57 replies to this topic

[stephen_b]

I found out that I have the CT variant of the MTHFR gene, which would mean that I have 65% of the MTHFR activity of someone with the CC variant, according to SNPedia. At the moment I'm taking a 2/3 dose of the new AOR B-complex plus 400 mg SAM-E.

It would be nice to have recommended supplement levels for each variant type.

Edited by stephen_b, 15 December 2009 - 07:59 PM.

[david ellis]

For some reason I thought Folate was B12. It's B9, so that's why I was confused above. Right now for Methylation, I am taking Metanx + TMG. Metanx is a prescription that has P5P, Methylfolate and Methylcobalamin.

The confusion is probably because the vitamins work so close together. If you don't have your methyl cobalmin (B12) ready, the Methyl Folate won't work. "Cobalamin deficiency may lead to folate deficiency which in turn increases homocysteine levels and finally may result in the development of cardiovascular disease or birth defects." from en.wikipedia.org

[david ellis]

The confusion is probably because the vitamins work so close together. If you don't have your methyl cobalmin (B12) ready, the Methyl Folate won't work. "Cobalamin deficiency may lead to folate deficiency which in turn increases homocysteine levels and finally may result in the development of cardiovascular disease or birth defects." from en.wikipedia.org

More detail on genetic deficiency from wikipedia.
"Methylene-THF (CH2FH4) is formed from THF by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methyl tetrahydrofolate (CH3-THF) can be made from methylene-THF by reduction of the methylene group with NADPH. It is important to note that Vitamin B12 is the only acceptor of methyl-THF. There is also only one acceptor for methyl-B12 which is homocysteine in a reaction catalyzed by homocysteine methyltransferase. This is important because a defect in homocysteine methyltransferase or a deficiency of B12 can lead to a methyl-trap of THF and a subsequent deficiency[15]. Thus, a deficiency in B12 can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency. Another form of THF, formyl-THF or folinic acid) results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Finally, histidine can donate a single carbon to THF to form methenyl-THF.

In other words:

folate → dihydrofolate → tetrahydrofolate ↔ methylene-THF → methyl-THF "

So not only do we have to worry about the methyl-THF and the B12 deficiency we have to worry about the deficiency possible of homocysteine methyltransferase.

[magnelectro]

Two other dietary methyl donors that have been shown to reduce HCY include choline (1) and methylsulfonylmethane (MSM) (2). Choline is oxidized into betaine (TMG). Do you think that choline would be more beneficial than direct TMG supplementation?
Does anyone know how MSM fits into the methylation cycle? What is it's metabolic fate?
Looking at the methylation cycle diagram provided by 4eva and following emitecaps suggestion, does anyone know how to upregulate the transulfuration pathway?

ALSO, and probably more important than any supplement EXERCISE reduces HCY (3).

1. http://www.life-enha...ate.asp?ID=1042
2. http://www.medscape....warticle/538324
3. http://jcem.endojour...jcem;87/10/4496

Edited by magnelectro, 17 December 2009 - 05:46 PM.

[david ellis]

Two other dietary methyl donors that have been shown to reduce HCY include choline (1) and methylsulfonylmethane (MSM) (2). Choline is oxidized into betaine (TMG). Do you think that choline would be more beneficial than direct TMG supplementation?

Looking at the methylation cycle diagram provided by ??4eva and following emitecaps suggestion ??, does anyone know how to upregulate the transulfuration pathway?

Can't argue with supplementing choline because a shortage would cause trouble with neurotransmitters. But it might be that supplementing with TMG would allow the neurotransmitters to get their full share of choline (choline is converted into TMG) But if you are focusing on lowering homocysteine, TMG alone can do the job despite folic acid deficiencies. This is called the backdoor method.

There are two links to methylation maps, the previous link, is a map focusing on the autism constellation of genetic deficiencies. This link, is a complete Methylation Map. I didn't see MSM, but I did see SAMe on both maps.

[stephen_b]

There are two links to methylation maps, the previous link, is a map focusing on the autism constellation of genetic deficiencies. This link, is a complete Methylation Map. I didn't see MSM, but I did see SAMe on both maps.

Autism is odd in that everything is low, including homocysteine. It would seem that the whole cycle is impaired.

[magnelectro]

I wonder what methionine restriction does to these pathways...

[david ellis]

Looking at the methylation cycle diagram provided by ??4eva and following emitecaps suggestion ??, does anyone know how to upregulate the transulfuration pathway?

How about a link to the thread you wrote about?

[niner]

Can't argue with supplementing choline because a shortage would cause trouble with neurotransmitters. But it might be that supplementing with TMG would allow the neurotransmitters to get their full share of choline (choline is converted into TMG) But if you are focusing on lowering homocysteine, TMG alone can do the job despite folic acid deficiencies. This is called the backdoor method.

There are two links to methylation maps, the previous link, is a map focusing on the autism constellation of genetic deficiencies. This link, is a complete Methylation Map. I didn't see MSM, but I did see SAMe on both maps.

I looked at the site linked here, www.heartfixer.com, and am a bit concerned about it. On the one hand, I think that Nutrigenomics is a great thing, and is the way we should all be treating our nutrient needs, and indeed, I suspect many if not of us will be using it within the next five years. On the other hand, this site bears some hallmarks of quackery, and at least deserves to be approached with a questioning mind. The owner of the site seems to have bought into the idea that methylation cycle mutations are at the root of all disease. He is convinced that it is the cause of Autism, aside from mercury being a co-conspirator. He considers it to be the fundamental cause of all disease that is poorly understood by conventional medicine and has vague and inconsistent symptoms, like fibromyalgia, multiple chemical sensitivity, etc. Between such syndromes and the parents of autistic children, it seems like he is taking advantage of desperate people. He seems to treat any genetic variation that results in a decrease in enzyme activity as though that enzyme is completely dead. He doesn't seem appropriately quantitative in that regard. He says that 90% of his patients have a defect in a sulfite/sulfate pathway. That seems like an awfully high number. He doesn't say what the overall distribution of this mutation is in the population as a whole, or whether or not is is actually predictive of any disorders. If it is he should publish his findings, and if not, he should address that fact. The site is rife with reference to "toxins", which is usually a bad sign. He is selling the same supplements that he is prescribing, a clear conflict of interest. He engages in rather crass salesmanship, telling patients that this is going to be expensive, but that they should compare it to the cost of a new car... So the place smells a little fishy to me, despite the fact that I think Nutrigenomics is a fascinating methodology that will only get more powerful as we continue to unravel the pathways involved and the price of SNP scans continues to fall.

[stephen_b]

Suppression of Methionine-Induced Hyperhomocysteinemia by Glycine and Serine in Rats

The hyperhomocysteinemia induced by a dietary addition of 1% methionine was significantly suppressed by the concurrent addition of 1% glycine or 1.4% serine to the same degree. The methionine-induced increase in the hepatic concentration of methionine metabolites was significantly suppressed by glycine and serine, but the hepatic cystathionine .BETA.-synthase activity was not enhanced by these amino acids. When the methionine-supplemented diet was changed to the methionine plus glycine or serine diet, the plasma homocysteine concentration rapidly decreased during and after the first day. The hyperhomocysteinemia induced by an intraperitoneal injection with methionine was also suppressed by concurrent injection with glycine or serine, although the effect of serine was significantly greater than that of glycine. These results indicate that glycine and serine were effective for suppressing methionine-induced hyperhomocysteinemia: serine and its precursor glycine are considered to have elicited their effects mainly by stimulating cystathionine synthesis by supplying serine, another substrate for cystathionine synthesis.

Perhaps some implications here for lowering the impact of dietary methionine on longevity? Both glycine and l-serine are available as supplements.

Stephen

[OneScrewLoose]

Maybe the glycine is why TMG works? And also, straight serine or glycine might avoid some of the potential cholesterol problems found with TMG.

Right now I am only taking a good multi and hoping the regular forms of vitamins (no methyl forms) found in there will be enough. When I posted this thread, I was not on any vitamins. I am getting my homocysteine tested again tomorrow, and will post the results when I get back.

[magnelectro]

Maybe the glycine is why TMG works? And also, straight serine or glycine might avoid some of the potential cholesterol problems found with TMG.

I know of one HC recycling pathway that uses serine: "Mammals biosynthesize the amino acid cysteine via homocysteine. Cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This reaction uses pyridoxine (Vitamin B6) as a cofactor. Cystathionine β-lyase then converts this double amino acid to cysteine, ammonia, and α-ketoglutarate." (wikipedia) but I can't think of one that uses glycine off the top of my head.

Amino-acid imbalance has enormous potential for life extension without all the negative side effects of CR. See "Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila"

I wonder if you can lower homocysteine too much? In the absence of a plasma test or polymorphism diagnosis, does it make sense for healthy individuals to supplement methyl donors? Are there any drawbacks to high-dose supplementation for everyone?

[OneScrewLoose]

I recently got a blood test taking only my multi. It seems that my homocysteine levels stay low with just regular vitamins, as opposed to special methyl forms. When I had the original blood test, I was taking no vitamins.

[nootrope]

I have some questions on that site as well. IF the information there were reliable, it would seem a great place to learn more about how to adjust one's diet and supplementation for genetic polymorphisms. I'm a little confused though when they write that COMT val/val (+/+ in their nomenclature) is the LESS active version of the gene and leads to HIGHER dopamine levels, when I thought it was just the opposite.

Can't argue with supplementing choline because a shortage would cause trouble with neurotransmitters. But it might be that supplementing with TMG would allow the neurotransmitters to get their full share of choline (choline is converted into TMG) But if you are focusing on lowering homocysteine, TMG alone can do the job despite folic acid deficiencies. This is called the backdoor method.

There are two links to methylation maps, the previous link, is a map focusing on the autism constellation of genetic deficiencies. This link, is a complete Methylation Map. I didn't see MSM, but I did see SAMe on both maps.

I looked at the site linked here, www.heartfixer.com, and am a bit concerned about it. On the one hand, I think that Nutrigenomics is a great thing, and is the way we should all be treating our nutrient needs, and indeed, I suspect many if not of us will be using it within the next five years. On the other hand, this site bears some hallmarks of quackery, and at least deserves to be approached with a questioning mind. The owner of the site seems to have bought into the idea that methylation cycle mutations are at the root of all disease. He is convinced that it is the cause of Autism, aside from mercury being a co-conspirator. He considers it to be the fundamental cause of all disease that is poorly understood by conventional medicine and has vague and inconsistent symptoms, like fibromyalgia, multiple chemical sensitivity, etc. Between such syndromes and the parents of autistic children, it seems like he is taking advantage of desperate people. He seems to treat any genetic variation that results in a decrease in enzyme activity as though that enzyme is completely dead. He doesn't seem appropriately quantitative in that regard. He says that 90% of his patients have a defect in a sulfite/sulfate pathway. That seems like an awfully high number. He doesn't say what the overall distribution of this mutation is in the population as a whole, or whether or not is is actually predictive of any disorders. If it is he should publish his findings, and if not, he should address that fact. The site is rife with reference to "toxins", which is usually a bad sign. He is selling the same supplements that he is prescribing, a clear conflict of interest. He engages in rather crass salesmanship, telling patients that this is going to be expensive, but that they should compare it to the cost of a new car... So the place smells a little fishy to me, despite the fact that I think Nutrigenomics is a fascinating methodology that will only get more powerful as we continue to unravel the pathways involved and the price of SNP scans continues to fall.

[bocadillodelomo]

I scanned over all 3 pages but i think that b12 in active forms such as methylcobalamin AND adenosyl are very underrated when it comes to homocysteine. Not that folate isn't important, but usually because folate is the first thing to be recommended and not b12 for high homocysteine, it's overlooked. If you read the book "Could it be b12?" along with another forum on wrongdiagnosis using the "active b12 protocol", it states the important of b12 in the metabolization of homocysteine to methionine. Actually if you check out the autism forums and talk to the parents, they really are the pioneers when it comes to the MTFHR and COMT+ genetic stuff and b12 is as important, if not more important to supplement with folate.

how did you come to find that you have the (or suspect) the MTFHR genetic mutation? your homocystein could just be a b12 deficiency even. I would have also run a serum folate, serum b12 and an urinary MMA to be perfectly sure.

Either way, wouldn't hurt to supplement with a jarrow methyl b-12 1000 mcg (more if you are deficient), Solgar's metafolin, and a form of dibencozide/adenosyl such as Country life (only comes in 3000 mcg though). Also taking an active bcomplex like jarrow b-right can help. This is assuming you are infact undermethylating or need help in the methylation cycle, such as MTFHR mtuation. if you are COMT+, or overmethylator and low histimine, you'd most like tolerate the folinic acid (step in between folic acid and methyl folate). I'm somewhere in the middle..

Edited by bocadillodelomo, 24 January 2010 - 10:40 PM.

[stephen_b]

Has anyone ever investigated creatine supplementation for lowering homocysteine? Here's a rat study that showed good results (PMID 12969151):

Total plasma Hcy inversely correlated with plasma creatine concentrations (r =-0.39; P = 0.02). Plasma folate was higher in supplemented animals and hepatic tetrahydrofolate (THF) was higher in nephrectomized supplemented animals. Plasma vitamin B12 was similar in all groups, whereas hepatic vitamin B12 was higher in nephrectomized animals. CONCLUSION: Creatine supplementation can effectively lower plasma Hcy concentrations in an animal model of uremia and should be further investigated as a potential treatment for hyperhomocysteinemia in patients with ESRD.

Stephen

[Sillewater]

or DHA

Nutrition. 2010 Jan;26(1):112-9.
Docosahexaenoic acid decreases plasma homocysteine via regulating enzyme activity and mRNA expression involved in methionine metabolism.
Huang T, Wahlqvist ML, Li D.
Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.

[albedo]

I tested in 2008 the following changes in the supplementation stack and could get homocysteine down ~21% (12.8 to 10.1 mcmol/l) in about 6 weeks. Today I am doing no particularly targeted supplementation and it remains around 13 (ref. <16).

Folic acid (800 to 1600 mcg)
B12 (450 to 1450 mcg o/w 1000 mcg as methylcobalamin)
TMG (1050 to 2050 mg)
B6 (50 to 85 mg)
B2 (25 mg)
Magnesium (300 mg)
Zinc (~42 mg)
(average daily values)

For the marker rs1801133 (aka C677T) in the MTHFR gene I am genotype GG.

I wonder if I should accept my homocysteine value and not bother? Is there a new thinking about its optimal range?

[albedo]

I think this is relevant in this thread too and worries me (assuming high homocysteine is not good):
"Alpha-lipoic acid induces elevated S-adenosylhomocysteine and depletes S-adenosylmethionine"
http://www.ncbi.nlm....pubmed/19616616
Discussed HERE.

[albedo]

Maybe useful to post here that, provided you did your SNP profile with 23andMe, you can get a Methylation Analysis (at no charge) at Genetic Genie http://geneticgenie.org . I did it and it is very easy. You also get some explication of what the analysis means and some action you can take.

What I found amazing is the complexity of the homocysteine issue and what you can make wrong with wrong supplementation. I recommend you check it out. Herewith is an example (see: http://geneticgenie....alysis-example/) (red is mine)

"....MTHFR Mutations. First we’ll look at a few of your MTHFR mutations. According to research, these mutations are important and can be implicated in various disease states.
You have 1 heterozygous (yellow) mutation(s). These are generally not as bad as red homozygous mutation, but they may still worth paying attention to. They include MTHFR C677T
.... One function of MTHFR (Methylenetetrahydrofolate reductase) is to help convert homocysteine to methionine. A MTHFR C677T mutation means that the MTHFR enzyme may have trouble performing its task leading to high levels of homocysteine.....

.... CBS Mutations. CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine.....CBS defects are actually upregulations ....When one tries to take nutrients to support their methylation cycle before addressing the CBS upregulation, all the nutrients basically lead to nowhere. Instead of generating glutathione, the supplements may deplete the rest of the cycle.... There are many things one may need to avoid with a CBS upregulation. Some of the items include garlic, broccoli, eggs, onions, legumes, meat, Epsom salt baths, alpha lipoic acid, glutathione, chelating agents such as DMPS, NAC, Milk Thistle, various other supplements, and much more. Please look to other sources for foods and supplements that are high in sulfur....."

Edited by albedo, 23 February 2013 - 10:06 PM.

[david ellis]

Maybe useful to post here that, provided you did your SNP profile with 23andMe, you can get a Methylation Analysis (at no charge) at Genetic Genie http://geneticgenie.org . I did it and it is very easy. You also get some explication of what the analysis means and some action you can take.

What I found amazing is the complexity of the homocysteine issue and what you can make wrong with wrong supplementation. I recommend you check it out. Herewith is an example (see: http://geneticgenie....alysis-example/) (red is mine)

"....MTHFR Mutations. First we’ll look at a few of your MTHFR mutations. According to research, these mutations are important and can be implicated in various disease states.
You have 1 heterozygous (yellow) mutation(s). These are generally not as bad as red homozygous mutation, but they may still worth paying attention to. They include MTHFR C677T
.... One function of MTHFR (Methylenetetrahydrofolate reductase) is to help convert homocysteine to methionine. A MTHFR C677T mutation means that the MTHFR enzyme may have trouble performing its task leading to high levels of homocysteine.....

.... CBS Mutations. CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine.....CBS defects are actually upregulations ....When one tries to take nutrients to support their methylation cycle before addressing the CBS upregulation, all the nutrients basically lead to nowhere. Instead of generating glutathione, the supplements may deplete the rest of the cycle.... There are many things one may need to avoid with a CBS upregulation. Some of the items include garlic, broccoli, eggs, onions, legumes, meat, Epsom salt baths, alpha lipoic acid, glutathione, chelating agents such as DMPS, NAC, Milk Thistle, various other supplements, and much more. Please look to other sources for foods and supplements that are high in sulfur....."

albedo, the link you used for geneticgenie.org links to heartfixer for it's metabolic flowcharts. I wrote a post in 2009 linking to heartfixer and it was not well received. I did go to geneticgenie and uploaded my 23andme data. I received a list of my heterozygous and homozygous SNPs with advice. Thank you, albedo. Now, I am wondering about the advice that I received from geneticgenie, first, there is the problem of heartfixer's website. Then, there is the autism thing. It has been three years and I haven't heard anything exciting about successful autism treatments, and I think there is a close connection to geneticgenie's advice and the advice given to autism patients. Would the people here follow geneticgenie's advice? Thanks guys.

I looked at the site linked here, www.heartfixer.com, and am a bit concerned about it. On the one hand, I think that Nutrigenomics is a great thing, and is the way we should all be treating our nutrient needs, and indeed, I suspect many if not of us will be using it within the next five years. (Link to Niner's post)

[albedo]

Thank you. I have the same concern as you, David Ellis, about the recommendations I also received and cannot agree more with the concerns expressed by niner. I certainly will not follow blindly those recommendations but rather leverage those as guidelines and do further research. E.g. I do not carry the MTHFR C677T mutation but I do carry CBS C699T heterozygous mutation and BHMT-02 homozygous mutation; however, I am not going to, respectively, eliminate tomorrow all sulphur containing foods and supplements and stuff myself with SAMe and DMG. Remember also we do not know how genes are expressed, that is why we need to understand how pathologies appear and look at symptoms and RCTs.

I also believe with niner that nutrigenomics is a fascinating field, the way to go and just at the start of development. Not a case in the Country I live Nestle funded up to $600m a research institute in the area of personalized nutrition. I also wonder how computing and data management technology progresses (e.g. see the potential Watson has in oncology) will help in nutrigenomics and personalized nutrition.

Back to the point in scope, my Latin ancestors were saying "in medio stat virtus" ("in the center lies virtue") so maybe we should merge the services of geneticgenie (and their recommendations) with those of other providers, looking maybe at academic and less suspect sites. Do people here happen to know more on this?

Edited by albedo, 24 February 2013 - 10:15 AM.

[albedo]

Also found this SNPedia, http://www.snpedia.c...sko_Methylation with contrasting reporting:

" ...
The scientific credentials of Dr. Amy Yasko are strongly question by these sources

• http://www.quackwatc...rg/clayton.html
• http://www.scienceba...d-institutions/
• http://autism.about....en-a-victim.htm
• https://www.23andme....y/thread/12876/

While these are generally trusting

• http://geneticgenie....ation-analysis/
• http://www.heartfixe...trigenomics.htm
• http://www.dramyyask...pdf_02_file.pdf ...."

[david ellis]

Thank you. I have the same concern as you, David Ellis, about the recommendations I also received and cannot agree more with the concerns expressed by niner. I certainly will not follow blindly those recommendations but rather leverage those as guidelines and do further research. E.g. I do not carry the MTHFR C677T mutation but I do carry CBS C699T heterozygous mutation and BHMT-02 homozygous mutation; however, I am not going to, respectively, eliminate tomorrow all sulphur containing foods and supplements and stuff myself with SAMe and DMG. Remember also we do not know how genes are expressed, that is why we need to understand how pathologies appear and look at symptoms and RCTs.

I also believe with niner that nutrigenomics is a fascinating field, the way to go and just at the start of development. Not a case in the Country I live Nestle funded up to $600m a research institute in the area of personalized nutrition. I also wonder how computing and data management technology progresses (e.g. see the potential Watson has in oncology) will help in nutrigenomics and personalized nutrition.

Back to the point in scope, my Latin ancestors were saying "in medio stat virtus" ("in the center lies virtue") so maybe we should merge the services of geneticgenie (and their recommendations) with those of other providers, looking maybe at academic and less suspect sites. Do people here happen to know more on this?

So, of course, my DNA's expression also didn't match up 100% with Dr Yasko's predictions. I am taking chemistry this semester and biochemistry next. I hope then that I can make better sense out of things. Hopefully, someone here has experience using DNA SNPs and metabolic charts.

edit-removed duplicate of albedo's quote

Edited by david ellis, 24 February 2013 - 04:30 PM.

[Darryl]

I came across a few studies that question the role of homocysteine in cardiovascular disease - its very possible hyperhomocysteinemia is a coincident marker of too much animal protein and not enough greens:

Troen, Aron M., et al. "The atherogenic effect of excess methionine intake."Proceedings of the National Academy of Sciences 100.25 (2003): 15089-15094.

Mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels, whereas mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia without any increase in vascular pathology.... Some product of excess methionine metabolism rather than high plasma homocysteine per se may underlie the association of homocysteine with vascular disease.

Antoniades, Charalambos, et al. "MTHFR 677 C> T Polymorphism reveals functional importance for 5-methyltetrahydrofolate, not homocysteine, in regulation of vascular redox state and endothelial function in human atherosclerosis." Circulation 119.18 (2009): 2507-2515.

Vascular 5-MTHF, rather than plasma or vascular homocysteine, is a key regulator of endothelial nitric oxide synthase coupling and nitric oxide bioavailability in human vessels, suggesting that plasma homocysteine is an indirect marker of 5-MTHF rather than a primary regulator of endothelial function.

Wierzbicki, Anthony S. "Homocysteine and cardiovascular disease: a review of the evidence." Diabetes and Vascular Disease Research 4.2 (2007): 143-149.

Although the major studies that have reported to date show that vitamin supplementation was associated with a decrease in HCY levels, this failed to have any significant effect on cardiovascular risk ... these data suggest that HCY is a marker, rather than a cause, of CVD.

Elevated methionine and folate deficiencies are plausible as mediators of atherosclerosis. Excess methionine would increase IGF-1 and vascular smooth muscle cell proliferation, and is unique among amino acids in increasing mitochondrial ROS generation. Meanwhile, reduced folates are effective quenchers of the peroxynitrite-derived radicals which cause ischemia/reperfusion injury, and folic acid and its metabolite 5-MTHF offer a number of other vascular benefits:

Tawakol, Ahmed, et al. "High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease." Journal of the American College of Cardiology 45.10 (2005): 1580-1584.

Moens, An L., et al. "Effect of folic acid on endothelial function following acute myocardial infarction." The American journal of cardiology 99.4 (2007): 476-481.

Moens, An L., et al. "High-dose folic acid pretreatment blunts cardiac dysfunction during ischemia coupled to maintenance of high-energy phosphates and reduces postreperfusion injury." Circulation 117.14 (2008): 1810-1819.

Tian, Rong, and Joanne S. Ingwall. "How does folic acid cure heart attacks?."Circulation 117.14 (2008): 1772-1774.

Cagnacci, A., M. Cannoletta, and A. Volpe. "High-dose short-term folate administration modifies ambulatory blood pressure in postmenopausal women. A placebo-controlled study." European journal of clinical nutrition 63.10 (2009): 1266-1268.

Its worth noting that even humans without the MTHFR 677 C>T polymorphism do a poor job metabolizing synthetic folic acid in most supplements to the form active in the folate cycle:

Bailey, Steven W., and June E. Ayling. "The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake." Proceedings of the National Academy of Sciences 106.36 (2009): 15424-15429.

Edited by Darryl, 04 November 2013 - 02:55 PM.

[albedo]

There is a strong link between oxidation stress, homocysteine levels and brain disorders. Please refer to the good video (in 3 parts) from Dr. Andrew Rostenberg, much in line with blood's post, explaining the balance you need to achieve in homocysteine levels (not too low, not too high, possibly 4-8) and providing also some clinical evidence from his practice:

 

http://beyondmthfr.c...teine-part-iii/

[Adam Karlovsky]

Has anyone ever investigated creatine supplementation for lowering homocysteine? Here's a rat study that showed good results (PMID 12969151):

Total plasma Hcy inversely correlated with plasma creatine concentrations (r =-0.39; P = 0.02). Plasma folate was higher in supplemented animals and hepatic tetrahydrofolate (THF) was higher in nephrectomized supplemented animals. Plasma vitamin B12 was similar in all groups, whereas hepatic vitamin B12 was higher in nephrectomized animals. CONCLUSION: Creatine supplementation can effectively lower plasma Hcy concentrations in an animal model of uremia and should be further investigated as a potential treatment for hyperhomocysteinemia in patients with ESRD.

Stephen

 

 

It seems creatine does not have the same effect in humans.

 

Creatine supplementation decreased homocysteine plasma levels in rats but not humans: A critical review with meta-analysis 

We conducted a review and meta-analysis according to PRISMA guidelines.

Elevated Hcy blood concentration is related to the increased risk of mortality.

Creatine supplementation is effective in decreasing Hcy blood concentration in rats.

The creatine effect found in rats is not reliably reproduced in humans.

Poorly controlled humans studies may contribute to the divergence of results.

 

Well.. maybe the evidence is just bad because human studies are poorly controlled?

http://www.sciencedi...352385915300220

Edited by Adam Karlovsky, 22 February 2016 - 09:22 AM.

[albedo]

Interesting Adam. I am looking at homocysteine and do use a modest dose of creatine when exercising. I also would like to see a study stratifying for genotypes known to affect the homocysteine level. Maybe effects will appear. It is sometime the case that the picture of null results is completely changed when you take into account genetics.