Skyline's Journal: Progress & Experiments

[Skyline]

This is a thread to help me structure and track my progress and keep things controlled and get useful feedback. I'll also post summaries of what I've studied (my way of learning) that will hopefully be useful for others.

Background: Since May 2012 have had a variety of brain symptoms (headache, irritability, paranoia,altered state of consciousness), fatigue, strange nausea, vomiting, diarrhea, progressing to Neuropathy in August, blurred eyesight and unexplained fevers at times.

Test Results (received today): EBV (160:1) hs-CRP (0.34), Serum B12 (3,132 pg/ml), Homocysteine (9.68 umol/L).

Current tests on order: Yasko's Nutrigenomic's profile, 23andme, UAA/ UTM/ UEE with Yasko.
Current protocol: Fredd/ Rich Van Konyenberg methylation/ B12 protocol

Previous protocol: Jarrows Methylcobalamin 5Mg/ day for last 3 months, 1 month of Metafolin in September, vitamin D3, Vitamin K1+K2

Progress: I started the methylation protocol on Tuesday 11th December with:
Solgar Metafolin: 800 Mcg
Enzyme Therapies Methylcobalamin B12: 1Mg
Country Life adenosylcobalamin B12 (Dibencozide): 3Mg

Since starting the protocol I've had a variety of more extreme neuropathies and more insomnia.

Next Steps: I'm researching the high serum B12 which I had expected to be too low - instead it is extremely high.

 

[taniaaust1]

Your homocysteine level thou it is within range of 9.68 (normal range is usually 4-14umol/L).. is actually indicating an issue, you should follow up further.

Mine was only 8.9 umol/L and from that my specialist knew I had an MTHFR polymorphism (said it was too high thou still within range). As I wanted that then confirmed.. I had it followed up with a different bood test for MTHFR to see if I did have MTHFR and I turned out he was right.. my level of 8.9 was indicating MTHFR. Note.. your level is higher then mine (so even more likely you have it too and my specialist would certainly be telling you you have MTHFR).
9-18% of the population (different countries have it at different rates hence the percentage rates) have this polymorphism and it can really affect things including the methylation cycle. There are slightly different treatment protocols out there for the different types of this polymorphism (I have the worst type the C677T one). If you do a search for "MTHFR doctor" with your area.. you should be able to find someone who specialises in this and I think you will find you get a diagnoses with this on further testing.

 

[Sushi]

This is a thread to help me structure and track my progress and keep things controlled and get useful feedback. I'll also post summaries of what I've studied (my way of learning) that will hopefully be useful for others....

Next Steps: I'm researching the high serum B12 which I had expected to be too low - instead it is extremely high.

Hi Skyline,

Serum B12 is not an accurate test for patients with ME/CFS as it lumps together all types of B12 whether active, inactive, oxidized....It doesn't give you an good idea what your functional B12 is.

Rich used to suggest testing methylmalonic acid--an organic acid--which will give you a better idea of your B12.

Sushi

 

[Skyline]

Your homocysteine level thou it is within range of 9.68 (normal range is usually 4-14umol/L).. is actually indicating an issue, you should follow up further.

Mine was only 8.9 umol/L and from that my specialist knew I had an MTHFR polymorphism (said it was too high thou still within range).

Hi Tania,

Yes, optimum is under 8 uMol/ L. Thanks for your prompt as I didn't realize it was a clear indication of MTHFR polymorphism - I thought it was just probable.

My understanding for specialists is that Amy Yasko and Ben Lynch have the most data in this field (i.e. high number of patients = more data) and have a good background on it. I prefer to go to the best rather than take a local doctor as I've been very disappointed with their understanding of these areas.

So I've got the 23andme.com/ Yasko nutrigenomics tests that will tell me exactly what MTHFR I am. In the mean time I'm reading up on Yasko and Lynch's generic recommendations so I can put supports in place - as you say, I most certainly have some kind of MTHFR polymorphism.

Sorry to hear you have the worst MTHFR variant, I hope you are finding ways of 'managing' it.

 

[Skyline]

Serum B12 is not an accurate test for patients with ME/CFS as it lumps together all types of B12 whether active, inactive, oxidized....It doesn't give you an good idea what your functional B12 is.

Rich used to suggest testing methylmalonic acid--an organic acid--which will give you a better idea of your B12.

Hi Sushi,

Thanks. I'm aware that it isn't accurate, it was a quick test I could get done while I'm waiting for my Yasko UAA (Urinary Amino Acids) which I understand will help diagnose the B12 situation. Ideally the Methylation Panel from Health Diagnostics is recommended but they were very slow responding to me and have raised their price to $405 (not including shipping). So I decided to go the route of sets of Yasko's tests to get her feedback - which will be valuable.

My B12 situation hypothesis based on reading so far is:
A) Although my B12 is high it is either oxidized (non active) or unable to be transported - end result is my B12 is not active (the homocysteine result back this up).
B) I may be able to improve the situation using supplements which have no downsides while I am waiting on test results: active forms of B12 (Methyl, Adeno) and transport aids (e.g. Lithium).

 

[Sushi]

Hi Sushi,

Thanks. I'm aware that it isn't accurate, it was a quick test I could get done while I'm waiting for my Yasko UAA (Urinary Amino Acids) which I understand will help diagnose the B12 situation. Ideally the Methylation Panel from Health Diagnostics is recommended but they were very slow responding to me and have raised their price to $405 (not including shipping). So I decided to go the route of sets of Yasko's tests to get her feedback - which will be valuable.

My B12 situation hypothesis based on reading so far is:
A) Although my B12 is high it is either oxidized (non active) or unable to be transported - end result is my B12 is not active (the homocysteine result back this up).
B) I may be able to improve the situation using supplements which have no downsides while I am waiting on test results: active forms of B12 (Methyl, Adeno) and transport aids (e.g. Lithium).

Too bad that Health Diagnostics has raised the price. They always were slow and now they are inundated with nagalase tests (they seem to be the only ones who do it) and I think this slows them down even more.

I hope you do well with active B12--not everyone does (including me). I cannot take methyl and rather inject hydrox.

Good luck with it!
Sushi

 

[Skyline]

Progress/ Status - Day 1 to Day 5 of Simplified Methylation:
- Over the last few days I had a variety of 'excitatory' symptoms which were very uncomfortable (especially at nights of day 1 and day2 - I hardly slept because of them).
- Constipation from day 1 to 4 (i haven't had this issue for a while) - it resolved itself the same day I started taking more Potassium
- Increased stiffness and spasms in muscles - this seems to resolve when I take potassium now (potassium chloride 750mg, effective 325mg potassium). On Day 4 I'd built this up to 5,250mg potassium chloride (effective 2,625mg Potassium).
- Increased neuropathy: numbness in fingers, buzzing electricity / scratchy feeling in legs and arms, dull pain coming and going in arms
- On exertion (walking/ standing for a while) on Day 1 my muscles became very sore and remained sore until Epsom Salts bath in evening. On day 4 it seemed about half as sore and afterwards the pain didn't last.
- Day 3 and Day 4 sleep returned to normal - better on Day 4 and felt refreshed in morning, with good energy.
- Light headed feeling on Day 4 while walking around.

By day 4 my intake of supplements was:
Solgar Metafolin 800mcg
Enzymatic Therapies MethylB12 3,000 Mcg
Countrylife Dibencoenzide AdenosylB12 3,000 Mcg (unfortunately contains folic acid - how important is exchanging this for Source Naturals pure form?)
Potassium Chloride: 5,250 mg
L-Carnitine: 855 Mg

Based on current symptoms and Freddd's posts I am considering increasing Metafolin today on Day 5 - I will see how I feel later today and how my research goes.

Today's Research Tasks:
- B12 Transport and Ion Transport (Yasko and Lynch presentations)
- Lithium for transport (yasko)
- Manganese
- Fred Davis Protocol

 

[Skyline]

Too bad that Health Diagnostics has raised the price. They always were slow and now they are inundated with nagalase tests (they seem to be the only ones who do it) and I think this slows them down even more.

Yeah, I hope some more labs come to market with these tests.

I hope you do well with active B12--not everyone does (including me). I cannot take methyl and rather inject hydrox.

Thanks Could you be more specific about:
A) Why you cannot take Methyl?
B) Why you inject rather than use oral (e.g. sublingual)?

 

[Sushi]

Yeah, I hope some more labs come to market with these tests.



Thanks Could you be more specific about:
A) Why you cannot take Methyl?
B) Why you inject rather than use oral (e.g. sublingual)?

Every time I have tried methyl I have had a severe crash. Also, I was working with Rich and he recommended hydrox.

I inject hydrox for several reasons: 1) my doctor prescribed it 2) when I've taken it sublingual (I've used both Yasko drops and sublingual tabs) it hasn't had as much effect as injecting. Probably when you inject you are able to utilize more of it as some of the sublingual gets into the digestive tract.

Best,
Sushi

 

[Skyline]

Today's Research Task 1: Fred Davis' Protocol
One of the posts that contains the most information on Fredd's view of things is http://www.forums.phoenixrising.me/...rning-from-a-crash-relapse.20188/#post-309121

I found this information hard to dissect because of the way it is presented and the terms used. As a first stage of created a table/ chart separating the relevant pieces.

Fredd has defined cases by "Situation" - what action the person is taking, and "Symptoms groups".

In this chart I can scan along the situation, then scroll down to check the symptoms and see what Fredd's ideas are on diagnosis and treatment.
To get this up to something readable and more useful it needs:
A) Genetic mutation information (that is a huge part of situation which I'm not sure will be able to find much on in this forum, but maybe some parts or hints at least)
B) Tests that would verify diagnosis given.
D) Treatments: I have to collect more treatment information that I've seen scattered around the forum in his posts.
D) Some parts I've marked in pink which didn't seem clear enough - it would be great to have research references related to any of the diagnosis, test and treatment parts.

 

[Little Bluestem]

On Day 4 I'd built this up to 5,250mg potassium chloride (effective 2,625mg Potassium).

Are you aware that if potassium chloride is not sufficiently diluted, it can do nasty things to your digestive tract? Be sure to drink plenty of water with that.

 

[Skyline]

Are you aware that if potassium chloride is not sufficiently diluted, it can do nasty things to your digestive tract? Be sure to drink plenty of water with that.

Thanks for that - I'll look into it and see if there are better forms of potassium.

I should've upped my intake of food sources to avoid resorting to Tablets in the first place. Foods with a lot of potassium include:
- Main: Avocadoes, Salmon, Bananas, Dark green leaf veg (e.g. Spinach)
- Spices/ Herbs: Cayenne Pepper, Parsley, Turmeric
- Drinks: Coffee
- Others: Shallots, Onions, Sweet Peppers

 

[Skyline]

Some thoughts on Fred Davis' protocol - I find it easier to digest / compare now it is in table form.

There a couple of things I spotted:

1. Two groups diagnosed as "Folate Deficient" have the same symptoms as the others that are diagnosed as Hypokalemia. These are the situations:
E) Adding or increasing any of Vitamins D, A, E, or C, Magnesium, Zinc
I) Starting Metafolin low and titrating

I'm not sure what the mechanism would be for E), having more vitamins and minerals, that causes Folate deficiency. The only one I can think of is that the vitamins allow methylation processes to work faster and the folate gets used up. However, I have no idea if that kind of 'uncontrolled' use of folate by the body is possible - potentially if Active B12s are provided in large amounts?

2) IBS - Diarrhoea is marked as one of the Symptoms indicating possible "Folate Deficiency" where folic acid (or folinic acid has been consumed and there is a genetic mutation that prevents its effective conversion to 5MTHF). It struck me that potentially this could be a result of taking too much potassium - so to use that list of symptoms (Freddd describes as Group 3, you would need to verify that you have other symptoms. Stomach ache also could be potentially an effect of taking potassium tablets (especially chloride form?).

 

[Skyline]

Progress/ Status - Day 5 Saturday 15th December of Active B12:
- Diarrhoea
- Good high energy levels throughout the day
- Less leg muscle pains
- A few muscle spasms resolved by eating bananas and avocados
- Had one bout of altered consciousness (i'm starting to think this is raised Glutamate - excitatory activity) - I took some GABA but it had already subsided - want to test if GABA fixes it.

Day 5 supplements:
Solgar Metafolin 400mcg
Enzymatic Therapies MethylB12 4,000 Mcg
Countrylife Dibencoenzide AdenosylB12 1,500 Mcg
Potassium Chloride: 750 mg
L-Carnitine: 855 Mg

I'm titrating based on feeling up to 5,000 Mcg MethylB12 and 800 Mcg Metafolin.

Today's Research Tasks:
- B12 Transport (Transcobalamin and others)
- Lithium for transport (Yasko - facilitates B12 transport?)
- Manganese

 

[Skyline]

I reviewed two presentations yesterday:
Ben Lynch on MTHFR -

!
Amy Yasko on her new Ion Transport panel -

(only first part of presentation)

The Yasko presentation wasn't much use, it just refers to some new genes she has found correlate with autism and will be running panels on. I was hoping the Ion Transport has specific information on B12 transport, but was not the case.

Ben Lynches presentation was useful however - he's very structured in treatment which is a good thing, and detailed about it too.

Big takeaways:

Cofactors for Methylation can be: Zinc, Magnesium, B6, B2 and B12.
Excessive substrates: Can be an issue if you have too much SAM-e, glutathione (supplementing), or excessive cysteine


Two step approach (this is same as Yasko in principle):
Step 1. Reduce demands on methylation process (e.g. reduce environmental toxins, fix gut, reduce dietary toxins and issues, reduce infections).
Step 2. Increase capacity of methylation with supplementation of Methyl B12 and Methylfolate and cofactors (as necessary).

Why is Folic Acid bad:

FOLIC ACID is either processed slowly or not at all depending on your genes. The result is that unmetabolized Folic Acid builds up and it has been linked to decreased activity of Natural Killer cells. Lynch believes this is why Folic Acid supplementation is linked to cancer (i.e. NK cells important to fight off cancer and infections). There is a test from Metametrix for Unmetabolized Folic Acid levels.
Research References:
http://www.ncbi.nlm.nih.gov/pubmed/16365081
http://www.hindawi.com/journals/ogi/2012/485179/

You must make sure to eliminate all Folic Acid from your diet (supplements and enriched foods).


Methyl Trap
LOW B12 means 5MTHF can't get through - it requires B12 to process. In this case the 5MTHF does not get used at all. This is why you start with Methyl B12 supplementation.


Problems Resulting from MethylFolate Supplementation
IF they have COMT mutation --> give 5MHTF can lead to high dopamine levels (because is slower)

IF they have MAO A Mutation --> give 5MHTF can lead to high serotonin levels (because is slower)

IF someone is given 5MTHF (because of MTHFR) and also has COMT and MAO you get a lot of MOODS (aggressiveness, anxiety) etc.


How to Slow Down Overmethylation
If someone has COMT or MAO and is reacting badly or they have taken too much Methyl Folate too quickly you can slow it down by giving them Niacin.


HOW TO LOWER HOMOCYSTEINE: Different Pathways
- ADD Vitamin B6 - creates glutathione by converting homocysteine
- ADD BETAINE (Beets are high in Betaine)
- ADD TMG lowers homocysteine levels too
- ADD Vit B2 (RIBOFLAVIN) - lowers homocysteine also


Things to Cut Out to Help with Methylation

Dairy - cerebral folate antibodies go away when stop taking dairy

What Supplements to take
Deplin - scary dose - up to 7Mg - this is not necessary.
Recommends Metafolin, pure with nothing added (comes in 1,000 Mcg form) - it is regulated so you know you'll always get the same.
Other form of Metafolin is 800Mcg with other things added - the other things are useless so better to stick with 1,000Mcg form.
Magnesium Stearate - reduces absorption (this is included in many supplements, make sure isn't in yours)


HydroxyCobalamin

Hydroxycobalmin requires methylation to work so if you are low methylator with high homocysteine, you want to use methylcobalmin directly.


Glutathione Supplementation

Avoid supplementing with glutathione because it can cause feedback inhibition of methylation. The process is to have patients make it themselves through methylation.


Overview of his Treatment Protocol

 

[Skyline]

Updated supplementation based on research yesterday (Lynch and co-factors).

Solgar Metafolin 400mcg
Enzymatic Therapies MethylB12 5,000 Mcg
Source Naturals Dibencoenzide AdenosylB12 1,500 Mcg (NEW)
Potassium food sources (NEW)
L-Carnitine: 855 Mg

Co-Factors:
Vitamin B2 (riboflavin)
Vitamin B6 (investigate further - Yasko has some issues for some mutations)
Vitamin C (Lipoceutical 1,000mg)

Support
Probiotic - Bifidobacterium Longum (based on Metametrix GI results) 25mg
Probiotic - Saccharomyces Boulardii+ MOS (5 billion)
Probiotic - Bifidobacterium Bacillus Natto (Important)
Vitamin D3 - 8,000 UI
Life Extensions Super K (K1, K2)
Now Foods Krill Oil 1,000 Mg
Zinc Picolinate 25mg

 

[Skyline]

Progress/ Status - Day 6 Sunday 16th December of Active B12:
A) Energy: 10 - Good high energy levels throughout the day
B) Headaches: 9 - Very slight (hardly noticeable in evening)
C) Neuropathy: 3
- Very few to no muscle spasms
- Afternoon/ evening ability to walk and feeling in hand declined. Right leg stiff and harder to move (Worst day I've had to date for this)
D) Mood: 6 - More depressed mood than usual in evening
E) Other: Very cloudy/ dark urine with pungent smell

Note: 10 = Excellent/ no symptoms, 0 = "Hell"/ freakish symptoms

Day 6 supplements:
Solgar Metafolin - 1600mcg (last 800mcg 9pm in evening)
Enzymatic Therapies MethylB12 - 5,000 Mcg
Countrylife Dibencoenzide AdenosylB12 - 0 Mcg
Potassium Chloride: 1,500 mg
L-Carnitine Fumurate: 855 Mg

 

[Skyline]

Yesterday's Research:
I realized yesterday that some of the supplements I had been taking over previous months contained Folic Acid, Glutathione and NAC. It's a real mess frankly - I wasn't aware of the 'major' issues with folic acid and the supplements weren't marked clearly - including "now foods" who previously i trusted as a good brand. They put folic acid in many supplements.

I track everything I take, so I've estimated my intake of these since September to give the following picture:

I put this together assuming Fred Davis' assertions that folic acid, folinic acid and Glutathione/ NAC/ whey can interrupt healing/ methylation process - i.e. the worst case scenario to be conservative. Where the purple/ blue background is showing is where methylation would be blocked by either "paradoxical folate deficiency" or glutathione/NAC/whey interruption.

Based on this information my data is not very useful - all intake of B12 and Folate has been interrupted. It's notable that I felt better and was operating better in the period where there is no interruption. My main symptom was blurry eyes during that period, but I was mostly working - and even put feeling as "10" somedays.

At that period I had put down that improvement to "cold exposure" (Ice baths) and "heat - cold exposure" (sauna then cold shower) protocols I was following.

This just shows how careful you have to be with controlling experiments and data you collect. Going forward I will be trying 1 thing at a time and limiting supplementation to BARE ESSENTIALS to reduce possible interruption or introduction of new variables.

I have two hypotheses to test:
1) Possible paradoxical folate deficiency from A) My high B12 - serum test B) Intake over time of folic acid/ folinic acid
2) ZERO supplementation

I will test the first one today and possibly tomorrow - increase intake of Metafolin to at least 1.5:1 ratio, Metafolin to active MethylB12.

To date I have only tracked feeling as one general data point - it has become clear to me that I need to get more detailed to pinpoint what causes/ fixes what. I have overcome energy/ headaches issues which were the start of all this - but paradoxically have increasing neuropathy that is now the main issue.

[Note: Crux, also associates headaches with Methylfolate intake, and I had the first headache briefly when starting Metafolin the other day - so that is a possible link]

Question:
Has anyone seen a possible approach to reducing "unmetabolized folic acid" in the body? I have searched and found nothing as yet. Perhaps eliminating all source folic acid and loading Methylfolate is the only way.

Today's Research Tasks:
- Read and update specifics of Fred Davis' protocols and amounts taken into summary
- Investigate causes of high B12 and possible solutions
A) Transport (Transcobalamin and others)
B) Lithium for transport (Yasko - facilitates B12 transport?)
C) Manganese
- Cloudy urine/ smell

 

[Skyline]

Progress/ Status - Day 7-9 Monday 17-19th December of Active B12:
Energy: 10
Headaches: 9 to 10 (today none)
Neuropathy: 6
Mood: 8

Supplements Day 8/9:
Solgar Metafolin: 800 Mcg
Folinic Acid: 800 Mcg
Enzyme Therapy MehtylB12: 4,000 Mcg
Country Life AdenosylB12: 1,500 Mcg (Unfortunately contains folic acid 100 Mcg)

The last two days based on some reading I modified my supplements adding in the folinic acid and the Adenosylb12. If I had it I would also add in a small amount of hydroxocobalamin (hydroxoB12). The impact has been very positive, I've gone from a downward slide to feeling pretty good. A lot more functional. I even felt okay after running to catch a flight this morning (we'll see if that exertion hits me tomorrow).

More Research
Based on reading it looks like:
A) There are benefits to having both types of active folate (folinic acid and 5MTHF)
B) It is NOT SAFE to take methylcobalamin on its own - you must take AdenosylB12 with it.
C) Co-factors are improtant: I've added in B2, B6, B1 and Zinc to start with and have some B complex and overall mineral/ vitamin supplements coming (good ones from Thorne Research without folic acid etc).

I'm leaning towards a low dose more fragmented supplementation for methylation including small amounts of all the relevant B12s and folates. This distributes risk of 'missing out on' a key working part without any downside. I felt that the risk of not taking my country life AdenosylB12 was far greater than any negative from the amount of folic acid included in it.

Why? Folate without B12 can cause nervous system damage - I want to research this more thoroughly and write it up here. B12 without folate is NOT proven to damage the nervous system. So it's always better to err on the side of too much B12, too little folate rather than the opposite. High doses of folate really seem the worst approach given this fact.

Some Ideas / Questions to Explore
1. Does a dose of 'folate' that causes a headache imply damage to the nervous system? (I experienced headaches for first time in a while when i took a larger dose of folate, and I know others have commented on this recently E.g. Crux)
2. What is the genetic mutation (if any known?) that prevents folinic acid from being used by the body?
3. Is a low Serine value (deficiency) linked to an issue in Methylation? Can L-Serine help with this - or is there something upstream that should be looked at? Or will the methylation protocol deal with it?
4. Is a high serum value of B12 ever caused by a deficiency in folate? Meaning that active B12 is present, but not enough folate has been available (thus causing a Methyl trap from the folate side, rather than B12 as typically discussed) and the B12 builds up not having an escape route for processing.
5. While Fredd's opinion is that there is no such thing as 'detox', Yasko's work shows that the body is excreting metals and viruses/ bacteria when methylation is restarted.. is it possible that his increase of folate to overcome what he calls a donut - is actually overdriving methylation even faster to detox 'the symptoms' (i.e. overdriving detox). If so, is that a good thing? or a bad thing? Besides a potential risk of megadosing folate beyond active B12 in the body.

 

[Crux]

Hi Skyline;
I must say your method is exquisite. I'm in awe.
Tonight, I will think over some of your questions to try to contribute, if possible. ( or necessary)
It looks to me that you're well on your way to nailing it!

( Love the graphics )