against this mutation? Also increased choline intake?

 

Thank you for your feedback.

 

- I am also AG in the rs2987983. How worse is GG compared to AG in this case?

 

I do not know. As far as I can understand, the study differentiates only for TT and the carriers of the C allele, so meaning both CT and CC without further differentiation. CT is the case relevant for both of us thought, so why bothering? We both carry the allele for which isoflavones are protective at a specific dose. Key is “…For isoflavonoids, we found no overall association with risk of prostate cancer (Table III). However, when we stratified by nucleotide sequence in the SNP (-13950 T/C), risk decreased monotonically with increasing intake of isoflavonoids among TC/CC carriers, whereas no reduction in risk was seen for TT carriers…”.

 

When you take 1 as reference for TT you go down to 0.63 (for 116 mcg/day intake) which makes the -37% decrease in risk I mentioned in my post.

 

Attached File  Isoflavone intake and OR for PCa.png.jpg   236.56KB   5 downloads

http://www.ncbi.nlm....pubmed/16921512

 

- Is AA variation in the rs5275 polymorphism mentioned in the second study good then?

 

I do not think so. I think the protective allele for prostate cancer when taking salmon-type fish is the C (or G in 23andMe conventions: if confused with these conventions I find useful this link: http://www.snpedia.c...php/Orientation). But there seems to be no benefit if you do not have the variant. The study says:

“…Among subjects who were heterozygous or homozygous for the variant allele C of the SNP (+6365 T/C), high intake of salmon-type fish was associated with a significantly decreased relative risk of prostate cancer. Following multivariate adjustment, risk of prostate cancer was 72% lower among men who ate salmon-type fish once or more per week, when compared with men who never ate salmontype fish, whereas we found no significant association with salmon-type fish intake among subjects homozygous for the more common allele (T)…”

 

- I am AG in  Rs2236225 so how that compares to being AA or GG?

 

I guess simply you have less risk that me (AA) of being choline deficient at parity of other conditions, the risk allele hinting to requiring more choline being A.

 

- I am also TT in rs7946 - what recommendation have you found to act against this mutation? Also increased choline intake?

 

I would guess so and, as I have mutations in the BHMT too, the geneticgenie report recommends so. But there are no simple replies and here I think is the challenge of this emerging science, which can be overwhelmingly complex without use of more education and advances in AI and computing. I really refrain to jump too quickly to conclusions.  The issue looks confounded because of interactions with other possible mutation and folate status. There is some race differences too (Caucasian, Hispanic and African-American descent), see: http://www.snpedia.c...ndex.php/Rs7946.  The study says (full text at http://www.ncbi.nlm....les/PMC1256033/): “ … The requirement for choline (from diet or from PEMT synthesis) is spared, in part, by the availability of methyl groups from 1-carbon metabolism (via methyltetrahydrofolate) (42). It is possible that the PEMT SNP we describe will interact with other commonly known SNPs in humans. For example, the thermolabile variant (677C→T) of 5,10-methylenetetrahydrofolate reductase (MTHFR, E.C. 1.5.1.20) occurs in 15–30% of humans (43). We found that mice in which MTHFR was deleted develop fatty liver that resolves when mice are fed the choline metabolite betaine (43). These mice require more choline or betaine because homocysteine remethylation to methionine, in the absence of 1-carbon units via the folate pathway shifts to a pathway that uses choline as a precursor. Homocysteine can be remethylated to methionine by methionine synthase, using 5-methylfolate which is supplied by MTHFR (43). Alternatively, betaine:homocysteine methyltransferase (BHMT, EC 2.1.1.5) catalyzes a methyl transfer from betaine to homocysteine (43). When 5-methylfolate is not available, more betaine is required. Thus, humans who have diminished capacity to synthesize choline moiety via PEMT activity, and who have diminished capacity to form 5-methylfolate will have difficulty producing increased betaine from choline when it is needed for homocysteine methylation…”

 


Edited by albedo, 21 November 2015 - 02:57 PM.

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#16 albedo

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Posted 22 November 2015 - 12:59 PM

Continuing looking at choline, what I am discovering is the impact on DNA methylation. Even if this might seem trivial, we seem, with aging, progressing inexorably toward hypomethylation, which would mean our need of specific nutrients would increase over time if we want to push further away the appearance of several disease. Our needs looks far to be fixed in time.

 

“…Lack of methylation due to deficiency of methyl donors (e.g. folate, vitamin B 12 , choline and methionine) or inhibition of DNA methyltransferases during life leads to transposon activation and promoter silencing when the activated transposons insert themselves adjacent to a house-keeping gene promoter [12–14] . As a consequence of these mishaps occurring stochastically, there is a relentless shift towards global DNA hypomethylation and tumour suppressor gene silencing with age, which leads to alterations in the genotype (due to chromosome malsegregation), gene expression profile, cellular phenotype and an increased risk of cancer [12, 14]…”

 

http://www.ncbi.nlm....les/PMC3121546/

 


Edited by albedo, 22 November 2015 - 01:13 PM.

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#17 albedo

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Posted 26 November 2015 - 04:27 PM

This study points to a strong reduction of colorectal cancer when diminishing red meat consumption by looking at (fast) NAT1/NAT2 genotypes. There are several gene variants involved. The paper is on free access. It is not a big surprise for red meat (and smoking) but it is the first time I discover a genetic susceptibility.

 

Effect of NAT1 and NAT2 Genetic Polymorphisms on Colorectal Cancer Risk Associated with Exposure to Tobacco Smoke and Meat Consumption.

http://cebp.aacrjour...nt/15/1/99.long

 

Abstract

N-Acetyltransferases 1 and 2 (NAT1 and NAT2), both being highly polymorphic, are involved in the metabolism of aromatic and heterocyclic aromatic amines present in cigarette smoke and red meat cooked by high-temperature cooking techniques. We investigated the effect of differences in acetylation capacity, determined by NAT1 and NAT2 genotypes, on colorectal cancer risk associated with exposure to tobacco smoke or red meat consumption. In this population-based case-control study in Germany, 505 patients with incident colorectal cancer and 604 age- and sex-matched control individuals with genotyping data and detailed risk factor information were included. Genotyping of NAT1 and NAT2 genetic polymorphisms was done using a fluorescence-based melting curve analysis method. The association between genotypes, environmental exposures, and colorectal cancer risk was estimated using multivariate logistic regression. Colorectal cancer risk associated with active smoking was elevated after accumulation of 30+ packyears of smoking [odds ratio (OR), 1.4; 95% confidence interval (95% CI), 0.9-2.2] but not significantly modified by either NAT1 or NAT2 genotype. Exposure to environmental tobacco smoke was associated with an increased risk for colorectal cancer only among NAT2 fast acetylators (OR, 2.6; 95% CI, 1.1-5.9 for exposure in childhood and adulthood). Frequent consumption of red meat significantly increased colorectal cancer risk for the group comprising all NAT2 fast acetylators or carriers of the NAT1*10 allele (OR, 2.6; 95% CI, 1.1-6.1) but not among those with ‘‘slow’’ NAT1 and NAT2 genotypes. Our findings indicate that NAT1 and NAT2 genotypes may contribute jointly to individual susceptibility and that heterocyclic aromatic amines may play an important role in colorectal cancer associated with red meat and possibly also exposure to environmental tobacco smoke.

 

 

 

 



#18 pamojja

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Posted 26 November 2015 - 09:47 PM

This is nutrigenomics. It's exciting and the future, but we have a long way to go.

 

For anyone with a chronic condition being disappointed from the outcomes with standard medicine, and therefore already exploring nutrient-epigenetic options, the future is already here.

 

 

Abstract 309: Twelve Year Followup for Managing Coronary Artery Diease Using a Nutrigenomics Based Diet and Supplement Program With Quarterly Assessment of Biomarkers
  1. Steven R Gundry

+ Author Affiliations

  1. The Cntr for Restorative Medicine, Intl Heart & Lung Institute, Palm Springs, CA
Abstract

Introduction: Coronary Artery Disease (CAD) is thought to be progressive; standard protocols call for a low fat/low cholesterol diet, exercise, and lipid lowering agents in an effort to slow the onset of recurrent MI’s, stents, CABG’s, stroke, or death. This results in an approximate 30-40% new event rate in 5 yrs.

Methods: Based upon our experience using a Nutrigenomic-based, Lectin-limited diet to prevent/reverse Metabolic Syndrome and CAD, we have enrolled and followed 978 pts (aged 42-89 yrs) with known CAD, defined as previous MI, stent, CABG, or positive stress test/angiogram, positive Corus score greater than 30, into a diet and supplement based, physician coached program, which emphasizes large amts of leafy green vegetables, olive oil, radical reduction of grain, legumes, nightshades, and fruits; and 4 oz amts of animal proteins, emphasizing shellfish, wild fish, and grass fed meats, while avoiding commercial poultry (Matrix Protocol). All Apo E 4 genotypes ate large amts of shellfish and avoided animal fats and cheeses. All pts were instructed to take 2-4,000 mg of high DHA fish oil, 200mg of Grape Seed Extract, and 50 mg of Pycnogenol per day. Supplements were individualized based on results of Advanced Cardiovascular Risk Markers, which were sent to three core labs, (Berkeley Heart Labs, and Singulex, Alameda, CA, Health Diagnostics Labs, Richmond,VA) q 3 months and followed to measure compliance and to change supplement/eating regimens.

Results: Pts have been followed for 1.5 to 12 years (mean 9 yrs). While enrolled, 13/978 pts (1.3%) have received a new stent, two that were predicted by a rising Lp-PLA2, two required CABG, based on a rising Corus score, despite HDL’s of 110-120 mg/dl. There have been no MI’s, unstable angina. One pt underwent carotid endarterectomy ; one pt suffered a CVA and died, while in atrial fibrillation, A second pt expired from a ruptured cerebral berry aneurysm. Total CV events over 12 years is 16/978 (1.6%).

Conclusions: We conclude that simple Nutrigenomic-based dietary interventions, emphasizing lectin avoidance, with compliance and supplement choices based upon q 3 month assessment of biomarkers, represents a quantum leap forward in preventing/modifying Cardiovascular events in known CAD patients.

Key Words:
  • Author Disclosures: S.R. Gundry: Consultant/Advisory Board; Modest; SINGULEX.

  • © 2015 by American Heart Association, Inc.

 

 

With standard protocols (low fat/low cholesterol diet, exercise, and lipid lowering agents) 1 in 3 patients experiences a new adverse event within 5 years.

 

With Nutrigenomic-based dietary interventions (reduction of grains, real food, individualized supplementation) only about 1 in 60 patients experiences a new adverse event within 9 years.


Edited by pamojja, 26 November 2015 - 09:48 PM.

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#19 albedo

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Posted 27 November 2015 - 03:10 PM

 


 

 

 

 

With standard protocols (low fat/low cholesterol diet, exercise, and lipid lowering agents) 1 in 3 patients experiences a new adverse event within 5 years.

 

With Nutrigenomic-based dietary interventions (reduction of grains, real food, individualized supplementation) only about 1 in 60 patients experiences a new adverse event within 9 years.

 

I liked it Pamojja, impressive. Do you hav more details. Has this been published? Looks like a oral abstract in a congress.


 



#20 albedo

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Posted 28 November 2015 - 10:03 AM

A perspective at the future and what should be done to progress (regarding impact on prostate cancer) in particular with massive use of computing.

 

I also report the two tables in the review giving a list of SNPs we can check for our own (we discussed a couple in the previous posts):

 

Nutrigenetics and Prostate Cancer: 2011 and Beyond

Abstract
Background/Aims: Prostate cancer runs in families and shows a clear dietary involvement. Until recently, the key risk gene(s) have proved elusive. We summarise current understandings of
nutrient-gene interactions in prostate cancer risk and progression. Methods: A MEDLINE-based literature search was conducted. Results: Hypothesis-directed candidate gene approaches provide
plausible, albeit statistically weak, nutrient-gene interactions. These are based on early understandings of factors likely to impact on carcinogenesis, including both nutrient and genetic effects on androgen biosynthesis and action, xenobiotic metabolism, DNA damage and DNA repair. Non-hypothesis-directed genome-wide association studies provide much stronger evidence for other genes, not hitherto suspected for involvement. Although only a few of these have been formally tested for dietary associations in well-designed epidemiologic studies, the nature of many of the genes suggests that their activity may be regulated by nutrients. These effects may not only be relevant to prostate cancer susceptibility, but also to disease progression. Conclusions: It will be important to move beyond studying single nucleotide polymorphisms, into more complex chromosomal rearrangements and to epigenetic changes. For future progress, large international cohorts will not only need to provide proof of individual nutrient-gene interactions, but also to relate these to more complex nutrient-gene-gene interactions, as parts of pathways. Bioinformatics and biostatistics will be increasingly important tools in nutrigenetic studies beyond 2011.

http://www.ncbi.nlm....pubmed/21646812

 

Attached File  PCa gene studies.PNG   239.44KB   3 downloads

 

Attached File  PCa GWAS gene studies.PNG   331.08KB   3 downloads

 

From the conclusions: "...Early studies on nutrient-gene interactions on prostate cancer looked at nutrients and SNPs one at a time. In consequence, data were often far from compelling, and p values of most studies not greatly above significance. GWAS approaches have used hundreds of thousands of SNPs, and have the potential to identify a large number of potentially valid genetic associations with prostate cancer. However, these approaches do not generally integrate environmental factors such as diet. A number of well-powered validation studies will be necessary to elucidate clear mechanisms of how genetic polymorphisms influence the individual’s response to dietary factors in prostate cancer in terms of absorption and metabolism. Current commonly used approaches do not provide information on genomic rearrangements or on epigenetic events, and alternative technologies will be essential to integrate these into the evolving picture. Bioinformatics and biostatistics will also become increasingly important in designing future nutrigenetic studies on prostate cancer..."


Edited by albedo, 28 November 2015 - 10:15 AM.


#21 Aurel

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Posted 28 November 2015 - 09:05 PM

Albedo: Do you keep a spreadsheet for your SPN findings? I find it hard to keep track of all the studies which claim some correlation from SPNs to certain risks.



#22 albedo

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Posted 29 November 2015 - 10:46 AM

I do not Aurel and for the moment, as studying the field, I am just looking more in depth at what literature says on mutations related to a particular risk. The typical example is what I discovered on the effect of phytoestrogens intake and ER gene polymorphism on prostate cancer risk looking at rs2987983 as reported in my previous post.

 

Your question points indirectly and let me think to different conceptual frameworks of nutrigenomics and metabolomics. I am trying to clarify these to myself but basically it gets to the point of both using a scientifically validated integrated system biology approach where we understand the metabolic paths of nutrients (which can turn to be overwhelmingly complex) vs. what I called previously an AI approach  where we do not need that in first place but can quickly get to hypothesis generation, recommendations and treatments hypothesis to be further confirmed in dedicated studies. The following (free access) paper explains this in more details:

 

Attached File  Metabolomics approaches.PNG   149.33KB   3 downloads

http://www.ncbi.nlm....pubmed/22540256

 

"...Artificial intelligence approach

An alternative (Fig 2C) is to use systems data and associated detailed health outcomes data with artificial intelligence. For this, data for a large reference population would be assembled into a cumulative data matrix so that data for an individual can be queried against the matrix to obtain the best matches to directly predict outcomes. Although less attractive from a scientific point of view, this may be more effective in rapidly providing personal predictions for human nutrition because of the extensive variability of human diet, individual genetics, etc. An advantage of this approach is that the power of prediction would increase with the number of individuals in the database and the period of time over which data are collected. Progress with virtual clinical data warehouses (14; 96) and information systems (36; 105) provide capabilities to use metabolomics data to support this approach to personalized nutrition. Although there are many practical issues concerning policy and implementation of such new approaches, the conceptual development has advanced to enable nutrition scientists to effectively use nutritional metabolomics toward the long-term goal of improved individual nutritional assessment, health prediction and therapeutic intervention..."

 

"...An artificial intelligence approach can take advantage of nutritional metabolomics (systems data) as in Panel B but does not require mechanistic development. In this case, artificial intelligence approaches are used to compare personal profiles to profiles and outcomes within a reference population to obtain the best matches for prediction. This has advantages that there is no delay in building models and the power increases with the size of the reference population. On the other hand, due to the correlative nature of these statistical models, there is has no scientific foundation to facilitate development of new interventional strategies. Based upon Voit and Brigham (89)..."

 



#23 albedo

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Posted 29 November 2015 - 01:16 PM

Aurel, you might be interested to check this site:

 

http://www.diygenomi...pp/gen_data.php

 

"...Side-by-side comparison of consumer genomic services (deCODEme, Navigenics, and 23andme) by locus, gene, and variant for 20 conditions (diabetes, cancers, heart disease, etc.). If a company reviews the variant, the underlying research reference is posted in the table below. 'Sample data' displays the normal allele in green, the risk allele in red (risk allele identification methodology). 'Rank' is a composite score assigned to the variant by DIYgenomics per journal ranking, number of cases and controls, p-value, and odds ratio (rank assessment methodology)..."

 

Also, for the record here, there is a quite large initiative from New York Genome Center and Columbia University, called DNA.LAND which I am considering. I am not yet registered. My main interest, beside contributing to research, would be their so called "imputation":

 

" ... Fill in the gaps: convert your genome into a more complete sequence. DNA is inherited in chunks, which allows us to infer sites that occur on the same chunk even though they have not actually been sequenced..."

 

See also: http://www.nature.co...na-land-1.18514

 

"...This allows the project to infer the identities of gene variants that were not originally tested, filling in gaps on the basis of knowledge about specific markers that are often inherited together. Participants will be told about newly identified genetic variants uncovered by imputation. The researchers also have promised to tell participants if the work uncovers that they have relatives in the project database...."

 

 



#24 albedo

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Posted 04 December 2015 - 01:05 PM

Continuing looking at nutrigenomics, choline, non-alcoholic fatty liver (NAFLD) etc. I found an interesting (while quite complex) metabolomics (free access) study.

 

Metabolomics can be considered a sub-section of Nutrigenomics (not to be confused with Nutrigenetics), next to Transcriptomics and Proteomics, see picture from X. Zhang et al).

 

Attached File  Zhang et al Nutritional Research.PNG   60.06KB   2 downloads

 

The study exemplifies, looking at choline metabolism, the very interesting role of gut microbiota in the host metabolism and its importance regarding the damaging trimethylamine-N-oxide (TMAO) choline metabolite which is a right concern for NAFLD and atherosclerosis.

 

My bottom line concrete lesson is that, if you want to increase your level of choline, eventually because of your specific genotype, you are better off also to maintain a very healthy gut microbiota. Supplementation with good probiotics and prebiotics could turn to be a good idea.

 

Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

 

“… We show in this study a significant association between a specific metabotype, e.g., low plasma phosphatidylcholine (PC) and high urinary methylamines and genetic predisposition to HFD-induced NAFLD in mice” … “In fact, methylamines are coprocessed by gut microbiota: We have reported that germ-free mice do not excrete TMA and have shown the fundamental role of microbiota in TMA production from its precursor choline (26). Hence, urinary excretion of methylamines (TMA, TMAO, and dimethylamine) is directly related to gutmicrobiota metabolism. Thus, these metabolites can be used as a probe of microbial metabolism of choline in the metabolic crosstalk between host and symbionts. This microbial bypass leads to a reduction of choline bioavailability for the host (compared with the dietary fatty acid uptake in liver induced by HFD), as denoted by lower PC levels (see Fig. 8), and seem to trigger NAFLD in return (12). Such significant association indicates that the altered gutmicrobial metabolism of choline plays a role in the development of NAFLD, as detailed below…”

 

“…This work strongly supports the idea that complex metabolic disease traits are a product of extended genome (superorganism) perturbations under the influence of an external stressor, in this case, a dietary change. We show that a specific metabotype with low plasma PC and high gut microbiota-mediated urinary excretion of methylamines is associated with the predisposition to impaired glucose homeostasis and NAFLD…”

 

http://www.pnas.org/...3/33/12511.full

 

 



#25 albedo

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Posted 04 December 2015 - 05:18 PM

I looked at my selenium status and prostate cancer risk. I always wondered on this as population studies results are very confusing, finding null results or either positive or negative risk associations.

 

Again, if you look at genotype, you might start gathering some guidance.

 

E.g. this nice (open access) review has a section (4) on “Genetic Variants in Selenoprotein Genes and Prostate Cancer”. The Table 3 lists all the SNP’s you can look at and the references.

 

My preliminary and quick result is that, as my baseline is already pretty high with my diet and I use a very modest supplementation, I need basically no change, certainly not using the massive supplementation doses (e.g. 200 or even 400mcg/d) some recommend, I guess too generically.

 

Selenium and Chronic Diseases: A Nutritional Genomics Perspective

http://www.ncbi.nlm....les/PMC4446770/

 

Other cancers including breast and colorectal are also reviewed more in depth in their relation to selenium status.

 

From the conclusions I noted in particular:

 

“… This observation reveals an extra level of complexity when considering the relationship between Se and health, as the effects of a genetic variant on disease risk not only depends on the function of the corresponding protein but as well on the biological pathway it is involved in (and the presence of SNPs altering this pathway) and on the hierarchical distribution of Sec between selenoproteins and Se bioavailability…

 

… Another lesson from genetic epidemiological studies is that the role of selenoproteins and the consequences for downstream molecular targets may differ between tissues. These observations uncovered potential new clues to understanding the role of specific selenoproteins in certain tissues and molecular pathways and their implication in mechanisms underpinning diseases. The study of these mechanisms, using a functional genomics approach, has the potential to contribute to the identification of early disease susceptibility markers and to the design of novel disease prevention strategies, based on personalised dietary recommendations of Se to individuals, depending on their genetic makeup, Se status and other risk factors..."

 



#26 albedo

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Posted 06 December 2015 - 12:11 PM

I was looking at fish consumption (which I do, mostly using fatty fishes for anti-inflammatory, anti pro-inflammatory arachidonic acid reasons) and colon cancer risks. I found a study looking at rs9658163 (-789C>T) in PPARdelta exemplifying, similarly to the case of soy/isoflavones consumption posted before, an inverse association for the common genotype CC, meaning positive as the risk decreases, as well as an association, meaning more risky, for the different genotypes, here CT and TT:

 

Colorectal adenoma risk is modified by the interplay between polymorphisms in arachidonic acid pathway genes and fish consumption

http://carcin.oxford...6/2/449.long#T1

 

“…A statistically significant interaction was observed between fish consumption and SNP c.-789CàT in PPARd for adenoma risk. An inverse association was observed for those with the CC genotype and highest tertile (T3) of fish consumption as compared with those with the lowest tertile (T1) of fish consumption (OR 0.65, 95% CI 0.41--1.02). However, for those with the CT or TT genotype fish consumption increased risk (T3 versus T1, CC genotype: OR 2.22, 95% CI 0.78--6.36)…”

 

So not only you have a different response to quantity of foods you consume (here fish) per your genotype but also the response can go in a different sense and dietary recommendations should be different !



#27 Aurel

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Posted 06 December 2015 - 01:21 PM

Sadly 23andme is not recording this SNP (rs9658163)



#28 albedo

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Posted 06 December 2015 - 03:22 PM

...Metabolomics can be considered a sub-section of Nutrigenomics (not to be confused with Nutrigenetics), next to Transcriptomics and Proteomics, see picture from X. Zhang et al)...

 

I wish to make a correction to this statement which is conceptually very misleading. What I meant is that Nutrigenomics (not to be confused with Nutrigenetics) together with progresses in Genomics also uses the advances in the fields of Metabolomics as well as Transcriptomics and Proteomics. However, the latter technologies are not sub-sections of it.



#29 albedo

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Posted 06 December 2015 - 03:33 PM

Sadly 23andme is not recording this SNP (rs9658163)

That is strange. Are you sure? I was doing the 23andMe test in 2011 already, presumably using one of their early chip versions and that SNP is reported. I am CC. Have you been in the "Browse Raw Data" tab and entered rs9658163? If it does not work, I wonder (I am not using it though so I have no experience) if the DNA.LAND site I mentioned before can be used to infer your genotype via their "imputation" process.

 

Should I find something more I will let you know.

 


Edited by albedo, 06 December 2015 - 03:53 PM.


#30 sthira

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Posted 06 December 2015 - 06:14 PM

Sadly 23andme is not recording this SNP (rs9658163)


This is true for me also. rs9658163 isn't genotyped when searching the 23&me's raw data.





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