shouldn't I have low homocysteine?

[ebethc]

I'm still trying to understand my snp's and methylation, and one thing that's really confusing is that it seems that I should have high homocysteine. However, mine's normal... Given my snp's, does normal homocysteine levels indicate anything to me?

thanks

 

[PennyIA]

I have a couple snp's in common with you... but I HAD high homocysteine in 2004 (first time tested, after a blood clotting event); generally speaking MTHFR a1298c is NOT linked to high homocysteine levels - MTHFR c677t is more likely. It's just more complicated than that.

I was told to take folic acid, b12, b6 (and I took all the synthetics due to lack of knowledge of methylation). And I started dealing with b6 toxicity as well as what I believe now was methylation issues (folate deficiency, b12 deficiency) due to folic acid blocking the pathyways for other forms of folate and taking a form of the vitamins I couldn't process.

My homocysteine levels dropped significantly while I got increasingly sicker.

I've been trying methylation treatments for over a year now and my homocysteine levels remain normal even though my health has waxed and waned through out testing periods.

As best I can tell - other than using homocysteine levels to test risk of clotting? There isn't much about them that helps with chronic health issues.

 

[PeterPositive]

I'm still trying to understand my snp's and methylation, and one thing that's really confusing is that it seems that I should have high homocysteine. However, mine's normal... Given my snp's, does normal homocysteine levels indicate anything to me?

What is your homocysteine value?

As best I can tell - other than using homocysteine levels to test risk of clotting? There isn't much about them that helps with chronic health issues.

It's can help diagnose B12 deficiencies.

cheers

 

[melamine]

My homocysteine levels dropped significantly while I got increasingly sicker

I was less chronically damaged but much sicker when my homocysteine was...0?. Zero is what I recall it being. I didn't know anything about it, only that being below normal was not good. The only place I could find information about it at the time was Metametrix website. It made me afraid to take B12-6-folic after that.

It's can help diagnose B12 deficiencies.

My B12 level was more than double the upper end of "normal" when my homocysteine was in the basement. MMA was normal and B6 and folic were either high normal or very high.

 

[PeterPositive]

I was less chronically damaged but much sicker when my homocysteine was...0?. Zero is what I recall it being. I didn't know anything about it, only that being below normal was not good.

No, not zero With zero you'd be in deep dudu... homocysteine is very important in the right amount

As regards the "normal" values there are many opinions. My lab, for example, considered 20 as the top range, so when my tests came back with 22 I thought I was just moderately high where, indeed, it was excessively high because an optimal value should be 6-8

cheers

 

[melamine]

No, not zero With zero you'd be in deep dudu...

Maybe 0, yes! I remember thinking - this cannot be good! Maybe it was a mistake though. Anyway, I just had my homocysteine retested and it's now 9.1 (N= 4.0 - 15.4), which is a relief because I am starting a SMP, so that leaves plenty of room to go down without losing the necessary functions of it.

You didn't show a bottom range for the test you took, unless it's 6? and in that case why would the bottom be considered ideal (ideal for what?) instead of something more in mid-range? I wonder whether those ranges and recommendations may be skewed to cardiovascular disease without regard to other considerations.

 

[PeterPositive]

Maybe 0, yes! I remember thinking - this cannot be good! Maybe it was a mistake though. Anyway, I just had my homocysteine retested and it's now 9.1 (N= 4.0 - 15.4), which is a relief because I am starting a SMP, so that leaves plenty of room to go down without losing the necessary functions of it.

You didn't show a bottom range for the test you took, unless it's 6? and in that case why would the bottom be considered ideal (ideal for what?) instead of something more in mid-range? I wonder whether those ranges and recommendations may be skewed to cardiovascular disease without regard to other considerations.

No in general 6-8 is considered optimal because homocysteine is also a marker for oxydative stress, bad methylation, inflammation etc...

Values lower than 5-6 are not good because homocysteine is necessary for glutathione production, among other things, and we need plenty of that in our cells

cheers

 

[melamine]

No in general 6-8 is considered optimal because values homocysteine is also a marker for oxydative stress, bad methylation, inflammation etc...

In that case my 9.1 is not looking so good. Do you know how much P5P is recommended relative (if relative) to B12 and Folate/folinic acid?

 

[PeterPositive]

Your 9.1 doesn't look real bad. It's probably slightly elevated. Typically doctors will start doing something about it if it's > 10, at least in my experience. When I first tested my Hcy it was 98.6 Now it swings between 12-13. Even with that improvement my methylation panel sucked pretty badly...

If you (or your doc) suspects methylation issues it would be best to run a complete methylation panel as Hcy alone is not sufficient to really see what is going on.

cheers

 

[melamine]

98.6, WOW! I didn't know it could go that high! By methylation panel, can you tell me what that includes? I had a basic methyl test in 2010 where cysteine was the lowest of the 4-5 elements but nothing was entirely below range. It was not ideal by any means, but neither did it indicate anything so out of whack as to explain the state of my health.

 

[PeterPositive]

98.6, WOW! I didn't know it could go that high!

Me neither, and so my doc!

By methylation panel, can you tell me what that includes?

By methylation panel I mean the one recommended by Dr. Rich Van K. here:
http://phoenixrising.me/treating-cf...esults-of-the-methylation-pathways-panel-2011

It consists of several markers such as glutathione, sam-e, various forms of folate etc... The article has all of the details.

cheers

 

[ebethc]

What is your homocysteine value?

6.8, with a range of 0.0 - 15.0 umol/L... So right in the middle of the range.

If I take high l-methylfolate to stimulate BH4, then will that mess up something else? that's really what i'm worried about.

what did you do that made you better?

thanks

 

[PeterPositive]

6.8, with a range of 0.0 - 15.0 umol/L... So right in the middle of the range.

what did you do that made you better?

As I wrote in some of the previous posts, I had very high Hcy level which came down pretty quickly with the usual B vitamins but then got stuck at around 15-16.

From there I investigated methylation issues with 23andme and a methylation panel and found I had several issues with the folate and B12 pathways, so I started taking the right forms of vitamins such as methylfolate and methyl-B12.

I have improved significantly in terms of energy, mood and moderately in terms of inflammation and GI issues but I still have a long way to go. My methylation is still far from fixed and so is the rest of the problems.

If I take high l-methylfolate to stimulate BH4, then will that mess up something else? that's really what i'm worried about.

Your Hcy levels are perfect. I am not an expert with BH4 issues. It is usually a problem with MTHFR1298 mutations while I have the 677 double mutation.

You may want to take a look at this conversation:
http://forums.phoenixrising.me/inde...and-the-connection-to-folate-metabolism.9650/

cheers

 

[Critterina]

I'm still trying to understand my snp's and methylation, and one thing that's really confusing is that it seems that I should have high homocysteine. However, mine's normal... Given my snp's, does normal homocysteine levels indicate anything to me?

thanks

@ebeth,

Your CBS +/+ makes you use up homocysteine faster than normal, taking it from the methyl cycle to the sulfur cycle. This lowers homocysteine.

Your BHMT 08 +/+ makes an inefficient use of homocysteine. You also have the MTRR A66G +/- that makes inefficient use of homocysteine. Both of these enzymes keep the methyl cycle from cycling as efficiently. Your mutations raise homocysteine.

So, in all, instead of the the methyl cycle turning as it should, your homocysteine gets "drained off" more than "normal" and you're not regenerating methionine as efficiently as you might. The supplements that help in this situation are methylB12 (if you tolerate it) and TMG (trymethylglycine). They turn the homocysteine into methionine.

Your "normal" homocysteine, with these mutations, may be at the expense of normal methionine levels. That's how it was for me. If your methionine levels are good, all is well. Mine weren't, so I'm taking methylB12 and should get my test result soon (maybe now, if I would log in and look!) to show where my methionine is. My objective is to get my methionine levels normal without getting my homocysteine too high.

(Just a note, and you probably know this already, with the MTHFR A1298C +/-, you need a good reserve of methylfolate not to have the neuro symptoms (for me that's depression, for others anxiety, etc.). And taking methylB12 will use up more methylfolate than normal, so I think it's important that I take methylfolate when I take methyl B12.)

Hope this helps you understand how your SNPs play in to your homocysteine level.

 

[ebethc]

@ebeth,

The supplements that help in this situation are methylB12 (if you tolerate it) and TMG (trymethylglycine). They turn the homocysteine into methionine.

(Just a note, and you probably know this already, with the MTHFR A1298C +/-, you need a good reserve of methylfolate not to have the neuro symptoms (for me that's depression, for others anxiety, etc.). And taking methylB12 will use up more methylfolate than normal, so I think it's important that I take methylfolate when I take methyl B12.)

Hope this helps you understand how your SNPs play in to your homocysteine level.

@Critterina
Thank you!! Your explanation is exactly what I was looking for.. Was wondering if it's the step AFTER homocysteine that get's lost..

re TMG - thumbs up I"ve been using this lately, and think it really helps my brain fog. I think that my constant sinus swelling is due to (in part) the high humidity, and I feel like I absorb whatever's in the environment like a sponge. I've read that TMG is an "osmotic" or helps to balance water in cells.. I don't know enough about chemistry to pursue this idea, though..

I think stimulating the BH4 cycle would be KEY for me re inflammation/ joint pain/ brain fog/ fatigue... any thoughts on how to do this??
- I tried Arginine/Citrulline/Ornithine and it was great, then made me crash (higher inflammation, fatigue, depression). I think that it was the Arginine stimulating my EBV, but who knows...
- I've been reading about high-dose methylfolate this week and just started taking it. 8 mg / day.. I haven't noticed anything, but it's still early. Do you think that I have to take some M-B12 or Adeno B-12 along with it? I've been taking a general active B formula (thorne).
- I took a Norival a couple days this week and didn't feel a ton of relief.

LDN is still my "go-to" for pain relief, and hopefully it calms inflammation.
Astaxanthin is amazing.. Also take NAC & ALA

Where do you get methionine tested? is it in that Genova test w the amino acids, or just a regular old lab test?

Have you ever taken the Genova Biopterin test?

thanks again!!

 

[Critterina]

Wow, lots of questions, @ebeth!

Methylfolate is what most stimulates the BH4 cycle, so you should be on the right track. I find that higher doses of methylfolate (2-3 mg) depletes my tryptophan, so I supplement that (1500 mg). The tryptophan and methionine are just part of a regular old serum amino acid profile lab test. Both of them are essential amino acids - meaning they have to come from your diet - but tryptophan gets used up, methionine gets recycled.

There are some cofactors that you need for the biopterin cycle, too. Maybe someone else can help with that, since it's escaping me at the moment. B6? Magnesium? I don't know.

I've never taken a biopterin test, but since I have MTHFR A1298C +/- AND a history of depression (melancholy as a child, two episodes of depression as an adult, one requiring medication), it's a pretty good bet that my biopterin cycle/ serotonin production is at times compromised. Now that I'm histamine intolerant, my diet is restricted so my normal sources of dietary methylfolate to stimulate biopterin cycle (among other dietary things) are much less available to me.

Now from the biopterin cycle to the methyl cycle:

According to what I read, about half of your methionone should be fresh from your diet, half recycled from homocysteine. Both of us are impaired recyclers due to our SNPs (MTRR and BHMT 08), but our supplements will help that. TMG is one such supplement, B12 is the other...so...

Yes, I would definitely take some B12 when you are taking that much methylfolate. Especially since you have the MTRR A66G +/+. MethylB12 if you tolerate it, HydroxyB12 if you don't, but the MTRR means converting hydroxy will be slow, so methylB12 is much preferred. Adenosyl is good for something else, so not that. Your Thorne multi will have some methylB12 in it, but methylB12 is deactivated by stomach acid, so if like most multis, you take it with food, the effect is minimal. Be sure to use sublingual MB12.

Best of luck with what you try!

 

[ebethc]

@Critterina - one more question ... does high-dose methylfolate cause fatigue at first? It was stimulating at first, but I'm out of it today..

thanks again for your help!

 

[Critterina]

@Critterina - one more question ... does high-dose methylfolate cause fatigue at first? It was stimulating at first, but I'm out of it today..

thanks again for your help!

You know, everyone is so different, it's hard to tell. Folinic acid had that effect on me - could hardly stay awake 20 minutes after I took it. Some things to consider:
1. You may be coming down with something totally unrelated (cold virus, for example).
2. You may have used up a cofactor that was letting the methylfolate do it's job, and you'll have to figure out what that is (maybe get some help here from others, maybe trial and error.)
3. You might want to reframe your thinking about it - it was stimulating at first, then fatiguing. Not fatiguing at first. Don't expect to continue what you're doing and have it get better. I think you went over that cliff already.
4. Could it be that you're in "methyltrap"? I don't think your "fatigue" is as serious as what Freddd describes, but you could check it out.

Personally I'd vote for the cofactor theory, unless you come down with a cold tomorrow. Culprits may be potassium, magnesium, any of the B vitamins (1, 2, 3 (NADH), 6 (p5p), 7 (biotin), and 12 come to mind), D-ribose, Co-Q10, tyrptophan. Also, you didn't note any effect on mood or muscles that would be a clue. You'll have to be your own detective here, unless you can spring for some testing. NutrEval is great but my copay is like $700 now. An amino acid panel (serum) may be more affordable and point you in the right direction.

 

[ebethc]

4. Could it be that you're in "methyltrap"? I don't think your "fatigue" is as serious as what Freddd describes, but you could check it out.

@Critterina - I was wondering about methyltrapping - but I still don't understand what it is... too many methyls at once?? or, caused by a snp? (is it comt?) this is so hard w brain fog... sorry..

 

[Critterina]

@Critterina - I was wondering about methyltrapping - but I still don't understand what it is... too many methyls at once?? or, caused by a snp? (is it comt?) this is so hard w brain fog... sorry..

To be honest, I'm not sure I really believe the theory behind methyltrap. But some people experience something very bad, and they believe it's when they take too much methylfolate without adequate ways to use it up (which could mean that they have the MTHFR A1298C SNP and/or MTRR - those limit conversion of methylfolate to folinic acid and THF respectively). You can take MethylB12 to overcome the MTRR; not sure there's much to do to increase the conversion to folinic acid if you have the MTHFR A1298C. Look up the symptoms, though. I'm not sure yours match.

And you should know I'm a skeptic at heart. I don't mean anything personal by not buying into any particular theory yet. I'm sort of getting into the paradoxical folate deficiency, though, as my MCV (mean corpuscular volume) was up on my last blood test, about 30% since I started supplements - and if it goes too high, it's a sign of folate and/or B12 deficiency. I thought I had it with angular chelation and acne, but it turns out that was due to way too high a dose of HRT and a new shampoo I was allergic to.