Help with methylation panel results?

Hi,

I'm new here and just made my first post in the "Introduce Yourself" section, so I don't want to repeat myself here...

But I was hoping that someone (Rich?) could take a look at my methylation test results and give me a few tips. I'm just not sure what my next step should be (my doctor isn't familiar with the simplified methylation protocol)...

Here are my results:

Glutathione (oxidised): 0.54 (range 0.16-0.50)
Glutathione (reduced): 2.6 (range 3.8-5.5)

S-Adenosymethionine (RBC): 240 (range 221-256)
S-Adenosylhomocysteine (RBC) 53.8 (range 28.0-49.0)
5-CH3-THF: 15.3 (range 8.4-72.6)
10-Formyl-THF: 3.9 (range 1.5-8.2)
5-Formyl-THF: 4.70 (range 1.20-11.70)
THF: 0.40 (range 0.60-6.80)
Folic Acid: 14.8 (range 8.9-24.6)
Folinic Acid (WB): 12.7 (range 9.0-35.5)
Folic Acid (RBC): 382 (range 400-1500)

Adenosine: 24.8 (range 16.8-21.4)

Thanks!
Karina

Hi, Karina.

Here are some comments on your methylation pathways panel results:

You have pretty severe glutathione depletion, with a reduced glutathione value among the lowest I've seen (However, if it will make you feel any better, Dr. Audhya recently told me that he has seen one near 2.0).

Your oxidized glutathione is above its reference range, indicating that you are suffering from oxidative stress.

Your SAMe level is good, but your SAH level is above its reference range, meaning that you have a partial block in your methylation cycle. This is also reflected in the not-too-bad level of 5-CH3-THF in the presence of a very low value for THF. With such a low glutathione level, it is not surprising that methionine synthase is so seriously blocked, because you would have a severe functional deficiency of vitamin B12, and that will mean that your cells will have difficulty making methyl B12, which is needed as the coenzyme for this reaction.

Your other folates aren't too bad. The low RBC folic acid indicates that your lipid cell membranes are damaged, which would be expected when oxidative stress is present.

Your adenosine is high, but it may come down when the methylation cycle function has been restored.

I think that the simplified methylation protocol will help you, with some modifications: I think you should use methy B12 instead of hydroxo B12, because your glutathione is so low that your cells will have difficulty making the conversion at a fast enough rate. Also, in your other post, you mentioned low serine. Serine is needed to react with homocysteine in order to feed it to the transsulfuration pathway, which is necessary for making glutathione. The low serine may be largely responsible for your very low glutathione level.

I don't know what your other amino acids levels are (other than asparagine, which was also on the Spectracell panel). If you are low in methionine, glycine and/or glutamate/glutamine, this could also hinder the recovery of the methylation cycle and glutathione. You could run an amino acids panel to find out, or you could raise your protein intake or take a free form amio acids supplement.

As you probably know, your vitamin D level is low. Supplementing with D3 (perhaps together with rosemary leaf to increase its absorption) should help this.

You may have to work on your gut issues in order to increase your ability to absorb nutrients and excrete toxins, but if you are not losing weight, and you have at least one BM per day, your gut may be working well enough to handle the methylation treatment.

You didn't mention deficiency in glutathione on the Spectracell test, though you did mention low total antioxidant function. That's surprising in view of your very low glutathione on the methylation pathways panel. In cases like this, I suspect that there might be poor activity of the glutathione peroxidase enzymes because of genetic polymorphisms, or maybe selenium deficiency, because the Spectracell test is a functional test, while the methylation pathways panel measures glutathione directly.

Your immune system is not doing too well, as evidenced by the low NK function and the variety of pathogens your body is hosting. Bringing glutathione up by treating the methylation cycle block should help that.

Your HPA axis is pretty dysfunctional, but again, bringing glutathione up should help it.

I think those are all the comments I have. I hope they are helpful.

Best regards,

Rich

Dear Rich,

Thank you so much for your comments. I'm really grateful for your help!

I plan to work with my doctor in implementing the simplified methylation protocol. Is there a specific kind/brand of methyl B12 that you would recommend? And would supplementing serine be alright given my low cortisol levels? I may not be able to take the 'neurological health formula' because I have a strange reaction to oral magnesium (brain fog), but hopefully I'll still be able to see some benefits without that component.

I haven't run an amino acids panel.. could you tell me what lab offers that test? Strangely, the Spectracell test showed normal levels of glutathione (as well as glutamine, selenium and vitamin D, and all other nutrients other than those that I mentioned in my other post). Methionine and glycine weren't tested, though.

I've had low levels of vitamin D for years, despite supplementing at high doses for almost a year. I think the supplements may have actually depleted my magnesium stores, because at some point I stopped being able to tolerate vitamin D and developed symptoms of magnesium deficiency. So I have to avoid vitamin D for now :-/

My doctor wants to start treatment for Lyme this week (once my Bartonella results are in). Do you think I can/should start the methylation protocol at the same time? And do you think supplementing glutathione directly could be helpful as well?

Sorry for all the questions. But thanks again for your help, and your suggesting this test in the first place.. it's kind of cool to see what parts are malfunctioning and finally try to fix them.

Cheers,
Karina

***Hi, Karina. My responses are at the asterisks below:

Dear Rich,

Thank you so much for your comments. I'm really grateful for your help!

***You're welcome.

I plan to work with my doctor in implementing the simplified methylation protocol.

***O.K. I think that having a doctor on board is very important.

Is there a specific kind/brand of methyl B12 that you would recommend?

***I will suggest the ones Freddd has found to be best, since he has more experience with methyl B12 than I do. He recommends Jarrow Formulas or Enzymatic Therapy.

And would supplementing serine be alright given my low cortisol levels?

***I think so. It's phosphatidylserine that can impact cortisol levels.

I may not be able to take the 'neurological health formula' because I have a strange reaction to oral magnesium (brain fog), but hopefully I'll still be able to see some benefits without that component.

***I don't know how well this will work, but you can try. One of the main roles of the neuro health formula is to correct any deficiencies in vitamins and essential minerals that may be present. There are also some additional supplements in it that are specifically directed at the methylation cycle and related pathways. The nucleotides are there to help make new DNA and RNA until the folate metabolism has recovered. Do you have the same reaction to transdermal magnesium, such as from Epsom salt baths or "magnesium oil"?

I haven't run an amino acids panel.. could you tell me what lab offers that test?

***There are several labs that offer amino acids panels, in plasma or urine. I like the Metametrix plasma 40 amino acids panel, which can be obtained through some doctors, or without a doctor's order from www.directlabs.com

Strangely, the Spectracell test showed normal levels of glutathione (as well as glutamine, selenium and vitamin D, and all other nutrients other than those that I mentioned in my other post). Methionine and glycine weren't tested, though.

***I suspect that you may have a polymorphism in one or more of your glutathione peroxidase enzymes. I do think it would be worthwhile to see what your amino acids levels are. Two of the things that can cause lack of response on the methylation protocol are low amino acids and low vitamin or mineral cofactors.

I've had low levels of vitamin D for years, despite supplementing at high doses for almost a year. I think the supplements may have actually depleted my magnesium stores, because at some point I stopped being able to tolerate vitamin D and developed symptoms of magnesium deficiency. So I have to avoid vitamin D for now :-/

***Sorry about that. I don't understand how this would work.

My doctor wants to start treatment for Lyme this week (once my Bartonella results are in). Do you think I can/should start the methylation protocol at the same time? And do you think supplementing glutathione directly could be helpful as well?

***I don't know if you would be able to tolerate the usual symptoms exacerbation from both these treatments simultaneously. Some people have found that adding liposomal glutathione has been helpful. Others have not responded well to adding glutathione. I posted about this recently on another thread.

Sorry for all the questions. But thanks again for your help, and your suggesting this test in the first place.. it's kind of cool to see what parts are malfunctioning and finally try to fix them.

***O.K. I hope things work out well for you.

Cheers,
Karina

***Best regards,

***Rich

Hi Rich,

***I will suggest the ones Freddd has found to be best, since he has more experience with methyl B12 than I do. He recommends Jarrow Formulas or Enzymatic Therapy.

Thanks!

***I don't know how well this will work, but you can try. One of the main roles of the neuro health formula is to correct any deficiencies in vitamins and essential minerals that may be present. There are also some additional supplements in it that are specifically directed at the methylation cycle and related pathways. The nucleotides are there to help make new DNA and RNA until the folate metabolism has recovered. Do you have the same reaction to transdermal magnesium, such as from Epsom salt baths or "magnesium oil"?

Hmm, well, I can try the formula and see what happens. I don't have the same reaction to transdermal magnesium, which is what I use now (magnesium chloride). That's kind of what leads me to believe that my problem with magnesium lies somewhere in my gut - perhaps oral magnesium is affecting biofilms there? My stool analysis didn't show any yeast or parasites - only a pretty harmless opportunistic bacteria - but I suppose if there were biofilms, whatever they contained wouldn't necessarily get detected by the stool test.

***There are several labs that offer amino acids panels, in plasma or urine. I like the Metametrix plasma 40 amino acids panel, which can be obtained through some doctors, or without a doctor's order from www.directlabs.com

Cool, thanks.

***I suspect that you may have a polymorphism in one or more of your glutathione peroxidase enzymes. I do think it would be worthwhile to see what your amino acids levels are. Two of the things that can cause lack of response on the methylation protocol are low amino acids and low vitamin or mineral cofactors.

I'll ask my doctor to order this test for me - I can keep you posted

***I don't know if you would be able to tolerate the usual symptoms exacerbation from both these treatments simultaneously. Some people have found that adding liposomal glutathione has been helpful. Others have not responded well to adding glutathione. I posted about this recently on another thread.

Ah, alright. Guess I will have to experiment a bit, then.

***O.K. I hope things work out well for you.

Thanks! I'll post with my progress soon.

Cheers,
Karina

Karina,

Rich had some very good advice. I didn't see him spell it out blatantly though that oxidative stress means you are not taking enough anti-oxidants for your current situation. I would rate that #1 for fixing because nothing is going to work right under that severe condition (it will adversely regulate many of your methylation enzymes).

Also Vitamins D is essential to the correct reglation of one of your methylation enzymes (I forget which one, but Rich knows). I take a sublingual D by Superior Source from iherb that goes right into the blood stream. I take 5,000 units/day and 3 days a week I take two of them to average around 7,000 units/day (I have the VDR genetc defect and this dose has been proven to be what I need via blood tests). What you want is for your Vitamin D blood test to come back with value 70. (Don't let the doctors run you just barely above outright deficiency -- as they will do claiming that 50 is normal. I get this info from Life Extension www.lef.org). Since I have the VDR problem and have had to take high dose D I have experimented with optimal dose and it really is around 70. I can go to 80 w/o problem, but if I go as high as 100 it changes my ph so that I can get UTI's (which I never got before). I did measure my urinary ph and saw the problem immediately. The ph you will be at D level of 70 is perfect. I never heard of any magnesium tie in for D either. (I don't actually believe it. What is common though is for people to supplement with calcium w/o magnesium and screw up their ratio. Or consume a lot of dairy which contains Ca but little or no Mg. There is a ratio of Ca:Mg that must be maintained. Some say 2:1, some say 1:1, some say it depends on you -- John Johnson has a theory about what ratio these need to be in depending on your thyrodi at www.ithyroid.com).

Trif

Hi Trif,

Thanks for your comments. I'm trying to improve my antioxidant status by increasing glutathione (through fixing the methylation block and also by supplementing glutathione directly).

I took vitamin D in high doses for years, but my level is still at 17 and I can't tolerate the supplements anymore. I instantly get symptoms of magnesium deficiency (or excitotoxicity? I don't know for sure). Anyway, here's some info about vitamin D and magnesium if you're interested:

http://wholehealthsource.blogspot.com/2010/04/magnesium-and-vitamin-d-metabolism.html
http://www.vitamindcouncil.org/news-archive/2009/magnesium-and-vitamin-ds-co-factors/

I'm pretty sure I won't get better until my vitamin D levels are in the normal range. Hopefully one day I'll be able to take 5,000 IU like you do

Karina

I had the same magnesium problem with vitamin D, and now I can't tolerate much sun exposure. I rue the decision to continue to supplement D3 even as the magnesium/calcium problem became more obvious, as my liver problems got permanently worse afterwards. My liver now flares up for weeks after every excessive sun exposure or any intake of D3. I have found over time that B5 helps with the "photosensitivity", however the calcium in the B5 makes the magnesium problem worse past a certain dose.

Andy Cutler has said that heavy metal toxic people generally have difficulty keeping their vitamin D levels up, and suggests caution with supplementing it.

Supplementing glycine might bring down SAH, and an alternate path may be upregulated with niacinamide.

hi karina,

can i ask which test this is, and how much it cost?

thanks,
heather.

Ahh sorry, I didn't get notification emails for some reason and didn't see the last few posts until just now.

Heather, the test is the Methylation Pathways Panel from Health Diagnostics & Research Institute- it costs $295.

Fozzaw, I'm sorry to hear that :-/ Do you take magnesium now? And have you ever gotten your magnesium levels checked? No tests have actually shown that my magnesium levels are low. My serum and RBC magnesium levels were in the normal range, and the Spectracell test also showed a normal Mg level. Strange...

Hi Rich,

I just received the results of the Metametrix amino acids panel. I was wondering if I could post them or maybe send them to you?

It seems that many of my amino acids are high, and the only low value is for my Tryptophan/LNAA ratio. I haven't talked to my doctor about the results yet and don't really understand what they mean...

In any case, I started a slightly modified version of your methylation protocol several weeks ago:

B12 injections (Methylcobalamin 5mg 2-3x/week)
Folate (Folinic acid 800 mcg, L-methylfolate 400 mcg)
B complex (also contains folic acid 400 mcg)
Phosphatidylserine
Liposomal glutathione

Does that look reasonable? (I haven't experienced any changes yet, but I guess it's too early for anything to happen...)

Thanks!
Karina

Any particular reason why you would want to specifically supplement with folinic acid and folic acid? I personally would ditch both and stick with methylfolate. Do you know if you have any of those pesky MTHFR mutations? If yes, you may need way more methylfolate than you are currently taking. For reference, I currently take more than 5mg of methylfolate/day as I have one of the MTHFR mutations.

Hi nanonug,

My doctor told me to take the folinic acid (at 800-1600 mcgs/day)- also, it's part of Rich's simplified methylation protocol (albeit in smaller amounts). And the folic acid just happens to be in my B-complex - maybe I should try to find one without it?

I haven't tested for any of the MTHFR stuff. Maybe I should. Thanks for the tips. Btw, have there been any improvements for you with the methylfolate?

Karina

Hi, vitamink.

Yes, you could post your results as an attachment, or email them to me at richvank at aol dot com.

Your protocol looks pretty good, though I'll try to tell from your test results whether you need some minerals or amino acids in addition.

Best regards,

Rich

Hi Rich,

I've emailed you my results.. thank you so much for your help!!

Karina

What's your rationale for needing that much methylfolate?

Hi, Karina.

Yes, most of your amino acids are pretty high. That suggests a deficiency in P5P activity, which could be due to a deficiency in vitamin B6 or B2 or both. The B-complex should help with this. I can't tell about the status of your minerals from the available data. You might consider adding a multimineral to your regimen.

Best regards,

Rich

Thanks, Rich!

My B-complex contains 25mg of vitamin B2 (as riboflavin, riboflavin 5' phosphate) and 40mg of vitamin B6 (as pyridoxine hydrochloride, pyridoxal, 5' phosphate, pyridoxine alpha-ketoglutarate hydrochloride). Do you think this would be sufficient?

Also, could the amino acids be high because of a high-protein diet?

Thanks again,
Karina

Given that, 1) you don't know whether you have MTHFR mutations, 2) more than half the population has at least one mutation and, 3) folic acid is "poison" for people with MTHFR mutations, I would definitely ditch your B-complex. Folinic acid also doesn't do you much good if you have any MTHFR mutations.

Absolutely! Methylfolate, together with high dosage methylcobalamin (15mg/day) and a good multivitamin (I take Thorne Basic Nutrinets III) and a few other assorted things that you may or may not need, allows me to function almost normally (at least at 90% of my "peak" capacity.)

Ultimately, because it works!

Based on a very specific set of symptoms, I suspect I might be dealing with some kind of histamine overload. The higher levels of methylfolate are then necessary to support an increased need for S-Adenosyl methionine (SAM) as this is used by Histamine N-methyltransferase (HNMT) to convert histamine into N-methylhistamine. It probably doesn't hurt that methylfolate also increases production of tetrahydrobiopterin, resulting in higher neurotransmitters levels.