New, Inexpensive CBS Ammonia Fix

[aaron_c]

@xena

You mention that Nrf2 activators allow you to use 5-mthf without negative side effects. What are they? Can you also describe your bad reactions to meat (without nrf2 activators) or sulfur foods (without broccoli sprouts)?

 

[xena]

@xena

You mention that Nrf2 activators allow you to use 5-mthf without negative side effects. What are they? Can you also describe your bad reactions to meat (without nrf2 activators) or sulfur foods (without broccoli sprouts)?

That was a hell of an explanation of the Yasko stuff, Aaron. Appreciate it, also might have to come back to it when I'm less foggy

Meat makes me wheeze and cough, depressed, slightly sore muscles, tired

Sulfur is similar, but heavier on the depression and not pronounced wheezing

 

[keenly]

Agreed, and she deserves credit for fishing out that connection. However she believes BH4 is depleted because increased ammonia makes NOS run backwards and somehow that when it runs backwards it uses up BH4.

There are two things wrong with this. First, NOS is/are the enzyme(s) that produce NO. It doesn't come from anywhere else that I know of. The equation is:

2 L-arginine + 3 NADPH + 1 H+ + 4 O2 2 citrulline +2 nitric oxide + 4 H2O + 3 NADP+

Basically arginine is transformed into citruline + NO. Yasko argues that when we have extra ammonia it can cause NOS to run "backwards," taking citrulline and NO and creating arginine. But to have NO NOS has to run forwards in order to produce it. So there's no net change in the amount of citrulline from NOS. Even assuming high citrulline (and Naviaux found serum citrulline to be normal for us) it would mostly result in NOS inactivity as levels of arginine, citrulline, and nitric oxide reached an equilibrium. I don't see it resulting in a bunch of arginine production. Yasko's theory hinges partly on high citrulline causing high arginine synthesis via NOS, which appears to me impossible.

The second problem with Yasko's theory regarding NOS is that when NOS runs backwards it uses up BH4. BH4 is a cofactor for NOS but it is not "used up" by it (See Wikipedia: "Tetrahydrobiopterin provides an additional electron during the catalytic cycle which is replaced during turnover.") At best some of the NO that NOS produces will combine with superoxide to form peroxynitrite, which oxidizes BH4. This explanation wouldn't work, however, if NOS was somehow--magically perhaps--producing net movement towards arginine by using up citrulline and NO.

But Yasko isn't just wrong about how NOS effects BH4, she's wrong about how MTHFR effects BH4: She suggests that MTHFR runs "backwards" to convert BH2 (q-BH2 actually) to BH4, which has only been shown in vitro when you add very high concentrations of 5-MTHF--concentrations would almost certainly cause "methyltrap." Methyltrap is a condition where 5-MTHF cannot be converted because there is no B12 for methionine synthase, and MTHFR normally doesn't run backwards, thus methylfolate is "trapped." So even if we could reach the necessary concentrations of 5-MTHF to run MTHFR backwards, we would also create a "methyltrap," which is quite uncomfortable and unhealthy.

In summary, Yasko may be getting parts of treatment right but I think she's getting decent chunks of theory dead-wrong.



This is where Yasko's bad theories can lead to some bad or ineffective treatments, I believe.

Under Yasko's theory the problem is 1. That we make too much ammonia and possibly 2. That because of krebs cycle problems we might have uric acid cycle blocks that forces ammonia to use the NOS "shortcut." The second point was my original reasoning behind why malic acid helped me. But if we truly didn't have enough aspartate to combine with citrulline to form argininosuccinate then we should have high citrulline--and as I pointed out above, Naviaux didn't find this. Maybe we have low aspartate, maybe we have low malate, maybe supplementing malic acid or aspartate helps fill holes in our biochemisty and we feel better for that, but as far as I can tell aspartate isn't low enough to impact the urea cycle.

One final note: I have concerns with using Citrulline and Arginine as supplements. Even if one buys into Yasko's view of things, L-Citrulline would seem to be a bad choice, as it is essentially an ammonia carrier. And even if one were trying to unblock the urea cycle in order to move more ammonia through it, adding a molecule already carrying ammonia seems like a poor choice.

Arginine, like citrulline, is essentially carrying ammonia. Unlike citrulline, it is an amino acid used to make proteins and nitric oxide. Scientists have studied arginine as a possible way to prevent heart attacks. And there were some positive indications. But then this study which gave arginine to patients starting after their first heart attack was ended early when six patients in the treatment group died (none of the control group did). It may be that the difference had something to do with higher production of asymmetric dimethyl arginine from arginine; that since high ADMA:arginine is a risk factor for heart disease many heart attack patients have an already high ratio of ADMA:arginine, and adding more arginine only ends up producing more ADMA for them.

In any case, Naviaux found high serum arginine, so I'm not sure why we would want to supplement more.

Ornithine (and here I'm just reading off the biochemical pathways map, so I'm not sure how prevalent this is) can be converted to glutamate, and glutamate is what the body uses to transport ammonia. So if ammonia is really the problem, then excess ornithine is potentially a problem too.

So what do you recommend for high ammonia?

 

[aaron_c]

So what do you recommend for high ammonia?

What worked for me was a UV-B light--a "standard" dose seems to be about enough. Or sunlight, if you can get enough. BH4 pills also worked, they were just much more expensive.

Here is my thinking about this. The only thing I would add is that the situation I describe may only apply to people taking methylation supplements. And some people report sunlight making them tired, and I don't know if UV-B will do this to them too.

If you try either of these routes, I hope you will share whether they work. Whatever you do, good luck!

 

[keenly]

What worked for me was a UV-B light--a "standard" dose seems to be about enough. Or sunlight, if you can get enough. BH4 pills also worked, they were just much more expensive.

Here is my thinking about this. The only thing I would add is that the situation I describe may only apply to people taking methylation supplements. And some people report sunlight making them tired, and I don't know if UV-B will do this to them too.

If you try either of these routes, I hope you will share whether they work. Whatever you do, good luck!

Coincidentally I have just ran a Vitamin D test through Dr Yasko, and I am very low(10).

I will be trying to raise my levels moderately this spring/ summer. Cheers.

 

[xena]

Hey fwiw I found that supplementing vitamin D helped my ammonia issue a lot. Sunshine not as much.

 

[aaron_c]

Hey fwiw I found that supplementing vitamin D helped my ammonia issue a lot. Sunshine not as much.

How much sunshine were you getting (and how much of your body was exposed) vs how much oral vitamin D?

 

[xena]

An hour or more, most of my body, midday. I'm medium brown but even so it should be a significant amount. I'm suspecting that I'm Boron and or vitamin a deficient, apparently those are necessary for an effect. Between 8000 and 15000 iu oral

I'm thinking the wheezing really is from ammonia rather than sulfite. I ate a chicken thigh yesterday night with mild wheezing. Malate cleared it up. Today morning, another chicken thigh - no wheezing. I've had similar experiences before - I think it's because circulating vitamin D is higher in the day. I'm going to try an equivalent amount of sam-e tonight.

I do think that I'm getting an anxiety response from the sulfur. Trying to figure out how deal with that. I'm hesitant to try moly, Boron and manganese together again after the insomnia from last time. Sam-e helps a little with the anxiety, I think because methylation is used to degrade those neurotransmitters.

Needing to dose p5p every twelve hours to avoid getting agitated. I think that's necessary for Glutamate gaba conversion.

I took another 1 mg mb12 and 800 mcg mthf today a few hours ago and no negative symptoms so far....

 

[aaron_c]

Hmm. While that is a decent bit of sunshine, that is a whole lot of oral vitamin D. A truckload. So I'm not sure we can assume that sunlight failed due to some innate mechanism rather than simply dosage. Of course, getting more sun than that might be difficult. If the oral stuff works for you, so much the better.

I would also not suggest molybdenum together with boron. One or the other seems to work decently for me. Taking one or the other might at least help determine what is caused by issues stemming from sulfites.

I know there is more I should say, but I stupidly took boron with molybdenum yesterday so I didn't sleep well last night. Among other issues.

 

[Gondwanaland]

I ate a chicken thigh yesterday night with mild wheezing.

Chicken frequently causes me headaches/migraine and I think it is due to sulfites. I think the industry uses a lot of sulfites to preserve chicken meat.

@aaron_c was it you who mentioned that vit D from the sun is in the form of sulfate?

I am really intrigued by the anti-glycation supp I took (carcinine which is an analogue of carnosine/B-alanine). They are DAO blockers, so there is more B6 available for other metabolic routes. I felt that transsulfuration was especially upregulated (I could chop onions with no discomfort).

I took it for 2 weeks and then had a blood test:

tanked estrogen
tanked vit D 25OH
raised TSH

 

[aaron_c]

@aaron_c was it you who mentioned that vit D from the sun is in the form of sulfate?

Yup. Al la Stephanie Seneff.

 

[xena]

@Gondwanaland

Good thing to point out about the chicken, I didn't know that. I have that issue with beef too though and buy organic, no additives( as far as I know)

 

[xena]

@aaron_c

I think the dose is similar to what could be created in sunshine fairly quickly. I've read that it's like 10000 iu in ten to fifteen minutes, midday for fair skin. I think even adjusting for my skin tone, it's gotta be more than that in an hour. I do hear that skin synthesized d is water soluble unlike oral. Also I've been on a low sulfur diet for a few months... I'm guessing I'm quite depleted in sulfur.

Sorry about the insomnia :/ I tried 3 mg Boron today and think it has helped somewhat with the anxiety I think comes from sulfur. I'm going to try playing around with the moly, Boron and manganese. Though not all at once.

I think nos is involved with my pots and ammonia issues. When I took mthf at first yesterday, I felt like my extremities were finally getting some blood. I frequently feel like they get cold when I do something to encourage detox. I'm not sure what effects it. Today, they're cold again even after taking more mthf. My combo supplement has a nearly equal amount of mthf and mb12 which seems like an issue

 

[xena]

I started wheezing again tonight after skipping my dose of vitamin D today.

I then started Amy Yasko's 1298 liver support which has some Biopterin added. The wheezing stopped and my feet feel warm again.

I think the connection is NOS. I think the nadh also supports ammonia detox... And the green tea extract also supports bh4 recycling. Broccoli, milk thistle and Egcg are all nrf2 activators which I've found helps my symptoms before. Nrf2 induces NOS.

VITAMIN D3 (AS CHOLECALCIFEROL) 50 IU
VITAMIN B3 (AS NIACINAMIDE) 10mg
PROPRIETARY BLEND: 415mg
~LIVER EXTRACT (bovine, freeze dried)
~DANDELION ROOT EXTRACT
~TREHALOSE
~BROCCOLI EXTRACT
~MILK THISTLE SEED EXTRACT
~GREEN TEA EXTRACT (Leaf)
~NADH (stabilized)
~L-BIOPTERIN

 

[sflorence]

Reporting back.


Tried ornothine at like 2g/day and didn't feel anything. Also added in 4g of Arginine with it after the 2nd day.


Seems like the Urea Cycle is a tough battle to fight.

 

[Gondwanaland]

Biotin helps with ammonia.

 

[xena]

My ammonia issues cleared up with the addition of high doses of vitamin D. Thanks @aaron_c

I've observed biotin generally helps my mood, body heat production

I've been taking big doses of mthf and mb12 and four Yasko pills a day, including 50 mg p5p. I notice I still need Boron, manganese, and molybdenum daily to deal with anxiety that I think is caused by the sulfites. I think I seriously depleted my detox capacity on the low sulfur diet bc I started to improve globally only when i started to eat lots of whey and nac. I used to have horrendous side effects of depression from these and b6 prior to mold avoidance fwiw, which I think helped open up blood flow to my gut and liver and reduced inflammation globally. The methylation support alone had little effect. Actually that's pretty odd I guess but fortunately I've been feeling a bit better for several weeks consistently now which I think is mainly due to my detox working better.

 

[ebethc]

@xena

How high of a vitamin d dosage? How often?

 

[xena]

@xena

How high of a vitamin d dosage? How often?

15000 iu daily initially for a few weeks and now 10-15000 iu a few days a week

 

[Gondwanaland]

Since manganese is required for the conversion of ammonium ions to urea, a deficiency may lead to a ammonium toxicity.

Additionally, in the text linked there is reference to symptoms of Mn deficiency that resemble those of B2 deficiency.