250 replies to this topic

[albedo]

I am looking at free radicals and food antioxidants.

 

I passed a couple of years ago a simple and specific oxidative stress test which turned to be very positive. The practitioner told me that the test indicated, in his opinion, an optimal intake of antixoditative nutrients and supplements and I should not change strategy.

 

There is huge information out there but I read about two genes which caught my attention.

 

The first looks key in determining the required balance between healthy and unhealthy inflammatory response. The enzyme myeloperoxidase (MPO) is key to generate hypochlorous acid for antibacterial fight. Too much release of these free radicals, necessary to fight infection, can explain why chronic inflammation is harmful. One SNP (-463G>A; rs2333227) in the MPO gene is associated with its lower expression and reduced enzymatic activity as explained in this study:

 

Plasma myeloperoxidase level and peripheral arterial disease

http://www.ncbi.nlm.nih.gov/pubmed/21950958

 

I am reported (by dna.land imputation) as CT hence carrying the SNP and a partially reduced activity. This looks to me an indication I have genetically a balanced activity of the enzyme which on one side would require more anti-inflammatory foods compared to the situation if I were say CC (non carrier) but on the other side I should not overdo it with free radical quenchers (this seems more and more a good general strategy, anyway) as I am not TT.

 

Similarly, I looked at the catalase CAT enzyme, important against free radicals in particular hydrogen peroxide degrading it to water and oxygen. It is not the only one by far but it is important. It is quite known that too high hydrogen peroxide concentration is causative of early graying of hair. The SNP CAT -262 C>T (rs 1001179) is linked to a reduced catalase activity:

 

Association of CAT polymorphisms with catalase activity and exposure to environmental oxidative stimuli.

http://www.ncbi.nlm....pubmed/16298864

 

I am CC hence non carrier. If CT or TT you might consider increasing you catalase and generally your antioxidative weaponry but watch how tricky this can be: in women with the CAT -262 CC genotype, increasing consumption of fruits and vegetables reduces the already relatively low breast cancer risk but not in those with one or two T alleles as one would expect (see this reference).

 

We seems lacking a full understanding of the effects of antioxidants in foods and as usual it is good to be on the safe side and have a balanced view. Also this points again and again to the need of having (genetically) educated nutritionists and the use of AI in matching your genotype, phenotype and personal nutrition advise, imho.

Edited by albedo, 19 February 2016 - 05:17 PM.

[albedo]

I continued looking at the prostate cancer risk for specific SNP and nutrition interventions.

 

Some aspects were touched in my post here which looked at rs5275 of COX-2. This next new study looks to have a broader scope:

 

Dietary Omega-3 Fatty Acids, COX-2 Genetic Variation, and Aggressive Prostate Cancer Risk

http://www.ncbi.nlm....les/PMC2749066/

 

They looked and supported omega-3 intake for their anti-inflammatory effect and decreased risk of prostate cancer development and progression. “…Higher intake of any and total LC n-3s were significantly associated with a strong dose response reduction in prostate cancer risk…” (Table 3). Then they looked how the reduction is modified by several SNPs again on the COX-2 inflammatory regulating gene. They looked at 9 different SNPs (rs689466, rs20417, rs2745557, rs5277, rs2066826, rs5275, rs2206593, rs689470 and rs4648310) out of which 5 (rs2745557, rs5277, rs2206593, rs689470, rs4648310) had high statistically significant associations with prostate cancer (Table 5). For one (rs4648310), the risk reduction was even stronger when increasing omega-3 intake. The study “…demonstrates that the dietary long-chain omega-3 fatty acids (LC n-3), EPA, DPA and DHA, are inversely associated with aggressive prostate cancer. This potential protective effect may be modified by genetic variation in COX-2, whereby the deleterious effect of one SNP (rs4648310, +8897 A>G) was reversed by the LC n-3 effect…”

 

I looked at Table 5 and checked against my 23andMe results. My genotype turned out to be reference for the 5 SNPs, so I do not carry the mutations which are studied but you might wish to check yours and decide about your intake of omega-3 free fatty acids.

[albedo]

I continued looking at lipid metabolism and gene-diet interaction, adding to the post 55 in this thread.

 

Here I wish to list several other studies and accordingly what I retained as dietary recommendation to decrease my CVD risks.

 

"bad" LDL

      

First look at https://www.snpedia.com/index.php/APOE for a good understanding of the "APOE type" definition based on the two SNPs rs7412 and rs429358 of the APOE gene. I am a “typical” E3/E3 with decreased risk of Alzheimer Disease (x0.60 of average), being rs7412 (CC) and rs429358 (TT).  Now, compared with E3/E3, E2 carriers have about 20% less risk of CVD and E4 has higher risk. E2/E2 has 31% lower LDL when compared with E4/E4 (1).  APOE genotype can modulate the effects of typical saturated fat diets on lipid metabolism in a population with total fat intake less than 30% and higher LDL was found in all genotypes (2). I take this and the following supporting in my case a low saturated fat diet.

 

Second, if you are under statin treatment, the two SNPs (rs7412, rs429358) defining the E2, E3 and E4 isoforms of apolipoprotein E are significantly associated with percent reduction in LDL using atorvastatin (3). I am not yet under statins but use a far surrogate (as red yeast rice) which might also have some effect.

 

Third, look at rs405509 (intergenic, aka -219G>T). Carriers of the T variant show higher apoB and LDL when following a saturated fat diet and when compared with the GG genotype (4).  I do have both apoB in the higher range of the reference and LDL often higher than the reference. Confirming this phenotype, I am TT per 23andMe (or AA in dbSNP) and need to highly care about lowering my saturated fats and increasing vegetables to reduce CVD risk

 

"good" HDL

 

Look at rs1800588 of the LIPC gene (aka -514C/T). It may influence the levels of “good” cholesterol HDL. Generally, the T allele is considered to lead to higher protective HDL levels when consuming <30% of energy from fats (5). I am CT and this supports me (not really rigorously though) following the Zone diet approach (40/30/30 energy percentage from carbs/protein/fats). "...When total fat intake was > or =30% of energy, mean HDL-C concentrations were lowest among those with the TT genotype, and no differences were observed between CC and CT individuals...". Carriers of TT, “…may have an impaired adaptation to higher animal fat diets that could result in higher cardiovascular risk...” (6)

 

Triglycerides (TG)

 

Look at rs328 and rs1059611 on the LPL gene. Both SNPs have been related to lipid concentrations, in particular TG, and interact with plasma omega-6 level (7). “…Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P<0.001) …we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P<0.05)….” (7). I am respectively CC and TT for rs328 and rs1059611, not carrying the minor alleles, hence I assume I cannot say much from the study looking at my level of omega-6. In any case the latter is relatively low as I am trying to target a omega-6/omega-3 ratio of at least 2:1;  our seemingly ancestral 1:1 ratio looking very difficult to realize today.

 

I hope this helps!

 

1. Association of apolipoprotein E genotypes with lipid levels and coronary risk

http://www.ncbi.nlm....pubmed/17878422

2. Gene-diet interactions and plasma lipoproteins: role of apolipoprotein E and habitual saturated fat intake

http://www.ncbi.nlm....pubmed/11119301

3. An association study of 43 SNPs in 16 candidate genes with atorvastatin response

http://www.ncbi.nlm....pubmed/16103896

4. Apolipoprotein E gene promoter -219G->T polymorphism increases LDL-cholesterol concentrations and susceptibility to oxidation in response to a diet rich in saturated fat

http://www.ncbi.nlm....pubmed/15531693

5. https://www.snpedia....x.php/Rs1800588

6. Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism: evidence of a strong dose effect in this gene-nutrient interaction in the Framingham Study

http://www.ncbi.nlm....pubmed/12403660

7. Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism

http://www.ncbi.nlm....pubmed/21840003

 

[albedo]

While not suffering of hypertension I looked at SNPs recently found to affect metabolism disorders and in particular high blood pressure.

 

rs7903146 and rs17685538 in the TCF7L2 gene

 

“…Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). Methods: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. Results: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. Conclusions/interpretation: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR…”  (1)

 

I am CT for rs7903146 which is reputed bad in Promethease for other reasons but I interpret it good for my blood pressure. On the other side, being CG for rs17685538 with the minor allele being G confirms my previous post result to limit saturated fatty acids (also linked in the paper to my rs11196224 being CT hence carrying the minor T allele). The higher blood pressure in carriers of the minor allele G of rs17685538 looks limited to those with high saturated fatty acids plasma (SFA) concentrations only.

 

rs1042713 (aka G46A) in the ADRB2 gene

 

“… Mean (±SEM) PRA was significantly higher in participants in the DASH group than in participants in the control group (0.68 ± 0.03 compared with 0.54 ± 0.03 ng · mL−1 · h−1, P = 0.002). Serum aldosterone, urinary aldosterone, and urinary potassium concentrations were also significantly higher in the DASH group (P < 0.01 for all). We observed significant gene-diet interactions for changes in systolic blood pressure (SBP) and concentrations of aldosterone and urinary potassium (P for interaction = 0.048, 0.017, and 0.001 for SBP and aldosterone and urinary potassium concentrations, respectively). There was an association between the A allele of β2-AR G46A and greater blood pressure reduction and blunted aldosterone and PRA responses to the DASH diet…” (2)

 

The Dietary Approaches to Stop Hypertension (DASH) diet is rich in potassium, magnesium, and calcium and lowers BP at normal concentrations of sodium intake (see ref. 15 in the paper). I am AG for rs1042713 with A being the minor allele as reported by dbSNP and should respond better, in particular regarding blood pressure, to such a diet.

 

1. Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: from the LIPGENE study.

http://www.ncbi.nlm....pubmed/21115178

2. Beta2-adrenergic receptor genotype affects the renin-angiotensin-aldosterone system response to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern.

http://www.ncbi.nlm....pubmed/20519561

[albedo]

Sorry if this is repeat (I had a problem with my browser) and in case you have missed it.

 

I liked the following video by Dr. Rhonda Patrick. It is a simple introduction to the field and has the advantage to practically touch a small set of very well known SNP affecting the gene-diet interaction.

 

How to Personalize Your Nutrition Based On Genetics (Revised 3/19/15)

[albedo]

I went thought the above video of Dr. Rhonda Patrick. If you register to her site you can download a convenient transcript with the references listed and additional information. Recommended.

 

I thought convenient to resume here the genes, the SNPs and the influenced nutrients/markers/risks she discussed:

 

MTHFR (rs1801133, rs1801131) --> folate, vitamin B6, vitamin B12, choline

FADS2 (rs1535) --> alpha linolenic acid (ALA) to anti-inflammatory eicosapentaenoic acid (EPA) fatty acid conversion

FADS1 (rs174537, rs174548) --> arachidonic acid (AA) pro-inflammatory fatty acid level, LDL "bad" cholesterol , phosphatidylcholine

FUT2 (rs602662, rs492602) --> vitamin B12

APOE (rs429358, rs7412, rs429358) --> cholesterol, Alzheimer’s disease risk

FOXO3 (rs2802292) --> longevity

NBPF3 (rs4654748) --> vitamin B6

BCMO1 (rs7501331, rs12934922) --> beta-carotene to retinol conversion (vitamin A)

PEMT (rs7946) --> phosphatidylcholine

CYP2R1 (rs10741657, rs12794714, rs2060793) --> vitamin D levels

 

 

Edited by albedo, 02 March 2016 - 03:36 PM.

[albedo]

I mentioned magnesium and colorectal cancer risk in my post #52 in this thread.

Moreover, magnesium looks one of the most important nutritional factors for prevention of diabetes 2 (DMT2). It does not surprise me as it is involved with at least 300 different enzymatic reactions requiring it. When you combine this to the fact that many people are magnesium deficient and to the horrible sugar fed diet, I think looking at the magnesium status is important.

 

This is a very interesting study, even if replication is warranted, pointing to two SNPs in the TRPM6 gene shown to increase 2x the risk of DMT2 for magnesium intake less than 250mg/day!

 

Common genetic variants of the ion channel transient receptor potential membrane melastatin 6 and 7 (TRPM6 and TRPM7), magnesium intake, and risk of type 2 diabetes in women

http://www.ncbi.nlm....pubmed/19149903

 

“Our haplotype analyses suggested a significant risk of type 2 diabetes among carriers of both the rare alleles from two non-synomous SNPs in TRPM6 (Val1393Ile in exon 26 [rs3750425] and Lys1584Glu in exon 27 [rs2274924]) when their magnesium intake was lower than 250 mg per day. Compared with non-carriers, women who were carriers of the haplotype 1393Ile-1584Glu had an increased risk of type 2 diabetes (OR, 4.92, 95% CI, 1.05-23.0) only when they had low magnesium intake (<250 mg/day).”

 

[albedo]

I continued looking at magnesium as in my previous posts here and here

 

I went through a nice GWAS study (see reference below) which I liked because:

• It is based on a large cohort
• It is also reproduced in a different, equally large cohort
• It looks at both associative and causative effects in magnesium metabolism and transportation (Table 2 and 4)
• It looks at hypomagnesia but also at the physiologically associated estimated glomerular filtration rate (eGFR), fasting glucose, and bone mineral density (Table 3)

I checked all the quoted SNPs. Should you have the same patience and myself not being a geneticist maybe you can critic my conclusion:

 

I paid attention mainly to my causative and associative SNPs for which I am homozygous in the trouble making alleles presenting commonly or rarely:

• Associative (common): rs11144134 (in the TRPM6) is quite common and has the largest effect on the magnesium serum level; I am homozygous in the coded allele which is inversely associated to magnesium level (Table 2). The study reconfirms the known effect of TRPM6 polymorphisms already mentioned in my previous post in relation to diabetes risk
• Causative (common): rs848305, rs17251221, rs11569033 (Table 4)
• Causative (rare) for rs948100 in FXYD2 (Table 4)
• Associative (common): rs6746896, rs994430, rs4714146, rs2490281, rs3740393, rs11115332, rs2463021, rs4778439 and rs4778439 (Table 4)

While not homozygous, I do carry 3 other magnesium inversely associated alleles (rs3925584, rs448378 and rs4561213 in Table 2)

 

Bottom line: I can explain genetically, at least partially, my difficulties with magnesium absorption and the necessity for me to monitor serum levels and supplement with bioavailable forms as appropriate.

 

Reference

Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels.

"Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using approximately 2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5 x 10(-8)) or suggestive associations (p<4 x 10(-7)) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4 x 10(-7). Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels."

http://www.ncbi.nlm....pubmed/20700443

Edited by albedo, 11 March 2016 - 09:57 AM.

[albedo]

While only indirectly related to personal nutrition, I wish to post here an interesting study on the determination of functional SNPs following the GWAS associative studies.

 

GWAS has been hugely helpful to determine association between genetic variants and human disease. But causal variants determination increasing our susceptibility to disease is challenging. You can either follow the GWAS study with gene or protein expression studies or introducing a genetic variant in cell lines prior to assessing the impact on mRNA.

 

The following study follows the second path validated with a well known rs339331 SNP associated to prostate cancer in the very common T allele:

 

CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants

Abstract. The vast majority of disease-associated single-nucleotide polymorphisms (SNPs) mapped by genome-wide association studies (GWASs) are located in the non-protein-coding genome, but establishing the functional and mechanistic roles of these sequence variants has proven challenging. Here we describe a general pipeline in which candidate functional SNPs are first evaluated by fine mapping, epigenomic profiling, and epigenome editing, and then interrogated for causal function by using genome editing to create isogenic cell lines followed by phenotypic characterization. To validate this approach, we analyzed the 6q22.1 prostate cancer risk locus and identified rs339331 as the top-scoring SNP. Epigenome editing confirmed that the rs339331 region possessed regulatory potential. By using transcription activator-like effector nuclease (TALEN)-mediated genome editing, we created a panel of isogenic 22Rv1 prostate cancer cell lines representing all three genotypes (TT, TC, CC) at rs339331. Introduction of the 'T' risk allele increased transcription of the regulatory factor 6 (RFX6) gene, increased homeobox B13 (HOXB13) binding at the rs339331 region, and increased deposition of the enhancer-associated H3K4me2 histone mark at the rs339331 region compared to lines homozygous for the 'C' protective allele. The cell lines also differed in cellular morphology and adhesion, and pathway analysis of differentially expressed genes suggested an influence of androgens. In summary, we have developed and validated a widely accessible approach that can be used to establish functional causality for noncoding sequence variants identified by GWASs.

http://www.ncbi.nlm....pubmed/26398868

 

Also look at this:

 

Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.

http://www.ncbi.nlm....pubmed/19474294

[albedo]

Personalized Nutrition by Prediction of Glycemic Responses

 

Personalized Nutrition.PNG

 

"People eating identical meals present high variability in post-meal blood glucose response. Personalized diets created with the help of an accurate predictor of blood glucose response that integrates parameters such as dietary habits, physical activity, and gut microbiota may successfully lower postmeal blood glucose and its long-term metabolic consequences."

 

http://www.cell.com/...8674(15)01481-6

 

Well done video on the approach, exemplifying the need of personalized nutrition for predicting postprandial glycemic response:

 

 

 

Edited by albedo, 25 March 2016 - 10:07 PM.

[albedo]

I went thought the above video of Dr. Rhonda Patrick. If you register to her site you can download a convenient transcript with the references listed and additional information. Recommended.

 

I thought convenient to resume here the genes, the SNPs and the influenced nutrients/markers/risks she discussed:

 

MTHFR (rs1801133, rs1801131) --> folate, vitamin B6, vitamin B12, choline

FADS2 (rs1535) --> alpha linolenic acid (ALA) to anti-inflammatory eicosapentaenoic acid (EPA) fatty acid conversion

FADS1 (rs174537, rs174548) --> arachidonic acid (AA) pro-inflammatory fatty acid level, LDL "bad" cholesterol , phosphatidylcholine

FUT2 (rs602662, rs492602) --> vitamin B12

APOE (rs429358, rs7412, rs429358) --> cholesterol, Alzheimer’s disease risk

FOXO3 (rs2802292) --> longevity

NBPF3 (rs4654748) --> vitamin B6

BCMO1 (rs7501331, rs12934922) --> beta-carotene to retinol conversion (vitamin A)

PEMT (rs7946) --> phosphatidylcholine

CYP2R1 (rs10741657, rs12794714, rs2060793) --> vitamin D levels

 

Prophets has found that Dr. Rhonda Patrick put up on her FoundMyFitness site a new tool, still being developed/expanded, for nutrigenomics, linking to 23andMe database and providing your Rhonda's Genetic Report. I went though it and found useful information, she gives good links to literature and she is rightly cautioning that data are provided for research, educational and informational use only, not medical. Her work should be supported. Please refer to Prophet's post.
 

Edited by albedo, 26 March 2016 - 01:34 PM.

[albedo]

Also related to personalized nutrition, I thought useful to point here to the NU-AGE European project, also reported by Niner and myself somewhere else in this Forum on the microbiome, an in-depth studied subject by the leading NU-AGE project investigator, Dr Claudio Francesci, also known for promoting the so called inflammatory theory of aging:

 

"...The specific objectives of NU-AGE are to counteract the physical/cognitive decline by a whole diet intervention to assess the effect of a 65+ food pyramid using biomarkers to identify cellular/molecular targets/mechanisms responsible for the whole diet effect to perform genetic and epigenetic studies to assess the role of individual variability in the response to diet to adopt an integrative comprehensive approach to analyse the whole data set. The results of dietary intervention will be used to develop elderly-tailored functional foods. By dissemination activities and industrial exploitation NU-AGE will support EU strategies on nutritional recommendations, thus contributing to the implementation of legislation related to nutrition and health claims for elderly in Europe..."

http://www.nu-age.eu/about-project

Edited by albedo, 27 March 2016 - 12:40 PM.

[albedo]

 

Personalized Nutrition by Prediction of Glycemic Responses

 

Personalized Nutrition.PNG

 

"People eating identical meals present high variability in post-meal blood glucose response. Personalized diets created with the help of an accurate predictor of blood glucose response that integrates parameters such as dietary habits, physical activity, and gut microbiota may successfully lower postmeal blood glucose and its long-term metabolic consequences."

 

http://www.cell.com/...8674(15)01481-6

 

Well done video on the approach, exemplifying the need of personalized nutrition for predicting postprandial glycemic response:

 

 

 

The NYT run recently (Jan 2016) an article on the above quoted Weizmann Institute of Science's achievement and also quoted the European Food4Me project I started this personalized nutrition thread with:

 

A Personalized Diet, Better Suited to You

http://well.blogs.ny...ed-to-you/?_r=1

 

"...By combining data gleaned from subjects’ glucose responses with information about their gut bacteria, medications, family histories and lifestyles, the scientists devised an algorithm that accurately predicted blood sugar responses to foods the participants hadn’t yet eaten in the study..."

 

"...Dr. Mathers is the lead investigator of a six-month study, funded by the European Union, called Food4Me. Some 1,500 participants in seven European countries were randomly given personalized dietary advice based on their genetic data ..."

 

[albedo]

Here is an additional step forward by Big Blue and Italy, the sort of thing which will gather many smart people together and on topics several people in this Forum are thinking about at different levels. Clearly nutrigenomic and personalized nutrition will fit and I wonder if SENS might have join projects/co-funding interests too. Italy, their centenarians, the Mediterranean Diet (the right one though!), a fame for "good foods" and an excellence in science is likely not coincidental:

 

IBM Plans First Watson Health European Center of Excellence in Italy

"...launch its first Watson Health European Center of Excellence in Milan near the Human Technopole Italy 2040 research campus, supporting the government of Italy’s initiative to establish an international hub for the advancement of genomics, big data, aging, and nutrition..." (bold mine)

https://www-03.ibm.c...lease/49436.wss

[albedo]

Those being unfavorably homozygous for the C677T SNP in the MTHFR gene (rs1801131) might consider to check their vitamin status and, next to methylfolate, supplement also with riboflavin (vitamin B2) to lower risks associated to high homocysteine and the risks of cardio vascular diseases. In one case, for example, vitamin B2 was even more important than folate for osteoporosis (1).  The other risks which higher B2 intake might help lowering can be hypertension (2) and high homocysteine itself (3). This also adds to my previous post on riboflavin on this thread related to hypertension.

 

(1) Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.

http://www.ncbi.nlm....pubmed/17725378

 

(2) Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up.

http://www.ncbi.nlm....pubmed/22277556

 

(3) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.

http://www.ncbi.nlm....pubmed/16380544

Edited by albedo, 03 April 2016 - 07:36 PM.

[resveratrol_guy]

Those being unfavorably homozygous for the C677T SNP in the MTHFR gene (rs1801131) might consider to check their vitamin status and, next to methylfolate, supplement also with riboflavin (vitamin B2) to lower risks associated to high homocysteine and the risks of cardio vascular diseases. In one case, for example, vitamin B2 was even more important than folate for osteoporosis (1).  The other risks which higher B2 intake might help lowering can be hypertension (2) and high homocysteine itself (3). This also adds to my previous post on riboflavin on this thread related to hypertension.

 

(1) Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.

http://www.ncbi.nlm....pubmed/17725378

 

(2) Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up.

http://www.ncbi.nlm....pubmed/22277556

 

(3) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.

http://www.ncbi.nlm....pubmed/16380544

 

Can anyone explain to me how to look up MTHFR 677? I don't see any SNP code in that notation and Google isn't helping.
 

[sthira]

Those being unfavorably homozygous for the C677T SNP in the MTHFR gene (rs1801131) might consider to check their vitamin status and, next to methylfolate, supplement also with riboflavin (vitamin B2) to lower risks associated to high homocysteine and the risks of cardio vascular diseases. In one case, for example, vitamin B2 was even more important than folate for osteoporosis (1). The other risks which higher B2 intake might help lowering can be hypertension (2) and high homocysteine itself (3). This also adds to my previous post on riboflavin on this thread related to hypertension.

(1) Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.
http://www.ncbi.nlm....pubmed/17725378

(2) Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up.
http://www.ncbi.nlm....pubmed/22277556

(3) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.
http://www.ncbi.nlm....pubmed/16380544

Can anyone explain to me how to look up MTHFR 677? I don't see any SNP code in that notation and Google isn't helping.

rs1801131

[aribadabar]

 

Those being unfavorably homozygous for the C677T SNP in the MTHFR gene (rs1801131) might consider to check their vitamin status and, next to methylfolate, supplement also with riboflavin (vitamin B2) to lower risks associated to high homocysteine and the risks of cardio vascular diseases. In one case, for example, vitamin B2 was even more important than folate for osteoporosis (1).  The other risks which higher B2 intake might help lowering can be hypertension (2) and high homocysteine itself (3). This also adds to my previous post on riboflavin on this thread related to hypertension.

 

(1) Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.

http://www.ncbi.nlm....pubmed/17725378

 

(2) Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up.

http://www.ncbi.nlm....pubmed/22277556

 

(3) Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.

http://www.ncbi.nlm....pubmed/16380544

 

Can anyone explain to me how to look up MTHFR 677? I don't see any SNP code in that notation and Google isn't helping.
 

 

Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, and rs1801133 (C;T) heterozygotes have ~65% activity, compared to the unmutated variant, rs1801133(C;C).

[resveratrol_guy]

So 23andMe says that rs1801131 is G or T, but SNPedia says it's A or C. 23andMe says rs1801133 is A or G, but SNPedia says it's C or T. It's like they're talking about opposite sides of the double helix. Or, I'm just confused...

[aribadabar]

So 23andMe says that rs1801131 is G or T, but SNPedia says it's A or C. 23andMe says rs1801133 is A or G, but SNPedia says it's C or T. It's like they're talking about opposite sides of the double helix. Or, I'm just confused...

Both SNPs are regarding the MTHFR gene but the one that primarily governs the folate metabolism is rs1801133 . And yes, the A G C T discrepancy due to using the opposite strands of the DNA helix.

See the orientation article regarding this:

 

• A->T
• T->A
• C->G
• G->C

Edited by aribadabar, 04 April 2016 - 04:32 AM.

[resveratrol_guy]

According to SNPedia, then, I should have normal homocysteine levels, but also impaired folate metabolism. So the way I read that is that my homocysteine will get way out of whack if I fail to sustain sufficient (supranormal) folate intake. It certainly fits the data.

 

Nice work, both of you!

[aribadabar]

It looks like I am homozygous for both SNPs so I am doubly screwed. My hunch that B2 supplementation would also ( in addition to B6/B9/B12, and already added B1 for its nervous system beneficial effects) probably be required has been scientifically validated now.

 

Thank you for bringing this, albedo! 

[resveratrol_guy]

It looks like I am homozygous for both SNPs so I am doubly screwed. My hunch that B2 supplementation would also ( in addition to B6/B9/B12, and already added B1 for its nervous system beneficial effects) probably be required has been scientifically validated now.

 

Thank you for bringing this, albedo! 

 

Apart from taking the basic supplements required in your position, I suspect you could bring your risks of the more serious stuff back to baseline just by following some of the research here on Longecity. For example, honokiol has shown potent activity against various brain tumors. You risk is only about double the very low baseline risk, according to SNPedia. Honokiol alone might more than reverse that situation.

Edited by resveratrol_guy, 04 April 2016 - 02:34 PM.

[albedo]

I just looked at vitamin D after an informative post by resveratrol-guy and a very recent study on (decreased) cancer risk. I though useful to log it also in this thread:

 

Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study

http://journals.plos...al.pone.0152441

 

There is not a single week passing without good news about benefits of higher Vitamin D intake compared to RDA and this is surely one important addition.

 

However, I see limitations in applying it to myself as I am not a woman, hence prostate cancer, a concern of mine, is not considered. The authors also recognize a cancer non-specificity. Also, skin cancer, another concern of mine, is not included either.

 

Also it should be useful a mapping into the genetics which is not carried in the study. Dr Rhonda Patrick gives particular consideration to the CYP2R1 gene and rs10741657, rs12794714 and rs2060793. While my genotype is such the first two might tend to somehow “neutralize” as particularly associated to resp. higher and lower level of vitamin D, the 3^rd one is associated to a lower level but higher longevity hence supporting a cautionary approach in rushing to conclusions.

 

I still feel that my level (average 36.2 ng/ml (90 nmol/l) over 10 years) is not bad but I am ready to reconsider it to the light of the new study. Surely, I will ask my wife to retest and increase intake as she also has different cancer risks than mine. LEF has been advocating since a while a > 50 ng/dL (125 nmol/l) level, e.g. here. I have been always a bit skeptic to the light of the discussion on LC and risks of mortality, likely due to CVD, and my own 23andMe risk of atrial fibrillation.

 

I am scheduled to retest in summer after one year on a supplementation of 1000-2000 IU (summer and winter). I also kept using moderate K2 and increased magnesium due to potential problems with absorption. If I turn to be in the range of 30-35 ng/ml I might try to push it to the 40 or bit more as a new personal optimum and first step before more relevant evidence comes out. Will see .....

 

 

 

[albedo]

Adding to my previous post, I continued looking at Vitamin D.

 

The following large (30000+ individuals of European descent) GWAS study shows the power of nutrigenetics in particular here in discovering strong associations of very few numbers of genetic loci impacting clinically important and preventable risks (here up to 2.5x !) of Vitamin D insufficiency.

 

“…Variants at three loci reached genome-wide significance in the discovery cohorts, and were confirmed in the replication cohorts: 4p12 (overall P=1.9 × 10-109 for rs2282679, in GC); 11q12 (P=2.1 × 10-27 for rs12785878, near DHCR7); 11p15 (P=3.3 × 10-20 for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (P=6.0 × 10-10 for rs6013897). A genotype score was constructed using the three confirmed variants. Those in the top quartile of genotype scores had 2- to 2.5-fold elevated odds of vitamin D insufficiency (P≤1 × 10-26)…”

 

“…The identified SNPs may not be the causal variants, but rather in linkage disequilibrium with them…”

 

“…DHCR7/NADSYN1 is a novel locus for association with vitamin D status, but one with compelling biological plausibility…”

 

“…The gene at the second locus, CYP2R1, encodes a hepatic, microsomal enzyme first described in 2003…”

 

“…The third gene, GC, encodes DBP, a 52-59 kDA protein synthesized in the liver that binds and transports vitamin D and its metabolites (including 25-OH D and 1,25(OH)2D)...”

 

Common genetic determinants of vitamin D insufficiency: a genome-wide association study.

http://www.ncbi.nlm....pubmed/20541252

[albedo]

Next is a good study from leading researchers in the area of nutrigenomics. It reviews here, based on Medline research, the link to prostate cancer and I thought useful to log it in this thread as addition to findings in my previous post.

 

Tables 1 and 2 (and references therein) are useful to list the relevant SNPs and actionable nutrient interventions:

 

 candidate genes PCa.PNG   259.64KB   1 downloads

 

 GWAS PCa genes.PNG   383.97KB   1 downloads

 

The study educates on the different approaches (gene-candidate and GWAS) and gives a glimpse to future in particular with the results of the concrete NuGO network research, its creation of a ‘nutritional phenotype database’ (dbNP) “repository of publicly available data and knowledge to facilitate storage of biologically relevant, pre-processedomic data, as well as study-descriptive and study participant phenotype data.” and the necessity to move beyond the SNP study approach (e.g. using epigenetics and nutrient-gene-gene interactions).

 

Nutrigenetics and Prostate Cancer: 2011 and Beyond

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

 

 

 

[albedo]

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.

 

"This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food."

 

Molecular targets of dietary agents for prevention and therapy of cancer.

http://www.ncbi.nlm....pubmed/16563357

[albedo]

Excellent paper from one of the top scientist in the field, that while considering the challenges of personalized nutrition also gives a concrete plan and methodology to progress this research. I pop into the study looking at gene candidates for diabetes 2 (T2DM). Recommended. The Table 1 in the paper gives 11 candidate genes from genome-wide association studies, rs id's, risk/ref allele, risk allele frequency, odds (and references):

 

CDKAL1 rs7754840 C/G 0.31 1.12

CDKN2B rs10811661 T/C 0.83 1.20

CDKN2B rs564398 C/T – 1.12

FTO rs8050136 A/C 0.38 1.17

HHEX rs1111875 C/T 0.53 1.13

IGFBP2 rs4402960 T/G 0.29 1.14

IGFBP2 rs1470579 C 0.30 1.17

KCNJ11 rs5219 T/C 0.47 1.14

PPARG rs1801282 C/G 0.86 1.14

SLC30A8 rs13266634 C/T 0.65 1.12

TCF7L2 rs7903146 T/C 0.26 1.37

 

I am personally homozygous in the risk alleles for 3 and heterozygous for 4 out of the 11, hence I look at this risk carefully and watch my diet and biomarkers.

 

Nutrigenomics research for personalized nutrition and medicine

http://www.sciencedi...958166908000177

 

 

[albedo]

The genomics of micronutrient requirements

http://www.ncbi.nlm....les/PMC4434349/

 

"Healthy nutrition is accepted as a cornerstone of public health strategies for reducing the risk of noncommunicable conditions such as obesity, cardiovascular disease, and related morbidities. However, many research studies continue to focus on single or at most a few factors that may elicit a metabolic effect. These reductionist approaches resulted in: (1) exaggerated claims for nutrition as a cure or prevention of disease; (2) the wide use of empirically based dietary regimens, as if one fits all; and (3) frequent disappointment of consumers, patients, and healthcare providers about the real impact nutrition can make on medicine and health. Multiple factors including environment, host and microbiome genetics, social context, the chemical form of the nutrient, its (bio)availability, and chemical and metabolic interactions among nutrients all interact to result in nutrient requirement and in health outcomes. Advances in laboratory methodologies, especially in analytical and separation techniques, are making the chemical dissection of foods and their availability in physiological tissues possible in an unprecedented manner. These omics technologies have opened opportunities for extending knowledge of micronutrients and of their metabolic and endocrine roles. While these technologies are crucial, more holistic approaches to the analysis of physiology and environment, novel experimental designs, and more sophisticated computational methods are needed to advance our understanding of how nutrition influences health of individuals." (bold mine)

[albedo]

Two upcoming conferences, in EU and US, to check people and what is going on in this dynamic emerging new area of the nutrition research:

 

http://personalisednutrition-eu.com/

http://personalizednutrition-usa.com/