Request Assistance: Brainstorming Methylation Pathway Panel Results

[JasonUT]

Methylation Pathways Panel Results from 3/28/2017 Blood Draw: What are your thoughts?

Derivates:
S-adenosyl-methionine (RBC) - 227 (221 - 256)
S-adenosyl-homocysteine (RBC) - 48.3 (38.0 - 49.0)
Folic Acid Derivates:
5-CH3-THF - 8.9 (8.4 - 72.6)
10-Formyl-THF - 2.7 (1.5 - 8.2)
5-Formyl-THF - 1.20 (1.20 - 11.70)
THF - 0.79 (0.60 - 6.80)
Folic Acid - 10.6 (8.9 - 24.6)
Folinic Acid (WB) - 7.8 (9.0 - 35.5)
Active folate (RBC) - 330 (400 - 1500)

Nucleoside:
Adenosine - 21.5 (16.8 - 21.4)

Amino Acids in Plasma:
Cystathionine - 0.09 (0.00 - 2.00)
Homocysteine - 1.83 (0.00 - 2.00)
Cysteine - 6.22 (15.00 - 60.00)
Taurine - 55 (60 - 240)
Methionine - 21.40 (14.30 - 28.70)
Glutathione (oxidized) - 0.48 (0.16 - 0.50)
Glutathione (reduced) - 2.7 (3.8 - 5.5)

 

[alicec]

All folate forms are on the low side, especially inside the cell, though the reporting of folinic acid is confusing.

Another name for folinic is 5 formylTHF. These two are reported as if they are different substances and the values don't correspond. I'd be asking the people doing the test to clarify. What are they measuring for folinic acid and why is it so different from 5 formylTHF?

Your transsulfuration pathway is proceeding slowly. This is resulting in highish homocysteine (which feeds into it) and low cysteine and taurine (its products). This in turn is reflected in the poor ratio of oxidised to reduced glutathione. You are in a state of oxidative stress.

The blockage in the pathway starts at the first step, formation of cystathionine which is lowish after a highish homocysteine (which it is formed from) and gets worse as the pathway proceeds.

High adenosine would be inhibiting the ACHY enzyme which converts SAH to homocysteine. This is probably the reason that your SAH is highish (and why homocysteine is not even higher).

So I'd look to folate supplements, B6 to stimulate transsulfuration (several enzymes are B6 dependant, including the CBS enzyme which catalyses the formation of cystathionine) and overcoming oxidative stress.

 

[JasonUT]

@alicec , thanks for the feedback.

At the time of the test I was taking 12.6 mg of methylfolate. Prior to getting the MPP results, I increased to 15.6 mg methylfolate based on OAT and SpectraCell Micronutrient testing showing B9 deficiency. Maybe I will experiment with going even higher on B9. I have heard some doctors prescribing as high as 30 mg methylfolate daily.

I have switched from 60 mg Oral B6 to 25 mg Oral plus 15 mg sublingual P5P daily. I am hoping the sublingual form will have better absorption. I have also starting taking B2 sublingual, because I am deficient and I hear that B2 is needed to convert B6 to it's active P5P form.

How do you recommend "overcoming oxidative stress?" I currently take 500 mg Vitamin C four times per day.

Thanks for your thoughts.

 

[alicec]

A number of people on PR, including myself, report benefit from very high doses of methylfolate. Whether this high need reflects poor uptake, inefficient use/recycling, some kind of metabolic blockage or some other unknown factor is impossible to really know.

You do appear to have a high need given your results despite a fairly high supplement level. All you can do is make sure you are getting adequate amounts of all the other cofactors involved in the folate cycle (B2, B3, B6, B12, magnesium, zinc) and keep experimenting with folate dose.

I'm forever trying to reduce my folate supplements ($$$) and sometimes manage on lowish doses for a while but eventually symptoms which I have come to recognise as my particular folate deficiency symptoms reappear and I have to increase the dose. I have gotten it down from a high of 40 mg but only to about 25 mg. Despite the expense it makes such a difference to how I feel that it is worth it.

Adequate amounts of these cofactors may also mean high doses - at least for a time. You will need to experiment.

As for dealing with oxidative stress, there is no easy answer. Glutathione is the master antioxidant but it is backed up by layers of other systems which between them maintain the redox state of the cell.

Some people report benefit from direct supplementation of glutathione though many find this problematic. Precursors such as N-acetyl cysteine may be better if you can tolerate it. While cysteine formation is the rate limiting step, adequate supplies of the other two constituents glutamate and glycine could also be important.

Stimulators of glutathione production such as r-lipoic acid, milk thistle, could be useful.

Vit C is an important element of the back-up layers and so is vit E and selenium. A mixture of antioxidants, fat and water soluble, with overlapping mechanisms, would probably be a good idea.

 

[JasonUT]

@alicec

I feel like I'm so close yet so far from figuring this stuff out.

I have confirmed b1, b2, b3, b6, and b9 deficiency via SpectraCell micro nutrient and OAT.

Wow and this whole time I was worried about CBS up-regulation because I have dreaded CBS gene defects. Apparently I have the opposite problem despite the gene snp defect.

I was thinking about NAC as a precursor because I'm deficient in glutathione and taurine. MPP considers cysteine of 6.22 as "extreme" deficiency. It appears there are some NAC formulations that include selenium and molydbedum. Would this be a good choice?

 

[alicec]

I was worried about CBS up-regulation because I have dreaded CBS gene defects

That is a myth.

some NAC formulations that include selenium and molydbedum. Would this be a good choice?

Maybe, depends on how much is present.

Sounds like you have a series of functional deficiencies. Maybe you need to address digestion.

You might need high doses of many nutrients for a while.

 

[JasonUT]

Maybe, depends on how much is present.

NOW Formulation:
NAC - 600 mg
Selenium - 25 mcg
Molybdenum - 50 mcg

Doctor's Best Formulation:
NAC - 600 mg
Selenium - 50 mcg
Molybdenum - 50 mcg

Maybe you need to address digestion.

Yes

 

[alicec]

Could be a bit low in both selenium and molybdenum. Often around 200 ug/day selenium is recommended. I took 1 mg molybdenum daily for a while.

It might be better to try them all separately.

 

[Kathevans]

I'm forever trying to reduce my folate supplements ($$$) and sometimes manage on lowish doses for a while but eventually symptoms which I have come to recognise as my particular folate deficiency symptoms reappear and I have to increase the dose. I have gotten it down from a high of 40 mg but only to about 25 mg. Despite the expense it makes such a difference to how I feel that it is worth it.

Not to throw this thread off its subject matter, but I don't think I've read of people going as high as 40mg/day of folate. Except maybe Fred.

I've been ramping up lately after having gotten more selenium and molybdenum on board (a mere pittance at 150mcg/day compared to your 1mg!) and reached 24 mg and felt kind of frantic that I'd only ordered three bottles from iHerb! I've been titrating both Adenosyl B12 and the folate learning to distinguish the deficiency symptoms of both in my body. Lots of headaches for folate, to be sure, and head tightness and tingling. I am also working on amalgam removal, so at bottom I'm not sure when I'll know exactly what's what.

Anyway, thanks for sharing. I always appreciate your clear scientific contributions...! As well as your bold experimentation!

 

[JasonUT]

Current Selenium and molybdenum dosing

I decided to try the NOW NAC 600 mg. I started with 600 mg capsule at breakfast for 1 week and then added a second 600 mg capsule at dinner.

Selenium: 25 mcg multi + 2 mcg electrolyte drink + 50 mcg NOW NAC = 77 mcg Total per day

Molybdenum: 25 mcg multi + 5 mcg electrolyte drink + 100 mcg NOW NAC = 130 mcg Total per day

I think I will likely add another 600 mg NAC at lunch eventually.

 

[JasonUT]

Summary of HDRI lab interpretation here.

 

[JasonUT]

My nutritionist agrees with the high sulfur loading treatment strategy as a possible solution to low trans-sulfuration status. He spoke of his own personal experience in which he slowly worked up to 15 grams of MSM per day to lift/fill his trans-sulfuration pathway.