Newbie could use some advise please

[mason]

Hi,

I have been struggling with anhedonia, anxiety, poor speech fluency and brain fog for years now and have recently been trying to work out if my methylation cycle is perhaps not working as it should.

All methyl donors ive tried - SAMe, TMG, Methyfolate give me bad anxiety.

The only time i feel any relief from my symptoms is either when I have a cold or infection or when I am hungover when I rarely have a few drinks.

I was hoping someone could give me some advise from my 23andme report as I really don't know where to start.

I have tried taking 1000mcg of hyrdroxocobalamin and just 200mcg of Methylfolate but this just gives me a really flat mood and anxiety.

Anyway my 23andme results were:



Homozygous for

VDR Bsm

MAO-A R297R

MTRR K350A



Heterogeneous for

MTHFR A1298C

BHMT-02

BHMT-08

Any advice would be greatly appreciated
Thanks

 

[Sherpa]

200mcg methylfolate can be a high dose for some people. I would try at 25 to 50mcg and go up from there. 1 capsule of Yasko's All-in-One Multivitamin has only about 25mcg of folate.

 

[caledonia]

Your SNPs aren't that bad in the scheme of things, although the MTHFR A1298C, MAO, and VDR Bsm would have you trending towards having mental health issues.

You could also take a look at your detox SNPs (also via Genetic Genie) and see if you have problems with GSTP, GSTT, GSTM (glutathione production).

A Nutreval test would be a good overall test to see what's going on functionally. There could be gut issues or toxic metals as well as various nutrient deficiencies. This test will also tell you if you have methylation cycle problems.

Typically ME/CFS patients have pristine diets, but if that's not you, there are some things that could be done there, such as going gluten and dairy free, getting "folic acid" out of your diet and supplements and so forth.

Read/watch the first four links in my signature - Methylation Made Easy, SNPs Interpretation Guide, Start Low and Go Slow and Roadblocks to Successful Methylation.

 

[mason]

Thanks for the replies

I know that my last hair test showed high aluminium, could that be effecting BH4 levels enough to cause my problems?
I had all my mercury fillings removed in February and did some metal detoxing after that but I could tolerate high doses of ALA with no reactions so assumed my mercury load probably wasnt that bad.

I have tried supplementing with BH4 capsules at 2.5mg perhaps I should increase the dose.
I can tolerate high doses of Hydroxocobalamin (5000mcg) ok but when I add methylfolate it makes me feel worse.

I can order this nutreval test from the UK:

http://www.gdx.net/uk/product/35

Its very expensive is it the right one?

Here are my detox SNP's from genetic gene I seem to be +/- for GSTP1 I105V not sure if thats much of a problem, but I have supplemented with liposomal glutathione in the past with no real benefit.


CYP1A2 164A>Crs762551CC+/+
CYP1B1 L432Vrs1056836CG+/-

CYP1B1 R48Grs10012CG+/-

CYP2C19*17rs12248560CT+/-
CYP2D6 S486Trs1135840GG+/+
CYP2D6 100C>Trs1065852AG+/-
CYP2D6 2850C>Trs16947AG+/-
CYP2E1*1B 9896C>Grs2070676CG+/-

GSTP1 I105Vrs1695AG+/-

NAT2 I114Trs1801280CT+/-
NAT2 R197Qrs1799930AG+/-

NAT2 K268Rrs1208AG+/-

 

[caledonia]

@mason

Yes, that is the correct Nutreval test.
http://www.heartfixer.com/AMRI-Nutrigenomics.htm
http://www.heartfixer.com/AMRI-Nutrigenomics.htm
Read this from Heartfixer - outside of CBS, this sounds like you:

MTHFR A1298C: 5,10-MethyleneTetraHydroFolate Reductase (Þ BH4)
The MTHFR C677T defect effects the “forward reaction”, the conversion of THF in to 5-methyl folate. MTHFR A1298C has no adverse affect on 5-methyl folate production, but it does compromise the “backward” reaction, whereby 5-methyl folate is converted back in to THF, in the process generating one molecule of BH4. Individuals with abnormalities in CBS and BHMT will be low in BH4, as it is being used up detoxifying ammonia that these defects have generated, so their combination with MTHFR A1298C leads to a BH4 deficiency double whammy. DHPR is the enzyme that regenerates BH4 from BH2. It is poisoned by mercury, lead, and especially aluminum. These toxins are wide spread in our environment, and individuals with Methyl Cycle abnormalities have particular trouble dealing with them. The result is a progressive drain on BH4, a progressive impairment in neurotransmitter production, and conversion of arginine not in to nitric oxide but instead in to free radicals such as superoxide and peroxynitrite. We treat MTHFR A1298C with 5-methyl folate supplementation (aiming to push the reaction backwards) and, after your other Methyl Cycle challenges have been addressed, with nutritional doses of BH4. Metal detoxification will help here and with every other biochemical function in your body, and will be part of your overall program. We will also endeavor to decrease your need for BH4. If you are COMT (-/-), we can provide nutritional support to help maintain dopamine levels, such that you will need to use less BH4 to generate more. If you are MAO A (-/-), we can do the same thing with serotonin precursors such as high tryptophan foodstuffs. The basic philosophy is to stimulate the action of still open pathways to take the stress off your impaired pathways.

The GSTP would have an impact on glutathione. When supplementing with glutathione, you need to add NAD to make sure it converts to the good reduced glutathione, instead of the bad oxidized glutathione.

So it sounds like metals are your main problem, along with the BH4 depletion from your SNPs.

Mercury and lead also impact MTHFR and MTR/MTRR and can cause methylation issues even if you don't have mutations there.

When you take methylation supplements it will cause metal detox. As the metals come out, you will likely feel worse. You should go very low and very slow, at a rate that you don't feel adverse effects from the metal detox.

Both B12 and methylfolate are required to make methyl groups. When you supplement with just one or the other, it will cause methyl trapping and no methyl groups will be made. That's why you could tolerate hydroxycobalamin, but had trouble when methylfolate was added. Plus the amounts were too high for starting doses.

Have you done a followup metal test after chelating with ALA?

Were you using Andrew Cutler's protocol or just taking some ALA every day? Supposedly if you don't dose the ALA every four hours, it will just reabsorb and possibly go to the brain.

 

[mason]

That does all make alot of sense to me,

It says about supplementing BH4 AFTER methyl cycle challenges have been addressed - does that mean there is no point taking BH4 now?
It also says that if you are COMT -/- as I am they can give nutritional support to maintain Dopamine levels. What supplements do you think they mean? I know low dopamine is my main problem as I do very well on Tyrosine but the results don't last long and are inconsistent.

I have tried boosting serotonin with 5HTP and tryptophan in the past with no benefit.

You say I need to add NAD to convert glutathione - what is that? Is that the same as NADH? Would I still need that even with liposomal glutathione?

I mainly detoxed mercury with pectasol/Algin - I tried the cutler protocol I could take quite high doses of ALA with no problems upto 600mg per day, most people who are mercury toxic can barely tolerate a 10mg. I did notice that my thinning hairline got alot worse when taking any sulphur supplement though especially ALA.

I will order another hair test though.

Regarding Ammonia - I have been on a high protein diet (including 2/3 protein drinks per day) for the last 10 years.
However I cut right back on the protein a couple of months ago but noticed no improvement. I wonder how long ammonia stays in the system and I should detox for that too.

So basically i'm thinking I should carry on detoxing heavy metals especially Alluminium, perhaps also ammonia and start taking low doses on B12/Methyfolate.

What dose Methylfolate/B12 do you think would be best - is there a certain ratio to the two?

Sorry for all the questions, your help is much appreciated

 

[mason]

I can't afford the nutreval test at the moment but would like to know if I have sulphate/ammonia issues.

I know the sulphate strips are used on here but has anyone used the ammonia strips - are they worth using and if so how much would be too much?

Thanks

 

[wootah88]

I'm curious about the answer to this question as well...

 

[ljimbo423]

I know low dopamine is my main problem as I do very well on Tyrosine but the results don't last long and are inconsistent.

Hello @mason, I use to take about 4,000 mg (4 grams) a day of l-tyrosine with moderate improvement. I swicthed to n-acetyl-tyrosine and now only take 700mg a day with MUCH better results. Because it does not last long I take it 4 times a day.

As far as methylation supplements like SAM-e, TMG, methylfolate etc. My experience is to start at a very low dose and slowly increase as is tolerated. Taking 50mg slow release niacin every 30-60 minutes until symptoms subside can help reduce anxiety from the methylfolate and other methylation supplements.

I couldn't find a slow release tablet smaller than 250mg so I buy 250mg tablets of slow release niacin and cut them into quarters. The slow release form helps to prevent flushing from the niacin. Good luck!

 

[cph13]

@mason
Hi! Ive been around 4 sometime. Im more a lurker. Much of ths is over my head. I don't c an answer here to your BH4 question.
Were u able to resolve it?Curious!!!

My tryptophan was borderline low; I supplemented/l-tryptophan 500mg. My serum amino acid test came back even lower. I was.taking p5p to the point of overloading/toxic levels (swanson hcy formula has p5p n i was taking more for.the.tryptophan)

I have interpeted in some of my readings that bh4 can be necessary for tryprophan. Am I correct?

I was really doing good for 4 months than I was told about my b-6 being hi n the next day my tryptophan lower.than before supplementing. I STOPPED ALL b-6/p5p and tryptophan. Tried tyrosine; no results. I'm back on tryptophan @500mg feeling, mehhhhh. I am also Curious about this yarrow b12. Has it gotten better. I'm on 4,000mcg. enzymatic for 1 1/2 yrs. I am on ALL the co factors. (AND THAN SOME). My neurotransmitters are all messed up. I have into drs. Tried straterra, modofinal and low dose amantidine they did nothing for ny mood or sleep. Stopped it all. This is an expensive scary proposition. All comments welcome. Happy healing. XO C

 

[mason]

I have tried Acetyl L Tyrosine before but didn't notice the same effects as standard Tyrosine for some reason

I am sure BH4 also plays a part in Tryptophan synthesis. However i'm personally not sure if the BH4 is the answer for me. I have continued the low protein diet and was taking low doses of Methyfolate and Hydroxo B12 but even low doses increases my brain fog and just doesnt allow me to function.