248 replies to this topic

[albedo]

At the border between personalized nutrition and medicine (which should be kind of a continuum in a self enriching balance), to me the following looks important and worth attention when considering the evidence, the diabetes (DM) and cardiovascular disease (CVD) costs and the simplicity of treatment using Vitamin E in haptoglobulin (Hp) 2-2 genotypes. I do not know an easy way to genotype for Hp though (comments?).

 

Please allow me to use the wording of the study (bold mine):

 

“People suffering from diabetes mellitus (DM) are prone to an array of complications in target organs. Accelerated atherosclerosis is prevalent in this population, and is a leading cause of morbidity and mortality. Interventions to tightly control plasma glucose levels have been proven vital in the control of microvascular complications[1, 2]. However, the importance of strict glycemic control on macrovascular clinical outcomes is a matter of considerable debate[3]. Additionally, interventions to control cardiovascular (CV) risk such as life-style interventions and pharmacotherapy with statins and angiotensin converting enzyme inhibitors are not always applicable, due to patient preferences or related costs[4], as well as questionable effectiveness[5, 6]. In this respect, it is of paramount importance to assess new and novel approaches to control atherosclerosis in DM, outside the scope of traditional health-care.”

 

“Dr Levy is the author of a series of patents which claim that the Hp genotype is predictive of CVD in individuals with DM and that vitamin E may be used in combination with the Hp genotype”

 

“Haptoglobin (Hp) is an abundant plasma glycoprotein synthesized by hepatocytes. Two classes of functional alleles (1 and 2) have been identified at the Hp locus on chromosome 16q22, with homozygous (1-1 or 2-2) and heterozygous (2-1) genotypes possible”

 

“The best known function of Hp is to bind free hemoglobin (Hb) released from red blood cells[21], which is released into the blood during the natural turn-over of red cells. Free Hb is capable of causing considerable oxidative tissue damage as a result of its heme iron. However, whenever Hb is released into the circulation it immediately binds to Hp with extremely high affinity (Kd ~10-15) to form an Hp-Hb complex. The binding of Hp to Hb serves to inhibit the oxidative potential of Hb by preventing the release of heme iron from Hb[25-27].”

 

“Studies have shown that Hp 2-2-Hb complexes are cleared less efficiently than non Hp 2-2-Hb complexes [25, 27]. In DM individuals this phenomenon is more pronounced due to the down regulation of CD163, particularly in Hp 2-2 individuals[30]”

 

“Meta-analysis of the HOPE and ICARE data showed that vitamin E significantly reduces a composite of CV mortality, MI and stroke in Hp 2-2 diabetes patients (OR 0.58, confidence interval (CI) 0.4-0.86), while having no influence in Hp 1-1 or Hp 1-2 diabetes patients[42].”

 

“The requirements for Hp typing, although not readily available for commercial use, are expected to be simple and inexpensive. In the broader context of public, policy-makers’, and professionals’ attention moving towards personalized medicine[47]..”

 

Is it time to screen for the haptoglobin genotype to assess the cardiovascular risk profile and vitamin E therapy responsiveness in patients with diabetes?

http://www.ncbi.nlm....pubmed/22427005

[albedo]

Herewith an excellent initiative (Quisper), out of EU funded projects such as Food4Me and NU-GO to operate an IT platform to integrate scientifically validated data for personalized nutrition advice:

 

"...The purpose of Quisper is to enhance health of the public by organizing, developing and exploiting an independent and scientifically sound digital information platform as a supporting tool for creating marketable personalized nutrition and lifestyle advice services as well as for research in the area of health oriented dietary behaviour change and the role of personalizing nutrition and lifestyle advice..."

 

"...The origin of Quisper is the EU-funded QuaLiFY project (Quantify Life – Feed Yourself). We’ve been working together for two years to create a platform called Quisper, which is short for Qualify Server Platform or Quality information services for personalised advice..."

 

The beta version is limited for the time being to research organizations and companies. I am checking for a possibility to access it and will possibly report here if successful.

 

http://quisper.eu/qsp4you/

 

Edited by albedo, 30 April 2016 - 03:37 PM.

[albedo]

Interesting prospective, case-control candidate gene, replicated study, looking at metabolic syndrome (MetS) measured by ”… waist circumference, increased fasting blood glucose, increased triacylglycerol (TAG), decreased HDL cholesterol (HDL-C), and increased systolic/diastolic blood pressure..” and link to omega-3/omega-6 fat intake. (bold mine)

 

"...rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers..." (odds 1.65)

 

“…Such an approach may also be useful in developing personalized dietary recommendations wherein genetic profile may determine choice of dietary therapy to aid responsiveness to dietary fatty acid…”

 

It has been pointed that the fact that the dominant G allele predisposes to MetS hints to that we evolved a mean to efficiently store excess calories which was beneficial in the past. However, the environment has dramatically changed (obesity epidemic) and the minor allele A maybe have been evolved recently to advantage us in recent times.

 

Leptin Receptor Polymorphisms Interact with Polyunsaturated Fatty Acids to Augment Risk of Insulin Resistance and Metabolic Syndrome in Adults

http://jn.nutrition..../140/2/238.long

[albedo]

Looks like a very interesting read. Trying to get hold of the paper:

 

Nutritional interventions for Alzheimer's prevention: a clinical precision medicine approach

http://www.ncbi.nlm....pubmed/27116241

 

Alzheimer's disease (AD) is a major source of morbidity and mortality, with the disease burden expected to rise as the population ages. No disease-modifying agent is currently available, but recent research suggests that nutritional and lifestyle modifications can delay or prevent the onset of AD. However, preventive nutritional interventions are not universally applicable and depend on the clinical profile of the individual patient. This article reviews existing nutritional modalities for AD prevention that act through improvement of insulin resistance, correction of dyslipidemia, and reduction of oxidative stress, and discusses how they may be modified on the basis of individual biomarkers, genetics, and behavior. In addition, we report preliminary results of clinical application of these personalized interventions at the first AD prevention clinic in the United States. The use of these personalized interventions represents an important application of precision medicine techniques for the prevention of AD that can be adopted by clinicians across disciplines.

[albedo]

For the women on this Board, a suggestive hint to how lowering risks of breast cancer, if it turns to be true. In any case an additional reason to test status in your next blood tests. I am happy on the negative risk correlation with folate:

 

Plasma Riboflavin and Vitamin B-6, but Not Homocysteine, Folate, or Vitamin B-12, Are Inversely Associated with Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition-Varese Cohort

http://jn.nutrition....bstract?papetoc

 

"Conclusions: High plasma vitamin B-6 and riboflavin may lower breast cancer risk, especially in premenopausal women. Additional research is necessary to further explore these associations."

 

"Plasma homocysteine, folate, and vitamin B-12 were not associated with breast cancer risk."

 

[albedo]

This paper by G Bowman (now at Nestlè) et al. makes a good case on the effects of nutrition on cognition and brain volume. In particular, it looks at the effects of vitamins B (B1, B2, B6, Folate and B12), C, D, and E status (group BCDE) on cognition and volume MRI in the dementia-free oldest (87 average age). If you look at Table 3 you could see the best pattern is with the BCDE group compared with the worst pattern (trans fats). Similarly in Table 4 for brain volume. Other nutrients seem to play an intermediate role.

 

More in detail the text says:

 

“… Subjects with higher BCDE scores had better global cognitive function, particularly in domains of executive, attention, and visuospatial function. Participants with higher plasma trans fat scores had worse cognitive function overall (memory, attention, language, processing speed, and global). Subjects with higher NBP5-marine omega-3 scores had better executive function…”

 

“… Subjects with higher plasma BCDE scores had more TCBV and those with higher trans fat scores had less TCBV…”

 

Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging

http://www.ncbi.nlm....les/PMC3280054/

ABSTRACT

Objective: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders.

Methods: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n  104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. Results: Mean age was 87 [1] 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine -3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine -3 pattern and white matter hyperintensity volume.

Conclusion: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population.

[albedo]

This paper by G Bowman (now at Nestlè) et al. makes a good case on the effects of nutrition on cognition and brain volume.....

 

Dr Gene Bowman presented these and other results under the title "Novel Therapeutic Nutrition" at the last week Brain Forum 2016 in a four speaker session dedicated to holistic therapeutic approaches to AD. The paper I found is 1 out of 3 quoted in his slides.

 

 

(see 02:36:40 and on)

 

Moreover, if you are interested to the full four speakers session on AD check same link above at 01:54:10 and on.

[9lives]

My 2 cents to an already great thread .... I recently stumbled upon a personalized/ gene-based diet website which is very comprehensive and does all the work for you. It's literally a gold mine. Here's how to use it:

1) Get your 23andMe DNA results
2) Create an account on gbhealthwatch and connect it to 23andMe (free)
3) Look at your results for macronutrients, vitamins, minerals, and health conditions. It may suggest increasing/decreasing these nutrients (likely in comparison to your DRI's), or bypassing certain genetic defects (such as MTHFR)

I would say lifestyle factors and lab results should be considered when putting together your eating regimen. Also, the epigenetic foods that others have posted are another piece of the puzzle. I have a list that I've been maintaining as well.

[albedo]

Thank you 9lives for posting. I did not know about that company. It adds to a list of 50+ I know having entered the market with more or less success. Some have shut down operation, some do not offer DTC (Direct To Consumer) services and are associated to health professionals. Use them as general guidelines for your own research and as base of discussion eventually with clinicians and/or dieticians.

[tunt01]

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.

 

 

I read through this study.  I was wondering how you determine your required intake of choline.  Are you testing creatine kinase or just relying on homocysteine?

[albedo]

An interesting interplay between folate/methionine status and selenium supplementation, the latter being quite controversial:

 

Benefits of Selenium Supplementation on Leukocyte DNA Integrity Interact with Dietary Micronutrients: A Short Communication

http://www.ncbi.nlm....les/PMC4882662/

 

"... Our extreme subgroup data showed that Se supplementation benefits for the leukocyte DNA integrity is accomplished only by those with lower dietary folate and higher dietary methionine intakes. For those with sufficient levels of folate intake and lower levels of methionine intake, Se supplementation was not favourable for the leukocyte DNA integrity. Se supplementation significantly increased the CCK18 levels at both extremes, indicating increased homeostatic apoptotic potential of this supplement. The extremes of H₂O₂-induced DNA damage had no significant association with the CCK18 levels, although a trend is seen among those with lower folate and higher methionine intakes recording non-significantly higher CCK18 levels. Our complete dataset reiterates the influence of supplemented Se on DNA integrity especially in the presence of high methionine intake..."

[albedo]

 

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.

 

 

I read through this study.  I was wondering how you determine your required intake of choline.  Are you testing creatine kinase or just relying on homocysteine?

 

 

Thank you for the interest and bringing this up. Unfortunately, I did not test so far for the creatine kinase so basically I am just watching at homocysteine as well as all the B vitamins. Yes, “...serum CPK may be a useful clinical marker for choline deficiency in humans...”(1). It might be a very good idea and complement the homocysteine test. I am scheduling a new set of test and I will look into it. It also relates to muscle mass loss, a condition we tend to have with age and read that increased creatine kinase after choline depletion is a sign of damaged muscles (2). Also, I still think that, with my moderate PPC intake, the use of a good probiotics is good strategy

 

You seem looking at all this in detail, would like to know your findings! Thanks.  

 

(1) Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts.

http://www.ncbi.nlm....pubmed/15213044

 

(2) "...Abnormally elevated biomarkers of organ dysfunction in the blood, including creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase, are corrected upon choline repletion..."

http://lpi.oregonsta...trients/choline

 

Edited by albedo, 30 May 2016 - 02:23 PM.

[tunt01]

I was reading this blog post about MTHFD1 and it made me remember your thread.  I am heterozygote for MTFHD.  I don't have any final views yet.  Per the paper:

 

 

Humans were deemed to have signs of organ dysfunction associated with choline deficiency if they had more than a 5-fold increase of serum CK activity while on the choline depletion diet and if this increased CK resolved when they were returned to the repletion diet (9), or if they had an increase of liver fat content by 28% or more while on the choline depletion diet and if this increased liver fat resolved when they were returned to the repletion or ad libitum diet (20). 

 

 

 

I will test creatine kinase when I re-test homocysteine.  I'm not sure it will tell me anything, but the cost is tiny.  I don't have any firm views on this, but I think I have very similar genetics to you.  I think I need to spend some time better understanding the pentose pathway.

[albedo]

I was reading this blog post about MTHFD1 and it made me remember your thread.  I am heterozygote for MTFHD.  I don't have any final views yet.  Per the paper:

 

 

Humans were deemed to have signs of organ dysfunction associated with choline deficiency if they had more than a 5-fold increase of serum CK activity while on the choline depletion diet and if this increased CK resolved when they were returned to the repletion diet (9), or if they had an increase of liver fat content by 28% or more while on the choline depletion diet and if this increased liver fat resolved when they were returned to the repletion or ad libitum diet (20). 

 

 

 

I will test creatine kinase when I re-test homocysteine.  I'm not sure it will tell me anything, but the cost is tiny.  I don't have any firm views on this, but I think I have very similar genetics to you.  I think I need to spend some time better understanding the pentose pathway.

 

You are better off not having final views in this area, they might be dangerous ... ;-)

 

More seriously, I guess you cannot say much after MTHFD1 because of heterozygoticy while I have it worse being homozygous. Thank you for the blog. I was in particular also intrigued by the comment (1) on adrenal fatigue which I might be suffering. 

 

After you post I decided to include CK in the next tests, on the choline and muscle health rationale.

 

(1) "...Taken together, this could, in theory, mean people with an MTHFR or MTHFD mutation are more prone to adrenal fatigue, assuming the science linking thiamine status to adrenal function is correct..."

 

Edited by albedo, 30 May 2016 - 03:42 PM.

[albedo]

For those concerned by iron over absorption and storage the following genes and their variants should be evaluated prior to trying and counteract (e.g. with IP6 etc ..): HFE, HJV, TFR2 and HAMP.

 

Probably the most important is HFE with the following variants most likely increasing risk of iron storage:

 

rs1800562 --> risk allele A (http://www.snpedia.c...x.php/Rs1800562)

rs1799945 --> risk allele G (http://www.snpedia.c...x.php/Rs1799945)

rs1800730 --> risk allele T (http://www.snpedia.c...x.php/Rs1800730)

 

The rs1800562 seems to be the most relevant in terms of clinical hemochromatosis.

[tunt01]

 

 

More seriously, I guess you cannot say much after MTHFD1 because of heterozygoticy while I have it worse being homozygous. Thank you for the blog. I was in particular also intrigued by the comment (1) on adrenal fatigue which I might be suffering. 

 

Heterozygotes behaved like homozygotes in the study.

 

[9lives]

I happen to be heterozygous for MTHFR C677T and homozygous for MTHFD1 1958G>A. I've been following the methylation research of Dr. Ben Lynch and Dr. Amy Yasko, and I was able to fix my chronic anxiety and homocysteine levels. Their research corroborates the findings on the downstream effect on choline deficiency and adrenals as a result of undermethylation. I think fixing choline should fix CK. However it's a bit frustrating that while a lot of progress has been made in methylation treatment, there still doesn't seem to be any clear answers for MTHFD1 blocks in particular. 

 

This is a work in progress, but my current workaround for myself is this:

* I can't post any links yet, but Google for Ben Lynch's "folate methionine cycle pathway planner" to find the diagram I'm referring to 

1) Treat the methionine cycle independently with TMG, especially if you have the BHMT mutation. This is a bypass to help you synthesize the SAMe, phosphatidylcholine, creatine, gene expression, all the things that are dependent on that cycle. Note that BHMT is only in the liver, kidneys, and eyes, but MTHFR is in every cell. So, ...

2) Treat the folate cycle independently. Supplementing with methylfolate is good, because you can't produce enough without a fully functioning MTHFD1 gene. You still need folate rich foods/ supplements from a raw food source because even though MTHFD1 is still working (albeit harder), you can't produce purines for DNA synthesis if you're not engaging the proper pathway and just taking methylfolate. De novo purine synthesis is not sufficient either to meet your needs.

3) Take methylcobalamin to treat the methionine and folate cycle as a group. Allows excess methylfolate to get pushed through the methionine cycle or recycled to THF.

 

 

[9lives]

@prophets - can you please share the link to that study? I'm curious to know if the cohort had other mutations affecting methylation (which would likely have a compounding effect), or if they were able to isolate for each mutation.

[tunt01]

@prophets - can you please share the link to that study? I'm curious to know if the cohort had other mutations affecting methylation (which would likely have a compounding effect), or if they were able to isolate for each mutation.

 

 

The study is discussed above in prior comments.

[albedo]

... Heterozygotes behaved like homozygotes in the study...

I agreed your post. I am a bit surprised the AA genotype seems to behave similarly as AG. My guess is that in the heterozygous situation the “positive” allele, in this case G, is working very efficiently for the expression and doing its job despite the risky A allele. The study brings some limitations with statistics as the author also indicate, another reason to better test my choline levels in the next works at least indirectly looking at both homocysteine and CK. I definitively need to understand all this better, post more as you discover. Thank you for having brought this up as I missed that aspect.

 

[albedo]

Because of my markers, I am very caution with dairy but I admit I have it hard to eliminate it. It is also very high in my list of things to watch for the increasing risk of prostate cancer.

 

These two studies point to common genotypes for four SNPs useful to watch if we are concerned by our cholesterol levels and dairy consumption:

 

“…Genetic variations in ABCG5, CYP7A1, and DHCR7 may contribute to differing responses of serum cholesterol to dairy intake among healthy adults…”

 

ABCG5 (ATP-BINDING CASSETTE, SUBFAMILY G, MEMBER 5), rs6720173, GG homozygous

CYP7A1 (CYTOCHROME P450, SUBFAMILY VIIA, POLYPEPTIDE 1), rs3808607, G carriers

DHCR7 (7-DEHYDROCHOLESTEROL REDUCTASE), rs760241, A carriers

 

Common Variants in Cholesterol Synthesis– and Transport–Related Genes Associate with Circulating Cholesterol Responses to Intakes of Conventional Dairy Products in Healthy Individuals

http://jn.nutrition....5/1008.abstract

 

 

In another prior study the same group of authors report, next to ABCG5, CYP7A1, also an additional SNP for the SREBF2 gene:

 

“…These findings accordingly suggest the existence of a gene-diet interaction modulating the impact of dairy intake on circulating cholesterol levels…”

 

SREBF2 (STEROL REGULATORY ELEMENT-BINDING TRANSCRIPTION FACTOR 2), rs2228314, GG homozygous

 

The impact of dairy consumption on circulating cholesterol levels is modulated by common single nucleotide polymorphisms in cholesterol synthesis- and transport-related genes

http://www.fasebj.or...pplement/1038.4

 

I had no time yet to get hold and read the full papers but checked my status: GG, GT, GG and CG for the above SNPs ordered from top to bottom.

[albedo]

..... I've been following the methylation research of Dr. Ben Lynch and Dr. Amy Yasko, and I was able to fix my chronic anxiety and homocysteine levels. Their research corroborates the findings on the downstream effect on choline deficiency and adrenals as a result of undermethylation. I think fixing choline should fix CK....

 

Thank you for your post. I liked the information you provided and the link to Dr Ben Lynch. I just listened his interview of Quantified Body: lot of good information and a balanced view coming from real clinical experience: https://thequantifie...n-dr-ben-lynch/.
 

[albedo]

Two polymorphisms of the C3 gene (Complement Component 3) would be important to look at to modulate risks of metabolic syndrome in particular adapting the intake of PUFA.

 

“…rs11569562 GG homozygotes had decreased MetS risk compared with minor A allele carriers …which was augmented by high plasma PUFA status… GG homozygotes had lower C3 concentrations than those in AA homozygotes (P = 0.03) and decreased risk of hypertriglyceridemia compared with A allele carriers …which was further ameliorated by an increase in long-chain n–3 (omega-3) PUFAs…or a decrease in n–6 PUFAs…

 

…rs2250656 AA homozygotes had increased MetS risk relative to minor G allele carriers… which was exacerbated by low n–6 PUFA status…”

 

Complement component 3 polymorphisms interact with polyunsaturated fatty acids to modulate risk of metabolic syndrome.

http://www.ncbi.nlm....pubmed/19828715

 

I also have touched on other genes impacting metabolic disorders also here, and here resp. for TCF7L2 and FTO.

Edited by albedo, 05 June 2016 - 01:27 PM.

[albedo]

I continued to look at cholesterol, probably one of the best characterized and clinically validated biomarkers for CVD. I pop into this truly outstanding review paper, very complete and one of the few looking at gene x diet interactions:

 

Nutrigenetics of cholesterol metabolism: observational and dietary intervention studies in the postgenomic era

http://www.ncbi.nlm....pubmed/26117841

 

The Fig 1 resumes the SNPs analyzed in the paper and makes a good point in emphasizing something we tend to forget and we should keep in mind when considering nutritional recommendations, i.e. the smallness of impact on phenotype of common SNPs vs. the rare ones:

 

 Cholesterol SNPs.PNG   78.3KB   2 downloads

 

“Cholesterol metabolism is a well-defined responder to dietary intakes and a classic biomarker of cardiovascular health. For this reason, circulating cholesterol levels have become key in shaping nutritional recommendations by health authorities worldwide for better management of cardiovascular disease, a leading cause of mortality and one of the most costly health problems globally. Data from observational and dietary intervention studies, however, highlight a marked between-individual variability in the response of cholesterol metabolism to similar dietary protocols, a phenomenon linked to genetic heterogeneity. This review summarizes the postgenomic evidence of polymorphisms within cholesterol-associated genes relative to fasting circulating cholesterol levels under diverse nutritional conditions. A number of cholesterol-related gene-diet interactions are confirmed, which may have clinical importance, supporting a deeper look into the rapidly emerging field of nutrigenetics for meaningful conclusions that may eventually lead to genetically targeted dietary recommendations in the era of personalized nutrition.” (red mine)

 

Edited by albedo, 13 June 2016 - 10:05 AM.

[albedo]

Cardiovascular disease protective SNP alleles in PON1 gene with high polyphenols intake:

 

rs854549 --> C

rs854552 --> C

rs854571 --> T

rs854572 --> C

 

Interaction between polyphenols intake and PON1 gene variants on markers of cardiovascular disease: a nutrigenetic observational study

http://www.ncbi.nlm....pubmed/27338244

 

"... Using a nutrigenetic approach, we identified protective genotypes in four independent polymorphisms that, at Bonferroni level (p ≤ 0.0028), present a significant association with increased HDL level under high polyphenols and anthocyanins intake, compared to risk genotypes (rs854549, Beta = 4.7 per C allele; rs854552, Beta = 5.6 per C allele; rs854571, Beta = 3.92 per T allele; rs854572, Beta = 3.94 per C allele)..."

 

"...PON1 variants could represent novel biomarkers to stratify individuals who might benefit from targeted dietary recommendation for health promotion and strategies of preventive medicine..."

 

Edited by albedo, 05 July 2016 - 02:39 PM.

[albedo]

In addition to my previous posts here and here, additional evidence pointing at sub-optimal levels of riboflavin (vitamin B2) here interacting with the C677T MTHFR status and blood pressure:

 

Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition.

 

"Clinical deficiency of the B-vitamin riboflavin (vitamin B2) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5-13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required." (red mine)

 

http://www.ncbi.nlm....pubmed/27170501

 

[albedo]

Epigenetic Modifications by Dietary Phytochemicals: Implications for Personalized Nutrition

http://www.ncbi.nlm....les/PMC4153856/

 

"...Such findings suggest that not all individuals respond identically to a diet. The single-nucleotide polymorphism, copy number, epigenetic events, and transcriptomic homeostasis influence the response of food components and ultimately health, including cancer risk.

 

Based on the studies mentioned in this review, it is clear that these phytochemicals act on the different epigenetic targets leads to the epigenetic modifications. Some of dietary phytochemicals (such as Genistein, Phenethyl isothiocyanate, Curcumin, Sulforaphane, Organosulfur, Compound, Resveratrol and Indole-3-carbinol) act on the inhibition of deacetylation of histone protein, whereas other phytochemicals (such as EGCG, Genistein and Curcumin) act on the inhibition of acetylation of histone protein during epigenetic modifications. Dietary phytochemicals (such as EGCG, Genistein, Organosulfur, Compound, Lycopene, Phenethyl isothiocyanate, Curcumin, Sulforaphane and Resveratrol) inhibit the DNA methylation process by activating DNA methyletranferase enzymatic activity. It has also been reported that some of dietary phytochemicals play an important role in the modulation of overall epigenetic modifications (Histone modifications, DNA methylations and miRNA)..."

[albedo]

I did not read the full paper and just wonder how common these SNPs are and how personalized nutrition can modulate the children cognition risks they would imply:

 

Associations Between the KIAA0319 Dyslexia Susceptibility Gene Variants, Antenatal Maternal Stress, and Reading Ability in a Longitudinal Birth Cohort

http://onlinelibrary...s.1534/abstract

 

"Abstract.  Maternal stress during pregnancy has been associated with detrimental cognitive developmental outcomes in offspring. This study investigated whether antenatal maternal perceived stress and variants of the rs12193738 and rs2179515 polymorphisms on the KIAA0319 gene interact to affect reading ability and full-scale IQ (FSIQ) in members of the longitudinal Auckland Birthweight Collaborative study. Antenatal maternal stress was measured at birth, and reading ability was assessed at ages 7 and 16. Reading data were available for 500 participants at age 7 and 479 participants at age 16. FSIQ was measured at ages 7 and 11. At age 11, DNA samples were collected. Analyses of covariance revealed that individuals with the TT genotype of the rs12193738 polymorphism exposed to high maternal stress during pregnancy possessed significantly poorer reading ability (as measured by Woodcock-Johnson Word Identification standard scores) during adolescence compared with TT carriers exposed to low maternal stress. TT carriers of the rs12193738 SNP also obtained lower IQ scores at age 7 than C allele carriers. These findings suggest that the KIAA0319 gene is associated with both reading ability and general cognition, but in different ways. The effect on IQ appears to occur earlier in development and is transient, whereas the effect of reading ability occurs later and is moderated by antenatal maternal stress."

[albedo]

Along the same line of predicting postprandial glycemic response using AI posted previously, the following metabolomic approach seems to have a more powerful prediction capability (as compared to purely genetics) to predict diabetes looking at the mostly correlated 3x branched chain amino acids (leucine, isoleucine and valine) and 2x aromatic amino acids (phenylalanine, tyrosine) profiles (e.g. see Table 2 and 3 of the following study)

 

"...Individuals in the top quartile of individual plasma amino acid levels had a 2- to 3.5-fold higher odds of developing diabetes over the 12-year follow-up period, compared with those whose plasma amino acid levels were in the lowest quartile. Odds ratios for the metabolites remained strong when models were further adjusted for parental history of diabetes, and serum triglycerides, which were higher in cases than controls. Findings were also similar after adjustment for dietary intake of protein, amino acids, and total calories, and in the subgroup of individuals with propensity scores in the lowest tertile..."

 

"...There has been interest in genetic risk prediction, but the known diabetes polymorphisms add modestly to risk assessment27,28. For instance, known polymorphisms are only associated with 5% to 37% increases in the relative risk of diabetes, compared with the 60% to 100% increases in risk that we observed with elevation in amino acids...."

 

I think the combination of powerful "omics" technologies (here metabolomics and to less extent genomics) and the discovery of clinically relevant biomarkers (potentially here the 3x BCAAs and 2x AAAs) when combined to AI and machine learning are very powerful tools to proactively and aggressively pursue dietary changes for people at high risk (and contain, by the same token, the explosive costs of the epidemic).

 

We need well trained doctors and dieticians to help!

 

Metabolite Profiles and the Risk of Developing Diabetes

http://www.ncbi.nlm....les/PMC3126616/

 

 

 

 

[albedo]

Nice study. I found better explained two complementary approaches to personalized nutrition exemplified in Fig. 3, sort of traditional vs. AI, which I touched also here:

 

Diet–microbiota interactions as moderators of human metabolism
http://www.nature.co...ature18846.html

"It is widely accepted that obesity and associated metabolic diseases, including type 2 diabetes, are intimately linked to
diet. However, the gut microbiota has also become a focus for research at the intersection of diet and metabolic health.
Mechanisms that link the gut microbiota with obesity are coming to light through a powerful combination of translationfocused
animal models and studies in humans. A body of knowledge is accumulating that points to the gut microbiota as a
mediator of dietary impact on the host metabolic status. Efforts are focusing on the establishment of causal relationships
in people and the prospect of therapeutic interventions such as personalized nutrition. "(bold mine)