Elevated Homocysteine

[Nathan777]

Quick question maybe you guys can give some insight into. I'm homozygous MTHFR C677T (does it matter, maybe, maybe not, but worth mentioning) and had my doctor check my homocysteine level last appointment based on that. Homocysteine came back at 13.9, which is technically in range (5-15), but obviously not healthy for a 31 year old male based on numerous studies that I've seen. So homocysteine is easy enough to lower - B12, methylfolate, P5P, TMG, B1, lower methionine intake, etc., but I also keep seeing that lowering homocysteine doesn't actually improve cardiovascular and neurodegenerative outcomes. So is elevated homocysteine just a marker for something else and typical B vitamin "treatment" is merely correcting a lab value rather than tackling whatever is actually causing the elevation? And if so any idea what that might be and how to correct whatever the real issue is?

 

[fractal]

Great question. I have the same MTHFR C677T mutation and lowered my Homocysteine from 13 to 9 in 3 months using this. Swanson Ultra Activated Homocysteine 60 Veg Caps - Swanson®
https://www.swansonvitamins.com/swanson-ultra-activated-homocysteine-formula-60-veg-caps
I am also following Chris Masterjohn's MTHR protocol, but I'm not sold on the choline supplementation. https://chrismasterjohnphd.com/2017/08/12/living-with-mthfr/

 

[Nathan777]

Great question. I have the same MTHFR C677T mutation and lowered my Homocysteine from 13 to 9 in 3 months using this. Swanson Ultra Activated Homocysteine 60 Veg Caps - Swanson®
I am also following Chris Masterjohn's MTHR protocol, but I'm not sold on the choline supplementation. https://chrismasterjohnphd.com/2017/08/12/living-with-mthfr/

I'm playing around with a similar product, Homocystex Plus by Dr. Ben Lynch's company https://www.seekinghealth.com/homocystex-plus-60-capsules and also making sure to get 3-5g creatine, glycine, plenty of protein, trying to get dietary folate from OJ, fruit, and liver as greens/legumes just don't agree with me, and 1-3 egg yolks a day. But I guess my worry is that I'll lower my homocysteine lab, go wow great work, then drop dead of a heart attack some day because I never actually corrected whatever was causing the issue. Maybe it just depends? Maybe some CVD patients with high homocysteine have theirs elevated due to lifestyle choices and B-vitamins aren't going to correct those issues if they don't look into them, whereas people like us, where it seems obvious what's causing the elevation, maybe tackling it with the B's is actually exactly what we need since deficiency/methylation inefficiency is the root cause of the elevation?

Also found some interesting studies on hypothyroid and homocysteine which are another avenue I may look into:
Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hy... - PubMed - NCBI

A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism.

Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. - PubMed - NCBI

On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate.

 

[Nathan777]

To add I think this quote I found sort of came to the same conclusion I'm starting to. Namely that lots of things can cause elevated levels of homocysteine, and if your elevated levels of homocysteine AREN'T caused by deficiencies in the vitamins you use to correct it, then you can't expect to have actually lowered your risk factor. i.e. someone with diabetes or liver disease may be able to artificially drive down their homocysteine by oversupplying their body with B's and TMG, etc., but since the lack of those nutrients wasn't the cause of the elevation then nothing has actually changed. Whereas in our case, if we assume it's the C677T causing the elevation, and correct/support the methylation cycle, then maybe we're all good...

Lack of benefit in treating high homocysteine levels with vitamins | BC Medical Journal

The first doubts about the causal role of homocysteine were expressed after the reported lack of association between CAD and a specific genetic polymorphism affecting MTHFR (677C→T).[8,9] Normally it would be expected that if a particular substance in blood causes a disease and its level is related to a genetic polymorphism, then that polymorphism would also be related to the disease.

While enzyme deficiencies caused by mutations in the CBS gene and the MTHFR gene are related to very high levels of homocysteine with vascular consequences,[9] a number of other causes of hyperhomocysteinemia (see Table 1) are known to be proven risk factors for vascular disease, and it is difficult to separate the effect of these factors from the specific consequences of hyperhomocysteinemia. In addition, blood sample handling, such as inadequate chilling, can also increase plasma homocysteine levels.

 

[ddjd]

7 is supposedly good for homocysteine.

Remember you need homocysteine to produce Glutathione also through your CBS enzyme. So there could be a dodgy gene there also.

Have you checked your PEMT gene- important for methionine synthase? your MTR/MTRR (b12) gene?

 

[Nathan777]

7 is supposedly good for homocysteine.

Remember you need homocysteine to produce Glutathione also through your CBS enzyme. So there could be a dodgy gene there also.

Have you checked your PEMT gene- important for methionine synthase? your MTR/MTRR (b12) gene?

Good post thanks! My CBS look good, all -/- on StrateGene, PEMT +/-, het for MTRR. Report attached, curious what you can make of it. Got my degree in economics so this biochem stuff is still a bit intimidating lol.

 

[jitsmonkey]

Quick question maybe you guys can give some insight into. I'm homozygous MTHFR C677T (does it matter, maybe, maybe not, but worth mentioning) and had my doctor check my homocysteine level last appointment based on that. Homocysteine came back at 13.9, which is technically in range (5-15), but obviously not healthy for a 31 year old male based on numerous studies that I've seen. So homocysteine is easy enough to lower - B12, methylfolate, P5P, TMG, B1, lower methionine intake, etc., but I also keep seeing that lowering homocysteine doesn't actually improve cardiovascular and neurodegenerative outcomes. So is elevated homocysteine just a marker for something else and typical B vitamin "treatment" is merely correcting a lab value rather than tackling whatever is actually causing the elevation? And if so any idea what that might be and how to correct whatever the real issue is?

Nathan I am traveling right now so I don't have anything at my fingertips but I recall several articles I read a few months ago regarding the connection between leukotrienes and their connection with homocysteine levels. Something along the lines of Montelukast, Zafirlukast, possibly Gama-Tocopherol or even Taurine may be of asst. Once I get back I will see if I can find the refs. Haidut has a few good posts specifically on countering Leukotrienes and these lukast drugs.

 

[Nathan777]

Nathan I am traveling right now so I don't have anything at my fingertips but I recall several articles I read a few months ago regarding the connection between leukotrienes and their connection with homocysteine levels. Something along the lines of Montelukast, Zafirlukast, possibly Gama-Tocopherol or even Taurine may be of asst. Once I get back I will see if I can find the refs. Haidut has a few good posts specifically on countering Leukotrienes and these lukast drugs.

Really fascinating thanks! So maybe I should be doing more to keep arachidonic acid intake low? I mean I already do the obvious things, but even cut back on egg yolks and liver? Which then plays into choline and folate deficiency... Definitely all the more reason to avoid overt PUFA consumption though. Also found this study which is pretty detailed and interesting: Effect of Polyunsaturated Fatty Acids on Homocysteine Metabolism through Regulating the Gene Expressions Involved in Methionine Metabolism

The possible mechanism by which n-3 PUFA regulate Hcy metabolism was also investigated [12, 24]; Piolot reported the apparent interaction of n-3 PUFA and NO on Hcy metabolism in healthy people [24]. They suggested a probable mechanism by which n-3 PUFA supplementation can reduce the production of Hcy. The reduced Hcy concentrations observed in their study are attributed to possible oxidative stress induction by n-3 PUFA and stimulation of the oxidative catabolism of Hcy [25]. Investigators have previously reported increased susceptibility to oxidative stress due to n-3 PUFA supplementation [26].

In summary, dietary intake of 22:6n-3 and CLA decrease the plasma concentration of Hcy. Different PUFAs have different effects on the mRNA expression of key genes involved in Hcy metabolism; n-3 PUFA upregulates expression, while n-6 PUFA down-regulates mRNA expression of Mthfr, Mat1a, Cbs, Pemt, Gnmt, Mtrr, and Bad. n-3 PUFA and CLA down-regulate mRNA expression of Cept1, Etnk1, and CLA upregulates mRNA expression of Mat1a and Cbs.

 

[Travis]

Quick question maybe you guys can give some insight into. I'm homozygous MTHFR C677T (does it matter, maybe, maybe not, but worth mentioning) and had my doctor check my homocysteine level last appointment based on that. Homocysteine came back at 13.9, which is technically in range (5-15), but obviously not healthy for a 31 year old male based on numerous studies that I've seen. So homocysteine is easy enough to lower - B12, methylfolate, P5P, TMG, B1, lower methionine intake, etc., but I also keep seeing that lowering homocysteine doesn't actually improve cardiovascular and neurodegenerative outcomes. So is elevated homocysteine just a marker for something else and typical B vitamin "treatment" is merely correcting a lab value rather than tackling whatever is actually causing the elevation? And if so any idea what that might be and how to correct whatever the real issue is?

I think you should lower it because it's highly correlated to lipid peroxidation in the brain (r = .92). Homocysteine can form a free radical on the α-carbon, and can also cross the blood–brain barrier.

'There were significant positive correlations between the CSF concentrations of homocysteine and HNE (r = 0.924). There was also a significant positive correlation between the plasma concentration of homocysteine and the CSF concentrations of homocysteine (r = 0.850) and HNE (r = 0.092). These results demonstrate that there is a relationship between increased homocysteine concentrations and increased HNE concentrations in Alzheimer’s disease.' ―Selley​

Hydroxynonenal is a lipid peroxidation product.

Selley, M. L. "The effect of increased concentrations of homocysteine on the concentration of hydroxynonenal in the plasma and cerebrospinal fluid of patients with Alzheimer’s disease." Neurobiology of aging (2002)​

 

[ddjd]

Good post thanks! My CBS look good, all -/- on StrateGene, PEMT +/-, het for MTRR. Report attached, curious what you can make of it. Got my degree in economics so this biochem stuff is still a bit intimidating lol.

Join the strategene Facebook group. Definitely worth it. I'll take a look later