138 replies to this topic

[aribadabar]

 I read that it can decrease the endogenous production.

 

Can you please provide a link to that study?

 

Given that the endogenous production falls 10% per decade anyways I don't see supplementation being that negative.

[albedo]

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.

[SearchingForAnswers]

I wonder if this holds true for a1298c patients?

 

It's strange, my wife is c6777t homozygous, and really doesn't manifest symptoms. I'm a1298c homozygous, and I get them all. Not fair!

[albedo]

I wonder if this holds true for a1298c patients?

 

It's strange, my wife is c6777t homozygous, and really doesn't manifest symptoms. I'm a1298c homozygous, and I get them all. Not fair!

I do not know for you, the study does not mention this other mutation. It would be interesting to know how your wife is on the a1298c and her homocysteine. E.g. see this study:

 

The 1298A→C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine

" ...Recently, a second common mutation (1298A→C; glutamate to alanine) was reported, but this mutation was suggested to increase homocysteine only in individuals who carried the bp677 variant....In the Family Heart Study, fasting homocysteine was significantly higher (P<0.05) in individuals heterozygous for both substitutions, compared to individuals who carried only the 677C→T variant. This study suggests that two variants in MTHFR should be assessed as genetic risk factors for hyperhomocysteinemia."
 

Edited by albedo, 16 November 2015 - 02:52 PM.

[Kingsley]

. . .

 

Very interesting study, particularly for me as a hypertensive (or pre-hypertensive) person homozygous (TT) for C677T.  I'm skeptical though whether most of us homozygotes would get any benefits from further upping our riboflavin intake.  The study was limited to Europeans not taking B-vitamin supplements.  As noted by albedo and in the study, U.S. foods are fortified with riboflavin; plus most of us on this site probably supplement with B-vitamins anyway.

 

Makes you wonder if all the noise about C677T is overblown for those with sufficient riboflavin status.  I can't get past my personal subjective experience though of suffering increased cognitive deficits if I do not take methylfolate regularly or semi-regularly. 

[xEva]

Guys, I just got my geneticgene report and, out of 26 markers, 6 are 'no call'. Out of the remaining 20, only 5 are normal, 4 are homozygous (COMT V158M, COMT H62H, VDR Taq, MAO-A R297R) and the rest are heterozygous.

Am I gonna die tomorrow?

But seriously, how bad is it? and where do I start? With what supplements?

I'm sorry to have to ask, it's just a bit too overwhelming for now.

Thanks a lot

PS
but on the SNPmedia I read that those AAs TTs CCs GGs cannot be fully trusted, because of the differences in orientation when the data are read --?? Or was it the thing of the past?

[world33]

Hi xEva,
 
I suggest you to try nutrahacker.com (the basic version is free after filling a questionnaire) to see which supplements are recommended. Do not panic you are not gonna die tomorrow :-)
For the COMT V158M (rs4680) and COMT H62H (rs4633) homozygous mutations nutrahacker suggests the hydroxycobalamin type of Vitamin B12 (being hydroxycobalamin very unstable IM injections are best, sublilingual such as Perque Activated B-12 Guard second best)
For the VDR Taq (rs731236 ) homozygous mutation you can supplement with Vitamin D and make sure to get 10/15 minutes daily of sunshine especially in winter months.
For the MAO-A R297R (rs6323) nutrahacker suggests progesterone but I would not bother.
I would not worry at all if I were you.

Edited by world33, 17 November 2015 - 08:33 AM.

[xEva]

world33, thanks a lot!

nutrahacker was down for a week (apparently, due to a hack into the site). I just tried it again. It seems up but I got this message: "Your 23andMe account does not have a profile that has been genotyped." -?

I have read some MTHFR threads here, on 23andme and the dedicated site but my head is still swollen from info overload (despite having the allele for 'increased cranial capacity' lol). So far, just judging from my experience with supplements, I recall that methylated B6 was pretty good for me (though a normal variety was good too, maybe not quite as much -?)

And I'm confused about B12. Promethease also reported this:

rs602662(A;A)
Higher vitamin B12 levels The reduced activity of the FUT2 enzyme with the A allele may decrease susceptibility to bacterial infection and indirectly lower the risk of vitamin B12 malabsorption, thereby resulting in higher vitamin B12 concentrations in A allele carriers.

..and I don't recall various forms of B12 doing anything special for me. Also, despite being female, my hemoglobin has always been at the high end of normal (maybe due to perennially higher B12 -- or something else?). So.. I'm still struggling to reconcile all this info and appreciate whatever you can suggest.

[YOLF]

 

. . .

 

Very interesting study, particularly for me as a hypertensive (or pre-hypertensive) person homozygous (TT) for C677T.  I'm skeptical though whether most of us homozygotes would get any benefits from further upping our riboflavin intake.  The study was limited to Europeans not taking B-vitamin supplements.  As noted by albedo and in the study, U.S. foods are fortified with riboflavin; plus most of us on this site probably supplement with B-vitamins anyway.

 

Makes you wonder if all the noise about C677T is overblown for those with sufficient riboflavin status.  I can't get past my personal subjective experience though of suffering increased cognitive deficits if I do not take methylfolate regularly or semi-regularly. 

 

I don't think they add all that much riboflavin... it's like 25-25% RDV, the 100-500mg doses is like 5000% or something ridiculous like that and iirc, the effects were either dose dependent or something else like that. 

 

I love taking B complexes.

[xEva]

PS to my previous post

Promethease has more on B12:

rs492602(C;C)
Higher B12 levels in women
30.1% Frequency

it seems not everything is clear-cut.

Edited by xEva, 17 November 2015 - 03:10 PM.

[Kingsley]

Guys, I just got my geneticgene report and, out of 26 markers, 6 are 'no call'. Out of the remaining 20, only 5 are normal, 4 are homozygous (COMT V158M, COMT H62H, VDR Taq, MAO-A R297R) and the rest are heterozygous.

Am I gonna die tomorrow?

But seriously, how bad is it? and where do I start? With what supplements?

I'm sorry to have to ask, it's just a bit too overwhelming for now.

Thanks a lot

PS
but on the SNPmedia I read that those AAs TTs CCs GGs cannot be fully trusted, because of the differences in orientation when the data are read --?? Or was it the thing of the past?

 

I'll just respond briefly to say no, you're not going to die.  The SNP's identified as allegedly problematic by geneticgenie and other sites are usually very common, and for some SNP's there is no evidence whatsoever of any harmful effect.  For those SNP's that are actually significant, it usually just means that you have a slightly greater or lesser risk statistically for certain conditions.

 

As I've stated in previous posts, that's not to say that there is zero merit in those sites or their supplement recommendations or that you shouldn't explore your results.  But individual SNP's are rarely worth getting in a twist over even if displayed in deadly red color on geneticgenie : ).

[albedo]

I tend to agree with Kingsley. I also look at geneticgenie and similar sites but try as much as I can to go a little deeper in the science of each SNP and read what the background studies really tell. There are concerns about the seriousness of some of the sites and the recommendations too and I do not follow blindly. I am posting in the Personalized Nutrition thread what I discover relevant in general and for my own specific case.

Edited by albedo, 17 November 2015 - 08:53 PM.

[world33]

PS to my previous post

Promethease has more on B12:

rs492602(C;C)
Higher B12 levels in women
30.1% Frequency

it seems not everything is clear-cut.

 
Hi xEva,
 
Nutrigenomics is at its infancy stage and, from what I have read and learnt (I am not a genetic expert nor a biologist), some mutations might work positevely (upregulation) and some negatively (downregulation) on levels of metabolic substances (homocysteine levels for example).
Nutrahacker.com is not the bible of nutrigenomics and does not reference which scientific studies they take into consideration when reccommending or discouraging supplements. In addition nutrahacker consider a limited number of genetic mutations (above one hundred if I am not wrong). I find nutrahacker a good starting point to identify the supplements to try especially for low genotype frequency genetic mutations. I have tried most of the supplements reccommended by nutrahacker and some were life changing (methylfolate, molybdenum, NAC and even better glutathione) where others did not have any effect at all (manganese, TMG, zinc). Sometime nutrahacker also suggest one supplement for a specific mutation and then discourage the same supplement for a different one making things even more confusing. Trying is the best option in my opinion, discard those supplements that do not have any effect and keep those that have a positive effect.
Vitamin b12 has never killed anyone and hydroxycobalamin is the safest one because it is converted in other forms only when needed if I am not wrong.

You can also try knowyourgenetics.com from Dr Yasko. Please note that all supplements reccommended by the knowyourgenetics.com are sold by a company owned by Dr Yasko so there could be a conflict of interest there. I have never bought any supplement from her company (they suggest too many by the way and some RNA ones are considered useless by some experts) but I still found valuable some of the information in their report.

Geneticgenie.org and livewello.com are also useful resources but are for advanced users and do not give any advise on what supplements to try.

I attach my nutrahacker full report (not the free basic version) so that you can compare your genetic mutations with mine and take some hints on what supplements to take and what not to take keeping in mind, once again, that it is not the bible ;-) .

Attached Files

•  NutraHacker_Detox_and_Methylation_Report_Customer_Full_Report_Fabio.pdf   24.78KB   7 downloads

[xEva]

Thank you guys! Good to know I'm not gonna die tomorrow. And yes, yesterday I did read one paper on MTHFR allele frequency distribution in various populations. There was an interesting thought there as to why these variations are maintained. From what I gathered, maintaining these variations in a population is somehow beneficial for that population survival in changing conditions (famine was mentioned as well as levels of folate in available food). So, being heterozy on most of the alleles I so far consider a plus. The ones that are homozy definitely require more reading on my part.

Special thanks to world33
While 23andme is still transitioning to "a new experience" (supposedly then health reports will become available to their new US customers) I used their 'Mendel family' reports to look up the SNPs and compare. That was tedious but very enlightening. So, thanks very much for sharing your report.

[YOLF]

 

Guys, I just got my geneticgene report and, out of 26 markers, 6 are 'no call'. Out of the remaining 20, only 5 are normal, 4 are homozygous (COMT V158M, COMT H62H, VDR Taq, MAO-A R297R) and the rest are heterozygous.

Am I gonna die tomorrow?

But seriously, how bad is it? and where do I start? With what supplements?

I'm sorry to have to ask, it's just a bit too overwhelming for now.

Thanks a lot

PS
but on the SNPmedia I read that those AAs TTs CCs GGs cannot be fully trusted, because of the differences in orientation when the data are read --?? Or was it the thing of the past?

 

I'll just respond briefly to say no, you're not going to die.  The SNP's identified as allegedly problematic by geneticgenie and other sites are usually very common, and for some SNP's there is no evidence whatsoever of any harmful effect.  For those SNP's that are actually significant, it usually just means that you have a slightly greater or lesser risk statistically for certain conditions.

 

As I've stated in previous posts, that's not to say that there is zero merit in those sites or their supplement recommendations or that you shouldn't explore your results.  But individual SNP's are rarely worth getting in a twist over even if displayed in deadly red color on geneticgenie : ).

 

Probabilities are hardly the way to handle this. The idea behind it is to determine what behaviors do and don't prevent things and weed out all the things in your life that aren't conducive to getting them. You can't just say it's only a risk and doesn't mean anything... look at the general state of your health, if you are healthy and vigorous, you will stay that. If you are concerned and practice prevention, you will likely avoid more than if you are not. Teaching that it's random probability b/c we don't have a thorough enough understanding might as well be the same as hammer nails into people's coffins. Never allow anyone to believe that it just won't happen to them... that doesn't exist, if it doesn't happen, it doesn't happen for a reason and you need to find that reason. 

 

Now as far as any site being accurate... give it a try and see how it makes you feel. Does it make you feel younger? Happier? Healthier? More energetic? What does stopping it do? Ask yourself how you feel. If you feel better and don't start hitting highs and lows, you're doing good for yourself. Think about it, unless you sustain an injury, working out is going to make you feel better and make you healthier unless you over do it. Do you feel better in that sense? Yes? Keep it up. No? Do some more thinking and consider other factors that might effect the efficacy of it. Try some things out and repeat the process. Makes you feel worse? Stop doing it, it's not good for you and is probably bad for you. At the very least, stop the dosage. Don't commit to taking things long term that don't work. Most supplements that are worth anything will give you nearly immediate benefits if you need them.

[Kingsley]

 

Probabilities are hardly the way to handle this. The idea behind it is to determine what behaviors do and don't prevent things and weed out all the things in your life that aren't conducive to getting them. You can't just say it's only a risk and doesn't mean anything... look at the general state of your health, if you are healthy and vigorous, you will stay that. If you are concerned and practice prevention, you will likely avoid more than if you are not. Teaching that it's random probability b/c we don't have a thorough enough understanding might as well be the same as hammer nails into people's coffins. Never allow anyone to believe that it just won't happen to them... that doesn't exist, if it doesn't happen, it doesn't happen for a reason and you need to find that reason. 

 

Now as far as any site being accurate... give it a try and see how it makes you feel. Does it make you feel younger? Happier? Healthier? More energetic? What does stopping it do? Ask yourself how you feel. If you feel better and don't start hitting highs and lows, you're doing good for yourself. Think about it, unless you sustain an injury, working out is going to make you feel better and make you healthier unless you over do it. Do you feel better in that sense? Yes? Keep it up. No? Do some more thinking and consider other factors that might effect the efficacy of it. Try some things out and repeat the process. Makes you feel worse? Stop doing it, it's not good for you and is probably bad for you. At the very least, stop the dosage. Don't commit to taking things long term that don't work. Most supplements that are worth anything will give you nearly immediate benefits if you need them.

 

 

I was only making a narrow point about the significance of individual SNP's.  Most studies supporting an effect of particular SNP's on health conditions find at most a minor statistical association.  In other words, SNP's are drops in an ocean of genetic variation.  By the same token, this doesn't mean that you should ignore disease risks just because it's not written in your SNP's--quite the opposite. 

 

I agree with your points about trial and error and supplementation, from which I have benefitted greatly.  By the way, I didn't down-vote you; I value all discussion. 

[NeuroNootropic]

Anyone here find methylfolate makes their memory and brain fog worse? I've noticed that while methylfolate improves my focus and decreases my fatigue, it also seems to worsen my memory and brain fog. What's worse is that it seems to be decreasing the benefits I get from different supplements and drugs. Rhodiola no longer gives me a strong reduction in anhedonia, but rather a subtle one. Same with Wellbutrin, I also no longer get a honeymoon period when starting Wellbutrin.

 

Selegiline used to make my memory almost photographic but methylfolate completely prevents this.

 

Any thoughts? I'm taking 1000 mcg every 3 or 4 days and I take 1000 mcg of sublingual methylcobalamin once a week. I find too much b12 makes me extremely sleepy.

 

Anyone know if methylfolate affects COMT and to what degree?

[albedo]

 

 

Probabilities are hardly the way to handle this.....

 

I was only making a narrow point about the significance of individual SNP's.  Most studies supporting an effect of particular SNP's on health conditions find at most a minor statistical association.  In other words, SNP's are drops in an ocean of genetic variation.  By the same token, this doesn't mean that you should ignore disease risks just because it's not written in your SNP's--quite the opposite. 

 

I agree with your points about trial and error and supplementation, from which I have benefitted greatly.  By the way, I didn't down-vote you; I value all discussion. 

 

Tend to agree again with Kingsley. Also, consider that in the vast majority of cases, the impact on phenotype of common SNPs is very low compared to rare SNP. We should always take that into account. A good example is when you look at cholesterol's SNPs as in the chart included in my post on the Personalize Nutrition thread, here.

 

[YOLF]

Well, I can't agree with you, I think the importance is understated for a variety of reasons, some being that families have generally found and promoted ways to keep themselves healthier to the next generation. If we look at those who are adopted, or of unknown family origins, they are much more likely not to benefit from this kind of thing and because of so many wars and orphaned children during them, more people will be in those situations while the majority of data from genetics comes from those who are wealthy enough to afford the testing and copays and all that. So the risks are simply understated, not to mention the effect of the underlying assumptions which are that you're going to age and die anyways and we all have to die someday. For this community, all of those minor effects really add up to some very significant synergies. Take for instance supplements which alone have minor effects, but which combined with others are much more effective. HGH inducers that succeed in 600% increases have ingredients which alone might only raise HGH by 20%. The blood given in parabiosis doesn't look wildly different from old blood, but the small synergies of hardly significant variations make all the difference. I could take more time to better explain this, or even expand on the number of examples, but I'll keep it short.